FDA´s final REMS Guideline

The U.S. Food and Drug Administration (FDA) affirms its commitment to efficient adoption of Risk Evaluation and Mitigation Strategy (REMS) plans and to making sure they do not impede generic drug development by issuing the final REMS guidance for industry. The guidance clarifies how the FDA determines whether a REMS is necessary to ensure that the benefits of a drug outweigh its risks. It finalizes the draft guidance, issued on September 21, 2016.

Drugs must have an appropriate benefit-risk balance. One tool to ensure this balance is a Risk Evaluation and Mitigation Strategy (REMS). This is a drug safety program that the FDA can require for certain medications with serious safety concerns. The agency may also require elements to assure safe use (ETASU) as part of a strategy to mitigate a specific risk. These elements may, for example, help to ensure providers have or provide to patients all the appropriate information to appropriately prescribe or dispense the medication.

The final guidance clarifies how the FDA applies six factors that impact the agency’s decision-making process regarding whether a REMS is required for a particular drug and what type of REMS might be necessary:

• The seriousness of any known or potential adverse events that may be related to the drug and the background incidence of such events in the population likely to use the drug;
• The expected benefit of the drug with respect to the disease or condition;
• The seriousness of the disease or condition that is to be treated with the drug;
• Whether the drug is a new molecular entity;
• The expected or actual duration of treatment with the drug; and
• The estimated size of the population likely to use the drug.

While REMS are a critical tool designed to reinforce medication use behaviors and actions that support the safe use of that medication, some companies also use REMS to delay the entry of generics. When a generic drug applicant wants to market a generic version of a drug that has a REMS with ETASU – the brand and generic drug makers are required to develop a single, shared REMS program unless the FDA waives that requirement and permits the generic drug to use a different, comparable aspect of the ETASU (see also single, shared system REMS for a brand product and its generic equivalents). According to the agency, branded sponsors have in some cases refused to sell samples of brand products with REMS with ETASU impacting distribution of the drug to potential generic competitors. Generic drug developers need the samples of the brand drug to develop their generic product (e.g. for bioequivalence studies). In May 2018 the FDA therefore started with an available and updated list of companies that have potentially been blocking access to the samples of their branded products.

More information can be found in FDA´s final guidance REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary.