The FDA has released its draft guidance on Risk Evaluation and Mitigation Strategies, or REMS, laying out guidelines for how pharmaceutical companies should follow the plans, and describing the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 The draft guidance for industry entitled ‘‘Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications,’’ 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The new draft guidance describes the format and content of a proposed risk evaluation and mitigation strategy, including REMS supporting documentation, the content of assessments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 The draft guidance was issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115).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