FDA Finalizes Guidance on When REMS Programs Are Needed

The FDA this week finalized a 2016 draft guidance that explains when the agency deems a Risk Evaluation and Mitigation Strategy (REMS) program to be necessary for a given drug.

A REMS program is a risk management plan that can include elements to make sure that the benefits of a drug outweigh its risks. REMS may also include elements to assure safe use (ETASU) in cases in which drugs that are proven to be effective are associated with a serious risks that requires mitigation in order for product approval or continued marketing. ETASU may include provider training, patient monitoring, mandatory registries, or other strategies.

REMS programs have come under increased scrutiny from a variety of stakeholders, including outgoing FDA Commissioner Scott Gottlieb, MD, who said that the misapplication of these programs, specifically with respect to shared-system REMS programs that are agreed upon between innovator drug makers and biosimilar or generic developers, “can block the timely entry of a generic competitor” despite the fact that the Food and Drug Administration Amendments Act of 2007 specifies that REMS programs must not be used to delay generics.

The new guidance, which is among the deliverables required of the agency under the reauthorization of the prescription drug user fee program, explains that the FDA considers 6 factors in deciding whether to require a REMS program: the seriousness of any known or potential adverse events (AEs) that may be related to the drug and the background incidence of those AEs in the population of likely users of the product, the expected benefit of the drug, the seriousness of the disease that the drug will treat, whether the drug is a new molecular entity, the expected or actual duration of treatment, and the size of the population likely to use the drug. These 6 factors, taken together, inform whether a REMS will be instituted, and no single factor, says the FDA, is determinative.

The FDA’s guidance acknowledges that, particularly with respect to REMS with ETASU, there exists a measure of burden for patients and providers. Therefore, it says, the FDA considers whether REMS can be designed to be compatible with established drug distribution, procurement, and dispensing systems, and considers whether patient access could be restricted by the program. Selection of REMS elements may also be influenced by the extent to which they have been used in clinical trials, and by what is known about those elements and tools.

Other guidance recently issued on the topic of REMS include a January 2019 draft guidance on survey methodologies to assess REMS goals that relate to knowledge; many REMS programs include knowledge-related goals, such as informing patients and providers about the risks associated with a drug. When these goals are part of a REMS, the management plan generally includes a survey to evaluate understanding of the drug’s safe use and risks. The guidance gives industry direction on designing and conducting surveys to assess that knowledge.

Additionally, the FDA published a January 2019 draft guidance on REMS assessment planning and reporting. The document explains how to develop a REMS assessment plan, and how the program’s goals, objectives, and design impact upon the selection of metrics and data sources used to assess whether the program is meeting its goals.