FDA Issues 2 Draft Guidance Documents on REMS Programs

FDA Commissioner Scott Gottlieb, MD, on Thursday announced new draft guidance documents aimed at limiting the potential for drug makers to abuse Risk Evaluation and Mitigation Strategy (REMS) requirements. The announcement comes on the heels of President Donald Trump’s drug pricing plan, which called on the agency to issue guidance on how manufacturers use REMS programs to delay competition from follow-on products.

While REMS are intended to uphold patient safety by providing such materials as medication guides or package inserts (and requiring activities like provider training and patient counseling in some cases), REMS have come under fire as a way that makers of innovator drugs can stave off competition from generics and biosimilars; because originator product manufacturers and biosimilar or generic drug developers must agree on a single, shared REMS system for originator and follow-on products, REMS programs can potentially be abused to delay the market entry of cheaper drugs.

“Our safety programs shouldn’t be leveraged as a way to forestall generic entry... Our market-based system for rewarding innovation is dependent on this kind of legal competition,” said Gottlieb in a statement.

The first guidance document, “Development of a Shared System REMS,” outlines the process and recommendations for developing a shared system REMS program, under which applicants share in the implementation and maintenance of any database and infrastructure for the program and share in carrying out assessments.

The guidance indicates that, while a single shared system is only required by law for drugs subject to abbreviated New Drug Applications (ANDAs), the FDA recommends using such systems for biosimilars, as well, and encourages applicants to work jointly with reference product sponsors to develop REMS programs early.

The agency indicates that it will initiate discussions about forming a shared system REMS when such a program is appropriate. In cases in which an industry working group (IWG) is used to facilitate negotiations on a REMS program, the IWG should identify a single point of contact to communicate with the FDA. The FDA itself will not advise on business arrangements or arbitrate disputes. The agency suggests that shared system REMS applications complete their submissions on the same day when possible, and suggests that the applicants use a Type V Drug Master File for submission.

The second guidance document, “Waivers of the Single, Shared System REMS Requirement,” describes how the FDA will consider granting a waiver of a shared system REMS program for ANDA applicants for reference drugs with Elements to Assure Safe Use (ETASU), which are required medical interventions or other actions that healthcare professionals must undertake to prescribe or dispense a medication.

The guidance indicates that the FDA will grant a waiver on a case-by-case basis. Under current law, the FDA can grant a waiver if an element of the ETASU is protected by a patent or is otherwise entitled to protection, and the FDA further plans to determine in individual cases whether the burden of forming a shared system outweighs the benefits of having such a system in place.

Potential benefits of a shared REMS program include opportunities that arise from increased efficiency (both for the drug companies, who have the opportunity to share costs, and for the health system, which will benefit from a streamlined process). The potential burden of forming such a program includes lengthy negotiation between the follow-on’s developer and the innovator product’s sponsor, and the burden to the healthcare system created by delayed follow-on market entry.

The FDA says that it can consider providing a waiver at any time, whether upon the request of an applicant or at its own initiative. An ANDA applicant, says the FDA, may propose its own REMS program together with its waiver request (inclusive of a discussion of why the burden of forming a shared system is too great in its case), and the FDA will review it as part of the drug approval process.