FDA Seeks Comments on DTC Study

The Food and Drug Administration is seeking public comment on its investigation of the impact of communicating risks in direct-to-consumer prescription drug television advertisements.  Readers know of the importance of the DTC context in drug litigation.

The notice announcing the comment period notes that prescription drug advertising regulations (21 CFR 202.1) require that broadcast (TV or radio) advertisements present the product's major risks in either audio or audio and visual parts of the advertisement; this is often called the "major statement." There is concern that as currently implemented in DTC ads, the major statement is often too long, which may result in reduced consumer comprehension, minimization of important risk information and, potentially, therapeutic noncompliance due to fear of side effects. Not all agree; one possible resolution is to limit the risks in the major statement to those that are serious and actionable, and include a disclosure to alert consumers that there are other product risks not included in the ad. For example, the disclosure could be, "This is not a full list of risks and side effects. Talk to your doctor and read the patient labeling for [drug name] before starting it."

The Office of Prescription Drug Promotion  plans to investigate the effectiveness of this "limited risks plus disclosure" strategy through empirical research, with the hypothesis that, relative to inclusion of the full major statement, providing limited risk information along with the disclosure about additional risks will promote improved consumer perception and understanding of serious and actionable drug risks. 

 

The FDA invites comments by 4/21 on: 

• whether the proposed collection of information is necessary for the proper performance of the FDA's functions;
•the validity of the methodology and assumptions used;
• ways to enhance the quality, utility and clarity of the information to be collected.

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FDA Issues Draft Guidance on Social Media

The U.S. Food and Drug Administration recently took a small step towards providing industry with the long-awaited guidance on how pharmaceutical makers may communicate about their products on social media like Twitter. 

In July, 2012, Congress gave the FDA two years to come up with comprehensive policies on Internet promotion, and FDA has now released for comment the draft guidance document entitled, "Fulfilling Regulatory Requirements for Postmarketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics." It is the first of what is certain to be a series of guidance documents on this subject. 

This draft guidance is intended to describe FDA’s current thinking about how manufacturers, packers, and distributors (firms), that may either be the applicant or acting on behalf of the applicant, of prescription human and animal drug and biological products (drugs) can fulfill regulatory requirements for postmarketing submissions of interactive promotional media for their FDA-approved products. 

FDA states that a company will be responsible for product promotional communications on sites that are owned, controlled, created, influenced, or operated by, or on behalf of, the firm. Such product promotional communications may include firm-sponsored microblogs (e.g., Twitter), social networking sites (e.g., Facebook), firm blogs, and other sites that are under the control or influence of the firm. In determining whether a firm must submit promotional material about its product to FDA, the Agency considers whether the firm, or anyone acting on its behalf, is influencing or controlling the promotional activity or communication in whole or part. Thus, a firm is responsible if it exerts influence over a site in any particular, even if the influence is limited in scope. For example, if the firm collaborates on or has editorial, preview, or review privilege over the content provided, then it is going to be responsible for that content, says the document. A firm is responsible for promotion on a third-party site if the firm has any control or influence on the third-party site, even if that influence is limited in scope. For example, if a firm collaborates, or has editorial, preview, or review privilege, then it is responsible for its promotion on the site and, as such, that  the site is subject to submission to FDA to meet postmarketing submission requirements. 

FDA said it recognizes the challenges of submitting promotional materials that display real-time information and thus in the draft makes recommendations for submitting interactive promotional media. The main point of this part of the draft guidance is that marketers don’t always need to obtain FDA pre-clearance on planned tweets or an online posting before it is sent out.  If a firm submits interactive promotional media in the manner described in this draft guidance, FDA intends to exercise enforcement discretion regarding the regulatory requirements for postmarketing submissions related to promotional labeling and advertising.

The draft does not address such things as how risks can be communicated within the character-limits of media like Twitter, and  what constitutes acceptable use of hyperlinks. Clearly, more to come.

 

Energy Drink Case Subject to Primary Jurisdiction

We have posted before about the important doctrine of primary jurisdiction.  Last week, a defendant obtained dismissal of a proposed class action over its energy drinks under this theory. See Fisher v. Monster Beverage Corp., No. 12-2188 (C.D. Cal. 11/12/13).

Plaintiffs sued individually and as putative class representatives for  allegedly "unfair and deceptive business and trade practices on behalf of anyone who purchased for personal consumption any of the Monster-branded energy drinks sold under the Monster Rehab® brand name and the original Monster Energy®."  Plaintiffs alleged various misrepresentations on the labels of the Original Monster and Rehab Varieties cans, including language that the drink "quenches thirst, hydrates like a sports drink, and brings you back after a hard day's night", that it would "RE-FRESH, RE-HYDRATE, REVIVE," and is "the ideal combo of the right ingredients in the right proportion to deliver the big bad buzz that only Monster can."  Plaintiffs alleged these statements were  misrepresentations because the cans do not hydrate like a sports drink, and allegedly cause dehydration; because "it is not the ideal combo of the right ingredients in the right proportion" and because the statement omits the potential health risks associated with such drinks.  Plaintiffs also alleged claims related to Monster's advertising "strategy."  Plaintiffs alleged that Monster specifically "targets" youth despite the caffeine levels in Monster Drinks.

The court tackled a number of challenges, including standing, preemption (some claims were preempted by the Nutrition Labeling and Education Act), and the absence of particularity in many of the fraud allegations.  But our focus here is on primary jurisdiction.  The primary jurisdiction doctrine allows courts to stay proceedings or to dismiss a complaint without prejudice pending the resolution of an issue within the special competence of an administrative agency; it is most often invoked if a claim involves an issue of first impression or a particularly complicated issue Congress has committed to a regulatory agency.  The courts traditionally weigh four factors in deciding whether to apply the primary jurisdiction doctrine: (1) the need to resolve an issue that (2) has been placed by Congress within the jurisdiction of an administrative body having regulatory authority (3) pursuant to a statute that subjects an industry or activity to a comprehensive regulatory authority that (4) requires expertise or uniformity in administration.  The court determines that an otherwise cognizable claim implicates technical and policy questions that should be addressed in the first instance by the agency with regulatory authority over the relevant industry rather than by the judicial branch.

Defendants argued that the FDA has jurisdiction over issues involving food safety and labeling, and the FDA has specialized expertise in the "technical and policy" questions involved here; the FDA has commenced a science-based evaluation of the safety of caffeine-containing food products, including energy drinks. They also argued that the FDA has primary jurisdiction because the agency has special competence over the matters involving the alleged inadequate warnings and failure to warn issues in this case.  The court agreed that the matters at issue here have been placed by Congress within the jurisdiction of the FDA pursuant to statute and regulations that require the FDA's expertise. The FDA has regulatory authority over food labeling. The FDCA establishes a uniform federal scheme of food regulation to ensure that food is labeled in a manner that does not mislead consumers. Second, plaintiffs' claims ultimately involve "technical and policy claims" about the effects of caffeine and whether Monster should be allowed to advertise and label their products in a way that appeals to a younger demographic. Plaintiffs cited to studies examining the effects of "energy drinks" in general, demonstrating that issues raised in the complaint may affect an entire industry. 

Third, the FDA has taken an interest in investigating and resolving whether energy drinks, including Monster, contain proper levels of caffeine. The FDA's interest in regulating the safety of caffeine weighed in favor of exercising the primary jurisdiction doctrine.  Thus, the Court found that plaintiffs' claims were covered under the Primary  Jurisdiction Doctrine.  

 

 

Class Action Rejected Per Primary Jurisdiction Defense

A California federal court recently rejected a putative class action alleging meal replacement bars sold in General Nutrition Centers Inc. stores somehow defrauded customers into thinking they were healthy because they were labeled with the term “zero impact.”  See Gabe Watkins v. Vital Pharmaceuticals, et al., No. 2:12-cv-09374 (C.D. Cal. 2013).  Readers may be interested in the discussion of primary jurisdiction.

On September 25, 2012, Plaintiff filed a Class Action Complaint in the Superior Court of California
for Los Angeles County. Plaintiff alleged that Defendants falsely labeled the Bars in violation of the Unfair Competition Law ("UCL"), Cal. Bus. & Prof. Code § 17200, et seq., and the Consumers Legal Remedies Act ("CLRA"), Cal. Civ. Code § 1750, et seq.  Defendants removed the action to federal court, asserting federal subject matter jurisdiction in reliance on the Class Action Fairness Act, 28 U.S.C. § 1332(d)(2).

Plaintiff asserted that while Vital and GNC marketed and advertised the Bars as 'ZERO IMPACT,' the Bars have an impact on consumers' carbohydrate, sugar and overall caloric intake, and to claim otherwise was "false and misleading."  However, the back of the wrapper features nutritional facts, an ingredient list, and a marketing statement, which notes that the low Dextrose Equivalent sugars contained in the Bars have less impact on blood sugar and glycemic index than most whole grain carbohydrates.  Plaintiff responded that the location and type size of the nutritional information and marketing statement allegedly made it too difficult to see and read.

Defendant moved to dismiss, arguing that the court should defer the question of whether the "ZERO IMPACT" label is misleading, to the Food and Drug Administration under the doctrine of primary jurisdiction.  Primary jurisdiction is a doctrine specifically applicable to claims properly cognizable in court that contain some issue within the special competence of an administrative agency.  Reiter v. Cooper, 507 U.S. 258, 268 (1993). While it is not to intended to secure expert advice for the courts from regulatory agencies every time a court is presented with an issue conceivably within the agency's ambit, it is a doctrine used by the courts to allocate initial decision-making responsibility between agencies and courts where such jurisdictional overlaps and potential for conflicts exist.  Syntek Semiconductor Co., Ltd. v. Microchip Tech. Inc., 307 F.3d 775, 780 (9th Cir. 2002). Typically, there are four factors present in cases where the doctrine properly is invoked: (1) the need to resolve an issue that (2) has been placed within the jurisdiction of an administrative body having regulatory authority (3) pursuant to a statute that subjects an industry or activity to a comprehensive regulatory scheme that (4) requires expertise or uniformity in administration. See United States v. Gen. Dynamics Corp., 828 F.2d 1356, 1362 (9th Cir. 1987). The doctrine is often most applicable where a claim requires resolution of an issue of first impression or of a particularly complicated issue that Congress has committed to a regulatory agency.

Here, the court concluded that the relevant factors weighed in favor of dismissing plaintiff's claims in deference to the FDA's primary jurisdiction.

Defendants contended that the FDA has primary jurisdiction over how a manufacturer may name
and label its food products and that the resolution of plaintiff's UCL and CLRA claims would clearly invade the FDA's primary jurisdiction. Indeed, Congress has granted the FDA regulatory authority over false and misleading food labeling as part of the Food, Drug, and Cosmetic Act. The primary jurisdiction doctrine was applicable in this case because the FDA has yet to consider the nutritional import of the claim "ZERO IMPACT" or in what context the claim might possibly mislead consumers about a product's nutritional content.

Plaintiff's claims centered on the argument that the nature of the marketing claim "ZERO IMPACT," combined with its location on the wrapper and larger type size, somehow created the impression that the Bars have no dietary impact at all.  But could not direct the court to any FDA rule, regulation, or guidance document discussing how the claim "ZERO IMPACT" or even the word "impact" can or should be used to describe a food product's nutritional content. Nor is there any evidence of the FDA bringing an enforcement action against anyone regarding the "ZERO IMPACT" claim or the nutrient content on its label.  Without any guidance about the context in which the FDA would find the claim "ZERO IMPACT" to be permissible, any determination on whether the term is misleading risked undermining, through private litigation, the FDA's considered judgments.

The FDA has issued some regulations with regard to the word "zero," but these are designed to
make sure that foods with claims like "zero calorie," "zero sodium," and "zero fat" contain the type
and amount of nutrients that a reasonable consumer would expect. See 21 C.F.R. §§ 101.60-101.62. Without more, however, there is no reasoned way for a court to determine whether the FDA regulations associated with labeling items as "zero calorie" and "zero fat" could encompass a claim like "ZERO IMPACT."   Calories, sugar, and fat are specific nutritional elements, but "impact" may refer to the effect those elements have on the human body.

In the absence of any FDA rules or regulations (or even informal policy statements) regarding the
use of the word 'impact' on food labels, the court declined to make any independent determination on whether defendant's use was false or misleading.  The court  concluded it lacked the FDA's expertise in guarding against deception in the context of food labeling.  See Pom Wonderful, 679 F.3d at 1178, and so it deferred this issue to the FDA to consider administrative action regarding the use of the "ZERO IMPACT" claim.

 

FDA Proposes Two New Food Regulations for Imports

 The U.S. Food and Drug Administration proposed two new rules last week that would impact imported food, including by establishing a program to accredit third-party auditors to certify foreign food facilities.  The rules were called for by the Food Safety Modernization Act of 2011, which revised the regulatory system to deal with risks of food-borne illness. We have posted before about the litigation that can arise from such situations. 

 

Under the proposed rules, which follow on regulations proposed earlier this year, importers would be accountable for verifying that their foreign suppliers are implementing modern, prevention-oriented food safety practices, and achieving the same level of food safety as domestic growers and processors. The FDA is also proposing rules to strengthen the quality, objectivity, and transparency of foreign food safety audits on which many food companies and importers currently rely to help manage the safety of their global food supply chains.

Imported food comes into the United States from about 150 different countries and accounts for about 15 percent of the U.S. food supply, including about 50 percent of the fresh fruits and 20 percent of the fresh vegetables consumed by Americans.

Under the proposed regulations for Foreign Supplier Verification Programs (FSVP), U.S. importers would have a clearly defined responsibility to verify that their suppliers produce food to meet U.S. food safety requirements. In general, importers would be required to have a plan for imported food, including identifying hazards associated with each food that are reasonably likely to occur. Importers would be required to conduct activities that provide adequate assurances that these identified hazards are being adequately controlled.

The FSMA also directs the FDA to establish a program for the Accreditation of Third-Party Auditors for imported food. Under this proposed rule, the FDA would recognize accreditation bodies based on certain criteria such as competency and impartiality. The accreditation bodies, which could be foreign government agencies or private companies, would in turn accredit third-party auditors to audit and issue certifications for foreign food facilities and food, under certain circumstances.
Importers will not generally be required to obtain certifications, but certifications may be used by the FDA to determine whether to admit certain imported food that poses a safety risk into the United States.

The FSVP proposed rule and the third-party accreditation proposed rule are available for public comment for the next 120 days. 

 

Supreme Court Issues Important Preemption Ruling

The Supreme Court last week reversed the First Circuit decision in Mutual Pharmaceutical Co. v. Bartlett, No. 12-142 (U.S., 6/24/13).

Readers will recall that in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011), the Supreme Court held that state tort law claims against generic drug manufacturers based on the alleged inadequacy of the drug labeling are preempted; under the Hatch-Waxman Amendments to the Food, Drug and Cosmetic Act, generic drug labeling must be the same as the labeling of the reference-listed drug. Because generic drug manufacturers cannot independently change the labeling, state law failure to warn claims are preempted.

Plaintiffs proceeded to hunt for exceptions, ways around the ruling.  One of the strategies was to resurrect design defect theories, which traditionally were not a major aspect of most drug plaintiff claims. This case was tried on a design defect theory of liability after the plaintiff’s failure to warn claims were dismissed prior to trial and the district court rejected the generic manufacturer’s preemption defense on the design claim.  The jury found for plaintiff, and defendant appealed, arguing that just as the manufacturer cannot alter the label, once a drug—whether generic or brand-name—is approved, the manufacturer is prohibited from making any major changes to the qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved new drug application.  In Bartlett, the First Circuit held that the plaintiff’s state law theory of liability could nevertheless be reconciled with federal law because, although the generic manufacturer could change neither the design nor the labeling, it could avoid liability if it stopped selling the drug entirely within the state.

The Supreme Court reversed.

New Hampshire imposes design defect liability where the design of the product created a defective condition unreasonably dangerous to the user. To determine whether a product is “unreasonably dangerous,” the New Hampshire Supreme Court employs a risk/utility approach under which a product is defective as designed if the magnitude of the danger outweighs the utility of the product. The New Hampshire Supreme Court has repeatedly identified three factors as germane to the risk-utility inquiry: the usefulness and desirability of the product to the public as a whole, whether the risk of danger could have been reduced without significantly affecting either the product’s effectiveness or manufacturing cost, and the presence and efficacy of a warning to avoid an unreasonable risk of harm from hidden dangers or from foreseeable uses.  

In the drug context, either increasing the “usefulness” of a product or reducing its “risk of danger” would require redesigning the drug: a drug’s usefulness and its risk of danger are both direct results of its chemical design and, most saliently, its active ingredients. Here, said the Supreme Court, redesign was not possible, as the FDCA requires a generic drug to have the same active ingredients, route of administration, dosage form, strength, as the brand-name drug on which it is based. Given the impossibility of redesigning the drug, the only way for the defendant to ameliorate the drug’s “risk-utility” profile—and thus to escape liability—was to strengthen the presence and efficacy of the warning in such a way that the warning avoided an unreasonable risk of harm from hidden dangers or from foreseeable uses.

That was, of course, preempted.  When federal law forbids an action that state law requires, the state law is “without effect.” Because it is impossible for generic manufacturers to comply with both state and federal law, New Hampshire’s warning-infused design defect cause of action was pre-empted with respect to FDA-approved drugs sold in interstate commerce.

The Supreme Court rejected the argument that a defendant could satisfy both laws by paying tort judgments or refraining from selling its product in that particular state. And rejected the “stop-selling” rationale as incompatible with its pre-emption jurisprudence. The Court's pre-emption cases presume that an actor seeking to satisfy both his federal and state law obligations is not required to cease acting altogether in order to avoid liability. Indeed, if the option of ceasing to act defeated a claim of impossibility, impossibility pre-emption would be all but meaningless. The incoherence of the stop-selling theory becomes plain when viewed through the lens of the previous cases. In every instance in which the Court has found impossibility pre-emption, the direct conflict between federal and state law duties could easily have been avoided if the regulated actor had simply ceased acting.

Interestingly, there is nothing in the Court's rejection of “stop-selling” limiting it to generic drugs; the rejection seems applicable to all federally regulated products because it's not based on the FDCA but is an argument “incompatible with our pre-emption jurisprudence.”

 

No Purchase, No Standing

Earlier this month a federal court reaffirmed that a named class representative in a proposed consumer class action against Ghirardelli Chocolate Co. lacked standing to assert claims about products he never bought. See Miller v. Ghirardelli Chocolate Co., No. 12-04936 (N.D. Cal. 4/5/13). We have posted before about plaintiffs overreaching in consumer fraud class actions. If a tree falls and no one is there, does it make a sound? If you never bought and used a product, how can you bring a “consumer” claim?

Plaintiff Scott Miller allegedly bought a package of “Ghirardelli® Chocolate Premium Baking Chips –Classic White” and then, on behalf of himself and other consumers, sued the Ghirardelli
Chocolate Company, complaining that defendant somehow deceived customers into thinking that this and four other products contained “artificial” or “imitation” ingredients, in violation of United States Food and Drug Administration (“FDA”) and state regulations.

Readers may know that Ghirardelli is one of America’s longest continuously operating chocolate manufacturers (more than 150 years) and that it is one of very few American manufacturers that make chocolate starting from the cocoa bean through to finished products. Ghirardelli accepts
only the highest-quality beans, rejecting as many as 30% of the beans that are offered it. Ghirardelli roasts the cocoa beans in-house to ensure the company’s signature flavor profile is consistently maintained in all chocolate products.

Miller filed suit in San Francisco County Superior Court, and Ghirardelli removed to federal
court and moved to dismiss the complaint. The court initially agreed that Miller lacked standing for products he had not purchased. At oral argument, however, plaintiff argued that the branding on the label meant that – under the FDA regulations and standards – the alleged harm was identical across product lines, and that established standing as to products he never used. Miller filed an amended complaint and Ghirardelli again moved to dismiss.

Hard as it may be to believe, there are a few cases that suggest that a plaintiff who does not purchase a product nonetheless may have standing if the products and alleged misrepresentations were substantially similar. E.g., Astiana v. Dreyer’s Grand Ice Cream, Inc., No. C-11-2910 EMC, 2012 WL 2990766, at *11 (N.D. Cal. July 20, 2012). But certainly where the alleged misrepresentations or accused products are dissimilar, courts tend to dismiss claims to the extent they are based on products not purchased. E.g., Larsen v. Trader Joe’s Co., No. 11-cv-5188-SI (Docket No. 41) (N.D. Cal. June 14, 2012), the court found that the plaintiffs lacked standing to bring claims based on products they did not purchase (wide range of Trader Joe’s products (cookies, apple juice, cinnamon rolls,biscuits, ricotta cheese, and crescent rolls). See also Stephenson v. Neutrogena, No. C-12-0426 PJH, 2012 U.S. Dist. LEXIS 1005099, at *1 (N.D. Cal. Jul. 27, 2012) (plaintiff brought suit over six Neutrogena Naturals products but had only purchased the purifying facial cleanser).

Even under the Astiana approach, here the products were too different: they look different; they have different uses (baking chips, drink powders, and wafers); they have different labels and different representations on packaging, and they are marketed and sold differently in that, for example, some are sold alongside each other, and some are sold in commercial markets and others in consumer markets. The logo, which plaintiff put so much emphasis on, was relatively unimportant considering the varying products, packaging and representations, and markets. Logos cannot be dispositive of what a product is and that a consumer determines what a product or characterizing flavor is by reviewing the label. Finally, the identity of the commodity here under FDA regulations was “white chocolate,” not “chocolate” as in the logo. That in turn means that a determination of standing required an examination of the entire label, and again, the five products and the alleged misrepresentations were not sufficiently similar.

FDA Issues Proposed Food Safety Rules

The FDA last week issued two highly anticipated proposed rules relating to food process safety, with a stated goal of preventing foodborne illnesses. Readers will recall our posts on the litigation that can arise from food safety issues. FDA has now released for public comment a proposed rule on Preventive Controls for Human Food and a proposed rule on Standards for Produce Safety.

These rules are two of the proposed rules that FDA says are key to the preventive food safety approach established by the 2011 FDA Food Safety Modernization Act. The proposed rules build on existing voluntary industry guidelines for food safety, which many producers, growers and others currently follow. FDA expects to soon issue its proposed rule on importer foreign supplier verification; future proposed rules will address preventive controls for animal food, and accreditation of third-party auditors.

The FDA will accept comments on the proposals for 120 days. While the effective date for the rules would be 60 days from publication of the final rule, the general compliance date would be two years after the effective date. For small businesses, the compliance date would be three years after the effective date, and for very small businesses four years after the effective date.

The proposed rule on preventive controls for human food would apply to facilities that manufacture, process, pack or hold human food. In general, with some exceptions, the new preventive control provisions would apply to facilities that are required to register with FDA under FDA’s current food facility registration regulations. The rule proposes firms have written plans in place to identify potential hazards, put in place steps to address them, verify that the steps are working, and outline how to correct any problems that arise. FDA says the proposed hazard analysis rules are similar to the "HACCP” (Hazard Analysis and Critical Control Points) regulations that govern the production of certain seafoods and meats. The proposed produce rule covers all fruits and vegetables except those rarely consumed raw, produced for personal consumption, or destined for commercial processing that will reduce microorganisms of public health concern.

FDA estimates that the total annual compliance costs for the two regulations will exceed $1 billion.  million, depending on the scope of the exemption for “very small businesses.” The draft appears not to offer an estimate of the benefits that might result from the new rules.

Primary Jurisdiction Doctrine Leads to Dismissal of Food Claim

As our loyal readers know, the plaintiffs bar is poised to bring proposed class action litigation against food and beverage sellers over virtually any ingredient, marketing, label, or advertising it can shoehorn into an alleged unlawful trade practice.  It is gratifying when a court recognizes that proper forum for many such complaints is the Food and Drug Administration, not in court.  A recent example arises from the proposed class action over an ingredient in yogurt.  See Taradejna v. General Mills Inc., No. 12-993 (D. Minn.,12/10/12).

Plaintiff Martin Taradejna brought this putative class action alleging violations under the Minnesota Prevention of Consumer Fraud Act, the Minnesota Unlawful Trade Practices Act, and the Minnesota Uniform Deceptive Trade Practices Act, related to the alleged mislabeling of Greek yogurt. Plaintiff alleged that Greek yogurt is typically strained to remove the whey, resulting in a creamier product, richer in protein and lower in lactose.  Taradejna alleged that rather than straining, Defendants chose to use Milk Protein Concentrate (“MPC”) when they entered the Greek yogurt market in 2010. A blend of dry dairy products, MPC is sold in a powdered form that typically retains all protein components of milk.  Defendants’ use of MPC in the manufacture of its Greek yogurt results in a product with the thickness and protein content typical of Greek yogurt.  And the labeling of Defendant’s Greek yogurt discloses MPC as an ingredient. Taradejna contended, however, that this Greek yogurt failed to comply with legal and regulatory rules governing the labeling of food because it contained significant amounts of  MPC, and thus was not true Greek   yogurt.  Consequently, Taradejna alleged that Defendants’ actions in marketing this product violated the various Minnesota consumer protection statutes.

The FDA regulates food product ingredients and labeling and creates definitions and “standards of identity” for certain foods. Standards of identity define the particular food, and describe its ingredients, and approved processes of manufacture; as far back as 1981, the FDA promulgated such standards of identity for yogurt, 21 C.F.R. § 131.200, low-fat yogurt, 21 C.F.R. § 131.203, and nonfat yogurt, 21 C.F.R. § 131.206.  Plaintiff alleged use of MPC as an ingredient is not permitted in yogurt. Defendants pointed to a publicly available response to questions raised with the FDA at a 2004 milk seminar, stating that milk protein concentrate can be used as an ingredient in yogurt to increase the nonfat solids content.  And in 2009, the FDA proposed additional regulations to permit the optional use of any safe and suitable milk-derived ingredient as an optional dairy ingredient in the manufacture of yogurt to increase the nonfat solids content of the food above the minimum required 8.25 percent.

Plaintiff sought to represent a national class that had allegedly paid too much for this Greek yogurt made another way.  Defendant moved to dismiss on several grounds, but the district court focused on primary jurisdiction, a common-law doctrine that is utilized to coordinate judicial and administrative decision making. See Access Telecomms. v. Southwestern Bell Tel. Co., 137 F.3d 605, 608 (8th Cir. 1998). The doctrine applies where a claim may be cognizable in the courts, but where enforcement of the claim requires the resolution of issues which, under a regulatory scheme, have been placed within the special competence of an administrative body. See Alpharma, Inc. v. Pennfield Oil Co., 411 F.3d 934, 938 (8th Cir. 2005).  Agency expertise is the most common reason that courts apply the doctrine of primary jurisdiction. In addition, courts apply the doctrine to promote uniformity and consistency within the particular field of regulation.

The underlying issue here was whether MPC is a proper or permitted ingredient in the yogurt. The court concluded that resolution of this question falls squarely within the competence and expertise of the FDA, pursuant to the authority granted to the Agency by Congress. Issues of food labeling are sufficiently complex that they are best left to FDA for consideration prior to judicial review.  See Lever Bros. Co. v. Mauer, 712 F. Supp. 645, 651 (S.D. Ohio 1989); Heller v. Coca-Cola Co., 230 A.D.2d 768, 769-70 (N.Y. App. Div. 1996).)  The current standard of identity for yogurt, the  Agency’s public statements about the standard, and the 2009 Proposed Rule all may impact the question, and the FDA is in the best position to resolve any ambiguity about the standard of identity for yogurt – a matter requiring scientific and nutritional expertise.

Moreover, said the court, given that the FDA has issued its 2009 Proposed Rule on the standard of identity for yogurt, it would be imprudent for a court, at this juncture, to substitute its judgment for that of the Agency’s while revision of the standard is pending. Moreover, the FDA’s ultimate decision on the permitted ingredients in yogurt would ensure national uniformity in labeling, utilizing the Agency’s special expertise in this regard.

So, bottom line, the court used primary jurisdiction to put these issues where they belong—with the FDA.

 

Supreme Court Declines to Review Medical Device Case

Earlier this week, the Supreme Court declined to hear plaintiff's challenge to the Fourth Circuit's decision on an important aspect of medical device law in Walker v. Medtronic Inc., No. 11-1418 (U.S. 10/1/12). 

The Court denied the petition for a writ of certiorari from plaintiff Walker, who appealed a Fourth Circuit decision that held that the 1976 Medical Device Amendments to the Federal Food, Drug and Cosmetic Act preempted her suit alleging that defendant's medical device caused her husband's death.  The denial may help to clarify the standard set forth in Riegel v. Medtronic, which held that state law requirements are generally preempted by the MDA.  More specifically, the case relates to the so-called “parallel violation claim” exception to the general rule of medical device preemption.  Readers may recall that some dicta in Riegel noted a theoretical possible exception for when a claim of a violation was "parallel" to and not different than the FDA's actual requirements.

The court of appeals, 2012 WL 206036, slip op. (4th Cir. Jan. 25, 2012), offered a very narrow view of this exception, a good thing for manufacturers.  Walker alleged he had used a Class III device designed to infuse a preset amount of  medicine into the fluid that surrounded his spinal cord.  Plaintiff passed away, and a claim was filed alleging that the device was defective, leading to a fatal overdose.  Plaintiff's attempt to evade the reach of preemption turned on language in the product literature that the device would give the specified dosages ±15%, language plaintiff said was a “guarantee of performance,” creating an un-preempted “parallel” violation claim. 

The court held the parallel exception is quite narrow. The FDA has performance standards, under which a manufacturer must guarantee a particular level functioning or performance.  The FDA may condition its grant of premarket approval upon such performance standards if it determines that a performance standard is necessary to provide reasonable assurance of the safety and effectiveness of the device. See 21 U.S.C. §360d(a)(1).  But the establishment of a performance standard is a highly formal process, requiring notice, findings of fact on risks, and comments from interested stakeholders.  

So, when a plaintiff asserts that a statement or representation or feature that hasn’t gone through the formal FDA procedure is a “performance standard,”  that is in fact asserting something different from or in addition to the FDA standards for the product within the meaning of the Act’s preemption clause. Thus, it is preempted.  The court of appeals concluded that the only mechanism for creating a binding, ongoing performance requirement is the creation of a performance standard. And the plus or minus 15 percent specification was not a performance standard.

That makes complete sense because the device in question was manufactured in full compliance with what the FDA required.   Expectations that may have been generated by literature surrounding the product are not the same thing as FDA standards. The device was not required to always dispense medication within the range of the plus or minus 15 percent.  And for plaintiff to try to sue over this feature would be to seek to impose a more demanding standard than that of the FDA, rather than just a parallel one.

Walker appears to be one of the first appellate court decisions to reject this type of claim on the basis that a mere device malfunction that does not relate to a formal performance standard is not going to be enough to establish a “parallel” violation claim. And the Supreme Court leaves it in place.

Federal Court Offers Cogent Analysis of Warning Causation in Drug Case

A New Jersey federal court granted summary judgment last week to a pharmaceutical defendant in a failure to warn case. See Baker et al. v. APP Pharmaceuticals LLP et al., No. 3:09-cv-05725 (D.N.J.).  The case should be interesting to our readers in part because there really isn't a huge amount of law on warning causation in the busy jurisdiction of New Jersey.

During a hospital stay, plaintiff Baker was administered the commonly prescribed drug heparin. Heparin is an anticoagulant: it prevents blood clots. The opinion noted that the drug is associated  with heparin induced thrombocytopenia (“HIT”), or low blood platelet count. HIT may in a few patients progress to a more serious adverse reaction called heparin induced thrombocytopenia  and thrombosis (“HITT”). Plaintiff received heparin during and after her surgery, and a few days later her  platelet count was down; but according to the opinion it was not known at what point her platelet count reached serious levels because no one measured her platelet level for several days, despite the hospital’s stated protocol to monitor a patient’s platelet count periodically in order to detect possible HIT.

Plaintiff suffered injury to her left foot and leg, and thereafter sued several manufacturers of heparin, asserting they failed to adequately warn of the serious side-effects associated with heparin use. The parties agreed that defendant’s heparin has always contained FDA-approved labeling, including risk disclosures and warnings. In 2001, the heparin label specifically disclosed the risk of HIT and HITT in the “Precautions” section.  In 2005, defendant submitted a supplemental NDA via the “changes being effected” process to include additional HIT and HITT information the “Warnings” section of its heparin labeling. See 21 C.F.R. 314.70. The FDA suggested several alterations, all of which defendant incorporated into the labeling, and the FDA found the updated labeling “acceptable” in June 2007. 

In New Jersey, product liability actions are governed by the New Jersey Products Liability Act (“PLA”). N.J. Stat. Ann. §2A:58C-1, et seq. Under the PLA, in failure to warn cases involving prescription drugs, if the warning or instruction given in connection with a drug has been approved or prescribed by the FDA, there is a rebuttable presumption that the warning is adequate. This is no ordinary rebuttable presumption, remarked the court. Compliance with FDA regulations gives rise to “what can be denominated as a super-presumption.” Kendall v. Hoffman-La Roche, Inc., 36 A.3d 541, 544 (N.J. 2012).  Indeed, the PLA’s presumption that an FDA-approved prescription drug label is adequate “is stronger and of greater evidentiary weight than the customary presumption referenced" in the rules of evidence. Bailey v. Wyeth, Inc., 37 A.3d 549, 571 (N.J. Super. Ct. Law Div. 2008), aff’d sub nom. Deboard v. Wyeth, 28 A.3d 1245 (N.J. Super Ct. App. Div. 2011).

In this case, there is no dispute that the heparin labeling was approved by the FDA. Therefore, defendant was entitled to the statutory presumption that its heparin labeling satisfied its duty to warn. Plaintiff tried to rebut the presumption, first, with allegations of deliberate concealment or nondisclosure of after-acquired knowledge of harmful effects by the pharmaceutical company, and second with allegations of an economically-driven manipulation of the post-market regulatory process. See McDarby v. Merck & Co., Inc., 949 A.2d 223, 256 (N.J. Super. Ct. App. Div. 2008).

However, significantly, all of the information plaintiff accused defendant of withholding was publicly available in published scientific and medical literature.  And defendant did in fact disclose much
of what plaintiff claimed was deliberately concealed or withheld. For example, when submitting its proposed updated label to the FDA in 2005, Baxter included several scientific articles and a number of adverse event reports relating to HIT and HITT.  As to the second rebuttal effort, plaintiff offered no real evidence that Baxter rejected the FDA’s proposed changes to heparin labeling, or asked pharmaceutical representatives to avoid discussing HIT and HITT when speaking to physicians, or manipulated the conclusions of heparin clinical trials, or did anything sufficient to "manipulate" the regulatory process.

The more interesting part of the opinion arises from the fact that even if a plaintiff is able to demonstrate that a prescription drug’s warning is inadequate, that plaintiff still must prove that the inadequate warning proximately caused her injury. See Campos v. Firestone Tire & Rubber Co., 485 A.2d 305, 311 (N.J. 1984). “To satisfy this burden, a plaintiff must show that adequate warnings would have altered her doctors’ decision to prescribe.” Strumph v. Schering Corp., 606 A.2d 1140 (N.J. Super. Ct. App. Div. 1992) (Skillman, J., dissenting), rev’d 626 A.2d 1090 (1993) (adopting Judge Skillman’s dissent).

The court noted that “a heeding presumption may be applicable to claims of failure to warn of the dangers of pharmaceuticals.” McDarby, 949 A.2d at 267. A heeding presumption allows one to presume that the plaintiff’s physician would not have prescribed the drug to the plaintiff if there had been an adequate warning; in other words, the plaintiff’s physician would have heeded the adequate warning. The heeding presumption is rebuttable and can be rebutted if the plaintiff’s physician was aware of the risks of the drug that he prescribed, and having conducted a risk-benefit analysis, nonetheless determined its use to be warranted. Also. a manufacturer who allegedly fails to warn the medical community of a particular risk may nonetheless be relieved of liability under the learned intermediary doctrine if the prescribing physician either did not read the warning at all, or if the physician was aware of the risk from other sources and already considered the risk in prescribing the product. In that context, the physician’s conduct is the superseding, intervening cause that breaks the chain of liability between the manufacturer and the patient.

Here, the doctor stood by his decision to administer heparin to Mrs. Baker. She required heparin by standard medical procedure, and well documented clinical knowledge, at several different  points during her operation and for several different reasons, he opined.  Since he was aware of the risks of the drug that he prescribed and, having conducted a risk-benefit analysis, nonetheless determined its use to be warranted, the presumption was rebutted as a matter of law.

Moreover, the prescriber testified in his deposition that he does not read the label of drugs he frequently prescribes, which includes heparin. Therefore, a different warning would not have made a difference in plaintiff's treatment or outcome because there was no evidence he would have reviewed it.

Finally, there was a third causation problem; the opinion notes that it was undisputed that, despite doctors orders, the Hospital failed to follow its own heparin treatment protocol. Had that monitoring occurred, Mrs. Baker’s physicians would have discovered the onset of HIT sooner. Plaintiff's own expert admitted that her injuries “would have been substantially mitigated” with a “good chance of avoiding" them.   Therefore, plaintiff failed to raise a genuine issue of material fact that it was the heparin labeling, as opposed to the conduct of the hospital, that caused her injury.

 Summary judgment on the warning claim.

Court Again Dismisses Claim Against "Non-Conventional" Alcohol Beverage

We posted last year about the dismissal of a motorcycle passenger's claim against the maker of a caffeinated alcoholic drink, seeking to hold the company liable for her crash-related injuries.See Cook v. MillerCoors LLC, No. 11-1488 (M.D. Fla.).

The operator of the motorcycle in the accident was killed, and the plaintiff Cook, who was a passenger, was injured. Prior to the crash, the driver allegedly had consumed several alcoholic beverages containing caffeine and other stimulants, manufactured by the defendant. Cook argued that such beverages were “uniquely dangerous” because they appeal to younger drinkers and because the addition of caffeine allegedly enables one to drink more alcohol without feeling as intoxicated as one normally would. Thus, she contended, consumers of these beverages are more likely to “engage in dangerous behavior such as driving.” She asserted the driver did not appear impaired, even though toxicology reports from his autopsy revealed that his blood alcohol level was 0.10 at the time of the crash.

The district court found flaws with the duty, breach, and causation elements of the claim. The court found that Cook had not established a duty to warn because “the dangers inherent in alcohol consumption are well known to the public.”  Readers can readily see why the court was reluctant to make an exception to the rule for the so-called "unconventional" beverage. There are hundreds of alcohol-containing products that are arguably not "conventional" in one way or another, by taste, ingredients, color, manufacturing process, advertising... To shift responsibility from the person who over-consumes one of these and then drives impaired is to send the absolutely wrong policy message.

Courts have typically recognized no duty on the beverage maker, regardless of a plaintiff's attempt to differentiate either themselves or the product. See, e.g., Malek v. Miller Brewing Co., 749 S.W.2d 521 (Tex. App. 1988) (finding no duty to warn despite claim that advertising led plaintiff to believe that “Lite” beer was less intoxicating than other beer); Pemberton v. Am. Distilled Spirits Co., 664 S.W.2d 690 (Tenn. 1984); Greif v. Anheuser-Busch Cos., Inc., 114 F. Supp. 2d 100 (D. Conn. 2000)(particular, alleged tolerance of an individual consumer); MaGuire v. Pabst Brewing Co., 387 N.W.2d 565 (Iowa 1986).

Plaintiff attempted to re-plead her claim, again alleging that the addition of stimulants that mask the intoxicating effects of alcohol was a defect, but also focusing on the supposed risks this formulation posed to youth. The court again found the complaint lacking. Alcoholic beverages are not considered unreasonably dangerous as defined by the Restatement (Second) of Torts, because the dangers associated with alcohol are well known.  Cook asserted that the risks are not common knowledge to youthful drinkers having experience only with conventional alcoholic beverages. This court was not convinced that “the special risks posed to youth” made the drink unreasonably dangerous from the perspective of the general public.  More significantly, Cook’s argument overlooked an important point: the alleged “special risks” manifest themselves only if the consumer chooses to drink in excess. The case law recognizes that anyone who drinks alcohol may become impaired and yet may not be able to discern his or her impairment. That does not make alcoholic beverages unreasonably dangerous or absolve the drinker of responsibility.

Moreover, the youth-based allegations did not change Florida law on causation, under which voluntary drinking of alcohol is the proximate cause of such an injury, rather than the manufacture or sale of those intoxicating beverages to that person. As to the plaintiff's warning theory, persons engaging in the consumption of alcoholic beverages may not be able to ascertain precisely when the concentration of alcohol in their blood, breath, or urine reaches the proscribed level, so they should in the exercise of reasonable intelligence, understand what type of conduct places them in jeopardy of violating the law. The degree of intoxication to be expected from any particular brand (or formulation) of alcoholic beverage does not require a special duty to warn, or give rise to a fact question about the warnings here.

The court distinguished Cuevas v. United Brands Co., Inc., 2012 WL 760403 (S.D. Cal. Mar. 8, 2012), as an economic injury claim brought under various consumer protection statutes and warranty theories which focused on the sale of the product allegedly in violation of FDA rules rather than its consumption.


 

House Passes FDA Reauthorization Bill

The House of Representatives last week passed a bill (387 to 5 vote) that would reauthorize the Food and Drug Administration's user fee programs and amend the rules regarding marketing exclusivity, medical device safety, drug importation, and other FDA programs. The "FDA Reform Act of 2012," H.R. 5651, reauthorizes and amends various user fee statutes, creates new and additional user fees, reauthorizes the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, changes the rules for public comment on draft guidance documents, and contains new provisions dealing with drug shortages.  The fees are supposed to reflect agreements negotiated between the FDA and industry regarding about $2.8 billion in user fees over five years.

The vote came shortly after the Senate approved its own version of FDA legislation, S. 3187 (the FDA Safety and Innovation Act). The Senate bill was also passed with bipartisan support.

The differences between the House and Senate bills now must be worked out in conference. The bills differ in a variety of ways, such as which antibiotics will be eligible for incentives, which include a five-year extension of market exclusivity. The bills also differ on the details of a national  track-and-trace system for drugs. The Senate bill also included language about Risk Evaluation and Mitigation Strategies (REMS) which is not in the House version. See a comparison of the bills here.  Various observers report that House and Senate leaders expect to have a compromise bill for the President to sign in early July.

 

Consumer Fraud Claim on "All Natural" Beverage Rejected

One trend we are keeping an eye on here at MassTortDefense is plaintiffs' aggressive and excessive use of consumer fraud act claims, micro-analyzing every ad, turning traditional puffing into some kind of nefarious marketing scheme.  Class certification in such cases can trigger the need to think about "blackmail settlements."

So all victories are worth noting, and last week South Beach Beverage Co. Inc., maker of SoBe drinks, garnered dismissal of a California putative class action alleging false claims about their "0 Calories Lifewater" drinks. See Charles Hairston v. South Beach Beverage Co. Inc,. et al., No. 2:12-cv-01429 (C.D. Cal. 5/18/12).

SoBe manufactures a diverse range of beverages, including teas and enhanced waters, that are characterized by exotic flavor combinations and added vitamins. In his First Amended Complaint, plaintiff alleged that during the last three to four years, he regularly purchased SoBe 0 Calorie Lifewater beverages (“Lifewater”), which are no-calorie, vitamin-enhanced, flavored water drinks. Plaintiff raised three challenges to Lifewater’s labeling, which he claimed he “read and relied on.” First, plaintiff alleged that the “all natural” label was potentially deceptive because Lifewater contains “deceptively labeled ingredients” that are “synthetic or created via chemical processing.” Second, plaintiff alleged that Lifewater’s labels are potentially misleading because the names of various fruits are used to describe the different flavors of Lifewater even though Lifewater allegedly does not contain any actual fruit or fruit juice. Third, plaintiff alleged that the use of the common vitamin name (e.g., B12) on the product labels is misleading because the vitamins added to Lifewater are "synthetic" or created via chemical processing.

As is typical, plaintiffs alleged causes of action including for: (1) California Consumers Legal Remedies Act – California Civil Code §§ 1750, et seq. (“CLRA”); (2) California False Advertising Law – California Business & Professions Code §§ 17500, et seq. (“FAL”); (3) California Unfair Competition Law – California Business & Professions Code §§ 17200, et seq. (“UCL”).

Defendants argued first that the claims alleged related to the use of fruit names to describe the various flavors of Lifewater and their use of common vitamin names were preempted by the express preemption provisions in the Federal Food, Drug, and Cosmetic Act (“FDCA”) and by the specific labeling regulations promulgated by the Food and Drug Administration (“FDA”). The court concluded that plaintiff’s claims related to defendants’ use of the names of various fruits to describe the different flavors of Lifewater were indeed preempted. See, e.g., Dvora v.
General Mills, Inc., 2011 WL 1897349 (C.D. Cal. May 6, 2011) (holding that CLRA and UCL claims
were preempted where the plaintiff was challenging the use of the words “Blueberry Pomegranate”
in labeling a cereal not containing any blueberries or pomegranates because FDA regulations
explicitly permit manufacturers “to use the name and images of a fruit on a product’s packaging to
describe the characterizing flavor of the product even where the product does not contain any of
that fruit, or contains no fruit at all”); McKinnis v. General Mills, Inc., 2007 WL 4762172 (C.D. Cal.
Sept. 18, 2007) (holding that use of “Strawberry Kiwi” to designate the flavor of yogurt containing
no fruit ingredients was “permissible to demonstrate the ‘characterizing flavor’ of the product”).

The court also concluded that plaintiff’s claims related to defendants’ use of the common names
of vitamins were preempted. See, e.g., 21 C.F.R. § 101.9(c)(8)(v) (recognizing that “Vitamin C” and
“Ascorbic acid” are “synonym[s]” that may be used in the alternative in a product’s nutritional
information labeling); 21 C.F.R. § 101.9(k)(4) (stating that the FDA will consider a food
“misbranded” if its “label or labeling represents, suggests, or implies” that “a natural vitamin in food is superior to an added or synthetic vitamin”).

Significantly, the court concluded that plaintiff could not avoid preemption of these claims by arguing that his claim related solely to defendants’ “all natural” representations and that he included his fruit name and vitamin name claims only as support for his “all natural” claim. Such an argument would effectively allow a plaintiff to always avoid preemption of those claims, and would undermine the purpose of the federal labeling standards which includes avoiding
a patchwork of different state standards.  These claims were dismissed with prejudice.

Plaintiff also alleged that the “all natural” labeling on defendants’ products was potentially deceptive because the product contains “deceptively labeled ingredients” that are
“synthetic or created via chemical processing.” However, plaintiff could not state a claim under the
CLRA, FAL, or UCL regarding defendants’ allegedly deceptive “all natural” labeling because once
the preempted statements regarding fruit names and vitamin labeling were removed, plaintiff’s claim is based on a single out-of-context phrase found in one component of Lifewater’s label.

The court concluded that plaintiff’s selective interpretation of individual words or phrases from a product’s labeling could not support a CLRA, FAL, or UCL claim. See, e.g., Carrea v. Dreyer’s Grand Ice Cream, 2012 WL 1131526 (9th Cir. Apr. 5, 2012).  Lifewater’s label did not simply state that it is “all natural” without elaboration or explanation. Instead, the “all natural” language was immediately followed by additional statements, like “with vitamins” or “with B vitamins.”  Lifewater did not use the “all natural” language in a vacuum. Thus, it was impossible for plaintiff to allege how the “all natural” language would be deceptive without relying on the preempted statements regarding fruit names and vitamins.

In addition, the court concluded that no reasonable consumer would read the “all natural”
language as modifying the “with vitamins” language and somehow believe that the added vitamins are suppose to be “all natural vitamins.”  Moreover, to the extent there was any ambiguity, it was  clarified by the detailed information contained in the ingredient list, which explained the exact contents of Lifewater. In this case, the ingredient list was consistent with the front label statement of “all natural with vitamins.”

The court concluded that the challenge to the “all natural” language on Lifewater was not deceptive as a matter of law.

 

Sunscreen Label Rules Deadlines Extended by FDA

Next weekend marks the unofficial start of the summer season, and readers will be heading out to the lake or beach, picnics and barbecues.  All the while taking time to reflect on the brave men and women who gave their lives for our freedom serving in the United States armed forces.  (Memorial Day was originally known as Decoration Day, a day to put flowers and flags on the graves of fallen Civil War soldiers.)

Those summer activities may call for sunscreen. On that topic, we note that the FDA recently announced a six-month delay on implementing new labeling rules for sunscreen.  The rules call for additional testing regarding ultraviolet A and ultraviolet B ray protection, and restrict use of certain "waterproof," "sweat-proof" and "sunblock" claims, also regulating claims for ‘‘instant
protection’’ or protection immediately upon application, or claims for ‘‘all-day’’ protection or extended wear claims.

The new rules were set to go into effect June 18, but industry groups like the Personal Care Products Council and the Consumer Healthcare Products Association noted the need for more time. FDA agreed that allowing adequate time for the 2011 final rule requirements to be
fully implemented is in the interest of public health.  Complex label redesign issues and the required broad spectrum testing just is going to take more time.

For example, sunscreens that pass the FDA's new broad-spectrum test procedure can be labeled as "Broad Spectrum" on the front label. And such products will be extremely valuable to consumers concerned about skin cancer risks. If the timeline for implementation discourages manufacturers from conducting broad spectrum testing, and instead prompts them to apply the labeling that the final rule establishes for products that have not been established to offer broad spectrum  protection, a major public health goal of the rule will be undermined.

FDA still encouraged manufacturers to introduce individual products bearing the new labeling as it becomes available, even in advance of the revised compliance date, which ranges from December 2012 to December 2013 depending on the product.

Readers, enjoy your holiday weekend.

 
 

Study Examines Impact of FDA Drug Risk Communications

A recurring topic here at MassTortDefense is the role of hazard communications in product safety, and the related issues of a consumer reading, heeding, or relying on such warnings.  This is particularly true in the area of prescription drug litigation, focused on over at Drug and Device Law.

So, that makes a recent study in Medical Care interesting reading: Dusetzina, et al.,  Impact of FDA Drug Risk Communications on Health Care Utilization and Health Behaviors: A Systematic Review.

The paper reviews the literature of the past 20 years on the impact of FDA drug risk communications on medication utilization, health care services use, and health outcomes.  These 50 or so studies covered roughly 16 therapeutic classes; most used medical or pharmacy claims and a few examined patient-provider communication, decision making, or risk perceptions.

The authors concluded that although some FDA drug risk communications had immediate and strong impacts, many had either delayed or no impact on health care utilization or health behaviors. These data demonstrate the complexity of using risk communication to improve the quality and safety of prescription drug use, and suggest the importance of continued assessments of the effect of future advisories and label changes, according to the authors.

Although not the focus of the article, the findings are relevant to those of us who need to think about the learned intermediary doctrine, preemption, and other legal warning doctrines.

Fruit Juice MDL Court Dismisses Claims

The Massachusetts federal court overseeing multidistrict litigation against 11 beverage companies, including Coca-Cola Co. and Del Monte Corp., alleging that their fruit juices contained trace amounts of lead, dismissed the claims last week.  In re Fruit Juice Products Marketing and Sales Practices Litigation, No. 11-2231 (D. Mass., 12/21/11).

Plaintiffs alleged that the defendants misled them into believing that certain of their products were safe, whereas the products in fact contained lead and posed a health risk, especially to children.  The issue had caught the attention of the FDA, which concluded that while several of the products contained trace amounts of lead, in each case the level found would not pose an unacceptable risk to health.  (The FDA’s conclusion was based in part on a guidance report it issued in 2004. The agency concluded that many food products contain small amounts of lead because the substance is in the environment naturally and also released through many human activities.)

The majority of plaintiffs’ claims were for violations of the consumer protection laws of states in which defendants maintained their principal places of business. Plaintiffs also brought claims under the consumer protection laws of all states in which potential class members purchased the  products. Finally, the plaintiffs alleged breach of the implied warranties of merchantability and fitness for a particular purpose and for unjust enrichment.

Defendants moved to dismiss on several grounds, but the foundational argument that plaintiffs lacked standing was fatal to all of plaintiffs’ claims, and was in the eyes of the court so compelling that it was unnecessary for the court to reach the numerous satellite theories that defendants offered.

To establish Article III standing, a plaintiff must first demonstrate that he has suffered an injury in fact.  Whitmore v. Arkansas, 459 U.S. 149, 155 (1990). The injury must be concrete and the alleged harm actual or imminent, and not conjectural or hypothetical. Los Angeles v. Lyons, 461 U.S. 95, 101-02 (1983). If a plaintiff fails to allege sufficient facts to satisfy this requirement, the case must be dismissed.

In this case, plaintiffs did not allege a sufficient injury in fact. Plaintiffs offered two potential theories of injury in fact. First, they alleged that the lead in defendants’ products posed a health risk and that, by consuming these products, they placed themselves and their children at risk of future harm from lead poisoning. Second, plaintiffs alleged that they suffered economic injury when they purchased products that defendants advertised as safe, but that in fact contained allegedly dangerous amounts of lead. Both theories, according to the court, ran into the same problem -- plaintiffs
failed to allege any actual injury caused by their purchase and consumption of the products.

The claim of exposure to “potential adverse health effects” or “potential harm” was insufficient for Article III standing. A threatened future injury must be “certainly impending” to grant Article III
standing.  In product liability cases, courts have held that to establish standing based on a threat of future harm, plaintiffs must plead a credible, substantial threat to their health.  E.g., Herrington v. Johnson & Johnson Consumer Cos., Inc., 2010 WL 3448531, at *3 (N.D. Cal. Sept. 1, 2010); see also Public Citizen, Inc. v. Nat’l Highway Traffic Safety Admin., 489 F.3d 1279, 1293-96 (D.C. Cir. 2007); Sutton v. St. Jude Medical S.C., Inc.,419 F.3d 568, 570-75 (6th Cir. 2005).  But the complaint here contained no allegations that either plaintiffs or anyone else ever suffered any type of injury from consuming the products. The products were not recalled, and in fact, the FDA found that at least some of the specific products did NOT pose an unacceptable risk to human health.

Plaintiffs made no allegations as to the amount of lead actually in these products, did not claim that any particular amount in the products is dangerous, and did not allege that any specific amount had caused actual injuries to any plaintiff. The court also stressed that plaintiff did not allege that the levels of lead in the products violated any FDA standards. Under these circumstances, the allegations of risk of future harm to class members were insufficient to meet the “credible or substantial threat” standard. The claim of potential future injury was simply too hypothetical or conjectural to establish Article III  standing.

The court cited a series of cases involving lead in lipstick, which we have posted on, making clear that the type of speculative future injury here cannot form the basis of a lawsuit. See Koronthaly v. L’Oreal USA, Inc., 374 F. App’x 257(3d Cir. 2010), aff’g 2008 WL 2938045 (D.N.J. July 29, 2008); Frye v. L’Oreal USA, Inc., 583 F. Supp. 2d 954 (N.D. Ill. 2008).

Plaintiffs’ second theory of injury in fact was equally flawed. Plaintiffs alleged that defendants promised to provide products that were safe for consumption, but that plaintiffs received products that posed a health risk to them and their children. Consequently, the products were unsuitable for their intended purpose -- consumption -- and supposedly valueless. Because plaintiffs supposedly would not have purchased these products if they had known the products contained any lead, they suffered an economic injury -- the price of the product -- when they purchased the products.

But because plaintiffs were unable to show that any actual harm resulted from consumption of the fruit juice products, their allegation of “economic” injury lacked substance. The fact is that plaintiffs paid for fruit juice, and they received fruit juice, which they consumed without suffering harm. Again, the products were not recalled, did not cause any reported injuries, and did not violate any federal standards. The products thus had no diminished objective value due to the presence of the lead. These plaintiffs received the benefit of the bargain, as a matter of law, when they purchased these products and were able to consume them.

Other courts that have addressed similar “benefit of the bargain” standing arguments agree that plaintiffs who have not been injured by an allegedly defective product generally do not have standing to sue the product’s manufacturer. See, e.g., Rivera v. Wyeth-Ayerst Labs., 283
F.3d 315 (5th Cir. 2002).  Plaintiffs’ allegations only support the contention that the levels of lead in the products were unsatisfactory to them. This allegation was simply insufficient to support a claim for injury in fact. 

 

 

Bill Introduced to Amend Post-Market Review of Medical Devices

Three U.S. Senators recently introduced legislation that would alter the U.S. Food and Drug Administration's post-market surveillance of medical devices.

Sens. Chuck Grassley, R-Iowa, Richard Blumenthal, D-Conn., and Herb Kohl, D-Wis. introduced the The Medical Device Patient Safety Act, S. 1995. Currently, the FDA can approve new moderate-risk medical devices through the 510(k) process if the product is found to be as safe and effective as a substantially similar medical device already on the market.  Though the agency can request clinical study data on proposed new devices under the 501(k) process, it is still viewed as a fast-track approval process, compared to the premarket approval process for new products in the high-risk device category.

The bill would give the FDA the authority require companies to submit post-market data as a condition for gaining approval for moderate-risk medical devices under the fast-track process.  The FDA could also order companies to conduct additional safety studies of devices after they are approved, and could grant conditional approvals pending the result of any ongoing trials. The proposed legislation would also require the FDA to assess recalls to determine whether they were implemented effectively.

The legislation follows concern from a GAO  study of the FDA's post-market surveillance of medical devices, and after a controversial Institute of Medicine report last July suggesting the FDA amend its current clearance system for medical devices. FDA had commissioned the IOM to conduct an analysis of the § 510(k) system in 2009. The IOM Committee was composed of twelve members: five doctors, three lawyers, and four academics. Specifically missing were innovators or any product developers familiar with the clearance process, and any representatives of patients or patient advocacy groups that have benefited from the development of medical devices under the current system.

As noted by the Advanced Medical Technology Association, however, expanding the FDA’s authority to require post-market studies as a condition of 510(k) clearance is unnecessary given that the agency already has broad authority to require manufacturers to conduct post-market studies for higher-risk devices cleared via 510(k).  The bill does not appear to limit when FDA may conditionally clear a device, thus leaving open the possibility that conditions of approval will simply become a regular part of 510(k) clearances. 

As to recalls, what may be "effective" for one type of device may not be as effective for another. It is important for the America public to realize that the medical technology industry has a well-documented safety record. Several recent studies have shown that for the vast majority of products cleared by the FDA, less than 0.5 percent are involved in a serious recall, a point GAO has emphasized as well. In addition, nothing in the GAO’s recommendations suggested a lack of diligence or inadequacy in medical technology companies’ implementation of recalls.

 

FDA to Issue BPA Decision in 2012

The FDA apparently will issue a final decision next Spring on an interest group's petition requesting a ban on the use of bisphenol A (BPA) in food packaging. This results from a settlement reached last week in Natural Resources Defense Council v. HHS, No. 11-cv-5801 (S.D.N.Y. 12/07/11).

FDA is agreeing to issue a final decision on or before March 31, 2012, settling a complaint by the NRDC that the agency unreasonably delayed a decision on its petition, which dates to 2008.  In reality, FDA continued to gather data on the issues, and has been looking at taking what it has called reasonable steps to reduce exposure to BPA in certain aspects of the food supply. For example, the American Chemistry Council has supported restricting the use of BPA in infant feeding bottles and spill-proof cups used by infants.

NRDC didn't want to wait for the science, taking the usual pro-plaintiff, anti-industry position that all gaps in knowledge should be filled in with worst-case scenarios. Studies employing standardized toxicity tests have in fact supported the safety of current low levels of human exposure to BPA. (FDA has been consulting with other agencies, including the National Institutes of Health (and National Toxicology Program), Environmental Protection Agency, Consumer Product Safety Commission, and the Centers for Disease Control and Prevention.)

And the interest group doesn't seem to care about the tremendous public health benefits that such products have provided. Any wide-spread ban of the product – or litigation accomplishing the same result -- may risk the public safety more than enhance it. Epoxy resins derived from bisphenol A are used to manufacture protective polymer coatings for the inner surface of metal food and beverage containers. This critical technology protects the contents of these containers from aggressive food products, thereby assuring a safe, wholesome, and nutritious food supply. Compared to other coating technologies, coatings derived from epoxy resins provide superior adhesion to the metal surface, greater durability, and higher resistance to the wide range of chemistries found in foods and beverages. These attributes are essential to protect the packed food from microbiological contamination, which is a significant food safety issue. 

Canning might be the single most important innovation in the preservation of food in history. More than 1500 food items are regularly packed in cans, making out-of-season foods globally accessible year-round. More than 90% of food and beverage cans use epoxy-based coatings because of their strength, adhesion, formability and resistance to chemical reactions in the food and drinks -- without affecting the taste or smell of the product. They protect the food from the container and from bacterial contamination. They give canned foods their long shelf-life.  Where is the cost-benefit analysis including these factors?

 

Class Action Complaint on 100% Natural Oil Dismissed

A federal court recently dismissed a proposed class action accusing a food company of misleadingly labeling cooking oils as 100% natural when they allegedly were made from genetically modified plants. Robert Briseno, et al. v. ConAgra Foods Inc., No. 2:11-cv-05379 (C.D. Calif.).

Quick research reveals that 88-94% of the nation’s crops of corn, soy and canola are grown from seeds that are the product of bioengineering.  There is no credible science that there are serious health issues with these products, and multiple peer reviewed studies on "GM" crops worldwide show farmers in underdeveloped countries have seen an increase in yield of about 29% from using them, along with decreased use of insecticide applications.

Plaintiff alleged that he regularly purchased Wesson Canola Oil, bearing labels that state the product is “100% Natural.” Plaintiff contended that contrary to these representations, ConAgra used plants grown from genetically modified organism seeds that have been engineered to allow for greater yield, and to be pest-resistant, to make Wesson-branded oils. He asserted that the genetically modified organisms are somehow not “100% natural,” and thus the labels and advertising are deceptive. Plaintiff filed a complaint seeking to represent a class of all persons in the United States who have purchased Wesson Oils from 2007 on. As is typical, he alleged
violation of California’s false advertising law (“FAL”), California’s unfair competition law (“UCL”), and California’s Consumer Legal Remedies Act (“CLRA”).

Defendant moved to dismiss. The first issue was preemption of the state law causes of action, based on FDA guidance regarding food labels. Federal preemption occurs, generally, when: (1) Congress enacts a statute that explicitly pre-empts state law; (2) state law actually conflicts with federal law; or (3) federal law occupies a legislative field to such an extent that it is reasonable to conclude that Congress left no room for state regulation in that field. Specifically, ConAgra argued that Briseno’s claims were preempted because the FDA has repeatedly concluded that bioengineered foods are not meaningfully different from foods developed by traditional plant breeding, and thus that the fact that a food product is derived from bioengineered plants need not be reflected on a product’s label. Plaintiff responded that he was not arguing that ConAgra was required to state whether its products were made from genetically modified plants. Rather, he contended that the decision to label its products “100% Natural” was misleading.

Courts have split on food preemption issues. Compare Dvora v. General Mills, Inc., 2011 WL 1897349 (C.D. Cal. May 16, 2011)(cereal-yes); Turek v. General Mills, Inc., 754 F.Supp.2d 956 (N.D. Ill. 2010)(snack bars-yes); Yumul v. Smart Balance, Inc., 2011 WL 1045555 (C.D. Cal. Mar. 14, 2011)(yes), with Lockwood v. Conagra Foods, Inc., 597 F.Supp.2d 1028 (N.D. Cal. Feb. 3, 2009)(pasta-no); Wright v. General Mills, Inc., 2009 WL 3247148 (S.D. Cal. Sept. 30, 2009)(granola bars-no).

Here, the court found no preemption on most of the complaint. The bulk of the complaint, said the court, alleged that use of the phrase “100% Natural” is misleading, and did not contend that additional information must be added to Wesson Oil labels. Regulations requiring that each product list its ingredients by their “common or usual name,” together with the regulations requiring that vegetable oils be denominated “ oil,” were inapplicable since plaintiff’s central argument was not that ConAgra cannot use the common or usual names of canola oil, vegetable oil or corn oil.

The FDA has expressed that it has no basis for concluding that bioengineered foods differ from other foods in any meaningful or uniform way, or that, as a class, foods developed by the new techniques present any different or greater safety concern than foods developed by traditional plant breeding. So, plaintiff, in essence, sought to create a distinction – between “natural” oils and those made from bioengineered plants when the FDA has determined that no such distinction exists. The court rejected this argument, refusing to read the FDA guidance as formal enough or clear enough on the issue.

Plaintiff did also seek an order requiring defendant to adopt and enforce a policy that requires appropriate disclosure of GM ingredients. Entering an order of this type would impose a
requirement that is not identical to federal law, and thus this particular prayer for such relief was preempted.

Rule 9(b) requires that in all averments of fraud or mistake, the circumstances constituting fraud or mistake shall be stated with particularity. The pleading must identify the circumstances constituting fraud so that a defendant can prepare an adequate answer to the allegations. While statements of the time, place and nature of the alleged fraudulent activities are often sufficient, mere conclusory allegations of fraud are insufficient. Even if fraud is not a necessary element of a claim under the CLRA and UCL, when a plaintiff alleges fraudulent conduct then the claim can be said to be grounded in fraud or to sound in fraud.

Plaintiff alleged that he regularly purchased Wesson Canola Oil for his own and his family’s consumption. But his complaint contained no allegations as to whether he became aware of the
representation through advertising, or labeling, or otherwise. He provided no information about how often he was exposed to the allegedly misleading statement. He did not allege how
frequently he purchased the product and over what period of time, whether he relied on
statements on canola oil labels, on a website, in advertisements, or all of the above,
whether the statements remained the same throughout the class period, or, if they did not, on
which label(s), advertisement(s) or statement(s) he relied.

Thus, this complaint did not afford ConAgra adequate opportunity to respond. Consequently, defendant's motion to dismiss was granted (without prejudice).


 

Chew on This: Consumer Fraud Claim on Snack Bars Preempted

The Seventh Circuit ruled earlier this month that federal food labeling law expressly preempts state law claims seeking certain additional health-related disclosures on chewy bars. Turek v. General Mills Inc., No. 10-3267 (7th Cir. 10/17/11).

The bars have been around since at least the early 1980's, but have grown into a nearly $2 billion segment of the food industry.  Consumers love their portability, and relatively low calorie count.

Plaintiffs brought a diversity class action suit under the Illinois Consumer Fraud and Deceptive Business Practices Act, and the Illinois Uniform Deceptive Trade Practices Act, alleging that the label of certain "chewy bars" was misleading regarding fiber content.  Specifically, the complaint alleged that the principal fiber, by weight, in the bars was inulin extracted from chicory root. The complaint describes inulin so extracted as a processed, "non-natural” fiber which was not as beneficial to consumer health as other fiber.

Those state law claims ran smack into a provision of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 343-1(a)(5), added by the Nutrition Labeling and Education Act of 1990, which forbids states to impose “any requirement respecting any claim of the type described in section 343(r)(1)
[of the Food, Drug, and Cosmetic Act] . . . made in the label or labeling of food that is not identical to the requirement of section 343(r).”  A state thus can impose the identical requirement or requirements, and by doing so be enabled, because of the narrow scope of the preemption provision in the Nutrition Labeling and Education Act, to enforce a violation of the Act as a violation of state law. See also In re Pepsico, Inc. Bottled Water Marketing and Sales Practices Litigation, 588 F. Supp. 2d 527, 532 (S.D.N.Y. 2008); “Beverages: Bottled Water,” 60 Fed. Reg. 57076, 57120 (Final Rule, Nov. 13, 1995). This is important because the Food, Drug, and Cosmetic Act does not create a private right of action. Medtronic, Inc. v. Lohr, 518 U.S. 470, 487 (1996).

The question thus became what requirements the federal law imposes on the labeling of dietary fiber. Section 343(q)(1) of the Act contains a requirement that the “label or labeling” of food products intended for human consumption state “the amount of . . . dietary fiber . . . contained in each serving size or other unit of measure.” Other requirements for labeling claims relating to dietary fiber are set forth in implementing regulations.  

The labeling of the products challenged by the plaintiff was compliant with these regulations relating to health claims for dietary fiber. See, e.g., 21 C.F.R. § 101.76. All the FDA’s requirements relating to labeling dietary fiber are requirements to which any labeling disclosures required by a state must be identical.  But the disclaimers that the plaintiff wants added to the labeling of the defendants’ inulin-containing chewy bars were not identical to the labeling requirements imposed on such products by federal law, and so they were barred, held the court of appeals. The information required by federal law does not include disclosing that the fiber in the product includes inulin or that a product containing inulin allegedly produces fewer health benefits than a product that contains only product that contains only “natural” fiber, for example. 

Even if the disclaimers that the plaintiff wants added would be "consistent" with the requirements imposed, importantly, consistency is not the test. Identity is, said the court.

The Seventh Circuit thus affirmed dismissal of the case. But clarified, procedurally, that when a state law claim is expressly preempted under section 403A of the Federal Food, Drug, and Cosmetic Act,” a dismissal on the merits is the proper outcome, with prejudice like other merits judgments, not dismissal for want of federal jurisdiction, as the district court had ordered.

This is a victory for consumers when one considers why Congress did not want to allow states to impose disclosure requirements of their own on packaged food products, most of which are sold nationwide. Manufacturers might have to print 50 different labels, driving consumers who buy the food products crazy. A granola bar you buy in California ought to look just like the one you buy in Maine.

 

FDA Issues Draft Guidance on Informed Consent Language

The FDA has issued draft guidance on the use of "Exculpatory Language in Informed Consent" agreements. The document applies to non-exempt human subject research conducted or supported by the Department of Health and Human Services, and is intended for clinical investigators, institutional review boards, and funding agencies that may be responsible for review or oversight of human subject research conducted or supported by HHS or regulated by FDA.

This document provides guidance on the regulatory prohibition on the inclusion of exculpatory language in informed consent in clinical trials and other research. Readers may know that under federal regulations, no informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

The document includes examples of language that OHRP and FDA consider acceptable as well as examples of language that the agencies would consider improperly exculpatory.

CHPA Comments on Draft FDA Guidance on Nanotechnology

Last week, the Consumer Healthcare Products Association (CHPA) submitted comments on the FDA’s draft guidance on nanotechnology, "Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, "  which we posted on before.

CHPA is the not-for-profit association representing the makers of over-the-counter medicines and dietary supplements, and the consumers who rely on these healthcare products. CHPA is one of the oldest trade associations in the United States. Nanotechnology holds great promise for this industry.

CHPA agreed with the FDA that proposing a "definition" for nanotechnology is not a straight forward process; applying a strict, universal definition of nanotechnology to the fields of drug research, drug product development and drug manufacturing would not be, in CHPA's view, an appropriate science-based approach.

Defining a nanomaterial as a structure between 1 and 100 nm, and using this definition to establish new regulations on products containing nano-sized materials, would, they asserted,  erroneously group drug products together to form a new category based on size of ingredients.  Nanotechnology is not a separate drug category, but a technology used to, among other things, generate nanometer-sized ingredients and excipients. Inclusion of nanometer-sized active ingredients or excipients in a drug product does not by itself determine a product's safety and efficacy (i.e. size alone is not itself an indicator of toxicity). 

CHPA agreed that the agency should distinguish between engineered nanomaterials and those
naturally occurring at the nanoscale.  There exist common pharmaceutical ingredients with a long history of use that should not be considered as "engineered nanomaterials" or as agglomerates of nanomaterials but which may have particles whose size naturally falls within this range.

CHPA also noted that NIOSH accurately refers to nanotechnology as the manipulation of matter on a near-atomic scale to produce new structures, materials, and devices.  Nanomaterials are mainly engineered for their novel chemical, physical, and quantum mechanical properties; at the nanometer size, many materials exhibit such unique beneficial properties that may not exist when at the micron size. CHPA argued it is appropriate to include in the description the notion of particles that are deliberately manipulated and controlled at the nanoscale, which also exhibit changes in physical, chemical, or electromagnetic properties, the existence of unique phenomena to enable novel applications.

For example, milling, a beneficial process for the manufacturing of many individual pharmaceutical ingredients, may create particles with a portion of the particle size distribution under 1 micron; however, the chemical properties of the milled ingredient usually do not differ drastically from that of the bulk ingredient.

The agency should give further consideration, said CHPA,  to the possibility that not all materials should be considered equal; each material must be evaluated on a case-by-case basis. For example, soluble nanomaterials might not be treated the same as insoluble ones.  

FDA Releases New Strategic Plan for Regulatory Science

This week the FDA released a plan for fostering innovative science. It is entitled the “Strategic Plan for Regulatory Science,” and it focuses on the agency’s goal to enhance the processes for developing and evaluating new medical products and materials.

The strategic plan describes the agency’s intent to collaboratively enhance the process for developing and evaluating promising new products and novel materials from fields such as cell therapy, tissue engineering, genomics, personalized medicine, advanced computing, and information technology. It reportedly also underscores the agency’s emphasis on food safety.

The plan also emphasizes the agency’s intention to study and improve how it communicates health information to consumers, particularly as communication technologies rapidly evolve and change the way people receive that information.

The priority areas listed in the report are:

  • Modernize Toxicology to Enhance Product Safety
  • Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes
  • Support New Approaches to Improve Product Manufacturing and Quality
  • Ensure FDA Readiness to Evaluate Innovative Emerging Technologies
  • Harness Diverse Data through Information Sciences to Improve Health Outcomes
  • Implement a New Prevention-Focused Food Safety System to Protect Public Health
  • Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S. and Global Health and Security
  • Strengthen Social and Behavioral Science to Help Consumers and Professionals Make Informed Decisions about Regulated Products
     

 

IOM Releases Controversial 510K Device Report

Earlier this week, an Institute of Medicine’s Committee released its report on the Public Health Effectiveness of the FDA 510(k) Clearance Process.  The report offers a variety of recommendations and suggested reforms for FDA’s 510(k)  premarket notification pathway, describing the device clearance process as badly flawed.

Readers of MassTortDefense know how the regulatory clearance process has impacted preemption of state law product liability claims, and the significant medical device litigation we have covered here.

The recommendations will likely spark a heated debate within the larger struggles over the need for future medical device regulations. But even before that step, a variety of observers, including the Washington Legal Foundation, have asserted that the FDA is statutorily barred from adopting any of the report’s recommendations.  The charge has been made that the Institute of Medicine failed to adequately balance the panel, in violation of §15 of the Federal Advisory Committee Act. Section 15(a) provides that an agency may not use any advice or recommendation developed by the committee unless it has complied with a requirement that the committee membership be “fairly balanced.”  Using advice from a committee that lacks fair balance would encroach upon the Congressional mandate that each Advisory Committee should be representative of a broad
range of viewpoints. 

FDA had commissioned the IOM to conduct an analysis of the § 510(k) system in 2009.  The IOM
Committee was composed of twelve members:  five doctors, three lawyers, and four academics. Specifically missing were innovators or any product developers familiar with the clearance process, and any representatives of patients or patient advocacy groups that have benefited from the development of medical devices under the current system.
 

 

FDA Releases Draft Guidance on Nanotechnology

The U.S. Food and Drug Administration last week released draft guidance designed to move the process forward of providing its regulated industries with greater certainty about the use of nanotechnology (which generally involves materials made up of particles that are one billionth of a meter in size). The guidance outlines the agency’s current view on certain issues about regulated products that contain nanomaterials or involve the application of nanotechnology.

FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms. The term is perhaps most commonly used to refer to the engineering (i.e., deliberate manipulation, manufacture or selection) of materials that have at least one dimension in the size range of approximately 1 to 100 nanometers. For example, theNational Nanotechnology Initiative Program defines nanotechnology as the understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications. Other factors such as function, shape, charge, the ratio of surface area to volume, or other physical or chemical properties have also been mentioned in various published definitions.

Our readers know that nanotechnology, the science involving manipulation of materials on an atomic or molecular scale, is an emerging technology with a broad range of potential applications, such as increasing bio-availability of a drug, improving food packaging, and in cosmetics.

The draft guidance document, “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology,” represents a first step toward providing some regulatory clarity on the FDA’s approach to nanotechnology. Specifically, the agency named certain characteristics – such as the size of nanomaterials used and the exhibited properties of those materials – that may be considered when attempting to identify applications of nanotechnology in regulated products.

For products subject to premarket review, the FDA intends to apply the points contained in the draft guidance, when finalized, to better understand the properties and behavior of engineered nanomaterials. For products not subject to premarket review, the FDA will urge manufacturers to consult with the agency early in the product development process so questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be adequately addressed.

In 2006, the FDA formed the Nanotechnology Task Force, charged with identifying and addressing ways to better enable the agency to evaluate possible adverse health effects from FDA-regulated nanotechnology products.  The agency issued a report by the task force in 2007 that recommended that the FDA issue additional guidance and take steps to address the potential risks and benefits of drugs, medical devices and other FDA-regulated products using nanotechnology.

 

Food Safety Bill Advances in Senate

The U.S. Senate last week voted to move forward to the final debate on legislation aimed at amending regulatory controls on both domestic and foreign food supplies.  The Senate voted 74-25 to invoke cloture on S. 510, the Food Safety Modernization Act.  The bill is sponsored by Senate Majority Whip Dick Durbin, D-Ill., and a bipartisan group of 20 other Senators.

The procedural vote was designed to open the final round of the Senate's food safety debate, although it is unclear wither the Senate Democratic leaders will allow additional amendments to the bill on the Senate floor.  Some Senate Republicans have urged that they be allowed unlimited amendments during floor debate leading up to the vote on final passage.  While some amendments may be designed to strengthen the FDA inspection process of both domestic and foreign food production facilities, one highly controversial step would be if Sen. Dianne Feinstein, D-Calif. again offers an amendment to the bill that would impose a federal ban on the
use of bisphenol A in children's food packaging. 

That position does not hold substantial support in the Senate, and her shrill insistence on the ban delayed Senate action on a much larger and more comprehensive legislative package.  Indeed, a member of her own party, Rep. John Dingell (D-Mich.), criticized her in a public letter for holding up this bill.  Other key remaining issues include treatment of small farmers, and the role, if any, of local and state food inspections.

The bill would give the FDA new authority to track and halt contaminated food coming from domestic and foreign suppliers. Food facilities would be required to provide additional information to the FDA, submit to more frequent inspections and to develop their own tracking systems. The agency would also get new mandatory recall authority over tainted food, and additional authority to deal with misbranded or adulterated products.

The House passed a companion bill, H.R. 2749, the Food Safety Enhancement Act, by a vote of 283-142, in July 2009.  The typical conference committee to iron out differences may be an issue given the lateness in the lame-duck session in Congress. It is possible the House could vote to accept the Senate version, if it indeed passes.

There are about 76 million cases of food-borne illnesses every year in the U.S., leading to 325,000 hospitalizations and 5,000 deaths, according to the CDC.

 

Class Action Claims Against Labeling of Snack Food Preempted

Last week, a federal district court held that federal food labeling law does preempt state law claims attacking the use of phrases such as “0 Grams of Trans Fat” on snack food packaging. See Peviani v. Hostess Brands Inc., No. 2:10-cv-02303 (C.D. Cal., 11/3/10).

 In this putative class action, plaintiffs alleged that the defendant used misleading and deceptive statements to market the "Hostess 100 Calorie Packs" baked goods. In particular, plaintiffs alleged that the label noting "0 Grams of Trans Fat" was inconsistent with the products containing partially hydrogenated oils (PVHO).  Plaintiffs alleged that PVHO is linked to various health problems, and therefore is supposedly a "dangerous trans fat."

Plaintiffs alleged they purchased the 100 Calorie Pack foods relying on the no trans fat claim.  They asserted false advertising under the Lanham Act, violations of the California Unfair Competition Law, the California False Advertising Law, and the Consumer Legal Remedies Act. The two classes proposed were a restitution and damages nationwide class of those that purchased the foods, and an injunctive relief class of those who commonly purchase such foods.

Defendants filed a motion to dismiss, arguing that the claims were preempted by federal law.  The  court noted that the FDCA sets forth a comprehensive federal scheme for the regulation of food. In 1990, Congress passed the Nutrition Labeling and Education Act, 21 U.S.C. 341, which clarified FDA's authority to require and regulate nutrition labeling on food.  Two provisions directly apply to use of phrases like "0 Grams of Trans Fat."  One provision requires the labeling in the Nutrition Facts Panel to include the amount of saturated fat and total fat in each serving; and this regulation requires that if a serving contains less than 0.5 grams of trans fat, the amount "shall be expressed as zero."  Second, a regulation permits certain nutrient claims outside the Facts Panel about the level or range of a nutrient in the food, such as sodium, or calories or fat.  The NLEA permits such a statement as long as it is not false or misleading. 21 U.S.C. §§ 343(q) and (r).

The court noted that laws regulating the proper marketing of food are within the states' historic police powers, and thus subject to a presumption against preemption.  Nevertheless, consumer protection laws, such as those invoked here, are nonetheless preempted if they seek to impose requirements (through their use in litigation) that contravene the provisions of the federal law.  The NLEA contains an express preemption clause relating to any requirement  in state law that is not identical to the federal provisions.  But the court noted that implied preemption can accompany express preemption, as the essential inquiry always remains the substance and scope of Congress' intent to displace state law.

Plaintiffs alleged that the trans fat label outside of the Nutrition Facts Panel was an express nutrient content claim, and was false and misleading.  But the court noted that the FDA has declined to promulgate any regulation as to whether actual values must be used in labeling or rounded values may be used. In fact, the FDA has said that the difference between actual and rounded values are nutritionally insignificant, and thus either value relays the same basic information.  Here, since the phrase "0 grams of Trans Fat" is not false or misleading when used in the Nutrition Facts Panel, defendant's use of the exact same phrase elsewhere on the product label cannot be found false or misleading. If 0 and less than 0.5 grams mean, nutritionally, the same thing in the important Panel section, use of the exact same claim could not be misleading elsewhere on the label.

In essence, plaintiffs were trying, under state law, to enjoin on the label the use of the very phrase that federal law permits on another part of the label.  Plaintiffs' claims failed because they would impose a state law obligation for trans-fat disclosure that is not required by federal law.  (The plaintiffs' federal claim, for false advertising under the Lanham Act, failed for lack of standing,.)

The decision echoed Chacanaca v. Quaker Oats Co.,  No. 5:10-cv-00502 (N.D. Cal., Oct. 14, 2010), which dismissed similar claims over the phrase “0 Grams Trans Fat” on preemption grounds.

These types of claims illustrate the lengths to which plaintiffs are going to attack the food and beverage industries.  No one was sick from the snacks, which were labeled in exact accordance with explicit federal requirements.  Yet, a multi-count claim is brought in state court, with the legal theory that, in essence, federally approved language in one part of a food label is false and misleading under state law when it appears in another part of the same label. This is not about helping consumers.  How could it benefit consumers and clarify the information they have to make their own free and individual purchase decisions (with all the factors that go into what we decide to buy and eat) if the FDA-approved language in the Nutrient Facts Panel is allowed to be called false and misleading by a state court jury in California?


 

Democrats Release Discussion Draft of FDA Bill

Five Democratic Congressmen released a discussion draft of possible legislation that would alter the powers of the U.S. Food and Drug Administration.  The bill would increase FDA's authority and funding to regulate the importation of foreign-manufactured drugs, and also give the FDA the authority to mandate recalls for unsafe drugs.

Rep. John D. Dingell, Chairman Emeritus of the Energy and Commerce Committee, Rep. Henry A. Waxman, Chairman of the Energy and Commerce Committee, Rep. Frank Pallone, Chairman of the Subcommittee on Health, and Rep. Bart Stupak, Chairman of the Subcommittee on Oversight and Investigations, released a discussion draft proposal, which builds on H.R. 759, the Food and Drug Globalization Act, which was introduced by Dingell, Pallone and Stupak last year.

The discussion draft calls for "parity" between foreign and domestic drug facility inspections, would increase the number of pre-approval drug inspections, and would prohibit the importation of drugs into the United States lacking appropriate documentation of safety.  The legislation would also require manufacturers to take steps to ensure the safety of their supply chain.

The sponsors noted that the byproduct of Internet communications and a rapidly-evolving international marketplace is an increase in the purchase of medications from foreign sources. Cong. Pallone claimed that, “One of the downsides is quality control and one of the dangers is the threat to the health and safety of consumers. We need to find the best ways to vest the FDA with the ability and the authority to ensure the safety of medications consumed by Americans.”

Cong. Waxman said he would work with the FDA "and all stakeholders to move this legislation forward as soon as possible." But the current Congress is heading home for the November elections, and the measure's fate is unclear if Republicans take control of the House next year.

Appeals Court Vacates Verdict On Exclusion of Context Evidence

Comic Dimitri Martin notes, "I'm sorry" and "I apologize" mean the same thing -- unless you are speaking to the widow at a funeral.  The lesson? Context is key.

The New Jersey appeals court last week vacated a jury verdict for a woman who used the acne drug Accutane and allegedly developed inflammatory bowel disease (IBD).  See Kendall v. Hoffmann-LaRoche Inc.,No. A-2633-08T3 (N.J. Super. Ct.,  8/5/10). The court found that the trial court erred by restricting the defendant's use of evidence concerning the incidence of IBD in the general population to set a proper context.

Readers know that defendants frequently want to put evidence in a fuller context and give the jury a full picture.  Plaintiffs seem much less concerned that a jury will take evidence (a word in an email, a phrase in a memo, a point of data) out of context.

Some background- In 1982 the Food and Drug Administration approved the use of Accutane to treat recalcitrant nodular acne. Patients using Accutane have reported a number of common side effects. The alleged side effect that was centrally at issue in this case was the alleged propensity of Accutane to cause patients to suffer from inflammatory bowel disease. The exact scientific causes of IBD have not been conclusively established, said the court. IBD has been statistically associated with several factors, including family history, prior infections, frequent use of antibiotics, and possibly the use of contraceptives and nonsteroidal anti-inflammatory drugs.

Plaintiff underwent several courses of treatment. She had taken four courses of Accutane before she developed IBD, with no apparent gastrointestinal effects. Her medical records indicated that plaintiff's mother informed the treating physician that plaintiff had been diagnosed with an IBD, and that disease "has nothing to do with her Accutane use, according to her G.I. doctors."  Plaintiff took two courses of Accutane after she developed IBD, with "no evidence of exacerbation" of the
IBD.  But in early 2005, plaintiff suffered from excessive diarrhea, bowel incontinence, bloody diarrhea, fatigue, cramping, and abdominal pain. As 2005 progressed, plaintiff's symptoms
worsened, leading to surgery.

Plaintiff contends that if she had been warned that Accutane use could cause, or exacerbate, her IBD, she would not have taken the drug. She alleged that there was no specific reference to IBD, or that Accutane use could cause IBD, in any of the materials she personally received from 1997 to 2003.  However, prior to the use of Accutane by plaintiff, defendant revised the various warnings that it supplied concerning the drug. Roche amended the "WARNINGS" section of the Accutane package insert provided to physicians to include language about Inflammatory Bowel Disease.  In a "Dear Doctor" letter, dated August 1998, which was sent to board-certified dermatologists, Roche warned that patients taking Accutane should be monitored for IBD. Roche subsequently revised its product warnings for Accutane, with FDA approval, in 2000 and again in 2002. Plaintiff's expert opined, not surprisingly, that even the amended warnings contained in the later label were inadequate.

The appeal presented several issues, including statute of limitations, but for our readers we want to focus on the argument that the trial court abused its discretion in preventing Roche from adducing evidence as to the number of Accutane users and in limiting Roche's arguments to the jury concerning such data.

In opening, in her trial proofs, and in her counsel's closing arguments to the jury, plaintiff relied heavily upon the number of adverse case reports for Accutane and other quantitative evidence as
proof of at least two critical issues: (1) that a patient's use of Accutane can cause IBD and other gastrointestinal problems, and (2) that Roche allegedly acted too slowly and ineffectively in
responding to those risks with more forceful product warnings. Roche contended that the trial court unfairly curtailed its ability at trial to defend that numbers-oriented evidence and advocacy.

Prior to the trial in this case, plaintiff moved to bar defense counsel from presenting certain proofs and arguments concerning the background incident rates of IBD in the general population. That makes complete sense; how often do people get the disease when they aren't exposed? But, in
essence, plaintiff argued those general background rates are unreliable because symptoms of IBD are allegedly frequently under-reported.  The trial court agreed and precluded Roche from referring at trial to the background rates of IBD in the general population to disprove causation. The order did allow Roche only to present "factual testimony" to show that it acted reasonably based on such background rates, and only if "the numbers are not told to the jury."  The trial court did not, however, impose any restrictions upon plaintiff in her own use of numerical proofs at trial, other than a restriction against using the numbers in a specific formula.

Thus, during opening statements, plaintiff's counsel noted that she would present proof that Roche was aware of at least 104 reported cases of IBD, of which thirty-three cases were supposedly given a causality rating of possible or probable by the company. Plaintiff's counsel also cited in opening argument to an internal Roche report supposedly stating that, in 2002, there had been sixty-four reports of Crohn's disease (BTW, a form of IBD with no epidemiological link to the drug in any reputable study).  The trial court ruled that Roche could not argue that a comparison of those AERs vs. the background rate was a scientifically valid way to help evaluate the risk of a drug. Defendant was also curtailed in cross-examination of plaintiff's labeling expert,  particularly with regard to how Roche had analyzed certain data on Accutane that it had in fact presented to the FDA.

During the defense case in chief, the trial court did loosen her ruling and did permit a defense expert to explain to the jury that, in calculating the number of IBD cases in the exposed population, Roche had assessed the reported adverse events. Because it was suspected such events are under-reported, Roche already  factored in under-reporting. In calendar year 1988, when approximately one million patients took Accutane, there were only seven reports of IBD. From 1982 to 1999, when more than 32 million patients took the drug, there were only 206 case reports of IBD.

(Readers know that an adverse event report does not establish a causal relationship between the drug and a particular event. The FDA itself has warned that for any given ADE case, there is no certainty that the suspected drug caused the event. This is because physicians and consumers are encouraged to report all suspected ADEs, not just those that are known or even suspected to be caused by the drug. The adverse event may have been related to an underlying disease for which the drug was given, to other concomitant drug usage, or may have occurred by chance at the same time the suspect drug was administered. The courts have characterized ADEs as “complaints called in by product consumers without any medical controls or scientific assessment.” McClain v. Metabolife Intern., Inc., 401 F. 3d 1233, 1250 (11th Cir. 2005). Because the reporting system is not subject to scientific controls, data from it is subject to various statistical biases. It is likely that the mix of reported events does not represent an accurate sampling of those events that can occur while a person is taking any medication. Moreover, medical or media attention can stimulate reporting in a distorted manner, and known adverse reactions are more likely to be diagnosed and reported than others. See DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1050 (D. N.J. 1992), aff’d 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “have inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.”).)

However, the trial court here gave the jury a limiting instruction on this evidence that defendant on appeal argued was especially harmful, by accentuating to the jurors that Roche's internal corporate use of background numbers was supposedly, at least in some respects, "unscientific."  Defendant argued that the trial court's directive to the jurors that at least one use of the background numbers was not "scientifically accepted," placed a prejudicial and unnecessary spin on the proofs, to Roche's detriment.

The appellate court concluded it lacked confidence that this trial, when considered as a whole, provided a full and fair opportunity for Roche to contest, present, and advocate the relevant "numbers" evidence. Specifically, the trial court erred in forbidding Roche from placing into
evidence (and arguing) statistics about Accutane usage that could have made Roche's conduct and labeling decisions appear far more reasonable to the jury. The number of users evidence  could have given the jurors very relevant contextual background, and possibly led the jury to view differently Roche's pacing in upgrading the risk information on Accutane's label and package insert.  Even accepting, for the sake of argument, plaintiff's contention that adverse events are heavily under-reported, the quantity of actual users of a drug logically is a significant part of the
numerical landscape. At a minimum, the actual usage data for Accutane would go to "safety signaling" concerns, i.e., whether Roche had received sufficiently frequent adverse "signals" to take corrective action. Had Roche been allowed to fully present the statistics on users and other related counter-proofs, the jury would have had a fuller and more balanced picture of the data bearing upon the company's conduct in changing its label. See McCarrell v. Hoffman-La Roche, Inc., No. A-3280-07 (App. Div. Mar. 12, 2009), certif. denied, 199 N.J. 518 (2009).

The court recognized that the trial court's attempted conceptual boundary between using background data for purposes of evaluating "signals" and company conduct, but not for "causation," is a technical and somewhat elusive distinction. Increased reports of a medical condition occurring in a drug's users, as contrasted with the general population, may well provoke a drug maker to strengthen its labeling, even if such adverse reports may suggest only an association and not that the product is, in fact, "causing" such adverse results. In any event, the court of appeals felt there was no need here to draw the boundaries between causation and conduct with precision or with definiteness. The point remains that, even accepting, arguendo, as reasonable the trial court's prohibition upon Roche using background numbers to disprove causation (because of a concern about reporting), the trial as a whole did not provide Roche with a sufficient opportunity to make full and legitimate uses of such contextual evidence as part of its trial advocacy.  In particular, the jury instruction issued by the court went too far in characterizing to the jurors the use of background numbers to prove or disprove causation as "unscientific."

The case was remanded for a new trial.  And on remand, the defense will not be foreclosed from attempting to use the numbers evidence to show not only that the company acted reasonably in the manner in which it developed and modified the Accutane product warnings, but also to attempt (if it chooses to do so) to disprove general causation (along with the multiple epidemiological studies refuting causation).

Roche has successfully defended IBD claims in the federal cases brought to date, obtaining dismissals in each case that have been affirmed on appeal by the United States Court of Appeals for the Eleventh Circuit.

 

NRDC Sues FDA Over BPA

The Natural Resources Defense Council brought suit last week against the FDA for allegedly failing to take timely action in response to its petition asking the agency to ban the chemical bisphenol A. NRDC v. Sebelius, D.C. Cir., No. 10-1142 (filed 6/29/2010).

NRDC is one of a number of advocacy groups who allege that this important chemical, used to make polycarbonate plastics in water bottles and epoxy resins used to line cans containing food, causes harmful health effects, particularly to infants and children, including early puberty, reproductive abnormalities.

However, both the scientific process and the public interest are better served by allowing the FDA to complete its ongoing review of the science surrounding the safety profile of BPA -- at its own pace.  Just this January, the U.S. Department of Health and Human Services and the FDA made it clear that BPA has not been proven to harm children or adults.  EPA released its bisphenol A Action Plan in March 2010. Importantly, the agency clearly indicated that it does not intend to initiate regulatory action under TSCA at this time on the basis of human health concerns.

This observation is consistent with a draft assessment issued by FDA in 2008, and the scientific conclusions of many other government regulatory agencies around the world. In January 2010, the German Federal Institute for Risk Assessment (BfR, Bundesinstitut für Risikobewertung) wrote, “Following careful examination of all studies, in particular the studies in the low dose range of bisphenol A, BfR comes to the conclusion in its scientific assessment that the normal use of polycarbonate bottles does not lead to a health risk from bisphenol A for infants and small children. BfR is not alone in this assessment. The European Food Safety Authority (EFSA) and the U.S. Food and Drugs Administration (FDA) share this opinion. Japan, which has conducted its own studies on bisphenol A, does not see any need for a ban either.”
 

In January 2010, FDA Deputy Josh Sharfstein was quoted as noting the FDA does support the use of baby bottles with BPA because the benefits of sound infant nutrition currently outweigh the known risks from BPA. Nevertheless, and perhaps not surprisingly, the California Assembly passed legislation last week to ban the use of bisphenol A in children's food and drink containers beginning in 2012.  The bill passed by a vote of 43-31 vote. The Toxics-Free Babies and Toddlers Act (S.B. 797) moves to the state Senate for approval, since the Senate initially passed a different version early last month.

The bill provides that if the state Department of Toxic Substances Control begins to regulate the chemical through its “green chemistry’’ initiative, S.B. 797 would be repealed.  In the meantime, the law would would limit the level of BPA in baby bottles, toddlers' cups, and food and drinking containers.  Infant formula manufacturers would have until July, 2012, to stop using BPA in the coatings used to line their metal containers.

 

IOM Issues Food Safety Report Calling for Reform of FDA

report issued last week by the Institute of Medicine (IOM) and the National Research Council (at the request of Congress) concludes that the FDA is not well equipped to handle potential problems with the food supply.  "Enhancing Food Safety: The Role of the Food and Drug Administration" notes that food-borne illnesses cause more than 300,000 hospitalizations and 5,000 deaths in the U.S each year. Food-borne diseases are caused by a variety of bacteria—such as Escherichia coli or Salmonella—viruses, parasites, or chemical residues.  

The severity of these diseases and the frequency with which they occur spurred this evaluation of how well the current food safety system protects the public’s health. While food safety is regulated by several agencies, the FDA oversees approximately 80 percent of the U.S. food supply, including all produce, seafood, and cheeses. Some food safety experts and some in the media have criticized the FDA’s food safety system and questioned whether it properly safeguards Americans from food-borne diseases. Congress asked the IOM to examine the possible gaps in the current food safety system under the purview of the FDA and to identify the tools needed to improve food safety.

Readers know that many of these food issues have led to litigation.

The IOM determined that the FDA lacks a comprehensive vision for food safety and should take a risk-based approach in order to properly protect the nation’s food. In addition, the FDA should provide standards for food inspection so that states and the federal government follow the same rigorous methods for inspections, surveillance, and outbreak investigations. Most notably, the IOM recommends that Congress take legislative action to provide the FDA with the authority it needs to fulfill its food safety mission. Americans will continue to suffer from food-borne illnesses unless the FDA reevaluates and reworks its approach to food safety management, claims the report.

The FDA, which sponsored the report, responded that through the President's Food Safety Working Group, which includes all agencies involved in food safety, it feels it is making significant progress to ensure government agencies are working seamlessly to protect the American public. But the IOM concludes that in order for the FDA to better ensure food safety, legislative and organizational changes may be necessary. Most notably, it says, Congress should consider taking legislative action to provide the FDA with the additional authority it needs to fulfill its food safety mission. Within the FDA, authority over field activities should shift from its Office of Regulatory Affairs to its Office of Foods. Such a change will ensure that responsibility lies with well-trained personnel with specialized expertise in food safety and risk-based principles of food safety management, says the IOM.

Recognizing that organizational reform will pose challenges, the report recommends that the federal government move toward the establishment of a single food safety agency to unify the efforts of all agencies and departments with major responsibility for safety of the U.S. food supply. The committee recommends establishing a centralized, risk-based analysis and data management center in order to improve efficiency and work toward a safer food supply. This center would include staff and support resources necessary to conduct rapid and sophisticated assessments of short- and long-term food safety risks and to ensure that the comprehensive data needs to support the risk-based system are met.

With regard to legislative changes, Senator Harkin (D-Iowa), head of the Health, Education, Labor and Pension Committee is trying to bring legislation overhauling the food safety system to the Senate floor later this month. He is pushing S. 510, the Food and Drug Administration
Food Modernization Act
, which is co-sponsored by Sens. Dick Durbin (D-Ill.), and Judd Gregg (R-N.H.), among others.  The  bill would give the FDA new authority to track, detect, and halt contaminated food coming from either domestic or foreign suppliers. Food-handling facilities would be required to share additional information with the FDA. Inspections would be more frequent and industry would nee to construct risk-based preventive control plans. The FDA would also get new recall authority.

The House passed its own version of food safety legislation in July, 2009, as we noted.

House Hearing on FDA Progress on Food Safety

Last week, the House Subcommittee on Oversight and Investigations of the Energy and Commerce Committee, held a hearing to discuss the recent performance of FDA in ensuring food safety.

Witnesses included Michael R. Taylor, Deputy Commissioner for Foods, Food and Drug Administration; Steven M. Solomon, Assistant Commissioner for Compliance Policy, Office of Regulatory Affairs, Food and Drug Administration; Lisa Shames, Director, Agriculture and Food Safety, Government Accountability Office; Jodi Nudelman, Regional Inspector General for Evaluation and Inspections, Region II, Health and Human Services Office of Inspector General.

The hearing examined two reports relating to the Food and Drug Administration's management of international food imports and inspections of domestic food facilities. In September 2009, the Government Accountability Office (GAO) released a report on the safety of imported food, entitled Food Safety: Agencies Need to Address Gaps in Enforcement and Collaboration to Enhance Safety of Imported Food.  In the report, GAO examined FDA’s difficulties in coordinating information-sharing and enforcement efforts with Customs and Border Protection. CBP provides information on imported food shipments to FDA, but GAO found that the two agencies’ failure to assign unique identification numbers to import firms limited FDA’s ability to tackle problems with high-risk food shipments.  GAO also opined that FDA does not have sufficient authority to ensure importer compliance with existing requirements. After imported food enters the United States, it remains in the possession of the importing firm until the FDA approves its release. The importer posts a monetary bond with CBP that is intended to discourage the shipment’s unauthorized release prior to FDA approval. However, the report found that because the value of the bond penalty is low, GAO previously concluded that the system may not provide an effective deterrent.

FDA testimony last week acknowledged that GAO has raised some important issues in its report on imported food. The Agency apparently agrees with many of the GAO recommendations and will incorporate them, as appropriate, into both short-term and long-term initiatives to help ensure the safety of imported foods. FDA also admitted it has encountered certain problems with rolling out PREDICT (the Predictive Risk-based Evaluation for Dynamic Import Compliance Targeting system to improve import screening and targeting nationwide), due to difficulties with incorporating it into the Agency’s information technology infrastructure, which itself is in the process of undergoing major upgrades.


FDA officials also testified that enacting new food safety legislation is critical to strengthening FDA’s oversight of imported foods. H.R. 2749 would, among other things, provide valuable new tools, said the agency, for ensuring that importers reliably verify that the foods they import are produced in compliance with the same prevention-oriented standards that would be applicable to foods produced in the United States. For our food safety system to be effective, prevention must begin at the point of production, not at the port of entry, according the FDA.

The second report was from the Department of Health and Human Services Office of the Inspector General (OIG), and was entitled FDA Inspections of Domestic Food Facilities; it identified a number of challenges confronting FDA in safeguarding domestically produced food.  OIG found that, on average, FDA inspects only 24% of domestic food facilities annually; in addition, the number of inspections declined from 2004 to 2008.  The report also found that over the past five years, FDA has not inspected 56% of the food facilities subject to its authority.  OIG found that when violations were identified, FDA did not always take swift and effective action to ensure that these violations were remedied.  Additionally, OIG claimed that some facilities that had violations significant enough to warrant regulatory action refused to grant FDA inspectors access to their official records.

FDA claims the agency has already addressed many of the issues and recommendations noted in the report, and considerable progress is being made on others. FDA agrees with OIG’s assessment of the gaps in the Agency’s inspection authority. FDA is seeking more effective enforcement tools in accordance with OIG’s legislative recommendations. H.R. 2749 seeks to provide enhancements to FDA’s ability to trace the origin and distribution of tainted food. FDA would issue regulations that require food producers, manufacturers, processors, transporters, or holders to maintain a pedigree of the origin and previous distribution history of the food and to link that history with the subsequent distribution history of the food.  


 

Senator Urges House to Amend FDA Powers on Drugs

Like a cross-over episode from two bad TV shows, Sen. Chuck Grassley, ranking member of the Senate Committee on Finance testified before a subcommittee of the U.S. House of Representatives Committee on Appropriations last week.  His Senate Committee staff is generally regarded as having issues presenting a balanced or complete view of the FDA and industry's efforts to monitor the safety and efficacy of approved medication.

In his testimony, the Senator urged Congress to give the U.S. Food and Drug Administration more power to monitor drugs' safety after they enter the market.

He raised questions about whether or not various post-marketing studies sanctioned by the FDA were properly performed.  He talked about his twice-introduced legislation to establish an independent office of drug safety at the FDA, a Center for Postmarket Drug Evaluation and Research.  This entity would tackle the alleged lack of equality between the Office of New Drugs (OND), which decides whether to approve a drug, and the Office of Surveillance and Epidemiology (OSE). OSE, he said, is the office that monitors a drug’s safety once it’s on the market and being sold to patients.

The supposed imbalance between OND and OSE was apparent, he argued, in various drug safety issues that developed into major mass torts. Individuals in the office responsible for post-market surveillance should be allowed to provide an “independent opinion” based on the best available evidence, he asserted. He claimed vaguely that FDA physicians and scientists committed to post-market monitoring of drugs have sometimes been suppressed or ignored.

Other speakers included a Yale School of Medicine Professor who testifies for plaintiffs in pharma cases, and the Director of the anti-industry Health Research Group of Public Citizen.  More fair balance? Maybe after November.

 

FDA Proposes Regs on Direct-to-Consumer Prescription Drug Ads

The Food and Drug Administration has proposed to amend its regulations concerning direct-to-
consumer (DTC) advertisements of prescription drugs. Specifically, the proposed rule would implement a new requirement of the Federal Food, Drug, and Cosmetic Act, added by the Food and Drug Administration Amendments Act of 2007 (FDAAA), that the major statement in DTC television or radio advertisements relating to the side effects and contraindications of an advertised prescription drug intended for use by humans be presented in a clear, conspicuous, and neutral manner. See 75 Fed. Reg. 15,376 (3/29/10). FDA is also proposing standards that the agency would consider in determining whether the major statement in these advertisements is presented in the manner required by FDAAA.

Readers of MassTortDefense know how DTC ads have impacted products litigation, from effects on the learned intermediary doctrine, to influence on the jury pool, to forming part of the basis of substantive information-based claims.

Under the current regulations the presentation of risk information in an advertisement for a prescription human or animal drug is required to be comparable in prominence and readability to the presentation of effectiveness information in the advertisement. If an advertisement presents effectiveness information in a clear and conspicuous manner, risk information is required to be presented in a comparable manner.  The new proposal would require disclosure of the major side effects and contraindications of the drug in a clear, conspicuous, and neutral manner, regardless of the manner in which effectiveness information is presented in the advertisement.

The proposed regulations would define the required clear, conspicuous, and neutral manner, as being met if:

1. Information is presented in language that is readily understandable by consumers;
2. Audio information is understandable in terms of the volume, articulation, and pacing used;
3. Textual information is placed appropriately and is presented against a contrasting background for sufficient duration and in a size and style of font that allows the information to be read easily; and
4. The advertisement does not include distracting representations (including statements, text, images, or sounds or any combination thereof) that detract from the communication of the major
statement.

FDA said it recognizes that these standards require judgment in their application. Therefore, the agency does not intend to prescribe a set formula for ‘‘clear, conspicuous, and neutral’’ major
statements because there is more than one way to achieve these standards in a television or radio ad. FDA intends to be flexible enough to consider the variety of techniques sponsors may use to appropriately convey required risk information in prescription drug ads. Sponsors have the flexibility to be creative in designing their ads as long as all of the standards listed here are complied with such that the major statement is communicated effectively to consumers and the overall message
that the advertisement conveys to consumers is accurate and non-misleading.

Comments on the proposed rule are due by June 28, 2010.

FDA Official Testifies Before Congress on REMS and Sentinel

Last week, the House Energy and Commerce Committee's Health Subcommittee held a hearing on drug safety.  A quick report: Chairman Waxman's opening comments indicated that the committee was eager to hear about FDA’s implementation of the 2007 FDA Amendments Act, giving FDA the authority to require manufacturers to implement “Risk Evaluation and Mitigation Strategies” or “REMS.”

FDA Principal Deputy Commissioner Joshua Sharfstein indicated that using this REMS authority is “a work in progress” and acknowledged a "lack of clarity" in certain provisions of the law with respect to REMS. FDA recognizes that designing and implementing the most comprehensive REMS requires a careful balancing of the need to adequately manage risks and also to maintain patient access to important medications. In the design of REMS with elements to ensure safe use (the most comprehensive REMS programs), FDA is mindful, he said, that the elements to ensure safe use must not be unduly burdensome on patient access to the drug, and be designed to be compatible with established distribution, procurement, and dispensing systems for drugs.

If FDA determines that a REMS is necessary to ensure that the benefits of a drug continue to outweigh the risks of the drug, FDA can require manufacturers to have a REMS in place when a drug comes on the market, or implement one later if FDA becomes aware of new safety data. Most of the REMS with elements to ensure safe use include educating prescribers about the risks and appropriate use of the drug as a condition of certification or enrollment in the REMS program. Some programs require the prescriber to monitor the patient immediately following drug administration and for a period of time afterwards. 

The FDA official also gave a brief update on the Sentinel Initiative. FDAAA requires the HHS Secretary to develop methods to obtain access to disparate data sources and to establish a post-market risk identification and analysis system to link and analyze health care data from multiple sources. On May 22, 2008, FDA officially launched the Sentinel Initiative with the ultimate goal of creating and implementing the Sentinel System—a national, integrated, electronic system for monitoring medical product safety. The Sentinel System, testified the Commissioner, once up and running, will enable FDA to actively gather information about the post-market safety and performance of its regulated products—a significant change from the current, primarily passive safety surveillance systems. The law sets a goal of access to data from 25 million patients by July 1, 2010, and 100 million patients by July 1, 2012.

FDA has gathered public input on issues related to the creation and development of Sentinel, held numerous meetings and a public workshop, and established a working group consisting of representatives of numerous federal agencies to share information and discuss issues related to ongoing efforts that are complementary to Sentinel. FDA has awarded key contracts for a pilot project to gather information that will be essential to fully implementing the Sentinel System. As we posted about before, there is still work to be done to address significant issues with this plan.

One risk is that plaintiffs’ attorneys will find a way to misuse the system, to “find” spurious associations between drugs and effects, to assert a causal link based on the “government approved, government sanctioned” database program, and to blame the drug companies for not having seen that same link sooner. Fundamentally, the system creates a corresponding need to improve the ability to determine as quickly as possible which findings reflect a genuine and health risk. That determination may take epidemiological investigations or clinical trials before any conclusion about whether a product actually caused an event. And the new system doesn’t change the reality that sometimes patients suffer adverse events after receiving drugs because they are sick, not because the drug has any issues. Plaintiffs have no incentive to place the new product information uncovered in a context of the continuing benefits of the product for many patients, the lack of certainty in the findings, the limitations of the data, etc.

 

House Committee to Hold Hearing on FDA

The House Energy and Commerce Committee's Subcommittee on Health will hold a hearing titled, "Drug Safety: An Update from the FDA" -- tomorrow, Wednesday, March 10, 2010.

 At the hearing, the Food and Drug Administration will detail the Agency's views on current challenges and successes in the area of drug safety. Set to testify is Joshua M. Sharfstein, M.D., Principal Deputy Commissioner, Food and Drug Administration. 

 
 

New Food Safety Article Discusses Future Trends

From time to time, we have noted the significant litigation that may arise from food recalls.  For those readers interested in this area, we flag a recent article in the International Journal of Food Microbiology. Questeda, et al.,  "Trends in technology, trade and consumption likely to impact on microbial food safety," 10 I.J. Food Micro. 1016 (2010).

Experts from Unilever, the UK Food Standards Authority, and the US National Center for Food Safety and Technology outline what they think of as the key future threats to food safety, and strategies to tackle them. The article looks at current and potential future trends in technology, consumption, and trade of food that may impact on food-borne disease.  Among the most important factors driving an increase in the burden of food-borne disease in the next few decades were found to be the anticipated doubling of the global demand for food; the growing international trade in food; and a significantly increased consumption of certain high-value food commodities such as meat and poultry and fresh produce.

The article opines that the most important factor in reducing the burden of food-borne disease was an improved ability to first detect and investigate a food safety issue and then to develop effective control measures. Given the global scale of impact on food safety that current and potentially future trends have, it is observed that a key role may be played by intergovernmental organizations and by international standard setting bodies.

  

Nanotechnology Legislation Introduced in Senate

Two Democratic legislators have introduced a bill that would create an FDA program to assess the potential health and safety effects of nano-technology ingredients in various consumer products.  Sens. Mark Pryor (D-Ark.) and Benjamin L. Cardin (D-Md.) introduced the "Nanotechnology Safety Act of 2010," S. 2942, last week. Their introductory remarks here.

The FDA established a Nanotechnology Task Force, which issued a report in July 2007. In the task force report, recommendations were made regarding FDA’s future direction for regulating nanomaterial-containing products. Guidance development was included as one the recommendations. The FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology met In 2008. Among the agenda topics was a discussion of issues pertaining to the use of nanotechnology in drug manufacturing, drug delivery, or drug products.  Later, FDA held a public meeting to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology.

The bill would create a program for the scientific investigation of nanoscale materials included or intended for inclusion in FDA-regulated products, to address the potential toxicology of such materials, the effects of such materials on biological systems, and interaction of such materials with biological systems.  Specifically, FDA would be charged to assess scientific literature and data on general nanoscale material interactions with biological systems and on specific nanoscale materials of concern to Food and Drug Administration, and collect, synthesize, interpret, and disseminate scientific information and data related to the interactions of nanoscale materials with biological systems.

Nanotechnology applications in drug development are likely to have a significant impact on the products that FDA regulates. Products containing nanomaterials are being investigated for potential applications as therapeutics, and some products containing nanoscale materials are already on the market. While some of these nanomaterials are nanoscale versions of larger materials used in approved products, other nanomaterials are novel and have never been used in drug products. In 2009, the FDA introduced the "Nanotechnology Initiative", a collaborative effort between FDA and the Alliance for NanoHealth.

The proposed law would also require a report from FDA by 2012 that includes a review of the coordination of activities under the program with other departments and agencies participating in the National Nanotechnology Initiative. The bill would send $25 million annual funding to the agency for the program. The bill was referred to the Committee on Health, Education, Labor, and Pensions,

Many readers of MassTortDefense know that nanotechnology refers to a new field of technology that seeks to manipulate and control products, really matter, on the atomic and molecular scale, typically 100 nanometers or smaller. To give some sense of scale, one nanometer is one billionth, or 10-9 of a meter. A nanometer compared to a meter is the roughly the same ratio as that of a baseball to the size of the Earth. Or another analogy, a nanometer is the length a man's whiskers grow in the time it takes him to lift his razor to his face to shave. We have posted on this topic here, here, and here.
 

New Paper On Reduced Legal Oversight of FDA Warning Letters

The WLF has just published a thought piece, co-authored by your humble blogger and colleagues Jim Beck and Vincent Gallo, on how "Reduced Legal Oversight For FDA Warning Letters Amplifies Compliance And Liability Risks."
 

Last summer, the Commissioner of the Food and Drug Administration reversed existing, sound policy that required prior legal review of regulatory letters (Untitled and Warning Letters) by the Agency's Office of Chief Counsel. This reversal -- eliminating review of regulatory letters for legal integrity except in cases of "significant legal issues" -- is one of several changes instituted by the Commissioner to increase enforcement activity and purportedly to limit enforcement delays.

Our paper explores the potential problems with this policy reversal and the risks for industry.

BPA Update- Part II

Yesterday, we posted about events in the MDL.  Today, the science, and it probably shouldn’t surprise readers of MassTortDefense that studies suggesting a product bears some risk get far more media attention than studies showing a product is safe, even when the latter are more rigorous. Similarly, studies funded by industry are dismissed by the media as hopelessly biased, as if product sellers have no interest in exploring their products, but studies from a pro-plaintiff, pro-litigation, anti-business, pro-regulation, big government biased interest group are deemed “neutral.”

Such continues to be the case with BPA. Consumer Union came out with a report of BPA levels detectable in 19 canned foods. They admitted that the study was limited and that the tests only “convey a snapshot of the marketplace and do not provide a general conclusion about the levels of BPA in any particular brand or type of product tested.”  Levels in the same product purchased at different types or places or in other brands of similar foods might differ from CU test results, they acknowledged. Published reports have noted that the group refuses to release the names of the external laboratories they used for testing; and the "study" would not have been published in a peer-reviewed scientific journal without a detailed description of the analytical methods used. The CU also apparently relies on animal studies in which the animals were injected with BPA, instead of ingesting it. Basic toxicology would indicate that the route of administration is important.

However, BPA has been confirmed as safe for use in food contact materials by the world’s major regulatory agencies. The food contact materials in your supermarket, including epoxy can linings, meet current regulatory standards, and as importantly, actually enhance food safety and extend product shelf life. Thus, BPA-based epoxy coatings in metal packaging provide important and measurable health benefits by reducing the potential for the serious and often deadly effects from food-borne illnesses. This packaging enables the high-temperature sterilization of food products when initially packaged and continuously protects against microbial contaminants. The head-long rush by a few zealots to ban BPA overlooks the need to balance this factor.

The levels CU says it detected are substantially below the advisory level of 600 parts per billion established by the European Union as a level of safe consumption for all ages, and below current U.S. guidelines that establish the daily upper limit of safe exposure as 50 micrograms per kilogram of body weight. They thus do not pose a health risk to consumers, of all ages.

The media gave far less attention to a study released that is a significant development in better understanding the safety of BPA. See Ryan, et al., In Utero and Lactational Exposure to Bisphenol A, in contrast to Ethinyl Estradiol, Does not Alter Sexually Dimorphic Behavior, Puberty, Fertility and Anatomy of Female LE Rats (Toxicological Sciences 2009). The study was sponsored by the Environmental Protection Agency. The study conclusion states: “The lack of effect of BPA on female and male rat offspring after oral exposure to low doses in our studies is consistent with the lack of adverse effects on growth, vaginal opening, fertility and fecundity of low doses of BPA in several other robust, well designed, properly analyzed multigenerational studies (Cagen, et al.,1999; Ema, et al., 2001; Tinwell, et al., 2002; Tyl, et al., 2002).”  This new rodent study thus finds that low-dose exposures to BPA showed no effects on the broad range of reproductive functions and behavioral activities measured. Well-conducted, peer-reviewed studies such as this should provide the basis for reasoned government assessments and regulatory decisions -- not the murky at best, results driven CU report.


 

FDA Issues Strategic Plan For Risk Communication

The U.S. Food and Drug Administration last week issued a Strategic Plan for Risk Communication, outlining the agency’s new efforts to disseminate public health information. The plan lays out a framework for the FDA to provide information about regulated products to health care professionals, patients, and consumers. The purpose of the document is to describe the FDA’s strategy for improving how the agency communicates about regulated products. The strategy is intended to guide program development and research planning in a dynamic environment, where rapidly evolving technologies enable patients and consumers to become increasingly involved in managing their health and well-being.

The plan defines three key areas – FDA’s science base, its operational capacity, and its policy and processes – in which new strategic actions might help improve the FDA’s communication about the risks and benefits of regulated products. The plan also identifies over 70 specific actions for the FDA to take over the next five years.

 They include:

  • Designing a series of surveys to assess the public’s understanding of, and satisfaction with, FDA communications about medical products
  • Producing a research agenda for public dissemination
  • Creating and maintaining a useful, easily accessible internal database of FDA and other relevant risk communication research
  • Developing an expert model to characterize tobacco-use related consumer decision-making and better understand the likely impact of FDA oversight of tobacco products
  • Developing a “library” of multi-media communications on safe food practices for general education purposes and for use with crisis communications concerning food contamination episodes

The plan reflects the FDA’s belief that risk communications must be adapted to the needs of different audiences and should be evaluated to ensure their effectiveness. The plan also focuses on improving two-way communication through enhanced partnerships with government and non-government organizations. FDA noted that the public may not understand the context within which FDA makes decisions, for example, about recalls of particular foods or medical products.  By helping the public better understand how it approves and/or recalls products, FDA hopes to complement its premarket review and postmarket actions. In the past, FDA’s communication efforts arguably were largely restricted to overseeing the key vehicle for communicating risk information to the public—the labeling of FDA-regulated products. The process of negotiating with product manufacturers about changes to labeling or decisions to recall a product can be lengthy. Now, as the Internet and emerging technologies both enable and feed the public’s demand for greater transparency and communication frequency, these protracted waiting periods are giving way to communication in real time. Thus, designing a contemporary risk communication strategy is critical, says the plan, to FDA’s efforts to realize its potential for effective protection and promotion of health, enabled by 21st century knowledge and technology.

The plan comes three years after a study by the Institute of Medicine opined that the FDA had fallen short of its task of making sure that the drugs that come to the market are safe for use.  The IOM's recommendations included clarification of the FDA's role in gathering and communicating
additional information on the risks and befits of marketed products.  The FDA then created a new risk communication advisory panel to develop best practices for communicating the risks and benefits to the public.


 

FDA Releases Draft Guidance on Risk Evaluation and Mitigation Strategies

The FDA has released its draft guidance on Risk Evaluation and Mitigation Strategies, or REMS, laying out guidelines for how pharmaceutical companies should follow the plans, and describing the consequences for not doing so. The draft guidance for industry entitled ‘‘Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications,’’  follows on the Food and Drug Administration Amendments Act of
2007 (FDAAA) which added new provisions to the Federal Food, Drug, and Cosmetic Act giving FDA the authority to require REMS.

For every drug approved by the FDA, the risks associated with its use are communicated through the labeling/product package insert. The manufacturer or the FDA may determine that a formal ongoing effort may be needed to monitor and manage risk issues, and thus that a Risk Evaluation and Mitigation Strategy is necessary to go beyond traditional product labeling to ensure that the benefits outweigh the risks on an ongoing basis.  FDA may now require REMS for any NDA, ANDA, or BLA, at any stage of the product life-cycle.  REMS components include medication guides; patient package inserts; a communication plan for health care providers; elements to ensure safe use including requirements for those who prescribe, dispense, or use the drug; and a timetable for REMS submission.  About 60 medicines are currently sold with such plans.

We have posted before about the opportunities and pitfalls in REMS that could have a significant effect on future litigation involving the product. The REMS process may engender “bad documents” (a paper trail that casts the company or its products in a bad light). On the other hand, one of the common claims asserted in product litigation is that a manufacturer was aware of and failed to adequately warn about its product’s risk. As the REMS process is specifically designed to increase the effectiveness of warnings to the health care and patient communities, it may bolster a defense against the assertion that the manufacturer failed to provide adequate warnings.

The new draft guidance describes the format and content of a proposed risk evaluation and mitigation strategy, including REMS supporting documentation, the content of assessments and proposed modifications of approved REMS, what identifiers to use on REMS documents, and how to communicate with FDA about a REMS. The draft guidance was issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency’s current thinking on the format and content of proposed REMS, REMS assessments, and proposed REMS modifications.

REMS required by the FDA are subject to regulatory inspection and are enforceable under the FDCA as amended by FDAAA.  A drug may be considered misbranded if the responsible person for that drug fails to comply with a requirement of the approved strategy.  Firms that don't follow their plans will face fines of up to $10 million for a continued violation, according to the FDA guidance.
 

IOM To Study 510(k) Process for Medical Devices

The U.S. Food and Drug Administration announced recently that it had commissioned the Institute of Medicine (IOM) to study the premarket notification program used to review and clear certain medical devices marketed in the United States. (Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine is supposed to provide independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public.)

The IOM study will examine a premarket notification program, also called the 510(k) process, for medical devices. While the IOM study is underway, the FDA’s Center for Devices and Radiological Health (CDRH) will apparently convene its own internal working group to evaluate and improve the consistency of FDA decision making in the 510(k) process.

The FDA classifies medical devices into three categories according to their level of risk. Class III devices (highest level of risk) generally require premarket approval to support their safety and effectiveness before they may be marketed. Class I and Class II devices pose lower risks and most Class II devices and some Class I devices can be marketed after submission of certain premarket notifications— the 510(k) applications.  A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective -- that is, substantially equivalent -- to a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to pre-marketing approval. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims. Devices that present a new intended use or include new technology that presents new questions of safety or effectiveness may not be found substantially equivalent and thus may require premarket approval.

The 510(k) process was established under the Medical Device Amendments of 1976 with two goals: to make safe and effective devices available to consumers, and to promote innovation in the medical device industry. FDA says that during the past three decades, technology and the medical device industry have changed dramatically, making it an appropriate time for a review of the adequacy of the premarket notification program in meeting these two goals.

As part of the study, the IOM will convene a committee to answer two principal questions: Does the current 510(k) process optimally protect patients and promote innovation in support of public  health? If not, what legislative, regulatory, or administrative changes are recommended to achieve the goals of the 510(k) process? The IOM review is supposed to be completed in 2011.

The study comes after the U.S. House Subcommittee on Health held hearings concerning medical devices last June.  The Democratic majority said there is evidence of an approval system that is "broken" - - that its standards, its procedures and its rules don't meet modern needs of getting medical devices to those in need with sufficient confidence in their safety.  However, while critics point to a handful of device recall issues, more than 250,000 devices have gone through the 510(k) process.
 

FDA Launches Two Food Safety Initiatives

The U.S. Food and Drug Administration has launched two Internet-based initiatives that may be noteworthy for MassTortDefense readers involved in food safety issues.

First, the FDA has launched an Internet-based registry to track patterns in contaminated food.  The site, explained here, is a result of 2007 legislation requiring food facilities to report potentially dangerous products. Food industry officials are required to use the Reportable Food Registry to alert the FDA when they discover a risk that  their products might injure people or animals, the agency stated last week. By fostering real-time submission to the FDA of information on food safety hazards, the registry is supposed to enhance the agency’s ability to act quickly to prevent food-borne illness. The goal is to catch the problem before people get sick. 

Facilities that manufacture, process, or hold food for consumption in the U.S. must now tell the FDA within 24 hours if they find a “reasonable probability” that an article of food will cause severe health problems or death to a person or an animal. The reporting requirement, which applies to all foods and animal feed regulated by the FDA, does not reach infant formula and dietary supplements.

Any person who has to submit registration information to the FDA for a food facility that
manufactures, processes, packs, or holds food for human or animal consumption is deemed a “responsible party” and must follow the reporting requirement. A responsible party also must investigate the cause of the adulteration if the adulteration of food may have originated with the responsible party. 

The registry's proposal drew criticism from some industries, and they in fact had asked the FDA last month to extend the effective date for reporting. For example, national organizations representing the grain, feed, grain processing and pet food industries said that, at the very least, the FDA should exercise enforcement discretion in order to provide an appropriate phase-in period. FDA did not do so.

The launch of the FDA registry comes just as Congress is considering a new food safety bill that would give the FDA more funding and greater authority to order recalls of products. The House passed a food safety bill in the summer, and the Senate is expected to take up the issue later this fall.

At the same time, the administration is rolling out a new Web site designed to streamline food safety information for the public. Health and Human Services Secretary Sebelius announced the new Web site  last week. The site is a joint effort among HHS, the Department of Agriculture and the FDA.

The site will put food-related information from all federal agencies in one place.  It includes sections on how to "Keep Food Safe"; what to do in the case of suspected "Food Poisoning"; a section for industry relating to "Inspections & Compliance"; as well as food news, agency events (such as workshops, meetings, and conferences) for FDA, CDC, USDA; and educational materials on food safety.  Of particular interest to our readers may be the links to agency speeches and presentations, communications to Congress, and Congressional testimonies.

 

FDA Considering Rules on Acrylamide in Food

The FDA is considering issuing guidelines on acrylamide content in food.  The agency has published a notice seeking comments from industry on the issue.

Acrylamide is a chemical formed primarily in baked and fried foods by a reaction between sugars and the amino acid asparagine. The reaction is partly responsible for the golden color and tasty flavor of baked, fried, and toasted foods. In 2002, some Swedish scientists reported unexpectedly high levels of acrylamide in carbohydrate-rich foods and also published a study associating the chemical to cancer in laboratory rats. Further research subsequently determined that acrylamide can form in some foods during certain types of high-temperature cooking.

FDA has not yet issued guidance for manufacturers on reducing acrylamide in food. However, it is anticipated by the agency that new information will soon be available about the toxicology of acrylamide, which may shed light on acrylamide's potential carcinogenicity in laboratory animals. Readers of MassTortDefense know how difficult it is to leap from animal studies to causation conclusions in human beings, because of the physiological and metabolism differences between species, the excessive dosages that are (and typically must be) given to experimental animals, and the varying biological defense mechanisms that species have to environmental insults.

International efforts to develop approaches to acrylamide mitigation are also beginning to prove successful. Moreover, FDA is aware that at least some manufacturers in the United States are seeking ways to reduce acrylamide in their products. In this context, FDA is considering issuing guidance for industry on reduction of acrylamide levels in food products.

Health Canada recently added acrylamide to that nation’s toxic substances list, as part of its ongoing review of over 200 chemical substances in commercial use. It stated that current consumption levels “may constitute a danger in Canada to human life or health,” but it also acknowledged that research into a possible carcinogenic link for humans has so far been inconclusive.

In fact, dietary intakes of acrylamide are not related to increased risks of brain cancer, according to a recently released study of 58,279 men and 62,573 women, published by Maastricht University in the Netherlands. J.G.F. Hogervorst, et al., “Dietary Acrylamide Intake and Brain Cancer Risk,” 18 Cancer Epidemiology, Biomarkers & Prevention (2009).  Researchers have also reported in the Journal of the National Cancer Institute that dietary acrylamide was not linked to lung cancer risk, and that the compounds may even reduce the risk in women. "Lung Cancer Risk in Relation to Dietary Acrylamide Intake," 101(9) JNCI 651-662 (2009).

 

 

In seeking comments, the FDA has asked food manufacturers to respond with details of any manufacturing changes they have made, the success and cost-effectiveness of those changes, methods for acrylamide reduction that could be appropriate for smaller manufacturers, and changes to on-pack instructions for consumers to mitigate acrylamide formation.

 

 

Device Group Comments on FDA Draft Guidance on Risk Information

Readers of MassTortDefense know how FDA regulatory treatment of advertising and promotion can impact product liability litigation involving drugs and medical devices. Earlier this year, the FDA issued draft Guidance for Industry Presenting Risk Information in Prescription Drug and Medical Device Promotion.  This draft guidance describes factors FDA considers when evaluating advertisements (ads) and promotional labeling for prescription drugs, ads for restricted medical devices, and promotional labeling for all medical devices for their compliance with the Federal Food, Drug, and Cosmetic Act and relevant regulations. The draft guidance discusses factors that are relevant to the disclosure of risk information and provides numerous examples to illustrate FDA’s thinking on these factors. The recommendations contained in this draft guidance apply to promotional materials directed to both consumers and healthcare professionals.

As the comment period has drawn to a close, the medical device trade group AdvaMed has weighed in, arguing that the FDA's draft guidance on presentation of risk information in advertisements fails to adequately distinguish between devices and drugs.  The group asserts that the draft lacks content and specificity for device makers, and that a separate guidance document for medical devices is probably warranted. One example is the discussion in the draft of the important concept of over-warning, which is done solely with drug examples.

The comments also not the inherent differences between drugs as therapy and a device which requires a separate intervention (surgery) to be used. Because devices are often used in conjunction with other devices and drugs, communications with consumers of medical devices may need to focus more on a broader spectrum of risks and benefits of ongoing therapies, with a larger group of health care professionals.

AdvaMed also questions the draft's notion that risk information should be spread throughout a promotional piece, rather than located in one easy spot for the consumer to find.  Overall, the draft appears to focus on risk information without adequately discussing the intersection with benefit information.

The group agrees with a move towards the "reasonable consumer" standard for evaluating promotional pieces, and suggests the same direction be taken with DTC advertisements. Highly trained regulators cannot easily evaluate DTC ads as would an average consumer.   Finally, the group argues the draft should provide more specific guidance on use of the Internet for promotion, and the use of hyperlinks.  Increasingly the Internet is a source of information for medical consumers.

 

 

FDA Proposes That Adverse Event Reports Be Submitted Electronically

The Food and Drug Administration last week proposed new rules that would require adverse event reports related to approved devices, drugs and biologic products to be submitted electronically.  (Readers of MassTortDefense know how plaintiffs in mass tort litigation will attempt to use such reports to show the defendant company missed or ignored a "signal" of a safety issue with the product.)

When a drug or biological product is approved and enters the market, the product is introduced to a larger patient population in settings that may be different from clinical trials. New information generated during the post-marketing period can offer further insight into the benefits and risks of the product, and thus evaluation of this information is important to ensure the safe use of these products.

The FDA receives information regarding post-marketing adverse drug experiences from safety reports submitted to the agency. For nearly 35 years, FDA has received these post-marketing safety reports on paper. In recent years, some companies have voluntarily submitted these reports to
the agency in electronic format. Data from both electronic and paper reports are entered into FDA’s Adverse Event Reporting System (AERS) database. AERS is a computerized information database designed to support FDA’s post-marketing safety surveillance program for drug and biological products. The AERS database is used to store and analyze data received in post-marketing safety reports.

The FDA is proposing to amend its post-marketing safety reporting regulations to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. FDA is taking this action to improve the agency’s systems for collecting and analyzing post-marketing safety reports. The proposed change would help the agency, it believes, to more rapidly review post-marketing safety reports, identify emerging safety problems, and disseminate safety information in support of FDA’s public health mission. In addition, the proposed amendments would be a key element in harmonizing FDA’s post-marketing safety reporting regulations with international standards for the electronic submission of safety
information.

The FDA said the change will expedite the agency’s access to safety information and provide data to the agency in a format that would support more efficient and comprehensive reviews, and would enhance its ability to rapidly communicate information about suspected problems to health care
providers, consumers, applicants, and sponsors.

The agency says it is mindful of the security issues related to the confidentiality of data when safety
reports are submitted electronically, and will be prepared to respond promptly to changing
technology to ensure secure transmission of data.

BPA Update

The FDA's Science Board earlier this week heard  an update from the agency regarding the continued assessment of Bisphenol-A (BPA) in FDA-regulated products. (The Science Board to the Food and Drug Administration provides advice primarily to the Commissioner and other government officials on complex and technical issues as well as emerging issues within the scientific community.  The Board consists of a core of 21 members who are supposed to be authorities knowledgeable in the fields of food safety, nutrition, chemistry, pharmacology, toxicology, clinical research, and other scientific disciplines. Members represent academia and industry.)

At the meeting's update from the agency regarding the continued assessment of BPA,  the FDA Acting Deputy Commissioner briefed the agency's Science Board about agency plans to complete its evaluation of bisphenol A;  Dr. Goodman, who is also FDA's acting chief scientist, reportedly stated that the FDA will decide by Nov. 30 whether it will regulate bisphenol A in food packaging. FDA's National Center for Toxicological Research also described a variety of rodent and monkey studies that FDA is undertaking to further assess bisphenol A and potential health effects.

A representative of the Natural Resources Defense Council was among the public speakers who urged FDA to ban bisphenol A, despite the fact that the few studies of laboratory animals that have suggested an association with reproductive or developmental issues have used nonstandard test methods. Studies using standard protocols have not found any significant problems. The American Chemistry Council, BPA Joint Trade Association, and other industry groups argue that food and beverage containers made with BPA pose no undue risk of harm.  BPA is used in the lining of some food and beverage cans to prevent spoilage and is also used in a variety of other consumer products to enhance the structural integrity of plastic containers. Assessments conducted by Health Canada and California's Environmental Protection Agency suggest that dietary exposure would not pose risk to infants. Infant formula may be the most highly regulated food in the world.

Earlier this month, the Massachusetts Department of Public Health issued a health advisory   to parents and caretakers of children up to the age of two years suggesting they avoid the use of products that contain BPA for making or storing infant formula and breast milk. The state health agency further advised pregnant and breastfeeding women to avoid products that may contain BPA. The agency also noted that researchers caution that more research needs to be conducted.

Readers of MassTortDefense interested in BPA issue may want to look at "Science Suppressed: How America became obsessed with BPA,"  an in-depth examination by the STATS program at George Mason University of the science, risk assessment, and media coverage of the chemical, based on interviews with the lead authors of two major risk assessments, and focusing on the accuracy of the media's campaign to have the chemical banned. Some newspapers' coverage has had a knack, says the study, for avoiding research that showed BPA was safe, including risk assessments by the European Union, NSF International, Japan, and a lot more. Some of the media coverage has relied on a small circle of researchers whose work on BPA has been rejected by risk assessments across the world.


After the National Toxicology Program draft report was issued in early 2008, plaintiffs' attorneys nationwide began filing consumer class action complaints claiming violations of state consumer protection laws, fraud, breach of warranty, unjust enrichment, strict product liability, breach of contract and negligence. The lawsuits were consolidated as an MDL in the Western District of Missouri, last year (MDL-1967).  This multidistrict litigation consists of more than 25 cases that involve allegations concerning in baby bottles.

FDA Commissioner Outlines New Enforcement Plans

Readers of MassTortDefense know how FDA actions can instigate and affect potential mass tort litigation involving drugs and devices. Last week, in a presentation to the Food and Drug Law Institute (FDLI), new FDA Commissioner Margaret A. Hamburg revealed that the FDA will implement procedural reforms designed to allow the agency to act more quickly and aggressively on the enforcement of food, drug, and medical device regulations. The FDA commissioner told FDLI that the federal watchdog will be a leaner and meaner organization under her leadership.


In her remarks, the Commissioner noted that while impressed by the commitment to compliance that many companies have made – both in terms of their corporate culture and their investment in compliance systems -- her goal is for all companies to make and implement such a commitment in order to prevent harm to the public. A key part of the strategy to support private sector compliance is more effective enforcement against violations of the law. She suggested that such enforcement helps industry too – by maintaining a level playing field for safe products. Making sure that offenders are held legally accountable prevents companies from having to choose between doing the right thing and staying competitive.

An effective enforcement strategy depends on several key elements she said:

  • The FDA must be vigilant. Through regular inspections and follow-up on signals indicating problems, the FDA must work to identify and resolve problems early. Companies must have a realistic expectation that if they are crossing the line, they will be caught, and that if they fail to act, FDA will.
  • The FDA must be strategic, she continued. The agency must place greater emphasis on significant risks and violations, and use meaningful penalties to send a strong message to discourage future offenses.
  • The FDA must be quick. The agency must be able to respond rapidly to egregious violations or violations that jeopardize public health.

More specifically, she said the pathways for enforcement action can be too long and arduous. To address this, the FDA will set post-inspection deadlines. When the FDA finds that a firm is significantly out of compliance, it will expect a prompt response to the findings, generally no more than fifteen working days before the FDA moves ahead with a warning letter or enforcement action.

Second, the FDA will take steps to speed the issuance of warning letters. There will be a new policy to limit warning letter review to significant legal issues.

Third, the FDA will work more closely with regulatory partners to develop effective risk control and enforcement strategies. In many food safety cases, for example, local, state, and international officials have more authority to take action quickly than the FDA.

Fourth, the FDA will prioritize enforcement follow-up. After a warning letter is issued or a major product recall occurs, FDA will make it a priority to follow up promptly with appropriate action, such as an inspection or investigation to assess whether or not a company has made required changes in its practices.

Fifth, she said, the FDA will no longer issue multiple warning letters to non-compliant firms before taking enforcement action. And, in the case of significant health concerns or egregious violations, FDA will consider immediate action – even before issuing a formal warning letter.

Finally, the FDA is developing a formal warning letter “close-out” process. If the FDA can determine, usually based on a re-inspection, that a firm has fully corrected the violations raised in a warning letter, it will provide to the firm a “close-out” letter, indicating that the issues in the warning letter have been successfully addressed. One can imagine how the obtaining or failure to obtain a close-out letter may be anissue in litigation.
 

FDA Risk Communication Advisory Committee To Hold Food Meeting

FDA has announced a forthcoming meeting of the Risk Communication Advisory Committee.  This advisory committee provides advice and recommendations to the agency on a variety of regulatory issues. The meeting will be held on August 13, 2009, from 8 a.m. to 5 p.m. and August 14, 2009, from 8 a.m. to 2 p.m.

The Committee will discuss FDA’s external research on, and internal assessment of,  communications about food safety problems. This discussion will address research on consumer
knowledge of food recalls and plans for how to monitor communication effectiveness during the course of a recall. The goal of the discussion is to advise FDA on developing more effective communication strategies. The Committee will discuss FDA's external research on, and internal assessment of, communications about food safety problems. This discussion will address research on consumer knowledge of food recalls and plans for how to monitor communication effectiveness during the course of a recall. 

 

As background for this topic, the FDA directs the public to following sites:
FDA Peanut Product website.

 


•2006 FDA/FSIS Food Safety Survey Top-line Report

•Rutgers University Food Recall Surveys – Consumer Responses to Food Recalls: 2008 National Survey Report
Public Response to the Salmonella Saintpaul Outbreak of 2008
Public Response to the Contaminated Spinach Recall of 2006

Readers of MassTortDefense are well aware of the signifcant food recall issues, and subsequent litigation, in recent years.
 

Presidential Memo On Preemption Sends A Warning

Along with my partner Andy Gaddes, I taught a recent CLE seminar on products liability issues.  One of the topics the attendees -- in-house counsel from a variety of industries -- were most interested in was President Obama's May, 2009 memorandum to federal agencies reversing the Bush administration's well-reasoned preemption policy.
 
The new policy is contained in a memo, not a formal executive order, but it clearly expresses a new view of preemption. Cloaked somewhat ironically in the guise of "state's rights", the policy comes from an administration that apparently has no trouble expanding the role of the federal government in unprecedented ways, taking over the auto companies, banks, and others.
 
The memo provides that heads of departments and agencies should not include in regulatory preambles statements that the department or agency intends to preempt State law through the regulation except where preemption provisions are also included in the codified regulation.  Heads of departments and agencies should not include preemption provisions in codified regulations except where such provisions would be justified under the Administration's new interpretation of the legal principles governing preemption.  Finally, heads of departments and agencies should review regulations issued within the past 10 years that contain statements in regulatory preambles or codified provisions intended by the department or agency to preempt State law, in order to decide whether such statements or provisions are justified under the new interpretation of the applicable legal principles governing preemption.
 
The legal basis of the doctrine is not really that malleable. Federal preemption is derived from the supremacy clause of the Constitution that says federal law is the supreme law of the land and any conflicting state law or regulation is without effect.  The policy basis of the doctrine is equally clear: allowing each state to set diverse and individual safety standards can undercut needed uniformity and can subject manufacturers to expensive, unfair, and confusing requirements. It forces product sellers to potentially navigate a confusing, often contradictory patchwork quilt of up to 50 sets of laws and regulations.  Of course, the preemption issue affects more than traditional administrative regulation by the states: companies may become subject to regulation by litigation at the hands of the plaintiffs' bar. 
 
The new policy has the potential to create a real chilling effect in agencies that should be clear about the preemptive intent and reach of their regulations.  While the Obama administration claims its approach breaks no new ground, it may well fundamentally weaken the federal government's ability to address problems on a national level and thus may have untended consequences by allowing states to interfere with parts of the Obama administration's domestic agenda. Regulations for health care and climate change, for example, arguably cannot work absent preemption.
 
Preemption has been applied to drugs and medical devices, vehicular roof crush standards issued by the National Highway Traffic Safety Administration, mattress flammability standards issued by the Consumer Product Safety Commission, pesticides regulated by the EPA and a variety of other products.  A majority of the regulations containing preemptive language were issued by the FDA and NHTSA.   
 

 

Bill to Beef Up FDA Food Safety Power Passes Committee

The House Energy and Commerce Committee last week approved legislation that would give the FDA more funding and power to police food safety.  The unanimous voice vote for a version of the bill offered by committee Chairman Henry Waxman (D., Calif.) came after extensive negotiations between Democrats and Republicans. The "Food Safety Enhancement Act of 2009,"  H.R. 2749, will now go to the entire House.

The bill comes at least in part in response to recent outbreaks of illnesses traced to tainted spinach, peanuts, hot peppers and other foods. The legislation would give the FDA greater authority to order food recalls, impose new civil penalties, and require inspections of so-called high-risk food facilities at least once a year.  It also calls for companies to keep detailed records to help the FDA more quickly trace the distribution of tainted foods and track the source of the contamination.  Specifically, the FDA would be required to issue regulations that require food producers, manufacturers, processors, transporters or holders to maintain the full pedigree of the origin and previous distribution history of the food and to link that history with the subsequent distribution history of the food.
 

The Grocery Manufacturers Association, a food industry group, released a statement in support of the bill, after Democrats agreed to a number of changes. (For example, they added a cap so no company would be charged more than $175,000 in fees to pay for the new bill.)  Critics of the bill argue that it would impose a one-size-fits-all regulatory scheme on big and small farms and on national and local food producers; does not address the major underlying causes of food safety problems such as industrial agriculture practices and the consolidation of our food supply. Others assert that the bill, by apparently empowering the FDA to regulate how crops are raised and harvested, puts the federal government right on the farm, dictating to farmers "good farming practices" on organic farming, use of manure, GMO animal feed, animal drugs, and petrochemical fertilizers and pesticide issues.

At last report, the House hasn't scheduled a vote on the legislation. In the Senate, Illinois Democrat Dick Durbin has introduced similar food-safety legislation.

 

Investor Report Questions Reporting About Nano-Risks

New and more extensive government regulation may be in the future for a host of industries and products we have blogged about at MassTortDefense, including tobacco, medical devices, food, and drugs.  A new report from the "Investor Environmental Health Network" calls for regulations not of the products themselves, but new rules governing disclosure of potential liabilities that can arise from emerging product technologies like nanotechnology.

EHN is a partnership of investment managers who report they oversee more than $25 billion in assets. The new report identifies alleged "loopholes" in the current system of securities and accounting regulation that the group says prevent a complete reporting of a firm's potential liabilities. They point, as a case study, to the alleged danger of asbestos-like litigation risks for nanotechnology companies and investors, as potentially "ultra-hazardous" nanotechnologies enter the market.

They argue that nanomaterials, lighter and stronger than other materials, are used in hundreds of products already on the market, including many cosmetics and skin care products. They cite a  study published in May, 2008 which suggested certain carbon nanotubes could have similar health effects as asbestos; and they point to a concern that particles at the nano level will be able to penetrate membranes in the brain in a way traditional particles do not.  Materials can take on new properties at the nano level, becoming stronger, or better conductors of heat or electricity, for example. But what creates their potential for new applications across a range of industries, may also be the source of their risk. 

The report calls for more consistent liability estimates made to insurers and investors; benchmarking liabilities against other companies whose published litigation results could offer another estimate of liability; and several new disclosure regulations from the SEC.

Companies developing or contemplating selling products with nanotechnology will, of course, want to monitor these efforts, which seem at times to call for a level of foresight requiring a working crystal ball. This particular report appears to assume that all the potential risks of nanotechnology are real; that manufacturers have no interest in exploring the potential risks; and, if they do, certainly won't ever disclose them.  Begrudgingly, it admits that "a number of questions remain regarding whether carbon nanotubes will actually cause health harms to the same degree that asbestos did."  That's an understatement.  In fact, the published studies relate to only some forms of carbon nanotubes, and like any potentially toxic substance, the levels of exposure to carbon nanotubes by workers or consumers is a key issue in assessing risk.  Many of the current uses of nanotechnology are in FDA-regulated products where there is a demonstrated lack of dermal absorption. Similarly, regarding potential nanotechnology in food packaging, substances used in food packaging are already regulated by FDA as “food contact substances” with the burden resting on the sponsor of a new food contact substance to demonstrate its safety.

Currently, companies involved in nanotechnology regularly disclose to investors that there is no scientific agreement on the health effects of nanomaterials; they note that some scientists believe that in some exposure contexts, nanomaterials may be hazardous to an individual’s health or the environment. They disclose that the science of nanotechnology is based on arranging atoms in way not made in nature; that future research into the effects of nanomaterials may thus have an adverse effect on products using the new technology.  They also typically disclose that the future regulation and limitation of the kinds of materials used in or used to develop nanotechnology-based products could halt or delay the commercialization such products. Such disclosures would seem to put investors on adequate notice of an uncertain future; speculative and alarmist predictions of the "next asbestos" seem unwarranted.

FDA Issues New Draft Guidance on Presenting Risk Information

The FDA recently issued a new draft Guidance for Industry titled “Presenting Risk Information in Prescription Drug and Medical Device Promotion.”  This new guidance document represents a comprehensive and fairly detailed overview of the FDA’s approach to reviewing drug and device advertising, albeit with a somewhat surprising omission regarding Internet-specific guidance.

As readers of MassTortDefense know, promotional pieces: (1) cannot be false or misleading, (2) must reveal material facts, including facts about consequences, and (3) should present information about effectiveness and risk in a balanced manner. The guidance confirms that promotional pieces will be judged based on the “reasonable consumer” standard, essentially adopting the definition used by the Federal Trade Commission. Importantly, the FDA also adopts the FTC position that multiple interpretations of a claim are possible if they are all reasonable, and a violation will be found if any one reasonable interpretation violates regulations.

Finally, while the guidance acknowledges the different levels of expertise of consumers and healthcare professionals and notes that the FDA takes account the intended audience in determining compliance, the guidance specifically highlights the social science research finding that experts are “subject to the same cognitive biases and processing limitations as non-experts.”  As a result, it arguably gives insufficient credit to physicians’ abilities to understand important information and make appropriate prescribing decisions;  the recommendations listed in the guidance seemingly apply equally to promotional materials directed to consumers and healthcare professionals.

The general considerations the FDA will use in assessment include (1) use of language appropriate for the target audience, (2) appropriate use of signals (e.g., headlines, change of announcer), (3) appropriate framing of risk information (e.g., severity, specificity), and (4) hierarchy of risk information (i.e., most important risk information should come first).

More specifically, the FDA considers the quantity, materiality, and comprehensiveness of the risk information contained in the piece. Concerning quantity, the FDA notes that risk information should be comparable to benefit information and should include enough detail to convey an “accurate” impression of the product. Among the relevant factors are (1) the number of statements about benefits and risk, (2) the completeness and depth of detail about benefits and risks, (3) the amount of time or space devoted to benefits and risks, and (4) the use of components that enhance or distract from the presentation of risk or benefit information. In assessing materiality and comprehensiveness, the guidance notes that material risks are those that would influence a reasonable member of the target audience—often the most serious and the most frequently occurring risks.

Despite the guidance’s clear and intentional application to Internet advertisements, it makes no special mention of such advertisements and provides no specific guidance on issues unique to Internet promotion.

The comment period for this draft guidance ends August 25, 2009. Additional information, including information on how to submit comments, can be found here.

 

 

Federal Food Safety Working Group Invites Suggestions

The administration's Food Safety Working Group is collecting suggestions on its website for reforming federal food safety policy. Earlier this Spring, President Obama announced the creation of the Food Safety Working Group, chaired by the Secretaries of the Department of Health and Human Services and the Department of Agriculture. The President said in his address that the working group was designed to "bring together cabinet secretaries and senior officials to advise me on how we can upgrade our food safety laws for the 21st century; foster coordination throughout government; and ensure that we are not just designing laws that will keep the American people safe, but enforcing them."

The Working Group's charge is to ensure the country has safe food, to enhance food safety systems by fostering coordination throughout the government, and to enhance food safety laws for the 21st century. Apparently, the first work product from the Food Safety Working Group will be a set of principles and guidelines for improving food safety. The Working Group is receiving input from a broad range of stakeholders about their ideas for improving the food safety system. Others are invited to send their suggestions for reforming food safety policy, along with questions, comments, concerns. The Working Group can be reached through the White House comment form, or on twitter (hashtag #WHsafefood) or at their Facebook page.

Interested readers of MassTortDefense should think about reaching out to the Working Group with ideas for food safety that properly balance the importance of an adequate supply, the need for rapid transportation of foodstuffs, the public benefit of dietary choice and food options, the harmfulness of excessive governmental red tape; the need to avoid significant costs increases to the consumer in this challenging economic period, the inefficiency of government bureaucracy, the diversity and scope of the food service industry and its complex, multi-layered linkage with the supply chain, and other relevant concerns.

Most importantly to litigators, any thoughts would be welcome on safety steps that will not support or encourage additional litigation against the food industry. The CDC estimates that, each year, nearly 76 million people are affected by some type of food-borne illness, and approximately 325,000 Americans are hospitalized with a food-borne illness. Ultimately, this is because many pathogens continue to exist naturally in raw animal foods such as meat and poultry. Unfortunately, most food illness outbreak investigations fail to identify the real culprit, and some even identify the wrong source. In many cases, the claimants (who mistakenly think they got sick from the last thing they ate) sue the wrong party. Arguably, a significant part of the federal approach to food safety should focus on consumer and industry education, i.e., food safety educational programs that span the entire farm-to-table continuum, educating farmers, producers, distributors, food-handlers and consumers.

FDA To Revisit BPA Assessment

The U.S. Food and Drug Administration has reportedly agreed to take a further look at its 2008 decision that bisphenol A in certain food and drink containers doesn't pose a significant safety threat. Newly appointed FDA Commissioner Margaret Hamburg is reported to have put the agency's acting chief scientist in charge of the review, which could take 3-6 months. In her first appearance before Congress as commissioner, Hamburg told the House Energy and Commerce Subcommittee on Health that the FDA is re-examining its position on BPA.

Reps. Henry Waxman, D-Calif., and Bart Stupak, D-Mich., sent a letter to the FDA earlier this month asking the agency to revisit its earlier conclusion. The Committee on Energy and Commerce and its Subcommittee on Oversight and Investigations have been investigating the possible risks of the chemical BPA in consumer products and food product containers, particularly in infant formula containers and other items used by infants and children. The Congressmen pointed to the October, 2008, report of FDA's advisory Science Board Subcommittee, which raised questions about some data aspects of the agency's conclusion. "Based on this information, we request that FDA reconsider the Bush Administration's position that BPA is safe at current estimated exposure levels," said the letter.

In addition to their letter to the FDA, the legislators sent a request to the North American Metal Packaging Alliance, an industry group, creating a straw man about alleged tactics the industry might contemplate using in a future hypothetical public relations strategy to counter efforts to ban BPA. The duo requested a list of all attendees at group meetings, including their affiliations and contact information, certainly a chilling attack on the trade group member's right to free speech and freedom of association.

As reported here at MassTortDefense, FDA had already decided to support additional research with regard to its analysis of BPA safety in plastic baby bottles and food and drink containers. The FDA’s basic position remains that current human exposure to BPA in food-packaging materials provides an adequate margin of safety. FDA has been re-evaluating available data and planning for the acquisition of additional data that will strengthen the exposure estimates from all dietary sources of BPA, with particular attention to dietary sources relevant to infants and children.


Makers of BPA say that the chemical poses no known risk to human health at current exposure levels. In response to public demand, some manufacturers have begun introducing products for infants and children that are BPA-free. The Environmental Protection Agency has calculated that adults and infants can consume 50 micrograms of BPA per kilogram of body weight every day over a lifetime with little appreciable risk of harm.  But Democrats have introduced bills in Congress to ban the chemical.

 

FDA Food Inspection Audits At Issue

Published reports cite data suggesting that the FDA is having difficulty meeting its audit goals for food-safety inspections done contractually by states on its behalf.  The FDA is ultimately responsible for the safety of about 80% of the U.S. food supply.  It tends to focus on high risk foods, and contracts with approximately 40 states for inspections of other foods. Nationally, about half of all inspections are performed by states, according to the GAO.

The FDA audits state inspections done on its behalf, with a goal of auditing 7% of the state efforts so as to ensure quality inspections. Recently released data suggests the agency did not meet this audit target in at least 17 states, with five states receiving no audits in the last reporting period. The quality of state inspections came under intense scrutiny this year during the salmonella outbreak allegedly traced to Peanut Corp. of America in Georgia. And, as readers of MassTortDefense realize, the end result can involve mass tort litigation.  Experts hypothesize that so many state and federal resources are devoted to major food-borne illness outbreaks, audits may get postponed.

President Obama's selection to head the FDA, Dr. Margaret Hamburg, has pledged to make protecting the country’s food supply a major priority. And the new proposed federal budget calls for a $260-million increase for the FDA's food safety program. Part of the new funding would go to rebuild the ranks of inspectors; the number of FDA food inspectors has dropped since 2003. Hamburg has noted that the globalization of food production (about 20% of our food supply comes from abroad), the emergence of new and complex food technologies, and the risk of adulteration or deliberate terror attacks on our food supplies all raise major concerns. She proposes a shift from chasing outbreaks after they have occurred to trying to prevent them in the first place.
 

White Paper Explains Detrimental Impact of Proposed Medical Device Anti-Preemption Bill

Much of the debate over the preemption doctrine, certainly in the media and even in many legal circles, has focused on the alleged inadequacy of the FDA to regulate drugs and devices, and the purported consequent  need to have state juries of lay people “police” the health industry. Comparatively little attention has been given to the other impacts of eliminating federal preemption.

A new white paper demonstrates that erasing this doctrine would decrease access to life-enhancing medical devices, increase health care costs, and reduce medical device industry employment. Congressional Democrats are seeking to do just this in the device context -- the Medical Device Safety Act of 2009 was crafted in response to the U.S. Supreme Court's 8-1 ruling in February, 2008 in Riegel v. Medtronic, upholding preemption for certain medical devices when the devices, and their warning labels, had been approved by the U.S. Food and Drug Administration.


The Economic Impact of Eliminating Federal Preemption for Medical Devices on Patients, Innovation and Jobs” was authored by Ernst Berndt, professor in applied economics at MIT's Sloan School of Management, and Mark Trusheim. They argue that among the effects of the bill would be:

 • Reduced patient access to products and the health benefits they provide

• Unreliable, variable patient access to products and the health benefits they provide as varying state regulations and tort liabilities discourage or eliminate products in some regions but not others

• Increased medical costs and lower net public health compared to what could be achieved with increased medical device innovation and product introductions

• Increased defensive medical practices by physicians to avoid possible litigation, raising health costs and exposing patients to greater risks from the added unnecessary procedures

• Reduction in the number of products being developed as manufacturers and their investors respond to greater uncertainty regarding product approval and economic sustainability

• Transfer of health regulatory decisions to untrained, non-expert juries who are exposed to only a biased fraction of the scientific fact base on which to base their decisions


The authors compare the bill to what happened with vaccines: from 1967 to 2004 the number of vaccine makers plummeted from 26 to 3, leading to reduced access, higher costs, no new products, shortages of existing products, a fragile vaccine supply chain, reduced employment and increases in preventable illness. Congress had to step in and take the vaccines out of the traditional tort system.

Under the bill, the authors note, state juries would be asked to render decisions regarding device safety and efficacy based on a limited range of information focused on individual risk versus broad benefit at a trial typically lasting at most several weeks. Allowing state tort suits to do this will place state juries in the position of replacing, by overriding, professionally trained federal regulators in evaluating and quantifying the risks of medical devices. And unlike federal regulators, state juries will not balance, perhaps not even consider, the benefits to those for whom the medical devices enhances health and quality of life -- who of course are not parties to the action.
 

FDA To Hold Meeting on Risk Communication Strategies

The Food and Drug Administration’s Risk Communication Advisory Committee will be holding a public meeting on April 30, 2009, and May 1, 2009, at the Center for Drug Evaluation and Research Advisory Committee Conference Room, in Rockville, MD. On both days the Committee will discuss the Agency’s draft risk communication strategic plan and will be asked for comment and further advice on strategic priorities for research on effective risk communication.

That draft plan describes FDA’s strategy for improving how the agency communicates about regulated products. The strategy is intended to guide program development and research planning in a dynamic environment where rapidly evolving technologies enable patients and consumers to become increasingly involved in managing their own health and well-being. FDA has been looking to improve how it produces communications about the risks and benefits of regulated products, as well as how it oversees those communications produced by regulated entities. For example, as the Internet and emerging technologies have both enabled and fed the public’s demand for greater transparency and communication frequency, the traditional waiting periods for FDA guidance have given way to communication in real time. Designing a contemporary risk communication strategy is key to FDA’s efforts to reposition itself to realize its potential for effective protection and promotion of health, enabled by 21st century knowledge and technology.

Effective communication supports both optimal use of medical products and safe consumption of foods to maximize health. The IOM report on The Future of Drug Safety: Promoting and Protecting the Health of the Public (2006) focused on drug safety, but also highlighted communication more generally, referencing FDA’s mission of helping the public get the accurate, science-based information it needs. In response to an IOM recommendation, FDA launched its Risk Communication Advisory Committee in 2007 to give advice about FDA’s risk communication approaches for all FDA-regulated products.

The FDA has begun to identify research needs in this area, including on the broad topics of:

  • When and what to communicate
  • Reaching the audience (dissemination)
  • Ensuring audience understanding
  • Motivating audiences
  • Evaluating effectiveness of communications
     

CDC Report Indicates Lack of Recent Progress on Food Safety

A new report from the U.S. Centers for Disease Control and Prevention indicates that after "important declines" seen in previous years, the incidence of many food-borne illnesses in the United States has leveled off in the past few years.  U.S. health officials conclude that progress on food safety has plateaued, and that further measures are needed to prevent more food-borne illness.

The findings are from 2008 data reported by the Foodborne Diseases Active Surveillance Network (FoodNet), a collaborative project of CDC, the Department of Agriculture’s Food Safety and Inspection Service (FSIS), the FDA, and 10 state sites. Preliminary data from FoodNet indicate that diagnosed and reported illnesses from an array of bacteria, including campylobacter, cryptosporidium, cyclospora, listeria, shiga toxin-producing escherichia coli (STEC), shigella, vibrio and yersinia, have basically stayed the same since 2004.

In the case of salmonella, the bacteria recently found in peanuts and pistachios, infections may be trending upward. The report said that in 2008, 16 of every 100,000 people in the United States had laboratory-confirmed cases of salmonella infections. That translates into about 48,000 serious illnesses, since individual stool samples are generally sent to laboratories only when someone is suffering a severe bout. In 2005, the figure was 14 people per 100,000, or about 42,000 cases of laboratory-confirmed salmonella infections.

Part of the problem is that as food supply chains get longer, and global distribution networks more complex, there are simply more opportunities for things to go wrong, according to the CDC. If a manufacturer or distributor has wider reach, a single tainted ingredient can potentially infect large numbers of people. Often, therefore, outbreaks of food-borne disease can result in mass tort litigation.

Roughly 76 million people in the United States suffer food-borne illnesses each year, 300,000 are hospitalized, and 5,000 die, according to CDC estimates. Children younger than 4 are sickened by food more than those in any other age group, but adults over age 50 suffer more hospitalizations and death as a result of food-related infections.
 

The CDC report follows on the heels of a report released last week by the Inspector General of the U.S. Department of Health and Human Services finding that identifying the actual suppliers and distributors of tainted food products remains a serious issue. 

Report Reveals Issues With Traceability Of Food Products

Identifying the suppliers and distributors of food products remains a serious issue according to a report released last week by the Inspector General of the U.S. Department of Health and Human
Services.

Beginning in 2005, FDA required certain food facilities to maintain records identifying the sources, recipients, and transporters of food products. The purpose of these records is to allow FDA to trace an article of food through each stage of the food supply chain—from a retail shelf back to a farm—if FDA has a reasonable belief that a food product is adulterated and presents a serious health threat.

This new report was based on two primary data sources: (1) a traceability exercise of 40 selected food products and (2) structured interviews with the managers at the food facilities that handled the selected food products. Traceability is the ability to follow the movement of a food product
through the stages of production, processing, and distribution. Traceability includes both traceback and trace forward. Traceback is the ability to trace a food product from the retail shelf back to the farm. Conversely, trace forward is the ability to trace a food product from the farm forward to the retail shelf. Traceability is often needed to identify the sources of food contamination and the recipients of contaminated food in product recalls and seizures.

The issue of tracking the sources of food-borne disease outbreaks has gained attention since the massive recall of peanut-related products from Peanut Corp. of America earlier this year, which we have posted on.

For the traceability exercise, the agency purchased food products from different retail stores and attempted to trace them through each stage of the food supply chain back to the farm(s) or the border. The government asked the facilities that handled the food product for information about
their sources, recipients, and transporters, which was used in an effort to trace the product. The HHS inspector general's office and FDA representatives purchased 10 individual food products from retail stores in four metropolitan areas – New York, Chicago, San Francisco and Washington. The products included bottled water, manufactured ice, whole milk, eggs, plain yogurt, milled unbleached flour, plain oatmeal, fresh whole tomatoes, cut vegetables and fruit juice.


The department's inspector general's office found that retailers and distributors could trace the component ingredients of just five of 40 products purchased to the farm or country where the ingredients were produced. The inspectors were only able to locate facilities that likely handled the products for 31 of the products.

Several factors limited the ability to trace the specific food products through each stage of the food supply chain. These factors included: (1) processors, packers, and manufacturers not always maintaining lot-specific information, as required; (2) other types of facilities not maintaining lot-specific information because it is not required; (3) retailers receiving products not labeled with lot-specific information; and (4) the mixing of products from a large number of farms. These factors also affect the speed with which FDA can trace specific food products through the food supply
chain. In fact, more than half the 220 facilities contacted failed to meet federal requirements to maintain records about their sources, recipients and transporters of food. The report found that a quarter of the companies contacted did not even know about the requirements. 

In a food emergency, there could be serious health consequences if FDA cannot — at a
minimum — identify the facilities that potentially handled a contaminated food product.

The report recommends that:

  • FDA  should seek statutory authority, if necessary, to require all processors, packers, and manufacturers to create and maintain lot-specific information for food products. FDA should also extend the requirements regarding lot-specific information to other types of facilities, such as distributors, storage facilities, and retailers, in order to further strengthen the traceability of food products.
  • FDA should consider seeking additional statutory authority requiring food facilities to further strengthen the traceability of food products.
  • FDA should work with the food industry to develop additional guidance on traceability.
  • FDA should work with the food industry to develop standards for mixing raw food products from a large number of farms.
  • FDA should seek statutory authority to request facilities’ records at any time, as opposed to its current authority to request records only when FDA has a reasonable belief that an article of food presents a serious health threat.
  • FDA should develop education activities that focus on appropriate and reliable record-keeping systems.

 

FDA Introduces Nanotechnology Initiative

Last week the FDA introduced the "Nanotechnology Initiative", a collaborative effort between FDA and the Alliance for NanoHealth (ANH) and its eight member institutions. The alliance's eight academic institutions are the Baylor College of Medicine, the University of Texas' M.D. Anderson Cancer Center, Rice University, the University of Houston, the University of Texas Health Science Center at Houston, Texas A & M Health Science Center, the University of Texas Medical Branch at Galveston and the Methodist Hospital Research Institute in Houston.


The initiative is designed to push for the development of safe and effective implementation of nanotechnology into medical products. Under a Memorandum of Understanding, the FDA/ANH Nanotechnology Initiative will work to expand knowledge of how nanoparticles behave and affect biologic systems, and to facilitate the development of tests and processes that might mitigate the risks associated with nanoengineered products. The nanotechnology initiative with the Alliance for NanoHealth is an effort to engage resources and technical expertise in this rapidly advancing field.

FDA recognizes that nanotechnology holds great promise for the advancement of novel medical products. All outcomes from this public-private partnership will be placed in the public domain.
Readers of MassTortDefense know that nanotechnology involves the creation and use of materials at the level of molecules and atoms; it presents opportunities but also challenges for the FDA's entire regulatory product jurisdiction, from food to medical devices to therapeutics. Products from the new technology may also present product liability issues for manufacturers.

New Voluntary Guidelines For Device DTC Ads

The Advanced Medical Technology Association has just released a set of “Guiding Principles for Direct to Consumer Device Advertising. “ The principles are intended to help assure that patients have accurate and meaningful information about health care treatment options and encourage them to speak with their physician. Direct-to-consumer (DTC) advertising can be an important tool for educating patients about advanced medical technologies, which are making life better for patients through faster recovery and better outcomes and in many cases, reducing health care costs.

The Advanced Medical Technology Association (AdvaMed) is the world’s largest
association representing manufacturers of medical devices, diagnostic products, and
medical information systems. AdvaMed members and subsidiaries manufacture nearly
90 percent of the health care technology products purchased annually in the United
States and more than 50 percent of the health care technologies purchased annually
around the world.

The voluntary guidelines contain 13 principles that support compliance with the Food and Drug Administration’s and Federal Trade Commission’s existing direct-to-consumer regulations. They also include additional principles, which include revising or withdrawing ads when new safety-risk information comes to light; excluding any content designed to minimize risk information; educating healthcare professionals about new products or new-use indications before the launch of an ad campaign; and submitting TV ads for restricted devices to the FDA at the time of an ad’s release.

The principles were not an effort to ward off regulation from Congress and the new Administration, but to respond to concerns that have been raised in the media in recent months about some DTC ads. 

Readers of MassTortDefense know that plaintiffs try to make an issue of DTC advertising in failure to warn claims, and have succeeded in some contexts in having DTC advertising undermine the traditional learned intermediary rule.
 

New Food Safety Bill Introduced in Congress

Two years ago, there was a nationwide outbreak of E. coli linked to consumption of contaminated spinach from a California supplier. That was the 25th reported U.S. outbreak of E. coli infection that had been traced to contaminated leafy green vegetables since 1993. Each year, approximately 110,000 persons get this infection, and 50 of them die. This is despite greatly intensified efforts during the past decade on the part of federal food-safety agencies — the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) — to prevent the spread of such infections.


In a 2008 outbreak, Salmonella was diagnosed in 1407 persons in 43 states. At least 282 patients were hospitalized, and 2 patients died. Although initial epidemiologic evidence suggested that contamination of tomatoes grown in the southwestern United States might be the cause, eventually the outbreak was isolated from jalapeño and serrano peppers that had been grown on a Mexican farm. In the mean time, tomato consumption plummeted, and the industry lost an estimated $200 million in sales.

This year, the disease was diagnosed in 600 persons in 44 states and Canada traced to contamination of one Georgia producer's peanut butter and the processed foods of other manufacturers that contained the company's peanut butter or paste. Beyond a recall of all peanut products produced by the company since January 1, 2008, more than 400 food products (including cookies, crackers, cereal, candy, ice cream, and pet foods) have been recalled.

Many of incidents like these have led to products liability and mass tort litigation. E.g., In Re ConAgra Peanut Butter Products Liability Litigation, MDL-1845, 2008 WL 2885951 (N.D. Ga., July 22, 2008). And this issue has caught Congress’ attention. Senator Durbin last week introduced S.510, the “FDA Food Safety Modernization Act,” a new bill to amend the Federal Food, Drug, and Cosmetic Act with respect to the safety of the food supply. The bill calls for food manufacturers to conduct a Hazard Analysis and implement Risk-Based Preventive Controls; it calls for regulations to establish science-based minimum standards for the safe production and harvesting of those types of fruits and vegetables that are raw agricultural commodities for which the agency has determined that such standards minimize the risk of serious adverse health consequences or death.

The bill also calls for inspection of food makers’ facilities, according to their risk profile, based on the facility's history of food recalls, outbreaks, and violations of food safety standards, and the rigor of the facility's hazard analysis and risk-based preventive controls. Some facilities would be designated as high-risk facilities and subject to annual inspections. the proposed legislation would also upgrade the nation’s food-borne illness surveillance systems to improve the collection, analysis, reporting, and usefulness of data on food-borne illnesses by coordinating Federal, State and local food-borne illness surveillance systems, including complaint systems, and increasing participation in national networks of public health and food regulatory agencies and laboratories.

Regarding imports, the bill would require each United States importer to perform risk-based foreign supplier verification activities, and the FDA would be required to establish by 2010 an office in not less than 5 new foreign countries to provide assistance to the appropriate governmental entities of such countries with respect to measures to provide for the safety of articles of food and other products regulated by the FDA and exported by such country to the United States.
 

Update on BPA From FDA

The Food and Drug Administration has announced a public meeting on BPA to be held on February 24, 2009, by the Science Board to the FDA. This public advisory committee, whose function it is to provide advice and recommendations to the agency on FDA’s various regulatory issues, will discuss updates from the agency on the continued assessment of Bisphenol A in FDA-regulated products. The Science Board will also hear about the plans for (1) The review of FDA Center’s science programs, (2) the review of each Center’s projects within scientific priority areas.

The meeting will be held at the Hilton Washington DC, North/Gaithersburg, 620 Perry Pkwy., Gaithersburg, MD 20877. FDA intends to make background material available to the public no later than 2 business days before the meeting.

Late last month, the FDA and Health Canada’s Health Products and Food Branch hosted a meeting of representatives of U.S. and Canadian manufacturers and users of food packaging materials containing BPA to discuss what is being done to concerning the potential levels of the chemical in food. The meeting was also part of FDA’s efforts to assist industry in its voluntary BPA related efforts.


The meeting was designed to provide a forum for:
• Updating the industry on the FDA’s and Health Canada’s current activities and planned research to further assess the exposure to BPA and manage any potential risks from the chemical.
• Describing manufacturers’ research activities, their work to refine packaging manufacturing practices to minimize migration of BPA into food, and recent marketplace developments.
• Dialogue by the participants about further information from regulated industry stakeholders that would be helpful to the FDA and Health Canada in updating and refining their BPA risk assessments.
• Dialogue about the different uses of BPA in food contact applications and the variation in possible availability of fully functional and evaluated alternative substances.
• Discussion of the possibility whether, because of availability of alternative products, polycarbonate baby bottles could cease to be a substantial component of the North American market in the future.


With regard to BPA generally, based on all available evidence, the consensus of regulatory agencies in the United States, Canada, Europe, and Japan is that the current levels of exposure to BPA through food packaging do not pose an immediate health risk to the general population, including infants and young children.


Health Canada’s Health Products and Food Branch has concluded that current dietary exposure to BPA through food packaging uses is not expected to pose a health risk to the general population, including newborns and infants. However, using an extremely precautionary approach, the Government of Canada has taken steps to reduce exposure to BPA for infants and young children.
The FDA is currently preparing a detailed response to the October, 2008 review by the FDA Science Board of the agency's draft assessment of the safety of BPA for use in food contact applications. The draft assessment focused on the concerns for developmental toxicity identified in recent assessments of BPA, including those of the National Toxicology Program and their expert panel. For example, the FDA is reviewing research about the potential low-dose effects of BPA. 

Preemption Found In Medtronic MDL

The federal judge in the Medtronic Sprint Fidelis Leads MDL has ruled that all claims in the plaintiffs' master consolidated complaint are preempted. In Re: Medtronic, Inc. Sprint Fidelis Leads Products Liability Litigation, 2009 WL 35467 (D.Minn. 2009).

The Judicial Panel on Multidistrict Litigation transferred related cases involving Medtronic Inc.'s recalled Sprint Fidelis defibrillator leads to the District of Minnesota last February. The leads were recalled in late 2007, because of the potential for fracture, which can potentially cause unnecessary shocks or failure, possibly resulting in injury. 

Relying on the U.S. Supreme Court's decision in Riegel v. Medtronic, Inc., 128 S. Ct. 999 (2008), the MDL court noted that Congress has decided to limit medical-device manufacturers' liability in order to spur innovation. Plaintiffs' remedy, therefore, lies with Congress, and not with the courts. 

Every medical device intended for human use is placed into one of three categories by the FDA, based on the risks of injury or illness the device presents; each category is subjected to a different level of FDA scrutiny. Devices that either support or sustain human life or present a potential unreasonable risk of illness or injury” are categorized as “Class III” devices. Class III devices are subject to the greatest level of FDA scrutiny and “must complete a thorough review process with the FDA before they may be marketed.”  Buckman Co. v. Plaintiffs' Legal Comm., 531 U.S. 341, 344 (2001). Through this process, known as pre-market approval (“PMA”), a device maker must provide the FDA with “reasonable assurance” that its device is both safe and effective.

The PMA process is “a rigorous one.” Medtronic, Inc. v. Lohr, 518 U.S. 470, 477 (1996). Manufacturers must submit detailed information regarding the safety and efficacy of their devices, which the FDA then reviews, spending an average of 1,200 hours on each submission. When analyzing that information, the FDA weighs the probable benefit to health from the use of the device against any probable risk of injury or illness from such use. Accordingly, the FDA sometimes grants PMA to potentially life-threatening devices, if they offer great benefits in light of available alternatives. Riegel, 128 S.Ct. at 1004.

Here, the MDL court rejected arguments that a recall of the leads invalidated their premarket approval. Medtronic correctly noted that the PMA process is governed by a completely separate statutory and regulatory regime than that governing withdrawal of a PMA. Also, the PMA for the leads was in place at the time they were implanted, a crucial fact because liability under plaintiffs' various legal theories hinges upon whether the leads were defective at that time. More fundamentally, the federal interest that preemption is designed to protect is the PMA process, and preemption necessarily looks backward (to the time of PMA) rather than forward.

The court also rejected the plaintiffs' claims that they have asserted "parallel" claims and therefore preemption does not apply. For example, plaintiffs purported reliance on Good Manufacturing Practice or Quality Control guidance did not save the claims. In the absence of any specific requirement in the CGMPs/QSR that Medtronic weld the Sprint Fidelis leads in a certain fashion [that was plaintiffs' beef], holding Medtronic liable for such a welding “defect” would have imposed requirements “different from, or in addition to” those under federal law. This is equally true of plaintiffs' allegation that Medtronic used inadequate testing and quality-assurance methods. Plaintiffs simply could not identify any specific requirements in the CGMPs/QSR that were purportedly violated by Medtronic.

It is noteworthy that the court found dismissal with prejudice was appropriate. This complaint was filed after extensive preparation by the Plaintiffs' Steering Committee, which is made up of lawyers who are experienced in federal preemption litigation. In the MDL Court's estimation, if plaintiffs were aware of sufficient facts in order to avoid preemption, they would have already pleaded them.
 

GAO Adds To Critiques of FDA

The Government Accountability Office issued a report last week that listed the FDA as a "high-risk" area of the federal government. The GAO said the U.S. Food and Drug Administration was being hampered by globalization, more complex products, and laws that have made it more difficult for the FDA to ensure the safety of pharmaceuticals, biologic drugs, and medical devices. GAO says its work examining a variety of issues at FDA echoes the conclusions reached by others (think IOM) that the agency is facing significant challenges that compromise its ability to protect Americans from unsafe and ineffective products. FDA needs to, among other things, improve the data it uses to manage the foreign drug inspection program, conduct more inspections of foreign establishments, systematically prioritize and track promotional materials for review, and adopt management tools to ensure that drug sponsors comply with regulations on the presentation of clinical trial results.
 

The perception of the FDA and its ability to do an effective job is a crucial underlying feature in product liability litigation involving regulated drugs, devices, and food products. Jurors’ perceptions of the agency can affect a myriad of issues and themes the defense may wish to present.

Meanwhile, the Pharmaceutical Research and Manufacturers of America (PhRMA) asserts that the issue is a need for more resources for the FDA, to keep drugs safe. The agency “is being asked to do more than it can do” with current resources, the trade group says. Specifically, FDA needs more resources to conduct foreign inspections so the drug supply can be kept safe. PhRMA also said that FDA needs more resources to modernize because, for example, the agency still looks at clinical trial information on paper.
 

FDA Reports on Salmonella Outbreak

The FDA has reported on its investigation into the source of the recent Salmonella Typhimurium outbreak. At this time, the FDA and the Centers for Disease Control and Prevention (CDC) say they have traced sources of Salmonella Typhimurium contamination to a plant owned by Peanut Corporation of America (PCA), which manufactures peanut butter and peanut paste—a concentrated product consisting of ground, roasted peanuts—that are both distributed to food manufacturers to be used as an ingredient in many commercially produced products including cakes, cookies, crackers, candies, cereal and ice cream. In addition, PCA peanut butter is reportedly distributed to and institutionally served in such settings as long-term care facilities and cafeterias.

The FDA has notified PCA that product samples originating from its Blakely, Georgia processing plant have been tested and found positive for Salmonella by laboratories in the states of Minnesota and Connecticut. Connecticut and Minnesota have reported to FDA that samples of King Nut peanut butter tested in those states are a genetic match to the strain of Salmonella associated with the nationwide outbreak of Salmonella Typhimurium. The results from the Connecticut Department of Health Laboratory are from an unopened container of King Nut peanut butter.
 

On January 18, PCA expanded its previous voluntary recall to include more products and lot numbers relating to peanut butter and peanut paste products manufactured on or after July 1, 2008, at its plant because of potential Salmonella contamination. The peanut butter products being recalled are sold by PCA in bulk containers ranging in size from five (5) to 1700 pounds. The peanut paste is sold in sizes ranging from 35-pound containers to product sold by the tanker container. These products are not sold directly to consumers. PCA has stopped all production at its Blakely, Ga. plant as the FDA continues its investigation.


At least 85 companies bought peanut butter and peanut paste produced in the Georgia plant. More than 125 products including cookies, crackers, ice cream and even some pet food have been recalled in connection with the outbreak. Six deaths may be associated with the outbreak, the U.S. Centers for Disease Control and Prevention has said. The CDC said at least 486 people from 43 states and one person in Canada have been reported ill from the outbreak of the Salmonella typhimurium strain, with 107 of them being hospitalized. Salmonella can cause abdominal cramping, diarrhea and fever. 

Litigation has ensued, with at least one products liability suit in the Middle District of Georgia.

 

FDA Issues Guidance On Distribution Of Medical And Scientific Articles Regarding Off-Label Usage

The FDA has finalized guidelines for how manufacturers can distribute information to doctors about unapproved uses for drugs or medical devices. The ‘‘Good Reprint Practices for the
Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices’’
allows for the limited dissemination of medical journal articles describing off-label uses. The FDA proposed the guidelines in February, 2008 and took public comments before finalizing them.
 

Allegations of off-label promotion are common in mass tort litigation involving drugs and medical devices. Off-label promotion is illegal, but many critics of the industry and plaintiff lawyers seem to forget that doctors can prescribe drugs for any use they see as medically appropriate. The FDA in its guidelines confirms that the public health can be served when health-care professionals receive truthful and non-misleading scientific and medical information on unapproved uses. It will likely help practitioners to receive timely and accurate medical information in an environment where off-label use is common. The FDA's guidance will help assure that medical professionals receive timely and accurate medical information prior to the lengthy process of securing FDA approval for wider use. Such off-label use can save lives, especially in practice areas where there are few effective treatments. These off-label uses or treatment regimens thus may be quite important and may even constitute the medically recognized standard of care. Accordingly, the public health may be advanced by healthcare professionals' receipt of medical journal articles and medical or scientific reference publications on unapproved new uses of approved or cleared medical products that are truthful and not misleading.

This guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115), and suggest that the distribution be in the form of an unabridged reprint, copy of an article, or reference publication;  not be marked, highlighted, summarized, or characterized by the manufacturer in any way (except to provide the accompanying disclosures discussed in the guidance), and be accompanied by the approved labeling for the drug or medical device.

The guidance represents the agency’s current thinking on the dissemination of medical journal articles and medical or scientific reference publications on unapproved uses of approved drugs and approved or cleared medical devices to healthcare professionals and healthcare entities.
 

Opposition To Cert Petition In Colaccico: That Other Preemption Case

While much preemption focus has been on Levine v. Wyeth, including by posts here at MassTortDefense, other preemption decisions are winding there way through the federal appellate courts. Defendants Pfizer Inc., GlaxoSmithKline, and Apotex Inc. last week asked the U.S. Supreme Court to uphold a ruling by the U.S. Court of Appeals for the Third Circuit that failure to warn claims are impliedly preempted by federal law based on the regulatory history of the antidepressants at issue. Colacicco v. Apotex Inc., 521 F.3d 253 (3d Cir. 2008), Petition for Certiorari Filed, 77 USLW 3229 (Oct 02, 2008). 

Readers of MassTortDefense know that plaintiff Colacicco filed suit after his wife allegedly committed suicide while under treatment with a generic equivalent to Paxil. The district court for the E.D. of Pennsylvania found preemption. The appeal was consolidated with a contrasting preemption decision in the McNellis case out of the district court in New Jersey, involving Zoloft. The Third Circuit's decision was the first by a federal appeals court to address the preemptive effect of prescription drug law and regulation since the FDA had expanded on its guidance on the issue.

Plaintiffs sought certiorari, asking the Court to review the Third Circuit's decision; alternatively, they asked the court to hold the petition pending resolution of Levine, argued last month. But the Court should do neither, the manufacturers argued, and cert should just be denied.

Pfizer Brief

According to Pfizer's brief, the Third Circuit properly determined that plaintiff below McNellis sought a warning about suicidal behavior that conflicted with the federal warning requirements for Zoloft. For more than 15 years, the FDA had considered whether SSRIs were associated with an increased risk of suicidality in adult patients. The agency repeatedly determined that the scientific evidence did not support such a warning.

Pfizer notes there is no disagreement among appellate courts (a well-established basis for Supreme Court review) on preemption in SSRI litigation.  No other federal appeals court has ruled in a contrary way on the preemptive effect of the type of conflict at issue here. The 3d Circuit found preemption based on “the direct, real conflict” between plaintiff’s claim that New Jersey law required a warning about adult suicidality and the FDA's requirement—based on its repeated finding of no reasonable evidence of such an association—that only the FDA's approved warning be given. McNellis relied on the Court's decision in Sprietsma v. Mercury Marine, 537 U.S. 51 (2002) to argue that the FDA merely failed to act with respect to suicidality warnings, and that a federal agency's failure to act does not create a federal requirement triggering preemption. But the FDA “regulated with great specificity and care” in repeatedly finding no reasonable association between SSRIs and suicidality, and by requiring the manufacturer to provide the specified warnings.

As to the claim that the manufacturers failed to disclose information to the FDA, defendants assert that the lower court correctly found that this claim should be presented to the FDA first. In addition, Buckman preemption likewise prevents plaintiffs from evading a definitive FDA regulatory record by arguing that the FDA was somehow defrauded; the appellate court found that the preemption doctrine of Buckman v. Plaintiffs' Legal Committee, 531 U.S. 341 (2001), bars claims that the manufacturer withheld information from the FDA.

Direct Conflict

Arguing against even staying the petition until Levine is decided, Pfizer said the issues in the cases are distinct, asserting that the 3d Circuit's decision in this case is correct regardless of whether Levine is affirmed or reversed. Respondents point out what they see as distinct regulatory facts in that case, involving contraindication claims.

Brief for Apotex, GlaxoSmithKline

Apotex, a maker of generic Paxil, and GlaxoSmithKline, the maker of brand-name Paxil, also argued against review. Like Pfizer, they contended the 3d Circuit properly concluded that the FDA's repeated rejection of suicidality warnings preempts plaintiff Colacicco's claims.

The brief also argued that state law failure to warn claims challenging FDA-approved labeling should be preempted. To allow this sort of tort action to continue would place state-law juries in the position of second-guessing FDA decisions regarding the proper warnings for drugs. Lay juries should not be able to undermine the agency's expertise by second-guessing the agency's warning decisions. At its base, Colacicco's argument against preemption is the theory that a court, applying state law, has authority to decide whether GSK could have under federal law, and should have under state law, unilaterally added a suicidality warning to the Paxil labeling, despite FDA regulation.

Courts do not share concurrent jurisdiction with the FDA over drug labeling; there should be no preemption test that would require a court to delve deeply into internal FDA decision making. Specifically, the lower courts do not share jurisdiction with the FDA over the CBE regulation, which is the basis for the “could have, should have” argument, Apotex and GSK both wrote. FDA has made clear that CBE supplements fall squarely within its regulatory jurisdiction. Under Colacicco's theory, the lower court would be authorized to decide, without reference to the FDA, that a CBE supplement adding the putative warning could have been submitted, that the added warning would have been consistent with the FDCAct, and that FDA would have approved it. Thus, the lower courts would become “shadow” FDAs. That is not the scheme adopted by Congress for drug regulation.

 


 

FDA Studies A Revised Advisory On Mercury In Fish

The issue of mercury levels in fish has spawned litigation, including some controversial decisions about the preemptive effect of FDA policies on the regulation of labels of tuna. Now, the FDA is urging amendment of the 2004 advisory that women and children should limit how much fish they eat, saying that the benefits of seafood outweigh the health risks. Bottom line, people should eat more fish, even if it contains mercury.


Currently, the government suggests that women of childbearing years, pregnant women, nursing mothers, infants and children, can be harmed by the mercury in fish and should limit their consumption. In a draft report, FDA proposes to update the existing health advisory. The report argues that nutrients in fish, including omega-3 fatty acids, selenium and other minerals could boost a child's IQ. The greatest benefits, the FDA report said, would come from eating more than 12 ounces of fish a week, which is the current limit advised for pregnant women, women of childbearing age, nursing mothers and young children.


The FDA and the EPA both play a role in protecting the public from mercury contamination. The EPA investigates and regulates mercury and other contaminants in recreationally caught fish, while the FDA regulates mercury in seafood sold in markets and restaurants. States rely on the federal agencies in issuing their own advisories.


Not surprisingly, the Environmental Working Group attacked the draft report. But the National Fisheries Institute applauded the FDA's science-based approach, pointing out the amount of research since the advisory was last updated in 2004 suggesting the real risk to women and children is not eating enough seafood. A Harvard University study released in September of 2008 highlighted the benefits of a seafood rich diet. New research published in the Lancet in 2007 found that mothers who ate the most seafood during pregnancy had children with the highest developmental outcomes. A 2006 Institute Of Medicine report encouraged women to include seafood in their diets. The Harvard Center for Risk Analysis in 2005 wrote that curtailing fish consumption could lead to an increase risk of adverse health outcomes. 


 

FDA To Hold Workshop On "Sentinel" Initiative

The Food and Drug Administration is holding a public workshop entitled Sentinel Initiative: Structure, Function, and Scope. The workshop is co-sponsored by the FDA and the eHealth Initiative Foundation, and convened by the Engelberg Center for Health Care Reform at the Brookings Institution. The workshop is intended to bring together academia, government, patient, consumer, and provider groups, health care data owners, the pharma industry; and other interested organizations for an update on the current status of the Sentinel Initiative, and to allow for comment from all interested stakeholders.

In May, 2008, FDA launched the “Sentinel Initiative” – a new program with the goal of creating and implementing the Sentinel System--a national, integrated, electronic system for monitoring medical product safety.

The Sentinel System is being designed to enable FDA to pose targeted queries (consistent with privacy and security safeguards) of patient registry data, insurance claims data, and other large health care information databases, for information about medical products. FDA says this new system will strengthen the agency's ability to monitor the performance of a product throughout its entire life cycle, thus enhancing the protection and promotion of public health.

FDA's current post-market surveillance programs generate very important new risk information, but the adverse event reporting system depends on health care professionals and patients first recognizing a potential association between an adverse effect and a medical product, and then report it to FDA or the manufacturer. Some adverse events may never get reported.

Date and Time: The public workshop will be held on December 16, 2008, from 9 a.m. to 3:30 p.m. Location: The public workshop will be held at the Omni Shoreham Hotel, 2500 Calvert Street NW., Washington, DC 20008.
 

Creating an advanced surveillance system like Sentinel was one of the recommendations made by the Institute of Medicine in its 2006 report on ways to improve the safe use of drugs. The Food and Drug Administration Amendments Act of 2007 included provisions that call for the development of such a system. FDA believes patients will benefit because the agency will be able to identify potential problems sooner, better understand those problems, and ultimately, help health professionals and patients use medical products more safely.

The overall initiative is described in an FDA white paper titled, “The Sentinel Initiative—A National Strategy for Monitoring Medical Product Safety.” 
 

It is interesting to speculate about the potential impact of the system, especially on products liability litigation. Medicare collects data typically only when a medical provider is seeking payment. This claims data is less complete, and potentially less accurate than actual patient health records. Thus, utilizing Medicare data to assess health outcomes of drug use may be problematic. Of course, the new system doesn’t change the reality that sometimes patients suffer adverse events after receiving drugs because they are sick, not because the drug has a problem. And Medicare recipients use an average of 28 prescriptions in a year, compared with an average among all Americans of something like 12 prescriptions. Sorting out which medicine caused any single problem – if any did -- can be difficult.

In mass tort litigation, as readers of MassTortDefense know, plaintiffs frequently will attack defendants’ AER system, the resources devoted, the quality of the reporting. Even more frequently, plaintiffs will allege that the AE reports revealed a “signal” far sooner and far more clearly than the company thought; that the defendant missed or ignored the signal about potential adverse events in order to avoid the financial impact of a new label with a stronger warning. But if the FDA will eventually be able to query databases of tens of millions of patients almost simultaneously, presumably it will no longer have to wait for reports from the field, and the allegations of “missed signals” may lose all force.

To assess the accuracy of the Sentinel system, the FDA will initially conduct studies of drug side-effects that are already well known. And despite the potential issues, the Pharmaceutical Research and Manufacturers of America supported the FDA initiative, because it will allow regulators and health care professionals to move from reliance on voluntary reporting of side effects to a more proactive monitoring of medicines.
 

FDA Issues Guidance For Industry On Retaining Data From Clinical Trials

Limiting mass tort/class action exposure is a key part of the role of in-house litigators. In the drug and device areas, limiting plaintiffs' ability to take unfair advantage of clinical trials research is becoming a real focus. Issues include limiting liability due to alleged inadequate monitoring during trials, and preventing off-label and product liability claims associated with alleged under-reporting and over-reporting of data. Litigators need to offer their input on the company's determination of the extent to which data from ongoing clinical trials will be distributed, helping the company to assess the liability risks of disclosing and failing to disclose clinical trial data related to off-label uses. A thorny legal issue is the degree to which the First Amendment is a viable defense, and in a complex regulatory world the company needs to understand and comply with state as well as federal disclosure obligations.


Ideally, the company will be developing a framework for deciphering where scientific exchange ends and drug promotion begins, as a guide to avoiding language in describing clinical trials that could be construed as promotional while still providing fair and balanced information on clinical trials involving their products. The most prudent may be developing a strategic, long-term plan to protect clinical trial information from turning into grist for the plaintiff ’s case (and outside counsel can help with that too). That program may include training employees to recognize the litigation potential arising from clinical trials; maintaining protocols as to the language and terms that will be used in clinical trial reports; and minimizing common liability risks arising from posting of data by establishing thorough review processes.


Into this complex situation the FDA has issued new guidance for drug, biologic, and medical device companies about retaining data from clinical trial participants who no longer are participating in the trial, according to a notice just published in the Federal Register (73 Fed. Reg. 72807). The guidance document on Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials states that data must be retained for participants who decide to discontinue participation in a clinical study of an investigational product, who are withdrawn by their legally authorized representative, or who were discontinued from participation by the clinical investigator.
FDA's reasoning is that data resulting from these clinical investigations are used to support research applications and new product approvals;  thus it is critical that it has a complete and accurate data set available. While it may be appropriate to remove data from various reported figures, based on the study protocols, FDA worries that if data were to be removed from the study database altogether, the FDA may miss something that may be relevant to their decision-making.
 

The agency said it issued this guidance for immediate implementation to prevent the potential loss of important clinical trial data. If comments are received on the guidance, FDA said it will review the comments and revise the guidance as appropriate.
 

FDA Issues Import Alert For China Dairy Products

The FDA continues to take action to attempt to limit the impact of the China milk scandal on U.S. consumers. As part of its ongoing strategy to address the present problem with melamine contamination of consumer products exported from the People’s Republic of China, FDA has expanded its import controls on Chinese dairy products, and food and feed products manufactured in China that contain dairy ingredients. Candy, snacks, bakery products, pet food and other Chinese products that contain milk will now be detained at the border until tests prove that they are not contaminated. This action was taken to help ensure that only those Chinese dairy products (and food and feed products manufactured in China that contain dairy ingredients) which are not contaminated with melamine and melamine-related compounds reach U.S. consumers.

No adverse health effects have been reported in the United States from contamination with melamine of dairy products or dairy containing products. But melamine is not approved for direct addition to human or animal foods and no manufacturer is allowed to deliberately add it to any food for U.S. consumers.  Since melamine was discovered in infant formula in September it apparently has sickened more than 50,000 infants in China and killed at least four. Since that time, melamine has been found in a wide range of other products, including milk, eggs and fish feed. Testing by the FDA has detected melamine and cyanuric acid, a related contaminant, in a number of products that contain milk or milk-derived ingredients, including candy and beverages, according to the FDA alert. China is also one of the world’s biggest makers of supplements, and some protein powders and shakes are made largely with powdered milk.


The agency has at times blocked imports of individual food products, but it is rare for it to block an entire category of one country’s foods. The widely spread assessment is that food and feed dealers in China added melamine to their products because it increases nitrogen content to give the appearance in testing that protein levels meet specifications.

Concern has been expressed about delays spilling over to other food imports, but the FDA said the percentage of food subject to the import alert is small. Another possible issue is that private laboratories which perform product tests for FDA compliance already reportedly have long waiting lists. The agency said it won't release the imported food unless an independent laboratory verifies that representative samples contain no melamine or cyanuric acid, a melamine derivative.
At a broader level, one wonders what the alert may do to the recently negotiated opening of FDA offices in China. The timing of the FDA alert coincides with an upcoming  meeting between Health and Human Services Secretary Michael Leavitt and top Chinese health officials in Beijing.
 

Update on BPA

Several recent developments concerning BPA.


The Canadian government announced earlier this month that it intends to draft new regulations to prohibit the importation, sale, and advertising of baby bottles containing bisphenol A; the proposed bans are to take effect in 2009.


Environment Canada and Health Canada have released a scientific assessment, concluding that bisphenol A poses no danger to the general public, but expressing some uncertainty about its potential impact on infants up to 18 months of age. The scientific evidence of the neuro-developmental and behavioral impact of bisphenol A on rodent test subjects, although highly uncertain and not capable of easy extrapolation to humans, is apparently providing the basis for taking action to limit exposure to the substance for newborns and infants. The government plans also to allocate almost $2 million to support additional research on bisphenol A.


The first regulatory step comes as Environment Canada and Health Canada published a notice of their intention to designate bisphenol A as toxic under the Canadian Environmental Protection Act, a first step that allows the government to take regulatory action on the chemical. The agencies also issued a draft risk management approach for the chemical that aims to reduce releases of the substance into the environment. The proposed risk management plan, which is open to a 60-day public comment period that started on Oct. 18, said that BPA should be managed using a life cycle approach that prevents or minimizes its release into the environment.


The Canadian draft plan incorporates a regulatory ban on the import, sale, and advertising of polycarbonate baby bottles made with bisphenol A. It calls for the adoption of an “as low as reasonably achievable” principle in the packaging of canned infant formula, and indicates that the government will develop migration target levels for bisphenol A from infant formula cans to the formula they contain. The government proposes exploration of imposing migration targets for bisphenol A in canned foods in general.  The regulations will establish maximum bisphenol A concentrations in industrial effluents and will require the implementation of management systems for facilities where the substance is used, the draft plan said.


In addition, the plan calls for a survey on the content of bisphenol A in medical devices, further research on exposure of pregnant women to the substance, monitoring through the Canadian Total Diet Study, and additional environmental monitoring in waste water effluents and waters downstream from waste water treatment plants.


Meanwhile, back in the States…
State attorneys general from Connecticut, Delaware, and New Jersey called on manufacturers of baby bottles and baby formula to stop using BPA in their products. The AGs cite the recent studies in letters to the companies urging them to stop putting BPA into infant formula containers. “Mounting evidence suggests that BPA from the lining of these cans leaches directly into the infant formula,” claimed the AGs.


The AGs cited a February 2008 publication of the Work Group for Safe Markets, a coalition of liberal public health and environmental advocacy organizations, advocating without much support  that low levels of exposure to BPA may cause damage to reproductive, neurological, and immune systems during stages of fetal and infant development. They also cite the study released by Yale School of Medicine on BPA exposure and effects on brain function and mood disorders in monkeys.


The letters were reportedly sent to: Avent, Disney First Years, Gerber, Dr. Brown, Playtex, Evenflo, Abbott, Mead Johnson, PBM Products, Nature's One, and Wyeth.


Finally, the FDA Science Board Subcommittee on Bisphenol A has just released comments on the FDA’s draft exposure assessment of BPA. The Science Board provides advice primarily to the Commissioner of the FDA and other appropriate officials on specific complex and technical issues as well as emerging issues within the scientific community. This temporary Subcommittee was established by the Science Board and consists of two members of the Science Advisory Board and five scientists drawn from academia and government agencies. The focus of this Subcommittee is the scientific peer-review of the draft assessment prepared by the FDA of bisphenol A for use in food contact applications.

While the Subcommittee agrees with the focus of the draft assessment on dietary exposures to children, they believe that the FDA assessment would be strengthened by considering cumulative exposures and differential risk in neonates. They also recommend that the FDA exposure assessment be expanded to include a larger number of infant formula samples and that it rely on mean values rather than accounting for the variability in samples. Until the qualitative and quantitative information (including application of uncertainty factors) is revised, the Subcommittee cannot yet agree that the Margins of Safety defined by FDA are adequate.
 

FDA Updates Plans For Foreign Offices

The Food & Drug Administration (FDA) should be opening its new China office later in 2008. In the past couple years, as posted here at MassTortDefense, multiple imports from China have been at the center of safety concerns. Earlier this year, heparin allegedly contaminated with a counterfeit ingredient was blamed by some plainitff attorneys for some patient deaths; FDA has issued recalls of several foods imported from China that may have apparently been tainted with the industrial chemical melamine, which has been added to dairy products and resulted in hospitalization of thousands of children in China.

FDA staff posted at the China office will inspect facilities, provide guidance on U.S. quality standards, and later train local experts to conduct inspections on behalf of the FDA. The FDA will eventually open offices in the Chinese cities of Shanghai and Guangzhou, for a total of eight planned FDA staffers. The agency hopes a greater on the ground presence in China will help prevent unsafe imports, and the opening of a Beijing, China office later this year is just the first step in the FDA’s plan to expand its presence overseas. Over the next year, the agency plans to place as many as 60 food and drug regulators in offices worldwide, focusing on India, Latin America and the Middle East. The plan for permanent outposts marks a break from the agency's current practice of sending inspectors abroad on individual assignments.

Part of an updated import inspection plan may be to allow voluntary inspection, where manufacturers would pay third-party inspectors to verify that their plants meet FDA standards, although past attempts at a voluntary inspections system haven’t been well received by some overseas manufacturers. Democrats in the House of Representatives, offering yet another alternative, have proposed a program that would require companies to pay mandatory user fees to help finance additional FDA inspections.

Health and Human Services Secretary Michael Levitt is scheduled to travel to China next month to meet with health officials there to review joint efforts to ensure the safety of food and medical imports. The Consumer Product Safety Commission also worked to get people stationed in China. Under the current plan, the CPSC staffers who will be sent there eventually are not full inspectors. Their purpose will be to provide technical assistance to Chinese manufacturers and regulators.
 

FDA Releases Melamine Risk Assessment

The FDA has issued the results of its interim safety and risk assessment of melamine and melamine-related compounds in food, including infant formula. The purpose of the FDA interim safety/risk assessment, which was conducted by scientists in the Center for Food Safety and Applied Nutrition, was to identify the level of melamine and melamine-related compounds in food which would not raise public health concerns.

For infant formula, the safety/risk assessment concludes that at this time FDA is unable to establish any level of melamine and melamine-related compounds in infant formula that does not raise public health concerns. Melamine in baby formula has sickened more than 54,000 infants in China. The government there ordered the recall of more than 10,000 tons of formula. Last week, 12 more Chinese dairy companies were named as violators after tests found 31 batches of milk powder contaminated with melamine.Chinese officials believe that the contamination was intentional and  occurred at milk collecting stations, rather than on dairy farms. MassTortDefense has posted on this before.

In food products other than infant formula, the safety/risk assessment concludes that levels of melamine and melamine-related compounds below 2.5 ppm do not raise public health concerns. This conclusion assumes a worst case exposure scenario in which 50% of the diet is contaminated at this level, and applies a 10-fold safety factor to the Tolerable Daily Intake (TDI) to account for uncertainties.


According to the CDC, melamine is a synthetic chemical with a variety of industrial uses including the production of resins and foams, cleaning products, fertilizers and pesticides. It does not occur naturally in food. Animal studies have demonstrated that exposure to low levels of melamine produced no observable toxic effects. Exposures to high levels of melamine, or exposures to lower doses of melamine together with certain other chemicals, have caused urinary tract problems in animals. These have included urinary tract and kidney crystal and stone formation, and kidney failure. Exposures of animals to high doses of melamine over long time periods (years) have been associated with cancer of the bladder.

Because melamine is a component in plastics, there may be melamine in dinnerware, cups, and even Formica counter tops. But the amount of melamine that actually transfers from those products into food is very, very small, according to FDA.


Several melamine-contaminated foods found in recent weeks in the United States had far more than that amount of the chemical. White Rabbit candies from China were recalled after authorities in at least two states found melamine. And a New Jersey company announced that it was recalling Blue Cat Flavor Drink, after FDA testing found melamine. The chemical has also turned up in dairy products sold across Asia and, to a lesser extent, Europe.


The FDA guidelines were issued to help federal and state investigators checking for contaminated Chinese products as they enter the country and in grocery stores. To date, there have been no reports of illness from contaminated Chinese milk products in the United States. There are no approved uses for melamine to be added to food in the United States.

Melamine contamination was at the center of the tainted pet food scandal that resulted in more than 80 class actions and the creation of MDL 1850.  The federal judge overseeing the multidistrict pet food litigation has just issued final approval of a $24 million settlement that seeks to resolve claims over a massive recall of more than 90 contaminated dog and cat foods last year.

 

FDA Announces Meeting On BPA

The FDA has announced a forthcoming meeting of the Science Board to the Food and Drug Administration, on the topic of BPA. The Science Board provides advice primarily to the Commissioner of Food and Drugs and other appropriate officials on specific complex and
technical issues as well as emerging issues within the scientific community in industry and academia.  At the meeting, on October 31, 2008, the Science Board will hear about and discuss a review of the draft assessment of Bisphenol A for use in food contact applications by the Science Board BPA Subcommittee. The Board will also hear an overview of current methods for detection of contaminants in FDA-regulated products.

In early 2008, FDA formed an agency-wide BPA task force to facilitate cross-agency review of current research and new information on BPA for all FDA regulated products. Medical devices containing the chemical are now also on the FDA’s radar screen. See the note in FDA News.  BPA is used in dialysis tubing, blood oxygenators, and dental sealants. And now that an evaluation examining migration of BPA from food contact materials has been drafted, the agency is apparently planning to publish a document assessing the safety of BPA exposure from regulated devices, biologics and pharmaceuticals.

The FDA's recent assessment was particularly focused on the concerns for developmental toxicity identified in recent assessments of BPA, including those of the National Toxicology Program and their expert panel, based on animal data. FDA concluded that this data was insufficient to merit a change in the exposure levels the agency currently allows for BPA. FDA concluded that an adequate margin of safety exists for BPA at current levels of exposure from food contact uses, for infants and adults. This assessment represents a full examination of data considered pivotal to the relevant exposure levels associated with food contact substances, the FDA said.


 

FDA Holds Public Hearing on OTC Cough and Cold Medications In Kids

As previewed by MassTortDefense, the Food and Drug Administration held a public hearing on October 2, 2008, to obtain input regarding over-the-counter (OTC) cough and cold drugs marketed for pediatric use. Many of these nonprescription cough and cold drug products are marketed under the OTC Drug Review, which published a monograph describing the conditions under which certain OTC ingredients are considered to be generally recognized as safe and effective. These products contain ingredients that have been classified by the FDA as generally recognized as safe and effective since the 1970’s Recently, some potential safety and efficacy concerns have been raised regarding the pediatric dosing and use of certain active ingredients in OTC cough and cold drug products.

FDA is developing a proposed rule to revise the pediatric labeling guidance contained in the Final Monograph for Cough, Cold, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use.  Each year, U.S. consumers buy about 95 million packages of oral pediatric cough and cold medicines. 

Some doctors at the hearing urged regulators to seek removal of children's cough and cold medicines from store shelves until the products are found safe and effective. For example, Dr. Michael Shannon, professor at Harvard Medical School, testified that it is time for these products to be re-evaluated regarding their risk-benefit ratio. The American Academy of Pediatrics doesn't recommend any use of OTC cold and cough  medicines in children. In January, the FDA recommended against their use in children up to 2 years old. Treatment alternatives include providing fluids, nose drops, humid air and appropriate pain relievers.

The Consumer Healthcare Products Association pointed out that most reported side effects are caused by accidental overdose and misuse, which might suggest that changed packaging and improved education, rather than other measures, might be appropriate. The Association has begun a comprehensive, national education program that focuses on the root causes of adverse events and speaks directly to parents, day care providers, healthcare providers, and other caregivers. CHPA is partnering with a number of organizations in these efforts, including the American Pharmacists Association and the American Association of Family Physicians. These education campaigns underscore the importance of following the directions on the label, using the correct dose, storing medicines safely and consulting with a doctor if there are any questions.

Arguably, if pediatric cough and cold products are no longer available over the counter, parents may turn to other alternatives that may result in even more dangerous consequences for children. The industry is undertaking a comprehensive and scientifically rigorous efficacy and safety program for children age 2 to 12 in order to advance the science and ensure the highest level of scientific rigor. This program includes pharmacokinetic studies to confirm the dosing for the eight most commonly used OTC oral cough and cold ingredients. Once these dosing studies are finalized, they will begin other studies to revalidate the effectiveness of these medicines.

In reaction to the public hearing, FDA did not call for an immediate ban on over-the-counter cough and cold medicines for young children. John Jenkins, director of the FDA's Office of New Drugs, said the agency will propose changing its rules which could further restrict use of the products in children.

In response to the issues, following the hearing, makers of OTC cold and cough drugs announced they would start adding warnings against use in children younger than 4 years. That is, the leading manufacturers of these medicines are voluntarily transitioning the labeling on oral OTC pediatric cough and cold medicines to state “do not use” in children under four years of age.  (The risk of overdose is greatest in 2- and 3-year-olds, according to the Consumer Healthcare Products Association.) Pediatric antihistamines will also carry new labels telling parents not to use the medicines to sedate children of any age. The move comes out of an abundance of caution in an effort to promote the safe and effective use of these medicines.  FDA was quoted as being in support of these voluntary actions by CHPA, in part because the rulemaking process can take significant time.
 

Senate Panel Holds Hearing on DTC Advertising of Medical Devices

The U.S. Senate Special Committee on Aging held a hearing last week to examine issues related to direct-to-consumer (DTC) advertising for medical devices. The amount of medical device advertising directed to consumers on television or over the Internet was an estimated $193 million last year, a figure that is a small fraction of the volume of consumer advertising for prescription drugs. Yet, device DTC is getting increased attention.

At the hearing, medical, advertising, and consumer experts shared with the committee their opinions about DTC medical device advertisements, including whether health risks are appropriately conveyed to consumers. The hearing was called by liberal Democratic Committee Chairman Herb Kohl (D-WI), who has apparently already decided that Congress ought to be prepared to call for a future moratorium on DTC ads for new medical devices.

Dr. Daniel Schultz, the director of the Center for the Center for Devices and Radiological Health (CDRH) at the FDA, discussed the current status of their enforcement activities related to DTCA for medical devices. The CDRH is the division of the FDA responsible for the regulation of restricted medical device advertisements.

The head of Advanced Medical Technology Association (AdvaMed), related the organization’s current policy on DTC advertising and reaffirmed the medical technology industry’s strong support for truthful, non-misleading advertising of its innovative products. AdvaMed believes that in addition to being truthful and not misleading, all DTC advertising should use consumer-friendly language, disclose relevant risk information, and encourage patients to speak with their doctors in more detail. Current FDA rules governing direct-to-consumer advertising are adequate. FDA and FTC already have extensive legal authority to regulate false or misleading advertising for medical devices. FDA has a full range of potential remedies it can bring to bear, from issuing a warning letter to removing a product from the marketplace.

Indeed, while it is unproven that any advertisement will cause a patient to take a drug – as opposed to discuss a possible prescription with a physician – it seems even less likely that a medical device ad will do anything other than stimulate a patient to ask a doctor about a device: a patient does not agree to undergo surgery unless they think they have a serious need for it.

Direct to consumer advertising is a powerful educational tool that allows patients to learn of new technologies and treatment options in a timely fashion and can help to initiate important discussions between physicians and patients. DTC advertising is an invaluable tool to enhance the exchange of information and empower patients to ask questions about their own health. 
 

Nevertheless, the rest of the hearing lineup was stacked with opponents of DTC advertising: Dr. Kevin Bozic, a professor of orthopedic surgery at the University of California, San Francisco, provided an opinion of how DTC advertising supposedly has the potential to adversely impact the doctor-patient relationship, patient education, and health care costs and quality. Next, Dr. William Boden, a professor of medicine and public health at the University of Buffalo, and Dr. George Diamond, a senior research scientist at the Cedars-Sinai Medical Center, shared the findings of their recent article in the New England Journal of Medicine, offering their opinions about how DTC advertising can theoretically affect patient understanding of medical device effectiveness and risks.

Dr. Ruth Day presented expert testimony on how DTC advertising may influence consumer behavior. Also on the first panel was Ami Gadhia, policy counsel for the Consumers Union, who testified about her organization’s petition to the FDA in December, 2007 for pre-review and specific risk disclosures for medical device advertisements.
 

Latest BPA Update

Here is the latest on BPA:

1. NTP Issues Final Report

The National Toxicology Program issued its final report on bisphenol A (BPA) earlier this month. NTP continued its position from a much publicized draft report (see the post here) that it has some concern that the chemical – used in plastic bottles and other packaging -- could affect the development of the prostate gland and brain and potentially affect the behavior of fetuses, infants, and children. See The Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A.

The report provides the NTP’s current opinion on BPA’s potential to cause harm to human reproduction or development. The report is part of a review of the scientific literature on BPA and takes into consideration public and peer review comments received on the earlier draft report. According to NTP, about 2.3 billion pounds were produced in the United States in 2004, with more than 90 percent of the population being exposed to the substance.

The conclusions are based primarily on animal studies. The literature on experimental animal studies is filled with many conflicting findings, NTP says. And NTP admits that there remains considerable uncertainty whether the changes seen in the animal studies are directly applicable to humans, and whether they would result in clear adverse health effects. NTP also states that more research is clearly needed to understand exactly how these findings relate to human health and development. There are a number of remaining uncertainties in the scientific information on BPA, according to the report.

The NTP is an interagency federal research program at the National Institute of Environmental Health Sciences, part of the National Institutes of Health. The report uses a five-level scale ranging from negligible risk to serious concern.

The report expresses “minimal concern” that BPA exposure will affect development of the mammary gland or accelerate puberty in females. (Previously, NTP said it had some concerns about those effects, but a panel of experts concluded that the program overstated its concerns about mammary gland effects and early puberty.) The NTP expressed “negligible concern” that exposure of pregnant woman to BPA will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring. And the report also expressed “negligible concern” that exposure to BPA causes reproductive effects in non-occupationally exposed adults and “minimal concern” for workers exposed to higher levels in occupational settings.


The FDA responded to the final report, noting that it would consider this final report at FDA's Science Board meeting concerning the FDA’s draft assessment of bisphenol A.  Which brings us to development No.2.

2. FDA Meeting
FDA held a public meeting last week, with a range of scientists, industry representatives, and consumer advocates debating aspect of bisphenol A usage.

The focus of the meeting was the FDA’s draft risk assessment that found continued use of bisphenol A in food-contact materials would be safe. Among the highlights:

An EPA toxicologist who served on NTP's expert panel said the NTP's statements that it has "some concern" meant more research was needed. It did not imply that the NTP expert panel had concluded that harm was being caused by the chemical.

A toxicologist working at the National Institute of Environmental Health Sciences said that NTP reported it had "some concern" about neurological, behavioral, and prostate effects because the animal studies that found those effects involved exposures at levels similar to those expected for infants.

The head of the pediatrics department of the Medical College of Wisconsin suggested that FDA conduct or fund more exposure research to get a better understanding of infants' exposure. FDA’s estimates and NTP’s estimates of typical exposure were slightly different.

A representative of the polycarbonate business unit of the American Plastics Council noted that there have been at least two studies of bisphenol A levels in infant formula since FDA completed its study, including one by the Environmental Working Group. All have found levels comparable to what FDA used.

Other speakers noted that BPA is a relatively well studied chemical, and compounds that could be used as substitutes are unlikely to have as much information available about their safety. Clearly, some uses of bisphenol A, such as in children's bicycle helmets, provide many safety benefits. BPA has also been found to be safe with an unmatched performance in lining cans. The Environmental Working Group, said there are substitutes, in their view, already on the market for uses such as in baby bottles.

A toxicologist from the University of Missouri-Columbia worried that FDA's recommended tests might mean it would take many more years before the agency might take any necessary regulatory action to reduce exposure.

John van Miller of the American Chemistry Council, cited the multi-dose, multigenerational, significant studies conducted in accordance with internationally agreed-upon protocols that have found bisphenol A to be safe. The "Reproductive Health Technologies Project" disagreed and underscored the need for studies in their view.

The Bisphenol A Subcommittee is to brief FDA's Science Board later this Fall on the subcommittee's recommendations. The Science Board will then develop its own recommendations for BPA.


3. JAMA Study
The Journal of the American Medical Association published a study last week which has been reported in the popular press as showing that subjects with higher levels of bisphenol A in their urine were more likely to report that they had heart disease or diabetes. See Association of Urinary Bisphenol A Concentration with Medical Disorders and Laboratory Abnormalities in Adults.

Higher levels of human urinary BPA were reportedly associated with cardiovascular disease, type 2 diabetes, and liver-enzyme abnormalities, according to the study, which was discussed at the FDA public meeting. The study used data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The survey involved the measured urinary bisphenol A concentrations of 1,455 adults, ages 18 through 74 years. 
 

The investigators noted that orally administered BPA is rapidly and completely excreted by humans.  On of the limitations of the analysis is its cross-sectional nature: it does not offer longitudinal data demonstrating that BPA concentrations predict later onsets of biochemical change or disease. The authors cautioned that their method may have resulted in false-positive associations. The authors have recommended an independent replication of the study, and follow-up studies to explore their findings and to provide evidence on whether the associations are causal. Not well reported in the media is the fact that the research team used four methods to measure whether bisphenol A was associated with diabetes, but found that association in only one of the four methods. The study thus is primarily useful for generating hypotheses that can be tested, not for drawing any conclusions on human health effects.

 

FDA Meeting On Nano-Technology Spurs Debate

The FDA held a public meeting on September 8, 2008, to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology. In July 2007, FDA had issued a report analyzing scientific and regulatory considerations relating to the safety and effectiveness of FDA-regulated products containing nanoscale materials regulated by FDA, and making recommendations regarding these considerations. The Nanotechnology Task Force Report made recommendations which covered foods (including dietary supplements), food and color additives (including food contact substances), animal drugs and feeds, cosmetics, human drugs and biologics, and medical devices. Additionally, the Report summarized the state of the science for biological interactions with nanoscale materials.

The meeting included a plenary session led by Dr. Norris Alderson, head of the FDA Nanotechnology Task Force, followed by separate sessions for prescription and OTC drugs, cosmetics, medical devices, food additives, and others. FDA speakers reportedly were interested in comments on the circumstances under which the regulatory status of a product might change if nanoscale materials were utilized instead of the traditionally sized materials evaluated by regulatory officials when the product was first approved. 

Andrew Maynard, the chief science adviser for the Project on Emerging Nanotechnologies, told the FDA at the September meeting that they should view products containing nanomaterials as potentially "risk-added." Maynard said that materials with a dimension less than 100 nanometers exhibit unique properties due to their small size, and thus are “value-added." But, Maynard said, the unique properties exhibited by nanomaterials might also carry special risks. Francis Quinn, speaking on behalf of the Personal Care Products Council, offered a different perspective. For example, while nanoparticles are used in the early stages of developing sunscreens, by the time they are mixed with other ingredients they are no longer nanoscale and present no different risks than traditional sunscreens. Jay Ansell, senior director of the council, said no special labeling of nanoscale ingredients in cosmetics is needed.

But other speakers said the FDA needs to take a different approach as it contemplates regulating products containing nanoscale ingredients. The Conservation Law Foundation said that existing frameworks for assessing risks need to be updated to address nano-specific attributes such as particle characteristics. And a researcher from The George Washington University urged caution about the use of nanomaterials in dietary supplements.


As an aside, the latest report from the Project on Emerging Nanotechnologies addresses nano-scale silver. Silver Nanotechnologies and the Environment: Old Problems or New Challenges. The most common nanotechnology material currently used in the products is silver, which is mentioned in 235 product descriptions, such as silver-containing socks, baby carriages, air filters, coin-operated washing machines, and swimming pool treatments. 

The report asserts that widespread use of nanoscale silver will challenge regulatory agencies to balance important potential benefits against the possibility of significant environmental risk, highlighting the need to identify research priorities concerning this emerging technology. The issue of assessing the risks posed by nanoscale silver was highlighted after the Environmental Protection Agency’s (EPA) San Francisco office earlier this year imposed a fine of $200,000 on a California company selling computer keyboards and mouses coated with nanosilver. EPA issued the fine on the basis that the products should have been registered under federal pesticide law because of the company’s germ-killing claims. Due to its antibacterial properties, some have argued that the Federal Insecticide, Fungicide, and Rodenticide Act may be used to regulate many uses of nanoscale silver.

Nanosilver is a new challenge, says the report, a problem that fits poorly into the old boxes of the existing regulatory system. EPA is crafting a Federal Register notice that will invite comment on a citizen’s petition on nanoscale silver. EPA also has a 2007 white paper on nanotechnology.
 

FDA Releases First Quarterly Safety Signals Report

The U.S. Food and Drug Administration has posted on its website its first quarterly report listing certain drugs that are being evaluated for potential safety issues. FDA posted the reports in accordance with Section 921 of the Food and Drug Administration Amendments Act of 2007, which, among other things, directs FDA to inform the public each quarter of new safety information or potential signals of serious risk, based on the agency's review of adverse event reports. Specifically, FDA is to "conduct regular, bi-weekly screening of the Adverse Event Reporting System [AERS] database and post a quarterly report on the Adverse Event Reporting System Web site of any new safety information or potential signal of a serious risk identified by Adverse Event Reporting System within the last quarter."

FDA released the first quarterly report, listing 20 drugs. The information is provided based on a review of reports in AERS. The FDA staff in the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) regularly examine the AERS database as part of routine safety monitoring. When a potential signal of a possible risk is identified from AERS data, it is entered as a possible safety issue into CDER's Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) or into CBER's Therapeutics and Blood Safety Branch Safety Signal Tracking (SST) system. Potential signals of serious risks are normally based upon groups of AERS reports.

Drugs that appear on the agency's new "Potential Signals of Serious Risks/New Safety Information," are thus identified by FDA reviewers based on reports from the FDA's AERS database, which contains millions of reports of adverse events submitted to FDA by drug manufacturers, health care professionals and patients. For a drug to appear on this report, an FDA reviewer will have determined there is some reason to examine a drug more closely based on either the seriousness or number of AERS reports associated with the drug. The drugs for which issues have been identified are under evaluation for the listed potential risk. Each year, FDA receives about 400,000 reports of adverse events that people experienced around the same time period in which they were taking a drug.

An adverse event report does not establish a causal relationship between the drug and a particular event. The FDA itself has warned that for any given ADE case, there is no certainty that the suspected drug caused the event. This is because physicians and consumers are encouraged to report all suspected ADEs, not just those that are known or even suspected to be caused by the drug. The adverse event may have been related to an underlying disease for which the drug was given, to other concomitant drug usage, or may have occurred by chance at the same time the suspect drug was administered. The courts have characterized ADEs as “complaints called in by product consumers without any medical controls or scientific assessment.” McClain v. Metabolife Intern., Inc., 401 F. 3d 1233, 1250 (11th Cir. 2005). Because the reporting system is not subject to scientific controls, data from it is subject to various statistical biases. It is likely that the mix of reported events does not represent an accurate sampling of those events that can occur while a person is taking any medication. Moreover, medical or media attention can stimulate reporting in a distorted manner, and known adverse reactions are more likely to be diagnosed and reported than others. See DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1050 (D. N.J. 1992), aff’d 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “have inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.”).

MassTortDefense notes, that in contrast to how plaintiff attorneys seek to use the adverse event reports, or how the media has portrayed this new list, the appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. It may be too early to know whether there is an actual safety problem, and FDA’s analysis may ultimately conclude that there is no safety problem. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk. FDA also emphasizes that the listing of a drug does not mean that FDA is suggesting that prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication. 

Thus, the new quarterly reports should not change the existing view of the majority of courts that adverse event reports are ordinarily too unreliable to be used as proof of causation. See McClain, 401 F. 3d at 1250; Hollander v. Sandoz Pharmaceuticals Corp., 289 F. 3d 1193, 1211 (10th Cir. 2001); cert. denied, 537 U.S. 1088 (2002) (characterizing the case reports before the court as unreliable evidence of causation); Haggerty v. Upjohn Co., 950 F.Supp. 1160, 1165 (S.D. Fla. 1996), aff’d, 158 F. 3d 588 (11th Cir. 1998); In re Accutane Products Liability Litig., 511 F. Supp.2d 1288, 1298-1303 (M.D. Fla. 2007); Benkwith v. Matrixx Initiatives, Inc., 467 F. Supp. 2d 1316, 1327 (M.D. Ala. 2006); Leathers v. Pfizer, Inc., 233 F.R.D. 687, 694 (N.D. Ga. 2006). See also Glastetter v. Novartis Pharmaceuticals Corp., 252 F. 3d 986, 990-91 (8th Cir. 2001) (“Case reports make little attempt to screen out alternative causes for a patient’s condition. They frequently lack analysis. And they often omit relevant facts about the patient’s condition.”); Dunn v. Sandoz Pharmaceutical Corp., 275 F. Supp.2d 672, 682 (M.D.N.C. 2003) (“Case reports are not scientific proof of causation.”); Caraker v. Sandoz Pharmaceuticals Corp., 172 F. Supp. 2d 1046, 1050 (S.D. Ill. 2001) (rejecting expert opinions insofar as they relied upon case reports); Nelson v. American Home Products Corp., 92 F. Supp. 2d 954, 969 (W.D. Mo. 2000) (“At most, these case reports relay a basis for scientific hypotheses; they do not demonstrate a causal link sufficient for admission to a finder of fact in court.”); DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1051 (D. N.J. 1992), aff’d, 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “are not of a type of data that are reasonably relied upon by experts in the fields of epidemiology and public health.”); Siharath v. Sandoz Pharmaceuticals Corp., 131 F. Supp. 2d 1347, 1359-63 (N.D. Ga. 2001); Cartwright v. Home Depot USA, Inc., 936 F. Supp. 900, 905 (M.D. Fla. 1996).
 

FDA To Hold Meeting On BPA Issues

For those readers of MassTortDefense interested in the issues surrounding BPA, the FDA has announced a meeting of its Bisphenol A (BPA) Subcommittee of the Science Board.

The topic to be discussed is the draft assessment of BPA for use in food contact applications. The Subcommittee will hear and discuss the draft assessment of BPA for use in food contact applications, including oral presentations from the public. The meeting will be held on September 16, 2008.

The FDA draft assessment report finds that the chemical does not pose a serious health risk under current uses. The new assessment was particularly focused on the concerns for developmental toxicity identified in recent assessments of BPA, including those of the National Toxicology Program and their expert panel, based on animal data. FDA concluded that this data was insufficient to merit a change in the exposure levels the agency currently allows for BPA. FDA concluded that an adequate margin of safety exists for BPA at current levels of exposure from food contact uses, for infants and adults. This assessment represents a full examination of data considered pivotal to the relevant exposure levels associated with food contact substances, the FDA said.
 

FDA Finalizes CBE Rule, Reinforcing Preemption

The Food and Drug Administration has finalized the updated rule on using supplemental applications for changes to prescription drug, biologics, and medical device labels. The final rule, 73 Fed. Reg. 49603, allows manufacturers to submit a supplemental application to amend the labeling for an approved product to reflect newly acquired information. These supplements are commonly referred to as "changes being effected supplements" or "CBE supplements." The final rule becomes effective on Sept. 22, 2008. The final rule modifies 21 C.F.R. Sections 314, 601 and 814.

MassTortDefense would disagree with the media reports describing this as a “new” rule. In fact, the final rule affirms FDA’s longstanding position that a CBE supplement is appropriate to amend the labeling for an approved product only to reflect newly acquired information. But even though when it originally adopted this regulation FDA intended it as a limited, narrow, emergency exception to the general rule of Agency pre-approval of changes to prescription drug labeling, after preemption became a huge issue in prescription drug product liability litigation the regulation has been at times cited by courts as applying far more broadly than the FDA intended.

Plaintiffs argued that, since manufacturers are supposedly free to change their labels without prior FDA approval, there can be no conflict with state law holding them liable for not doing what the regulation supposedly allows. The plaintiffs thus have argued that the narrow exception swallows the rule that drug labeling changes are subject FDA pre-approval. Some courts have accepted this argument, and for example ruled that pharmaceutical defendants should have unilaterally strengthened suicide warnings for antidepressants – despite the FDA having evaluated the evidence of this alleged risk multiple times, concluding that there is no sufficient scientific basis for including a suicide warning. Compare McNellis v. Pfizer, Inc., 2006 WL 2819046 (D.N.J. Sept. 29, 2006) with Colacicco v. Apotex, Inc., 432 F. Supp.2d 514, 523, 527-28 (E.D. Pa. 2006). The Third Circuit's  take on this split is at Colacicco v. Apotex, 521 F.3d 253 (3d Cir. 2008).

FDA proposed the CBE procedure in 1982, making clear at the time that CBE supplements were intended to apply only if the sponsor became aware of newly discovered safety information that was appropriate for inclusion in the labeling for the product. Since then, the FDA has repeatedly tried, through amicus briefs, and in the 2006 preemption preamble, to inform courts of the limited scope of the regulation, with arguably mixed success. In briefs recently filed in the Supreme Court and in testimony before Congress, FDA has also stated a more generally applicable rule that is consistent with the examples of  cases finding preemption, and the principles set forth in the preamble to the 2006 Physician Labeling Rule,  that: (1) The labeling requirements are not a mere minimum safety standard, but rather strike a balance between risks and benefits, and (2) FDA's regulations permit changes in labeling without prior approval only in narrow circumstances. Specifically, FDA has explained that State law claims that "challenge labeling that FDA approved after being informed of the relevant risk" are preempted.

So now, the agency decided to change the regulation to say precisely what the agency has said it meant all along, with the hope that the lawyers and judges who have been ignoring it can’t do so any longer.

In January, several liberal Democrats in Congress wrote a letter to FDA questioning the basis for the proposed CBE rule, saying it appeared to be designed to shield pharmaceutical and medical device companies from liability sustained by consumers. But the rule does not alter the agency's current practices with respect to accepting or rejecting labeling changes proposed by a CBE supplement, reiterating the agency's longstanding view that the changes-being-effected mechanism is a narrow exception to the FDA's requirement of prior approval for labeling changes to approved products.

Under the rule, newly acquired information means data, analyses, or other information not previously submitted to the agency, which may include (but are not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) -- if the studies, events or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA. The final rule thus clarifies the meaning of "newly acquired information," such that the data, whether derived from new clinical studies, reports of adverse events, etc., needs to be new and different -- of a different type or greater severity or frequency than previously submitted to FDA. This limitation applies to data derived from new clinical studies, reports of adverse events, and new analyses of previously submitted data, alike. The final rule notes thus that there must be reasonable evidence of a causal association before a CBE supplement may be used to add or strengthen a contraindication, warning, precaution, or adverse reaction language.

The FDA rejected comments suggesting that a lower standard should be used under CBE for when a sponsor may warn, reiterating that it "interprets the Act to establish both a 'floor' and a 'ceiling', such that additional disclosures of risk information can expose a manufacturer to liability under the act if the additional statement is unsubstantiated or otherwise false or misleading." 

The new rule may be of some assistance in dealing with those courts that seem reluctant to recognize the longstanding view of the narrow scope of the CBE rule.  The rule limits the scenarios in which manufacturers of drugs, biologics, or medical devices can change a previously approved label in advance of the FDA’s formal review and approval mechanism. And the smaller the scope of things permitted in a CBE change, the greater the scope of conflict between FDA-approved labels and state court second-guessing of the warnings.  

FDA To Hold Public Meeting On Nanotechnology

The FDA will hold a public meeting on September 8, 2008, to gather information that will assist the agency in further implementing the recommendations of the Nanotechnology Task Force Report relating to the development of agency guidance documents concerning nanotechnology. The primary purpose of the meeting is to determine what factors the agency should consider in providing guidance on:

1) The information and data that may be needed to demonstrate the safety and effectiveness of FDA-regulated products containing nanoscale materials; and

2) The circumstances under which a product’s regulatory status might change due to the presence or use of nanoscale materials.

Nanotechnology allows scientists to work on the scale of molecules to create, explore, and manipulate materials measured in nanometers; billionths of a meter. MassTortDefense has posted on nano-issues here and here.

In July 2007, FDA issued a report analyzing scientific and regulatory considerations relating to the safety and effectiveness of FDA-regulated products containing nanoscale materials regulated by FDA, and making recommendations regarding these considerations. The Nanotechnology Task Force Report made recommendations which covered foods (including dietary supplements), food and color additives (including food contact substances), animal drugs and feeds, cosmetics, human drugs and biologics, and medical devices. Additionally, the Report summarized the state of the science for biological interactions with nanoscale materials.

In addition, FDA is working with the National Institutes of Health (particularly the NanoHealth Enterprise) to explore methods for receiving and sharing data relating to, for example, general product development, including research on failed product candidates, and biological interactions of certain characteristics of nanoscale materials.

The meeting will begin with a plenary session at which FDA will review the goals of the meeting and give a general overview of the analysis and findings of the Nanotechnology Task Force and agency activities since publication of the Report in July 2007. Following will be breakout sessions on medical devices, including diagnostics; prescription drugs, including
biological drugs, animal drugs and OTC drugs, including sunscreens; food and color additives, including food contact substances; dietary supplements; and cosmetics.
 

Think Tank Releases Nano-Technology Report

A Washington, DC think tank last week released a new report with suggestions on how the next administration should approach regulation of nano-technology in products.  The Project on Emerging Technologies is based at the Woodrow Wilson Center in Washington. The Project was established in 2005 as a partnership between the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts. The Project is dedicated to helping ensure that as nanotechnologies advance, possible risks are minimized, public and consumer engagement remains strong, and the potential benefits of these new technologies are realized.

Nanotechnologies are hailed by many as the next industrial revolution. They promise to change everything from the cars we drive to the clothes we wear, from the medical treatments our doctors can offer to our energy sources and workplaces. Although focused on very small particles, nanotechnologies offer large potential benefits. From new cancer therapies to pollution-eating compounds, from more durable consumer products to detectors for bio-hazards like anthrax, from novel foods to more efficient solar cells, nanotechnologies are changing the way people think about the future.

The Project on Emerging Nanotechnologies collaborates with researchers, government, industry, NGOs, policymakers, and others to look long term, to identify gaps in knowledge and regulatory processes, and to develop strategies for closing them. The Project's stated mission is to try to provide independent knowledge and analysis that can inform critical decisions affecting the development and commercialization of nanotechnologies.

A source of uncertainty for nanotechnology is regulation. The Project released a 28-page regulatory agenda for the next administration, noting that whichever candidate wins is going to have to deal with this issue, probably sooner rather than later. The next president has the opportunity to ensure that nanotechnology’s benefits will be maximized and its risks identified and mitigated, says the group. 

The report, Nanotechnology Oversight: An Agenda for the Next Administration, calls for the White House and federal agency policymakers to maximize the use of existing laws to improve nanotechnology oversight. Such measures include defining nanomaterials as “new” substances under federal toxics and food laws, thereby enabling the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) to consider the novel qualities and effects of nanomaterials. The group addresses whether the Federal Food, Drug and Cosmetic Act, the Toxic Substances Control Act and the Consumer Product Safety Act need to be amended to cover nanotechnology.

The Project notes that more nanotech products are hitting the market. From March, 2006 to February, 2007, the number of manufactured goods using nanotech tripled to 600.  For fiscal 2009, the federal government has devoted $1.5 billion to nanotech, a sum split up between various agencies. Under the Bush administration, EPA has a Nanoscale Materials Stewardship Program, which is endorsed by the Synthetic Organic Chemical Manufacturers Association, the American Chemistry Council and the NanoBusiness Alliance. Some state governments, however, are pushing forward with their own rules on nanotech.

Coincidentally, consumer advocates said this week that food produced by using nanotechnology is quietly coming onto the market, and they want U.S. authorities to force manufacturers to identify them. New consumer products created through nanotechnology are coming on the market at the rate of 3 to 4 per week, according to The Project on Emerging Nanotechnologies.

MassTortDefense has posted on nanotechnology here and here.

 

Partial Summary Judgment Granted in Aredia MDL

Novartis Pharmaceuticals Corp. has prevailed in a motion to end certain failure-to-warn claims in cases in the MDL relating to its bone cancer drugs Aredia and Zometa. The U.S. District Court for the Middle District of Tennessee granted defendant’s motion for partial summary judgment, dismissing claims of eight Texas-based plaintiffs. In Re: Aredia and Zometa Products Liability Litigation, No. 06-md-01760 (M.D. Tenn.) Opinion found here.

The motion was based upon a Texas statute which protects a defendant from any products liability claims involving failure to provide adequate warnings if the drug at issue and accompanying warnings were approved by the FDA. The statute creates the presumption such warnings were adequate, and then specifically explains how a claimant can rebut this presumption:

(b) The claimant may rebut the presumption in Subsection (a) as to each defendant by establishing that: (1) the defendant, before or after pre-market approval or licensing of the product, withheld from or misrepresented to the United States Food and Drug Administration required information that was material and relevant to the performance of the product and was causally related to the claimant’s injury. Tex. Civ. Prac. & Rem. Code Ann. § 82.007(b)(1).

The court noted that plaintiffs were correct that the language of the Texas statute specifically creates a rebuttable presumption that a defendant is not liable for failure-to-warn claims if the warnings provided with the product were approved by the FDA. The Texas Legislature, however, went on to establish certain evidentiary standards for rebutting this presumption. The presumption of adequate warnings, therefore, is unrebuttable unless one of the specific statutory provisions applies.  Here, the only possible exception was the so-called fraud-on-the-FDA exception. However, in Buckman Co. v. Plaintiffs’ Legal Comm., 121 S.Ct. 1012 (2001), the Supreme Court found that the plaintiffs’ state law fraud-on-the-FDA claims conflicted with and were therefore impliedly preempted by the Federal Food, Drug and Cosmetic Act. Noting that policing fraud against federal agencies is hardly a “field which the States have traditionally occupied,” the Court held that it is the FDA’s exclusive responsibility to police fraud or wrongdoing in connection with approval of products before the FDA. Id. at 1017.   The Court stated that fraud-on-the-FDA claims would “inevitably conflict with the FDA’s responsibility to police fraud consistently with the Administration’s judgment and objectives.” Id. at 1018. In sum, the Court opined, this sort of litigation would exert an extraneous pull on the scheme established by Congress, and it is therefore preempted by that scheme. Id. at 1020.

Under the Texas law, in order to rebut the presumption plaintiffs must establish that defendant withheld or misrepresented “required information” to the FDA. The Court found that the task of determining whether certain information was “required” by the FDA would raise the federalism concerns expressed in Buckman.

Second, the Texas statute also requires that the information which was withheld or misrepresented be “material and relevant” to the performance of the product. Because subsection (b) concerns misrepresentations to the FDA, it is reasonable to infer that the information must be “material and relevant” to the FDA. Determining what information would have been important to the FDA would also create the federalism concerns noted by the Court in Buckman.

Finally, the information which was allegedly withheld or misrepresented must, under the Texas statute, be causally related to plaintiffs’ injuries. Unless the withheld information would have resulted in some definite change by the FDA, such as either non-approval of the drug or a labeling change, such withheld information could not be causally related to a plaintiff’s injury. Again, in order to establish that the FDA would have acted differently if defendant had submitted accurate information, plaintiffs would have to “go behind” the FDA processes, raising the concerns sought to be avoided in Buckman.

The Court thus found that the requisite showing under the Texas statute is analogous to and sufficiently equivalent to asserting a claim of fraud on the FDA that the fraud claim/presumption defense/statutory exception is itself preempted under Buckman. For all these reasons, Defendant’s Motion for Partial Summary Judgment was granted.

The ruling on the Texas claims follows the MDL court's April ruling dismissing claims by Michigan plaintiffs. The court had relied on Garcia v. Wyeth-Ayerst Laboratories, 385 F.3d 961 (6th Cir. 2004), for the proposition that the Michigan fraud exception was also preempted under the U.S. Supreme Court's decision in Buckman.

Recent Preemption Ruling: Wait For Levine

A recent trial court decision shows the state of flux in applying the preemption doctrine in pharmaceutical cases. In the Celexa/ Lexapro MDL, the court denied without prejudice the defendant’s preemption motion, to allow further discovery and expressly because the United States Supreme Court has granted certiorari in Levine v. Wyeth, 128 S.Ct. 1118 (2008), to consider the extent to which prescription drug labeling judgments imposed on manufacturers by the FDA, pursuant to FDA's comprehensive safety and efficacy authority under the Federal Food, Drug, and Cosmetic Act, preempt state law product liability claims premised on the theory that different labeling judgments were necessary to make drugs reasonably safe for use. See In re Celexa and Lexapro Products Liability Litigation, 2008 WL 2906713 (E.D.Mo. July 24, 2008), found here.

 

FDA Advisory Committee Discusses Nano-technology Issues

The FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology met last week. Among the agenda topics was a discussion of current thinking on issues pertaining to the use of nanotechnology in drug manufacturing, drug delivery, or drug products. (The general function of this committee is to provide advice and recommendations to the agency on regulatory issues.) Scheduled to speak were representatives of the Office of Pharmaceutical Science at CDER, nano-medicine industry leaders, and academics.

MassTortDefense has posted on nano-technology here.

As CDER grapples with questions regarding how to regulate nanomaterial-containing products, several issues have surfaced, including 1) what are the types of nanotechnology applications that will be reviewed by CDER, 2) what are the unique features of these applications that may pose a scientific and/or regulatory challenge to reviewers, 3) are FDA’s current regulatory requirements adequate for the evaluation of nanomaterial-containing products, and 4) what can FDA do to expedite the development of safe and effective nanomaterial-based pharmaceuticals.

Nanotechnology applications in drug development are likely to have a significant impact on the products that FDA regulates. Products containing nanomaterials are being investigated for potential applications as therapeutics, and some products containing nanoscale materials are already on the market. While some of these nanomaterials are nanoscale versions of larger materials used in approved products, other nanomaterials are novel and have never been used in drug products. CDER has initiated a number of activities in order to evaluate how this new technology fits into the current regulatory framework. There have been questions raised about the need for “nano”-specific requirements, in part to aid the development of products containing nanomaterials, and in part because nanomaterial containing products may need to fulfill different regulatory requirements prior to approval.

The FDA established a Nanotechnology Task Force, which issued a report in July 2007. In the task force report, recommendations were made regarding FDA’s future direction for regulating nanomaterial-containing products. Guidance development was included as one the recommendations. FDA believes, however, that the preclinical studies currently required of sponsors are very comprehensive, and include many studies that measure endpoints that could predict possible injury in many organ systems. While general issues have been raised, no one has clearly communicated in what respect the current requirements might be lacking in their capacity to assess safety concerns from such products, and what might be other tests that would improve the predictive value of the current regulatory preclinical requirements.

Nevertheless, because it is widely accepted that there are unique features associated with
nanotherapeutic products, these unique features may lead to future challenges for the development, manufacturing, and possibly safety evaluation and review of these products. Accordingly, the committee was set to discuss:

1. Is CDER guidance needed for the development of nanotechnology-derived drug applications?
2. If guidance is needed from CDER, what areas should this guidance focus on?
3. In light of the many definitions of nanotechnology available, how should CDER define nanotechnology, for the purposes of guidance development?
4. Should particle size information be routinely requested of drug developers, regardless of whether nanomaterials are included in the product? How might this information help in the assessment of safety and efficacy of drugs?

Clearly this is no small issue.

 

European Food Safety Authority Weighs In On BPA

The European Food Safety Authority’s AFC Panel has issued a further scientific opinion report on the chemical bisphenol-A (BPA). MassTortDefense has posted on BPA here and here. The goal of the assessment was to focus on the chemicals’ elimination from the body and how that might relate to the risk assessment of BPA in humans. The work took into account the most recent data since the EFSA’s 2006 opinion report, which concluded that exposure to BPA is well below the Tolerable Daily Intake (TDI).  A TDI is a regulatory standard for dietary exposure calculated to ensure that no adverse effects occur.


About EFSA
The European Food Safety Authority is an independent European agency funded by the EU. The EFSA is governed by an independent Management Board whose members are appointed to act in the public interest and do not represent any government, industry, or private sector. EFSA’s role is to assess and communicate on all risks associated with the food chain. Since EFSA’s advice serves to inform the policies and decisions of risk managers, a large part of EFSA’s work is undertaken in response to specific requests for scientific advice from the European Commission, the European Parliament, and EU Member States. The AFC Panel focus is on food additives, flavorings, processing aids and materials in contact with food.

Conclusions

The key conclusion of the Panel on BPA is that after exposure, the human body rapidly metabolizes and eliminates the substance. This represents an important metabolic difference compared with rats, and suggests certain animal models are not all that useful. That is, people metabolize and excrete BPA far more quickly than rodents. This evidence further limits the relevance of low-dose effects of BPA reported in some rodent studies used for human risk assessment.

The Panel further concluded that the exposure of a human in utero to BPA would be negligible because the mother rapidly metabolizes and eliminates BPA from her body. The scientists also concluded that newborns are similarly able to metabolize and eliminate BPA at doses below 1 milligram per kilogram of body weight per day. This implies that newborns could effectively clear BPA at levels far in excess of the TDI of 0.05 mg/kg bw set by the Panel, and therefore its 2006 risk assessment remains valid. The TDI provides a sufficient margin of safety for the protection of the consumer, including fetuses and newborns, EFSA said.

EFSA took note of the U.S. National Toxicology Program’s draft brief on BPA, and of the Canadian government’s recent Draft Screening Assessment on BPA, which took into account findings from low-dose animal studies, notably with respect to neuro-developmental toxicity. It pointed out that these studies were limited in rigor, consistency and biological plausibility.

The new European report is consistent with the statements of the FDA that a large body of evidence indicates that currently marketed products containing BPA, such as baby bottles and food containers, are safe and that exposure levels to BPA from these products are well below those that may cause health effects.

Federal Court Reverses Self On Drug Preemption

Judge David F. Hamilton of the U.S. District Court for the Southern District of Indiana has reversed a prior decision and reinstated a Paxil suicide case that had been dismissed – properly in the view of MassTortDefense --  on preemption grounds last year. See Tucker v. SmithKline Beecham Corp./d/b/a Glaxosmithkline, No. 04-1748, (S.D. Ind. 7/18/08). See opinion here.  In granting plaintiff’s motion for reconsideration, the court violated the rule “if it ain’t broke, don’t fix it.”

Plaintiff Debra Tucker sued GSK on behalf of her brother, Rick Tucker, alleging that her brother committed suicide in September 2002 as a result of taking Paxil for three weeks. The claim was that GSK breached a duty to warn of an alleged increased suicide risk among Paxil patients. (MassTortDefense notes that the scientific evidence actually does not establish that paroxetine (the active ingredient in Paxil) causes suicide, suicide attempts, self-harm or suicidal thinking. On the basis of research in tens of thousands of patients taking antidepressants, including Paxil, there is no significantly increased risk of suicidal thinking or behavior in people age 24 and older and, in fact, in patients older than 65, there was a reduction in risk in suicidal thoughts and behavior.)

The defendant sought summary judgment on preemption grounds. The court correctly determined in September, 2007, that her claims conflicted with the FDA's labeling requirements for Paxil. The court said it believed the record showed that the FDA had rejected the hypothesis that there is a causal link between Paxil and suicide.

In granting the plaintiff's motion for reconsideration, the court said it had "failed to appreciate the fact that the ongoing ability, authority, and responsibility to strengthen a label still rest squarely with the drug manufacturer." In its new decision, the court first noted that under 21 C.F.R. §201.80, a manufacturer must revise labeling "to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved." Under 21 C.F.R. §314.70(c), a manufacturer may unilaterally add or strengthen a contraindication, warning, precaution or adverse reaction upon submission of a "changes being effected" [CBE] supplement. The court now thinks that the FDA's power to disapprove a label "does not make the manufacturer's voluntarily strengthened label a violation of federal law, which is what it would take to establish an actual conflict between state tort law and federal law.”  If the agency disapproves the revised label, the manufacturer simply stops distribution; there is no retroactive illegality.

The court’s new order rejected the FDA’s position that such failure to warn claims are preempted, calling the agency's position on preemption an "180-degree reversal" of its earlier stance. On reconsideration, the court thus gave "relatively little weight to the FDA's opinion on the preemptive effects of its regulations." In 2006, the FDA amended its regulations governing prescription drug labeling, clarifying the preemption of certain warning claims. The court adopted plaintiff’s argument that the 2006 Preamble was promulgated without notice-and-comment.

GSK argued that drug manufacturers will be forced to place scientifically unsubstantiated warnings on their drug products unless state law tort claims are preempted. But the causation requirements on plaintiffs will guard against this risk, the court said. In fact, thought the court, failure to warn litigation can reinforce the FDA's regulations, which already place the obligation to strengthen the warnings on a drug's label “squarely on the shoulders of the drug's manufacturer."  GSK's possible future risk of prosecution for distributing a misbranded drug would present a conflict only if GSK could say with absolute certainty that it will never have new evidence sufficient to trigger its regulatory obligations to revise its label to strengthen a warning with Paxil-specific language, but is forced to do so by state tort law, stated the new opinion.

Here’s why the new opinion got it wrong.
Regarding CBE, proposed changes in labeling typically are first submitted to the FDA for
approval. 21 C.F.R. § 314.70(a)-(d). A limited exception is with the use of a changes being effected supplement. 21 C.F.R. § 314.70(c). When a new safety issue emerges with a product, the pharmaceutical company may temporarily add to the product's labeling under this rule, which describes "changes that may be made before FDA approval." 21 C.F.R. § 314.70(c). Nonetheless, the FDA must still be notified and will subsequently review the modified labeling to ensure compliance with FDA regulations. In 1982, when the CBE procedure was proposed, the FDA stated, "these supplements would describe changes placed into effect to correct concerns about newly discovered risks from the use of the drug." 73 Fed. Reg. 2849 (Jan. 16, 2008) (quoting 47 Fed. Reg. 46622, 46623 (Oct. 19, 1982)). FDA’s longstanding position is that a CBE supplement “is appropriate to amend the labeling for an approved product only to reflect newly acquired information . . . to add or strengthen a contraindication, warning, precaution, or adverse reaction only if there is sufficient evidence of a causal association." 73 Fed. Reg. 2848 (Jan. 16, 2008). The FDA explicitly defines "newly acquired" as "data, analyses, or other information not previously submitted to the agency." Id. at 2850.

The holding of the court that any label change adding or strengthening warnings could always be made unilaterally, without FDA pre-approval, would lead to absurd and unreasonable results. If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval based on information that was previously available to the agency, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted. And plaintiff’s proposed reading of the rule would require manufacturers to make the same CBE change over and over again – despite FDA rejection of the change – in order to avoid liability, because a jury would be free to say – despite the FDA decision – that the manufacturer was free to make the change anyway. It just doesn’t make any sense for the CBE process to permit (and thus obligate, under plaintiffs’ view), a manufacturer to ignore an FDA-mandated label by unilaterally changing the warning to something else. Plaintiffs' construction of the current CBE regulation would permit (and thus obligate) manufacturers to repeat such changes again and again, each time the FDA rejects the proposed change – all without any new scientific evidence to warrant any change at all. Plaintiffs could argue that the “weight” or “accumulation” of evidence required a label change, even as the FDA has rejected changes based on each individual “new” evidence. The only way to prevent the CBE exception from becoming a vehicle for ignoring FDA labeling decisions is to limit it to new information. Any changes to a drug’s labeling without prior FDA approval must be based on new information establishing that risks arising from use of the drug are of a different type or greater severity than the risks of which FDA had previously been made aware – not cumulative new information that does not add to the information that was previously available to the agency.

Second, since this part of the argument is about interpretation of the scope of the FDA’s own CBE regulation, government views concerning that regulation are entitled to substantial deference, not the little weight given. Judicial deference to administrative positions on preemption, typically expressed in amicus briefs, has more or less been the rule, rather than the exception.

Third, regarding the supposed “reinforcing” aspect of tort claims, the new decision in this case would allow a jury to determine whether an FDA-approved label adequately informs physicians about a medication's risks and benefits, as the label generally has to be found to be inadequate before the manufacturer can be held liable. This could result in a patchwork of labels/warning information that vary from state to state for no good reason – the science in Maine is the same in California, even if the juries are not. And this would place doctors and patients in an untenable position. Indeed, state common-law tort actions based on the manufacturers’ failure to warn present the pharmaceutical manufacturers with particular difficulties. State standards of care undoubtedly would differ from state to state. Absent a determination that the FDA-approved labeling and the FDA’s refusal to require the warnings suggested by plaintiffs in this case preempt state tort actions, the manufacturers may be subjected to considerable liability based on varying standards, with no benchmark that they should follow.

The FDA, rather than a jury, has the responsibility to determine whether the labels on medicines offered in the U.S. are appropriate. The FDA has actively monitored the possible association between SSRIs and suicide for nearly twenty years, and has concluded that the suicide warnings desired by plaintiffs are without sufficient scientific basis and would therefore be false and misleading. This claim of supposed harmony or reinforcement by tort law is belied by what the plaintiffs always ask for:  that state courts provide a check on agency power; that state juries be allowed to make their own judgment on whether the label was adequate; and that FDA approval of a label, or rejection of an alternate label, doesn’t mean anything to the company’s potential liability.

Finally, regarding misbranding, a pharmaceutical company that independently institutes a change in labeling may be subject to penalty or seizure if the drug is deemed misbranded by the FDA. See 21 U.S.C. § 333 (authorizing penalties); 21 U.S.C. § 334 (authorizing seizure); 21 C.F.R. § 7.45(a) (providing authority to request recall). And it has never been required, for a conflict to exist, to show how many times the federal law was applied, or how significant the sanctions were. That the federal agency has the legal power to enforce the federal rule is, and ought to be, sufficient.

In its next term, the U.S. Supreme Court will take up a preemption question in Wyeth v. Levine, and we may see if the court got it right the first time or the second time.

Update on Salmonella

Quick follow-up to our recent post on salmonella in which we noted a current focus on peppers rather than tomatoes: Federal officials announced yesterday that they have found the bacteria in a jalapeño pepper from a small distribution facility in McAllen, Tex. Accordingly, they warned consumers to avoid eating raw jalapeños or products that contain them.


The company has stopped distributing jalapeño peppers and is recalling jalapeños sold since June 30 to customers in Georgia and Texas. Investigators don't know where the contamination occurred. CDC officials are hoping that another round of interviews with people who got sick since early June in Arizona and New Mexico will shed more light on the source of the outbreak.

FDA Still Puzzled By Salmonella Outbreak

Federal officials announced last week that all tomatoes currently on the U.S. market are safe to eat. But they admit they still don't know what's causing a salmonella outbreak that has affected thousands over the past three months. Jalapeno and other peppers remain under investigation. Tomatoes had been identified in early June as the likely source of one of the largest food-borne illness outbreaks in the past decade. There were more than 1200 confirmed illnesses linked to the outbreak. While new cases are still being found, the rate has slowed, according to the CDC.

The FDA says it's possible tomatoes caused some illnesses and that it's impossible to prove that they didn't cause any. But not a single contaminated tomato has been found. FDA tested 1,700 samples without finding traces of the outbreak. Apparently, this is not unusual: In half of all produce disease outbreaks, health investigators have never determined what made the people sick. The short shelf life of most fresh fruits and vegetables means it's less likely the items will still be in people's refrigerators when investigators arrive. And the complexity of the produce distribution system can be a large impediment.

Industry leaders are not so sure. They worry it was not a failure of traceability, but a lack of imagination. When the trace-back did not support the tomato hypothesis, investigators should have more quickly tried alternative hypotheses, they say.

In any event, a broad coalition of growers, distributors, restaurants, and retailers have been working on a national tracking system. The current proposal would utilize a global trade item number (GTIN). Every part of the distribution chain would be required to use a bar code encoded with the GTIN and the grower or shipper who produced it, the production lot it was part of, and the date it was packed or harvested. If the GTIN system were to be adopted, investigators could quickly determine where a box of fruit or vegetables came from, and thus whether it needs to be isolated or recalled.

This ability to better link up the product may impact product liability litigation: cause in fact is a basic element requiring plaintiffs to show that the product of the defendant caused his or her injury.  But industry recognizes that it is in everyone's interest to be able to trace back the source as quickly as possible and thus to take immediate action that will limit the number of people possibly affected.  And the inability to quickly trace back may have significant financial impact: The tomato warning, issued for varieties of fresh tomatoes, likely cost the industry millions of dollars, according to trade associations.

The L.A. Times recently reported on an AP poll that finds that nearly half of consumers have changed their eating and buying habits in the past six months because they're afraid they could get sick by eating contaminated food. Also, 86% of those polled said produce should be labeled so it can be tracked through layers of processors, packers and shippers, all the way back to the farm. The poll found that 80 percent of Americans said they would support new federal standards for fresh produce.

The Professors at the Mass Tort Litigation Blog have posted on this as well.

How To Deal With Litigation-Related Concerns In "REMS" For Biologics

Last year’s Food and Drug Administration Amendments Act gave the FDA increased authority to require Risk Evaluation and Mitigation Strategies (REMS)— safety plans similar to those previously known as Risk Minimization Action Plans (RiskMAP). A recent article in Corporate Counsel offers in-house counsel a note of caution concerning the relationship between REMS and the claims made in a typical personal injury or consumer fraud litigation.

For example, the authors note that if REMS are needed, identifying and implementing the appropriate measures will involve a substantial amount of internal work by the manufacturer as well as significant interaction with the FDA. Both include opportunities and pitfalls that could have a significant effect on future litigation involving the product. The REMS process may engender “bad documents” (a paper trail that casts the company or its products in a bad light). On the other hand, one of the common claims asserted in product litigation is that a manufacturer was aware of and failed to adequately warn about its product’s risk. As the REMS process is specifically designed to increase the warnings to the health care  and patient communities, the authors (full disclosure: colleagues of MassTortDefense) suggest it may constitute a solid defense against the assertion that the manufacturer failed to provide adequate warnings.


Waxman Seeks Preemption Drafts From FDA

Preemption of state law claims, particularly in the area of medical devices and drugs, has been a hot topic lately. MassTortDefense has posted on it here and here, and there are numerous good posts on the topic at Drug and Device Law.

In the latest development, Congressman Henry A. Waxman (D-Calif.), Chair of the House Committee on Oversight and Government Reform recently sent a letter to Food and Drug Administration Commissioner Andrew C. von Eschenbach, requesting information about the agency's stance on federal preemption issues under the Bush administration.

The FDA believes, correctly, that state product liability lawsuits which challenge or undermine or invite conduct inconsistent with the federal agency's authority can have a detrimental effect on public health.  Waxman calls this a "reversal of FDA's long-standing position on preemption.”  Waxman’s view about the FDA’s position isn’t so firmly grounded, as seen in the back and forth between the majority and the dissent in Colacicco v. Apotex Inc., 2008 WL 927848 (3d Cir. Apr. 8, 2008), concerning whether the FDA has been “inconsistent” in its positions towards preemption. Going back to the Clinton era (Bill), for example, the FDA has repeatedly stated that FDA regulations may displace both state legislative requirements and state common law duties. In 2000, the FDA fretted that consumers in court would have to prove that harm was linked to the substance based on a standard that might vary by jurisdiction or at the “whim of a jury.” 65 Fed. Reg. 43269, 43278-79 (FDA July 13, 2000). And in an FDA final rule regarding FDA-mandated adverse event reports in state-law civil litigation, the agency stated that implied preemption was appropriate because state or local laws, rules, regulations, or other requirements would impede FDA’s ability to monitor product safety after approval to ensure that human drug products, biologics, and medical devices are safe and effective for their intended uses. “Thus, under principles of preemption law, congressional intent to preempt State law can be inferred.” 60 Fed. Reg. 16962, 16963 (FDA Apr. 3, 1995). See also 59 Fed. Reg. 3944, 3948 (FDA Jan. 27, 1994).

Nevertheless, Waxman is asking for numerous documents from the agency, including:

-all documents since Jan. 20, 2001, concerning communications between FDA and private individuals about preemption;
-all documents since that date, relating to internal FDA communications about preemption;
-all documents since Jan. 20, 2001, relating to communications between FDA officials and officials in the Department of HHS, the White House, and other federal agencies about preemption;
-all amicus briefs since Jan. 20, 2001, filed by FDA in product liability suits; and
-all drafts since that date of the final drug labeling rules issued Jan. 24, 2006.

Liberal Democrats in Congress have been buzzing about the Supreme Court’s decision in Riegel v. Medtronic Inc., in which the Court held that federal law preempted state-law claims against the manufacturer of a medical device that went through the Food and Drug Administration's premarket approval process. And they introduced H.R. 6381 that would reverse the effects of Riegel in medical device lawsuits. Waxman’s letter also comes in anticipation of the Court’s consideration of the extent to which the Food, Drug and Cosmetic Act impliedly preempts state law claims against drug makers. See Wyeth v. Levine, U.S., No. 06-1249, review granted 1/18/08. Of course, DOJ/FDA filed an amicus brief arguing in favor of preemption in that case.

PhRMA Revises Marketing Code Regarding Interactions With Healthcare Professionals

The Pharmaceutical Research and Manufacturers of America (PhRMA) has just adopted measures to enhance the PhRMA Code dealing with Interactions with Healthcare Professionals. (PhRMA represents research-based pharmaceutical and biotechnology companies.) Attacks on the marketing practices of drug makers is a common feature in pharmaceutical mass torts, including criticisms of the relationships between healthcare providers and pharmaceutical companies.

Informative professional relationships between healthcare providers and pharmaceutical research companies are instrumental to effective patient care. While plaintiffs frequently malign interactions between the companies and prescribers, doctors appropriately rely on information about new medicines in order to enhance the quality of care they give patients. Providing doctors with up-to-date information on the medicines they prescribe improves patient care. Thus, reasons for interaction include:

• inform healthcare professionals about the benefits and risks of products to help advance appropriate patient use,
• provide scientific and educational information,
• support medical research and education, and
• obtain feedback and advice about our products through consultation with medical experts.

The new code will take effect in January, 2009. The code is voluntary, reflecting the fact that different companies may approach the issues differently, all well within the range of choices available to a reasonable manufacturer in a competitive environment.

Summary Judgment Ruling In New Jersey HRT Litigation

On July 11, 2008, the mass tort judge handling hormone replacement cases in New Jersey granted summary judgment dismissing Bailey v. Wyeth, No. L-999-06 MT (N.J. Super.), ruling that the labels used by defendants Wyeth and Upjohn were adequate as a matter of law. The failure to warn claims were dismissed because the plaintiffs could not overcome the presumption of adequacy of FDA-approved labels created by the New Jersey Products Liability Act (NJ PLA). The claims for fraud, negligent misrepresentation, and consumer fraud likewise failed because they are subsumed by the NJ PLA and could not be asserted as independent causes of action.

Because our firm is involved in HRT litigation, and because of past and current client relationships, MassTortDefense policy is to not offer extensive commentary on such decisions.  Here, however, for interested readers is the actual opinion.

Summary Judgment Ruling In New Jersey HRT Litigation

On July 11, 2008, the mass tort judge handling hormone replacement cases in New Jersey granted summary judgment dismissing Bailey v. Wyeth, No. L-999-06 MT (N.J. Super.), ruling that the labels used by defendants Wyeth and Upjohn were adequate as a matter of law. The failure to warn claims were dismissed because the plaintiffs could not overcome the presumption of adequacy of FDA-approved labels created by the New Jersey Products Liability Act (NJ PLA). The claims for fraud, negligent misrepresentation, and consumer fraud likewise failed because they are subsumed by the NJ PLA and could not be asserted as independent causes of action.

Because our firm is involved in HRT litigation, and because of past and current client relationships, MassTortDefense policy is to not offer extensive commentary on such decisions.  Here, however, for interested readers is the actual opinion.

Interest Group Releases Sunscreen "Analysis" As FDA Ponders Regulations

Just when you thought it was safe to head outside to your Fourth of July picnic, parade, and swim party, an investigation by the Environmental Working Group (EWG) is released alleging that nearly 1,000 brand-name sunscreen products either fail to adequately protect consumers or contain chemicals that may pose health hazards.

Before we all cancel our plans, note the EWG study is based on non-standard methods and data, as well as subjective judgments, admittedly “customized” safety and effectiveness ratings, and “on a unique, in-house compilation” of industry, government and academic data sources. For what its worth, the study concludes that only 15% of products analyzed met EWG's subjective criteria for safety and effectiveness, blocking both UVA and UVB radiation, remaining stable in sunlight, and containing few if any ingredients with “suspected” health hazards.  It thus ignores a fairly extensive, long-standing body of scientific data, as sunscreen products have been thoroughly studied and tested, and used safely for more than 30 years.


Interestingly, the study asserts that many sunscreens contain nano-scale ingredients that raise "concerns.”  (MassTortDefense has posted on nano-technology here.) EWG asserts that powder and spray sunscreens with nano-scale ingredients raise concerns, since the small particles might be absorbed through the lungs. EWG also asserts that some sunscreens absorb into the blood and thus also raise safety concerns. “Some release skin-damaging free radicals in sunlight, some could disrupt hormone systems, several are strongly linked to allergic reactions, and others may build up in the body or the environment.”

EWG complains that the FDA has not established rigorous safety standards for sunscreen ingredients that fully examines these effects. The activist group also asserts that FDA has approved just 17 sunscreen chemicals for use in the U.S., while at least 29 are approved for use in the E.U.

However, there are currently FDA safety and effectiveness regulations that govern the manufacture and marketing of all sunscreen products. Sunscreens are classified as drugs by the FDA, and the agency requires significant safety and efficacy data on every active ingredient before it is approved for use in a sunscreen product. The agency also has broad authority to inspect manufacturers, require adherence to strict manufacturing practices, and enforce rigorous, science-based regulations to ensure that sunscreen products are safe and effective for consumers.

Moreover, the FDA in 2007 did propose a new regulation that would set standards for formulating, testing and labeling over-the-counter sunscreen products with ultraviolet A (UVA) and ultraviolet B (UVB) protection. The proposed regulation creates a consumer-friendly rating system for UVA products designed to help consumers identify the level of UVA protection offered by a product. Ratings would be derived from two tests the FDA proposes to assess the effectiveness of sunscreens in providing protection against UVA light. The first test measures a product's ability to reduce the amount of UVA radiation that passes through it. The second test measures a product's ability to prevent tanning. This test is nearly identical to the SPF test used to determine the effectiveness of UVB sunscreen products.

The finalization of the sunscreen safety standards is a complicated regulatory undertaking, addressing complex scientific principles involving countless submissions of data. FDA must thoroughly evaluate all of this information in making the best possible regulatory and scientific decision for consumers.

In the proposed regulations, a "Warnings" statement in the "Drug Facts" box will be required of all sunscreen product manufacturers. The warning would say: "UV exposure from the sun increases the risk of skin cancer, premature skin aging, and other skin damage. It is important to decrease UV exposure by limiting time in the sun, wearing protective clothing, and using a sunscreen." While the warning is intended to increase awareness that sunscreens are one part of a sun protection program, it seems likely that most adults today understand that exposure to the sun may cause skin damage, up to and including skin cancer. Skin cancer is the most common form of cancer in the United States.The American Cancer Society has long designated May as Skin Cancer Awareness Month.

Many manufacturers provide significant science and risk information on websites, as well as links to organizations such as the American Cancer Society, the American Skin Association,  the Skin Cancer Foundation, and the National Cancer Institute.

FDA Responds to NEJM Article on Medical Device Approval Process

In this week’s New England Journal of Medicine, 359 NEJM 88 (July 3, 2008), the FDA responds in a letter to harsh criticism published in the Journal earlier this year on the issue of medical device approval. Dr. Daniel Schultz expresses concern “about several statements” in the earlier article that “may have misled readers.”  Readers of MassTortDefense know that significant product liability litigation has arisen over recalled medical devices in recent years.

In the earlier “Perspective,” Dr. William H. Maisel criticized the FDA’s decision to approve a device (an implantable cardioverter–defibrillator (ICD) lead) in 2004. See Maisel WH., “Semper fidelis -- consumer protection for patients with implanted medical devices,” 358 NEJM 985 (2008). Dr. Maisel is apparently a consultant for the FDA and a member of the Medicare Coverage Advisory Committee.

Obviously, no complex device can be 100% free of design, manufacturing, and performance flaws. Malfunctions inevitably occur, and manufacturers should be rewarded, not criticized, for identifying and correcting any problems. The demands placed on ICD leads, in particular, are intense: they must withstand hundreds of millions of repetitive cardiac cycles, survive in the hostile environment of the human body, and allow delivery of high-voltage energy at a moment's notice. A recent editorial in the Wall Street Journal opined that "the real danger to public health is the overreaction to medical risk," noting that some patients refuse to have a device implanted because of concern about potential malfunctions.

 
Maisel argued, however, that the agency is failing to fulfill its mission of helping the public get the accurate, science-based information they need. Essential consumer protections are currently lacking, allegedly. He argued it was “increasingly apparent” that improvement will require Congressional action.


Specifically, Maisel criticized the FDA for approving changes in the device/lead on the basis of bench testing rather than clinical data. However, FDA regulations allow manufacturers to apply for marketing of a modified device on the basis of bench testing, and many devices are approved in this way. This is not an inherently unsafe approach, Dr. Schultz noted. In evaluating an application involving a modified device, the FDA will analyze the proposed modification, determine the potential types of failure, and tailor testing requirements accordingly. In many cases, agency questions are best answered by performing appropriate engineering analyses, but in other cases, FDA may also require clinical data.  To require that these modified devices undergo clinical trials across the board as a condition of FDA approval would limit the availability of improved products. Also, most of these trials would, in any event, have insufficient power to detect small but clinically meaningful differences in performance.

 
Maisel also criticized some device manufacturers for continuing to market existing models while modified models await FDA approval. But there is nothing inherently wrong with doing so unless the older models pose undue health risks.

 

FDA Advisory Committee Holds Meeting On Contrast Agents

A Cardiovascular and Renal Drugs Advisory Committee to the FDA held a public meeting last week to discuss safety considerations in the development of ultrasound contrast agents. Briefing information from the FDA found here.

The meeting comes in the midst of litigation concerning this important type of medical product. For example, about 70 cases have been filed in more than a dozen jurisdictions alleging that gadolinium-based injectable contrast agents cause serious health problems. Plaintiffs claim that gadolinium in contrast solutions used in magnetic imaging causes Nephrogenic Systemic Fibrosis. The federal suits were consolidated in February into an MDL in the U.S. District Court for the Northern District of Ohio. IN RE: GADOLINIUM BASED CONTRAST AGENTS PRODUCTS LIABILITY LITIGATION, MDL No. 1909. The parties made science presentations to the the Court in April, 2008.

Representatives for the makers told panelists this week that the agents are not unduly unsafe and noted that many patients given the agents are already very sick. A number of physicians speaking to the panel urged further study, but said medical information gathered through use of the contrast agents outweighed their side effects. The agents give life-saving information.

Ultrasound contrast agents are "microbubble" (or "microsphere") drugs that are injected into the vascular system in order to improve the diagnostic information obtained from ultrasound-based images. The ultrasound contrast agents approved by the FDA are used in ultrasounds, such as echocardiography, and assist in the diagnosis of various conditions. The uniqueness of the physical and chemical properties of the ultrasound contrast agents, the technicalities of the ultrasound field and its rapid technical advances, combined with the unique design considerations for clinical studies of diagnostic imaging agents have all presented special challenges in the clinical development and optimal use of these agents.

The advisory committee was created to provide a public forum for review of the history of the currently marketed ultrasound contrast agents, to obtain opinions from the advisors regarding safety considerations in the development of these agents, and to begin to familiarize the committee members with the review of diagnostic imaging agents.

According to the FDA, post-marketing reports and new animal data prompted label changes for certain of these products in October, 2007. These changes included a black-box warning and contraindication for use of the products in certain patients with underlying cardiopulmonary conditions.

FDA has most recently been working with the manufacturers to develop a risk assessment and management program. In addition to physician education and enhanced oversight of clinical studies, this program consists of two studies. One is an observational study to be conducted using an administrative database in which mortality will be compared between critically ill patients who receive a contrast-enhanced echocardiogram and critically ill patients who undergo echocardiography without contrast. The second study will obtain pulmonary hemodynamic data from patients who are undergoing right heart catheterization as well as contrast-enhanced echocardiography.

Institute Releases Report on Drug Innovation Through Industry Research

A report just released by the Center For Medical Progress At The Manhattan Institute indirectly undercuts a favorite theme of plaintiffs in pharmaceutical mass torts.

Entitled “The Truth About Drug Innovation: Thirty-Five Summary Case Histories On Private Sector Contributions To Pharmaceutical Science,” the analysis assesses -- and rejects -- the argument that most of the important scientific advances that yield new and improved medicines do not result from private sector research, but instead are the fruits of research efforts financed or conducted by public agencies, such as the National Institutes of Health. The paper also indirectly undercuts a favorite plaintiff theme that scientific research undertaken by, or funded by, private industry is biased, tainted, poor science, and not worthy of a jury’s serious consideration.

The study compiled summary case histories of thirty-five drugs and drug classes (a group of drugs used to treat a given medical condition in similar ways) identified in the scholarly literature as important and/or that were among the most prescribed in 2007. The authors’ conclusions:


• the scientific contributions of the private sector were crucial for the discovery and/or development of virtually all of the thirty-five drugs and drug classes examined in this study.
• The companies’ scientific advances included topics within the basic science of biology and disease, processes relevant for given medical conditions, the applied science of discovering compounds that treat particular conditions; and the development of compounds with improved clinical (medical) effects.

In short, almost all of the drugs and drug classes examined in this study would not have been developed—or their development would have been delayed significantly—in the absence of the scientific or technical contributions of the pharmaceutical firms.

FDA and China Issue Joint Progress Report on Food Safety

The United States and China issued a joint progress statement last week that described the measures both have recently taken to improve the safety of international food and feed imports.
The safety of a variety of products and substances imported from China have been in the news, ranging from pet food, to toothpaste, to toys, to pharmaceutical ingredients. MassTortDefense has posted on this here and here.

According to the statement, both countries have improved the exchange of information on food safety and on the relevant regulatory systems. The U.S. has agreed to conduct training for Chinese officials on U.S. regulatory standards. Each has designated new emergency contacts and notification thresholds for import safety issues. The two countries have also been working towards an electronic certification system between the FDA and China's General Administration of Quality Supervision, Inspection and Quarantine to ensure that Chinese exports meet FDA standards for safety and manufacturing quality. The countries also agreed to increase their focus on inspection, supervision and laboratory testing of Chinese imports.

The document outlines steps taken by both nations in implementing the 2007 Memorandum of Agreement (MOA) on food and feed safety. The MOA established a bilateral mechanism to provide greater information and other assurances to enhance the safety of food and feed products traded between the two countries.

Finally, the report described the establishment of a cooperative mechanism to notify each other of significant risks to public health related to product safety or the gross deception of consumers, and to share information to facilitate each other’s investigation.

The report comes as Senator Sherrod Brown (D.-Ohio), in a letter to the FDA's Center for Drug Evaluation & Research, called on the agency to investigate outsourcing of drug ingredients, and just as China has granted diplomatic approval for the FDA to open three inspections offices in China that also will help increase China's ability to ensure delivery of safe foods, drugs and other products. The FDA reportedly hopes to open the offices in Beijing, Shanghai and Guangzhou before the end of this year, with a total staff of around 12 people.

House Committee Holds Hearing On Phthalates And BPA In Consumer Products

The House Energy and Commerce Committee’s subcommittee on Commerce, Trade, and Consumer Protection held a hearing last week on “Phthalates and Bisphenol-A in Everyday Consumer Products.” See webcast here.  (MassTortDefense has posted on BPA before, here and here and here.  Phthalates are chemicals used to soften polyvinyl chloride (PVC) and make it flexible.)


This testimony before Congress pointed out one of the major problems with the knee-jerk reaction of sensationalist media, liberal lobbyists, and uninformed legislators who quickly call for the banning of useful products as soon as any scientific reports even hint of a risk. A chemist from the Consumer Product Safety Commission noted that the banning of di-isononyl phthalate (DINP) from all children's products, could lead to substitute plasticizers that are not as fully studied, not as well known, or not as well characterized toxicologically. And banning BPA could lead to more children injuries.


In addition to the CPSC, officials of the FDA, NTP, and EPA testified as well before the House subcommittee on June 10th. Also, the Science and Environmental Health Network testified in favor of a ban, while the American Chemistry Council opposed it. The hearing came as House and Senate conferees are working out differences in their respective legislation to reform the CPSC. See the MassTortDefense post here on that. The industry voluntarily removed DINP from teethers, rattles, and pacifiers in the late 1990’s. The Senate version of the CPSC bill would essentially prohibit these phthalates from children's toys or child care articles: DINP, di-isodecyl phthalate (DIDP), di-n-octyl phthalate (DnOP), di-(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBP).

Bisphenol-A (BPA) was the other chemical at issue in the hearing. The CPSC official testified that its beneficial uses in items such as helmets and other protective gear to prevent injuries in children needs to be considered. A ban could result in less effective protection of children from head, eye, or bodily injury. Rep. Edward J. Markey (D-Mass.), a member of the House Energy and Commerce Committee, has introduced legislation that would prohibit the use of bisphenol-A in all food and beverage containers. (The “Ban Poisonous Additives (BPA)” Act, text here.)  But the Food and Drug Administration associate commissioner for science testified that available evidence indicates that food contact materials containing BPA currently are safe as exposures from food contact materials are well below the levels that may cause health effects.

The FDA formed a BPA task force in April that is reviewing current research on BPA, and looking at all products regulated by the FDA to better understand potential routes of exposure. The FDA also is looking at concerns raised by the draft report by the National Toxicology Program. See our post here.

Latest BPA Update: Peer Review Panel Weighs In On NTP Draft Report

Latest BPA update. Readers of MassTortDefense know that a recent draft report by the Center for the Evaluation of Risks to Human Reproduction (CERHR) of the National Toxicology Program (NTP) examined bisphenol-A (BPA). The CERHR/NTP draft report, issued April 15th for public comment, expressed "some concern" based on animal studies that the chemical might affect the neurological systems and behavior of fetuses, infants, and children. See our post here.


Officials from the U.S. Food and Drug Administration and the U.S. Consumer Product Safety Commission both told the U.S. Senate Committee on Commerce, Science and Transportation subcommittee on consumer affairs recently that bisphenol-A did not appear to pose sufficient risks that the product should be banned. Although review is ongoing, at this time those agencies have no reason to recommend that consumers stop using products containing BPA. The FDA's associate commissioner for science said that a large body of evidence indicates that currently marketed products containing BPA, such as baby bottles and food containers, are safe and that exposure levels to BPA from these products are well below those that may cause health effects. See our post here on this.


The NTP collected public comments on the draft and scheduled a June 11 peer review meeting for the draft. In comments on the NTP draft report, the American Chemistry Council asserted that the program relied on numerous studies of dubious and limited quality. Certain environmental groups sought stronger statements of concern.

The expert review panel has now concluded that the National Toxicology Program overstated some of the concerns about bisphenol A's potential developmental effects. At a meeting in Research Triangle Park, the panel, called the Board of Scientific Counselors, voted to revise the levels of concern stated in the NTP draft report on bisphenol A. In particular the “some concern" is to change to "minimal concern" regarding the neurological system and behavior of fetuses, infants, and children as might be affected by exposure to low levels of bisphenol A. (The toxicology program regularly uses "statements of concern" about different types of exposures and different groups that may be exposed to a chemical. The five levels of concern used by NTP are from highest to lowest: serious concern, concern, some concern, minimal concern, and negligible concern. )

Following its review of the draft report, the BSC panel decided that NTP had overstated bisphenol A's potential effects on mammary glands and the onset of puberty in young females. The panelists generally felt that there were insufficient scientific data to support any stronger level of concern than minimal.

The review panel said there was sufficient evidence in the studies considered by NTP to support its other statements of concern –minimal and negligible.

• The BSC accepted (7 yes, 4 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the conclusion of minimal concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on effects in the mammary gland. • The BSC accepted (7 yes, 4 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the conclusion of minimal concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on an earlier age for puberty in females.
• The BSC accepted (11 yes, 1 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring.
• The BSC accepted unanimously (12 yes, 0 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of negligible concern that exposure to bisphenol A causes reproductive effects in non-occupationally exposed adults.
• The BSC accepted (11 yes, 0 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of minimal concern for workers exposed to higher levels of bisphenol A in occupational settings.

The panel also accepted the mid-level “some” concern expressed in two areas.

• The BSC accepted unanimously (12 yes, 0 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of some concern for neural and behavioral effects of bisphenol A in fetuses, infants, and children at current human exposures.
• The BSC accepted (10 yes, 2 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of some concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on effects in the prostate gland.


The panel called for additional research to better understand bisphenol A's potential effects.

Public comments on the draft , transcripts, list of attendees, etc. found here.

FDA To Form Committee To Analyze BPA Issues

In the latest development on the issues surrounding Bisphenol-A in consumer products, the FDA announced that a subcommittee of the FDA's Science Board will hold a public meeting on the topic of BPA in plastics, review an Agency Task Force report on the topic, and deliver its findings to the Board's annual meeting this fall. Dr. Frank Torti, the FDA's principal deputy commissioner and chief scientist, has asked Science Board Chairwoman Barbara McNeil, head of Health Care Policy at Harvard Medical School, to establish a subcommittee to further assess BPA. (MassTortDefense has posted about BPA here and here.)

BPA is a chemical produced in large quantities for use primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics in turn have many important applications, including use in certain food and drink packaging, e.g., water and infant bottles, compact discs, impact-resistant safety equipment, and medical devices. Polycarbonate plastic can also be blended with other materials to create molded parts for use in mobile phone housings, household items, and automobiles. Epoxy resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. Some polymers used in dental sealants or composites contain bisphenol A-derived materials.

This development comes on the heels of the FDA forming an agency-wide BPA Task Force to facilitate review of current research and new information on BPA. That Task Force is reportedly assembling an inventory of FDA-regulated products that contain BPA. Eventually, the Task Force may make recommendations to the Commissioner of Food and Drugs.

In April 2008, the National Toxicology Program (NTP) of the National Institutes of Health published a draft report indicating that some studies in animals suggest that BPA may raise “some concern” about potential developmental effects in humans. The NTP is still collecting public comments on the draft and has scheduled a June 11 peer review meeting for the draft.

In mid-May, FDA officials assured a congressional panel that the agency had no reason to recommend that consumers stop using products containing BPA, noting that a large body of evidence indicates that currently marketed products containing BPA, such as baby bottles and food containers, are safe and that exposure levels to BPA from these products are well below those that may cause health effects. See our post on the hearing.

Of course, the litigation has already begun, notwithstanding the science, with a proposed class action filed over the use of BPA in baby bottles in the U.S. District Court for the Western District of Missouri.

Government Files Amicus Brief in Levine v. Wyeth

For those readers of MassTortDefense following the Levine v. Wyeth matter, here is the BRIEF FOR THE UNITED STATES AS AMICUS CURIAE SUPPORTING PETITIONER.

The agency, via the Solicitor General, argues that the FDA’s decision to approve a drug and its labeling reflects the agency’s expert evaluation of the health risks and benefits the product can provide; respondent’s claims are preempted because they challenge labeling that FDA approved after being informed of the relevant facts. When federal regulation is designed to strike a balance between competing risk/benefit considerations, state laws that strike a different balance are impliedly preempted because they interfere with the federal balancing. The amicus brief also notes that FDA’s labeling requirements do not qualify as a mere minimum safety standard, or floor, upon which state laws could add more stringent requirements.

The SG also addresses the Vermont Supreme Court’s conclusion that the FDA’s regulations allow drug manufacturers to easily change drug labels unilaterally. “Petitioner was not free to disregard FDA’s judgment concerning previously known risks.” Brief at 21. The “limited exception” to the general rule requiring FDA to approve any label changes requires submission of a supplemental new drug application to, albeit not prior approval by, the agency. And substantive changes may be made without prior FDA approval only to correct concerns about newly discovered risks from the use of the drug. If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval based on information that was previously available to the agency, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted.

FDA Launches Sentinel Initiative

On May 22, 2008, FDA launched the “Sentinel Initiative” – a new program with the goal of creating and implementing the Sentinel System--a national, integrated, electronic system for monitoring medical product safety.


The Sentinel System, once in place, will enable FDA to pose targeted queries (consistent with privacy and security safeguards) of patient registry data, insurance claims data, and other large health care information databases, for information about medical products. FDA says this new system will strengthen the agency's ability to monitor the performance of a product throughout its entire life cycle, thus enhancing the protection and promotion of public health.

 
FDA's current post-market surveillance programs generate very important new risk information, but the adverse event reporting system depends on health care professionals and patients first recognizing a potential association between an adverse effect and a medical product, and then report it to FDA or the manufacturer. Some adverse events are never reported.


Once the Sentinel System is up and running, FDA will have the tools to query specific adverse event data in large databases, like the Medicare database and in claims data and electronic health information maintained by private and federal entities who volunteer to participate in the Sentinel System. That is, the System will be created through public-private partnerships. It will rely on existing large electronic claims and medical records data sources maintained by private and government entities that agree to participate in this nationwide effort.

Creating an advanced surveillance system like Sentinel was one of the recommendations made by the Institute of Medicine in its 2006 report on ways to improve the safe use of drugs. The Food and Drug Administration Amendments Act of 2007 includes provisions that call for the development of such a system. FDA believes patients will benefit because the agency will be able to identify potential problems sooner, better understand those problems, and ultimately, help health professionals and patients use medical products more safely.

 
The overall initiative is described in an FDA white paper titled, “The Sentinel Initiative—A National Strategy for Monitoring Medical Product Safety.” The report is available at here.

Such a system could also ultimately facilitate data mining and other research-related activities. Researchers have said its full effects would take years to realize, however.


It is interesting to speculate about the potential impact of the system, especially on products liability litigation. Medicare collects data typically only when a medical provider is seeking payment. This claims data is less complete, and potentially less accurate than actual patient health records. Thus, utilizing Medicare data to assess health outcomes of drug use may be problematic. Of course, the new system doesn’t change the reality that sometimes patients suffer adverse events after receiving drugs because they are sick, not because the drug has a problem. And Medicare recipients use an average of 28 prescriptions in a year, compared with an average among all Americans of something like 12 prescriptions. Sorting out which medicine caused any single problem – if any did -- can be difficult.


In mass tort litigation, as readers of MassTortDefense know, plaintiffs frequently will attack defendants’ AER system, the resources devoted, the quality of the reporting. Even more frequently, plaintiffs will allege that the AE reports revealed a “signal” far sooner and far more clearly than the company thought; that the defendant missed or ignored the signal about potential adverse events in order to avoid the financial impact of a new label with a stronger warning. But if the FDA will eventually be able to query databases of tens of millions of patients almost simultaneously, presumably it will no longer have to wait for reports from the field, and the allegations of “missed signals” may lose all force.


To assess the accuracy of the Sentinel system, the FDA will initially conduct studies of drug side-effects that are already well known. And despite the issues, the Pharmaceutical Research and Manufacturers of America supported the FDA initiative, see here,  because it will allow regulators and health care professionals to move from reliance on voluntary reporting of side effects to a more proactive monitoring of medicines. 

Congressional Committee Holds Hearing on Preemption

The House Committee on Oversight and Government Reform held a hearing last week entitled, “Should FDA Drug and Medical Device Regulation Bar State Liability Claims?” Chairman Waxman’s opening statement opined that preemption was a "radical legal doctrine" being advocated by the pharmaceutical and device industries and the Food and Drug Administration (FDA). Patients allegedly injured by defective drugs and medical devices would no longer have the ability to seek compensation. “The result is that one of the most powerful incentives for safety - the threat of liability - would vanish.”  Waxman and other Democrats are of the view that FDA approval of drugs and medical devices before they are marketed “does not necessarily guarantee safety.”

Of course, the politicos' simplistic view ignores the fundamental reality that prescription products are typically unavoidably unsafe. Nothing guarantees complete safety.  They are complex products that carry risks, at least to some users. That is why the FDA weighs the risks and benefits for an indicated population, and a learned intermediary – doctor – is needed to obtain the product, someone who can balance the risks with the benefits for the particular patient.

The hearing follows on the Supreme Court decision in Riegel v. Medtronic,128 S. Ct. 999 (2008), and in anticipation of the Court’s decision in Levine v. Wyeth.


The witnesses included some leading opponents of preemption, from actor Dennis Quaid (who has a suit against Baxter), former FDA official David Kessler, and an editor from the New England Journal of Medicine (who editorializes against preemption). No one from the industry was scheduled to appear, apparently. The only two witnesses in favor of preemption were buried in later witness panels.  This led Congressman Christopher Shays (R-Conn.) to note that the hearing was more about plaintiff lawyers than public health. 


Most of the press coverage focused on Quaid (MassTortDefense liked him in “The Rookie”), who urged Congress on Wednesday to preserve patients' rights to sue drug makers for injuries, and recounted the story of his newborn twins’ medical scare – which apparently resulted from human error at the hospital and was unrelated to the safety and efficacy of Baxter's product. "I believe if preemption of lawsuits is allowed to prevail, it will basically make all of us, the public, uninformed and uncompensated lab rats," Quaid said.


The FDA currently and correctly believes that the important decisions it makes about the safety, efficacy and labeling of medical products should not be second-guessed by state court juries.  But should the Supreme Court recognize the role of preemption in the Levine case, this is yet another sign that some in Congress may seek to take action to overturn any ruling in favor of the doctrine.