FDA Releases Draft Guidance on Risk Evaluation and Mitigation Strategies

The FDA has released its draft guidance on Risk Evaluation and Mitigation Strategies, or REMS, laying out guidelines for how pharmaceutical companies should follow the plans, and describing the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 The draft guidance for industry entitled ‘‘Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications,’’ 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The new draft guidance describes the format and content of a proposed risk evaluation and mitigation strategy, including REMS supporting documentation, the content of assessments and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 The draft guidance was issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115).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.
 

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.
 

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.