On September 30, 2009, the United States Food and Drug Administration released a draft of its Guidance for Industry: Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications.
Although the FDA refers to the guidance as a draft, the document offers insight into the agency's current thinking about risk management for certain drug and biological products.
Background
In recent years, there has been concern over a perceived lack of communication between the FDA and the pharmaceutical industry regarding safety-related information for products regulated by the FDA. Some believed that the FDA had inadequate regulatory measures in place for obtaining post-market surveillance information of adverse events and safety risks. Another roadblock to effective FDA oversight allegedly stemmed from the limits to the agency's safety-related enforcement options after a drug received FDA approval. Specifically, the FDA's response to safety concerns was limited to market suspension or withdrawal of a product license; the FDA did not have the authority to require measures that would keep the product at issue on the market while working with the drug company to address the agency's safety concerns. These areas of concern provided the impetus for change.
FDAAA—Groundwork for Lifecycle Oversight
The Food and Drug Administration Amendments Act of 2007 (FDAAA) granted the FDA the authority to take an active, lifecycle approach in overseeing the drug approval process as a whole, from clinical trials to direct-to-consumer advertising to post-market regulation. The FDA could now require REMS for certain products, if the agency determined a REMS was necessary to ensure that the product's benefits outweighed its risks. REMS are risk management plans specifically tailored for each product, which may include medical guides and patient package inserts, special communication plans, and restrictions on distribution and use.
The FDAAA also gave the FDA options aside from suspension or withdrawal of a product license. Significantly, the act permitted the FDA to require post-approval studies or clinical trials for any product if necessary to assess a known serious risk, assess signals or serious risk, or identify a serious unexpected risk when available data indicates the potential for a serious risk. With respect to products already approved, the FDA may now require post-approval studies or clinical trials only if the FDA becomes aware of "new safety information."
A "Blueprint" for REMS
Janet Woodcock, M.D., the director of the FDA's Center for Drug Evaluation and Research, stated in the September 30, 2009, FDA news release that the new guidance will provide manufacturers with "a useful blueprint for how to develop these important safety strategies."
The draft guidance lists the content required for a proposed REMS, and the FDA's Web Site provides a template for a proposed REMS. Each element of a REMS is described in detail, suggesting what the FDA will be looking for in a proposed REMS and the supporting documentation.
The elements of REMS include product and content information; goals behind the REMS, such as a safety-related health outcome or mitigation or risk; additional components, including a medication guide, patient package insert, and communication plan; elements to ensure safe use, such as distribution restrictions; an implementation system that may require monitoring of the distribution and use of the product; and a timetable for REMS submission.
In the guidance draft, the FDA provides preliminary information on the content of assessments and proposed modifications of approved REMS. The document also details REMS policies for certain regulatory situations and provides information about who to contact at the agency about a REMS.
According to the FDA news release, additional REMS topics will be addressed in future draft guidances.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.