Preemption Found in Another Drug MDL

Implied preemption makes complete sense when it is evident that the FDA would not have permitted label changes that plaintiffs in private litigation say are required by state law. The latest example comes in the MDL litigation accusing various drug companies of failing to warn patients of alleged pancreas problems from Type 2 diabetes drugs; the California federal court recognized the FDA would have rejected the types of warnings plaintiffs demanded. See In re Incretin-Based Therapies Prods. Liab. Litig., No. 3:13-md-2452, 2015 WL 6912689 (S.D. Cal. Nov. 9, 2015).  The court concluded that defendants’ preemption defense was not only viable, but also dispositive of plaintiffs’ failure to warn claims. The record established that the FDA had specifically considered pancreatic cancer risk, commented publicly on the adequacy of drug labeling, and maintained its position that scientific evidence of a causal association between incretin mimetics and pancreatic cancer was indeterminate. Because an indeterminate causal association falls well below the federal regulatory standards required for labeling changes, clear evidence existed that the FDA would have rejected a reference to pancreatic cancer in product labeling.

This litigation involves claims that defendants failed to warn that four prescription drugs used to treat type 2 diabetes cause or increase the risk of pancreatic cancer. Plaintiffs are individuals with type 2 diabetes who were prescribed and consumed one or more of the prescription drugs in this group. The court first discussed Levine v. Wyeth, and its comment  that “absent clear evidence that the FDA would not have approved a change to Phenergan’s label” the Supreme Court would “not conclude that it was impossible for Wyeth to comply with both federal and state requirements.”  The court read Levine as providing the relevant conflict preemption standard (although there is an argument that the "clear evidence" notion arises from the unique procedural posture of the case, not as an evidentiary standard applicable in all preemption cases), but the case did not define what constitutes clear evidence. As such, application of the standard is necessarily fact-specific, said the court.  See Koho v. Forest Labs., Inc., 17 F. Supp. 3d 1109, 1118 (W.D. Wash. 2014) (“[T]he clear evidence standard is a fact based inquiry that depends on the express type of warning at issue and the particular facts of each case.”); Dobbs, 797 F. Supp. 2d at 1270 (explaining that ascertaining conflict preemption is “necessarily fact specific”).

Defendants cited multiple instances where the FDA had taken a position regarding pancreatic safety, including: (1) issuance of the FDA’s February 2014 assessment of pancreatic safety in the New England Journal of Medicine; (2) the FDA’s rejection of a citizen petition requesting the withdrawal of Victoza; (3) the FDA’s September 2014 conclusion that a causal association between incretin mimetics and pancreatic cancer is indeterminate; and (4) the subsequent approval of other incretin-based therapies without any reference to pancreatic cancer in the product labeling. Defendants argued that each instance represents the FDA’s opinion regarding pancreatic safety and its conclusion that current data does not support a pancreatic cancer label reference.
Plaintiffs argued that the evidence established the FDA has been aware of a pancreatic cancer safety "signal" for several years, and actively investigated the existence of a possible causal relationship between the drugs and pancreatic cancer.

It is worth noting, particularly, that in 2014, the FDA formally responded to a 2012 Victoza citizen petition. In doing so, the FDA again rejected adverse event data as evidence of a causal association between Victoza and pancreatic cancer. The FDA also concluded that any causal association between exposure to Victoza and pancreatic cancer is indeterminate at this time. Based on these conclusions, the FDA made no labeling change recommendations specific to pancreatic cancer. In September 2014, the FDA again reviewed pancreatic safety concerns in considering the safety of a higher dose of Victoza, marketed for weight loss. As part of a briefing document, the FDA acknowledged that pancreatic cancer had been “hypothesized but not proven” as a risk associated with incretin mimetics, and that “animal observations and clinical trial data reviewed by the FDA to date have not supported a causal association.” The FDA also reiterated its earlier conclusion that studies were “inconclusive” as to a causal association between incretin mimetics and pancreatic cancer.


These facts established that  the FDA has considered pancreatic cancer risk, the specific issue that plaintiffs allege defendants should have warned of or otherwise referenced in their product labeling. In addition to considering the specific issue raised by plaintiffs, the FDA had also  consistently concluded that a causal association between the drugs and pancreatic cancer was indeterminate. This falls below the science-based regulatory standards that govern what
must be included in product labeling. See 21 C.F.R. § 201.57(c)(6) (requiring reasonable evidence of a causal association); id. § 201.57(c)(7) (requiring sufficient basis to believe there is a causal association).  The FDA had also not required any of the defendants to add a pancreatic cancer warning, or required the inclusion of a warning in newly approved incretin-based therapies. That FDA inaction was "highly persuasive given the FDA’s comprehensive review of pancreatic safety and ability to mandate a labeling change if it concluded the regulatory standards were satisfied.

The court also rejected the standard plaintiff position that a defendant cannot establish preemption absent express rejection by the agency of a proposed labeling change it made. "Plaintiffs overstate the burden imposed by Levine."  While a CBE rejection would readily meet the clear evidence standard, it is not the only means by which a manufacturer can establish conflict preemption. The Supreme Court stated a manufacturer must demonstrate the FDA would have rejected a label change, not that the FDA did reject the labeling change.  Also, plaintiffs cannot establish the FDA’s substantial review of pancreatic safety in this posture was materially different from what the FDA would have done in response to a CBE, had one been submitted.  In fact, instead of reviewing data submitted by an individual manufacturer, the FDA considered a variety of data sources related to the entire class of incretin mimetics. Thus, "the facts of this matter are different in form only."

Notably, responding to citizen petitions is just as much within the FDA’s regulatory authority. The Victoza citizen petition rejection was written by the Director of the FDA’s Center for Drug Evaluation and Research, and constitutes the FDA’s official response to the request to withdraw Victoza from the market. Other courts to address conflict preemption have considered citizen petition responses as indicative of whether the FDA would reject a proposed labeling change. See, e.g., Mason, 596 F.3d at 395 (considering citizen petitions in clear evidence analysis); Koho, 17 F. Supp. 3d at 1117 (same); Dorsett, 699 F. Supp. 2d at 1157 (same).

The existence of an alleged "open safety signal" and the FDA’s ongoing review of pancreatic safety did not undermine the FDA’s previously articulated conclusions. The existence of a safety signal is not, without more, indicative of a causal association. FDA Guidance for Industry recognizes that signal generation is only the first step in pharmacovigilance and merely indicates the need for further investigation before any conclusions are drawn. Further investigation may or may not lead to the conclusion that the product caused the event. The existence of a hypothetical causal association is insufficient to satisfy the CBE standard. See Robinson, 615 F.3d at 869 (noting a label describing every serious disease that might or even arguably be caused by a drug would result in “information overload” making “label warnings worthless to consumers”); Mason, 596 F.3d at 392 (“While it is important for a manufacturer to warn of potential side effects, it is equally important that it not over-warn because over-warning can deter potentially beneficial uses of the drug by making it seem riskier than warranted and can dilute the effectiveness of valid warnings.”).

Thus, the FDA’s ongoing review of pancreatic safety, indeed any drug, is more indicative of the nature of drug surveillance than of the existence of a causal association. FDA continuously monitors every medication for new or evolving information as long as a drug is on the market. The potential for the FDA to reach a different conclusion in the future in light of new, future, scientific evidence or developments does not preclude a finding of preemption now. 

Sound analysis.

Advisory Group Recommends Cost/Benefit Analysis for CPSC Regulations

We have posted before about the impact of regulations on clients and indirectly on product litigation. Earlier this month the Administrative Conference of the United States, a federal advisory council, gave its approval to a policy recommendation encouraging independent regulatory agencies to apply formal cost-benefit analysis to their rule-making efforts. One affected agency would be the Consumer Product Safety Commission.

Readers may know that the ACUS is an independent federal agency dedicated to improving the administrative process through consensus-driven applied research, providing nonpartisan expert advice and recommendations for improvement of federal agency procedures. Its membership is composed of federal officials and experts with diverse views and backgrounds from both the private sector and academia.

Several independent regulatory agencies are not subject to the benefit-cost analysis requirements of various Executive Orders or legislation.  The ACUS undertook a project to examine the possible use of benefit-cost analysis at independent regulatory agencies and to highlight any innovative practices those agencies could use. The group adopted a recommendation encouraging agencies to voluntarily adopt certain practices that other agencies have developed when conducting regulatory analyses for major rules. The recommendation, first, identifies various policies and practices used in several regulatory agencies and offers a series of proposals to encourage their use in other agencies. For example, it recommends that each independent regulatory agency develop written guidance on the preparation of benefit-cost and other types of regulatory analyses.

Second, the recommendation highlights a series of analytical practices that OMB has promulgated in the past. For example, it recommends that agencies’ analyses be as transparent and reproducible as practicable, subject to the limitations of law and applicable policies (including preventing the disclosure of proprietary information or trade secrets, or other confidential information). The recommendation does not
seek to establish a one-size-fits-all approach to regulatory analysis, and recognizes that each agency must tailor the analyses it conducts to accord with relevant statutory requirements, its own regulatory priorities, and the potential impact of the analysis on regulatory decision-making to ensure proper use of limited agency resources. 

Note that during the debate on the measure, at least one CPSC commissioner argued against requiring a cost-benefit analysis.

Following the report, Senate Bill 1173 was introduced to require independent agencies to analyze the costs and benefits of new regulations and to tailor new rules to minimize unnecessary burdens on the economy. "The Independent Agency Regulatory Analysis Act of 2013" would apply to any proposed new rule with an economic impact of $100 million or more annually. Sponsors argue there is no good reason the independent agencies should not conduct the same important review other executive agencies must.


 

Report Issued on Use of Science in Regulatory Decisions

Scientists and policy experts from industry, government, and various nonprofit sectors worked on a report released recently by the Research Integrity Roundtable, designed to offer ways to improve the scientific analysis and independent expert reviews which underpin many important regulatory decisions. The primary audience for the report is federal agencies and their scientific advisory committees, but the ideas in the report may be relevant to others who work at the intersection of science and regulatory policy, including in Congress, the judiciary, and readers of MassTortDefense.  These issues can have important implications for persons interested in issues associated with chemicals, energy, land use, natural resources, agriculture, pharmaceuticals, and other areas in which science informs public policy.

Critics of the manner in which science is used in regulatory decision-making processes tend to raise two kinds of concerns. They question the composition of committees that are empaneled to recommend or review the science behind a possible regulatory decision and they question the way an agency or committee has reviewed the relevant scientific literature, charging that the reviewers used or omitted the wrong studies, and/or that the studies were not appraised appropriately. Obviously, some disputes over the "politicization" of science actually arise over differences about policy choices that science can inform, but not determine.

With that in mind, this report attempts to lay out some broad principles, guidelines, and practices designed in the view of the authors to limit the battling over conflict of interest and bias, and systematic reviews.  Accordingly, this report focuses on:

 How should panels be composed and the qualifications of prospective advisory panelists be vetted?
 How should concerns about biases and conflicts of interest of advisory panelists be handled?
 Which studies should agencies review when examining the scientific literature related to a regulatory policy issue?
 How should contending views regarding the relevance of particular scientific results to a regulatory issue and the credibility of those results be addressed?

For panel formation, the report concludes that a reasonable balance must be established between transparency and privacy. In the realm of qualifications, for example, balancing how much personal information should be revealed to the public by a prospective panelist who may be willing to serve in an advisory capacity, but may not want every aspect of his or her personal life or financial status released to the public.

In dealing with scientific studies, the report suggests a balance must be established in developing and applying objective and transparent criteria for establishing data relevance and reliability between the desire for complete data-sets and the reality that the relevant scientific literature is populated with studies from a wide variety of sources with varying degrees of data availability. In some cases, when proprietary information is involved, an appropriate balance must be struck between the public’s right to know and the legally based need to protect proprietary formulas, production processes, and related intellectual property. 

U.S. Chamber Describes Tort Reform Goals for 2012

Here at MassTortDefense we try to keep at least one eye on important tort reform efforts, and how they may impact  the litigation that we blog about.

That is why we reviewed with great interest the tort reform agenda of the U.S. Chamber of Commerce for 2012, which happens to be the organization's 100th year representing the business community.

The head of the Chamber recently delivered the organization's annual State of American Business address to its members. In it, he noted the need for significant regulatory and legal reform:

The regulatory avalanche confronting our job creators is unprecedented. The Labor Department has 100 rule-makings in the pipeline. Dodd-Frank requires 447 rules, 63 reports, and 59 studies. The health care law established 159 new agencies, panels, commissions, and regulatory bodies. EPA has some 200 regulations in the works. The Chamber supports necessary, sensible, and forward-looking regulations -- but not proposals that fail to meet that test. The Chamber is also working to modernize the overall regulatory system—including legislation to reform the permitting process and update the Administrative Procedure Act for the first time since the Truman administration. 

The Chamber's Institute for Legal Reform will continue to fight the expansion of excessive litigation that is sucking the vitality out of American businesses.  America’s civil justice system is the world’s most expensive, with a direct cost in 2009 of $248.1 billion, or 1.74% of the U.S. GDP.
The tort cost per person was $808 in 2009, a sevenfold increase from 1950 even when adjusted for inflation. While small businesses are responsible for 64% of all new American jobs, lawsuits cost them $105.4 billion in 2008—money that could be invested in more jobs, higher wages, or better benefits. Two out of three senior executives and litigators at America’s largest employers believe that the litigation environment in a state is likely to impact important business decisions at their companies, including whether to grow jobs or do business in a state.

A key focus for 2012 will be the alarming rise of third-party litigation financing. That’s where outside investors fund lawsuits in exchange for a share of the award or settlement. This can encourage the filing of frivolous claims. It may invite testing questionable claims in court. It probably provides an incentive to unduly prolong cases. And it raises serious ethical questions. Who does the lawyer really represent—his client or the outside financial backers?


 

Regulatory Reform Bills Pass House

We have posted before about legislative attempts to limit the harmful effects of excessive federal regulation on product sellers.  Readers know how those regulations can have an indirect but real impact on product liability litigation as well. The House passed two bills on this topic last week, and the White House indicated it would veto them if they passed the Senate.

The Regulatory Accountability Act (H.R. 3010) passed by a vote of 253 - 167.  It would require an agency to consider any reasonable alternatives for a proposed rule, and the potential costs and benefits associated with such alternatives. The Regulatory Flexibility Improvements Act (H.R. 527) passed by a vote of 263 - 159. It would require agencies to conduct initial and final regulatory flexibility analyses to describe alternatives to a proposed rule that minimize any adverse significant economic impact or maximize the beneficial significant economic impact on small business entities.

Republican sponsors have argued that the bills would help prevent oppressive agency regulations and force federal agencies to choose the least costly alternative when developing new  regulations. Federal regulations cost businesses more than $1.5 trillion each year, which has an obvious effect on job creation.

Given the current makeup, the Senate versions (S. 1606 and S. 474) are expected to face stiff Democratic opposition.  The bill is not listed among the Senate Majority's current legislative priorities. 

House Committee Tackles Regulations

The House Judiciary Committee held a hearing last week on a bill that would require federal agencies to evaluate the costs of proposed regulations before adopting them, and that would arguably make it easier for product sellers to challenge onerous regulations in court.

The hearing focused on the Regulatory Accountability Act of 2011 (H.R. 3010). Rep. Lamar Smith (R-Texas), the committee chairman, introduced the bill this Fall to propel needed changes in the regulatory system, updating out of date aspects of the Administrative Procedure Act, a 1946 statute.  The Senate version of the bill (S. 1606), was introduced in September, and was authored by Sens. Rob Portman (R-Ohio), Mark Pryor (D-Ark.), and Susan Collins (R-Maine). The Regulatory Accountability Act would be the first major revision of the APA’s core regulatory procedures.

The bill would require a more formal rule-making process, under which agency officials would have to defend their regulatory proposals to affected persons. Federal agencies also would be required to give greater weight to the impacts and costs of the proposed rules.  The proposal would limit the ability of agencies to regulate in the guise of voluntary “guidance” documents. (Readers know hos such regulations can impact mass tort and product liability litigation in a real way.)

Witnesses included C. Boyden Gray, Christopher C. DeMuth of the American Enterprise Institute for Public Policy Research, and Arnold Baker, owner of Baker Ready-Mix Building Materials.  Gray argued that the bill would strengthen judicial review of agency actions on questions of regulatory interpretation, factual issues, and cost-benefit analysis, at least in cases where the agency’s own process fails to satisfy the Act’s heightened requirements. Judicial review of agency action requires a delicate balance—the applicable standards of review are somewhat deferential, but those standards must be firmly enforced. The proposed Act strikes that balance well. DeMuth focused on the requirement of a cost-benefit standard, and the provision that agencies must adopt the least costly approach to achieving statutory objectives unless they demonstrate that the additional benefits of more costly rules justify the additional costs.  And Baker offered the example of a business struggling to stay afloat in a sea of regulations, and the need for agencies to do a much better job of understanding the full impact that their regulations will have on businesses and jobs – along with possible alternatives – before they impose the most costly new rules.

A number of law professors oppose the bill, but seem to forget that it is Congress' job to decide if and when regulatory burdens have become too excessive.

Meanwhile, the House Judiciary Committee approved last week the Regulations from the Executive in Need of Scrutiny (REINS) Act (H.R. 10), which would require a vote in Congress before any regulation with an economic impact of more than $100 million could go into effect. Federal regulations cost the economy $1.7 trillion each year. Congress would take a simple up-or-down vote on such huge new government regulations before they could be enforced. 

 

Multi-State Coalition On Chemicals Management Formed

Readers have been following our posts on new state efforts on chemical regulation, such  as California's Green Chemistry initiative. Now comes word that environmental officials from 10 state and local governments have formed an umbrella organization - the Interstate Chemicals Clearinghouse (IC2) - with the stated goals of promoting a clean environment, healthy communities, and a vital economy through the development and use of safer chemicals and products.

The states joining IC2 include California, Connecticut, Massachusetts, Michigan, Minnesota, New Jersey, New York, Oregon, and Washington.

The goals of the IC2 are to:

  • Avoid duplication and enhance efficiency and effectiveness of state, local, and tribal initiatives on chemicals through collaboration and coordination
  • Build agency capacity to identify and promote safer chemicals and products
  • Ensure that state, local, and tribal agencies, businesses, and the public have ready access to high quality and authoritative chemicals data, information, and assessment methods

Launched under the auspices of the Northeast Waste Management Officials' Association (NEWMOA), the new Clearinghouse says it will support state, local, and tribal health and environmental agencies with development and implementation of programs to promote use of safer chemicals and products; support the development of alternative assessment methods and identification of safer alternatives; share data and information on chemical use, hazard, exposure, and alternatives; share strategies and outcomes on chemicals prioritization initiatives; and build the capacity of agencies by sharing materials, strategies, and trainings.  IC2 has a number of projects planned in these areas.

The Northeast Waste Management Officials Association's announcement of the IC2 comes just as many chemical manufacturers are expecting that the federal government (including through an update to TSCA) will take the lead in regulating chemical products, not state regulatory agencies and legislatures.

Industry groups, including the American Chemistry Council, continue to believe that a patchwork of state and local programs has the potential to create more confusion for consumers and manufacturers, and may ultimately simply hamper investment, and threaten future job creation.  As we have noted, some of the bills introduced in the last Congress would have set an impossibly high hurdle for all chemicals in commerce, and were guaranteed to produce significant technical, bureaucratic and commercial barriers. Of particular concern to readers of MassTortDefense would be efforts to eliminate the current risk-based review system under TSCA and force EPA to use the so-called precautionary principle.

It seems more supportable that any overhaul of TSCA should include the notion that scientific reviews must use data and methods based on the best available science and risk-based assessment; must include cost-benefit considerations for the private-sector and consumers; must protect proprietary business information, and should logically prioritize reviews for existing chemicals.



 

EPA Releases First Chemical Action Plan

The Environmental Protection Agency recently issued its first Chemical Action Plan (CAP).  The plan deals with  phthalates, which are found in some food packaging and cosmetics.  But anyone in the chemical industry should take notice, as this CAP comes as part of EPA’s efforts to enhance the existing chemicals program under the Toxic Substances Control Act. EPA has identified an initial list of widely recognized chemicals, including phthalates, for action plan development based on one or more of the following factors: their presence in humans; persistent, bioaccumulative, and toxic  characteristics; use in consumer products; or production volume.

Although many in industry support  EPA’s effort to update agency actions for prioritized chemicals under TSCA, there is much to question in this effort so far, including the fact that the initial set of chemicals seem to have been selected based on their current “high-profile” nature. EPA should prioritize chemicals for the CAP program based on scientific criteria that reflect available hazard, use, and exposure information.  Despite the new Administration's campaign promises, there has been little transparency, and in fact great uncertainty, over the scientific basis for the selection of these chemicals.  Unfortunately, the CAP process to date provides no evidence of a systematic, science-based approach to chemicals management.

A large body of scientific data already exists about phthalates, and these products have been subject to numerous government safety assessments.  Bio-monitoring data shows that exposure to phthalates in the general public are below safety limits established by the EPA and the European Union. In assessing potential future restrictions on certain phthalates, EPA plans to weigh the relative toxicity and feasibility of phthalate substitutes. Identification of safer and affordable non-phthalate substitutes will be an important consideration in any action that would restrict the use
of these chemicals.  EPA intends to conduct a Design for the Environment and Green Chemistry alternatives assessment by 2012. The information developed could be used to encourage industry to move away from phthalates in a non-regulatory setting to expand risk management effects beyond whatever regulatory action might be taken under TSCA, or could be used as input to a regulatory action. 

EPA also intends to lay the groundwork to consider initiating in 2012 rulemaking under TSCA section 6(a) to further regulate phthalates. Readers know how regulatory events can spawn and impact toxic tort litigation.  It should be noted  that an Action Plan is intended to describe the courses of action the Agency plans to pursue in the near term to address its concerns. The Action Plan does not constitute a final Agency determination or other final Agency action.

 

 

 

 

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.