FDA Drafts on Shared System REMS

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The U.S. Food and Drug Administration (FDA) released two new draft guidance documents on Risk Evaluation and Mitigation Strategy (REMS):

• Development of a Shared System REMS, and
• Waivers of the Single, Shared System REMS Requirement.

These two drafts have been published online on May 31, 2018. Comments on both draft guidance documents can be submitted in the next 60 days.

Development of a Shared System REMS
According to the FDA, pharmaceutical sponsors can use REMS requirements to block generic drugs from making a timely entry to market. To mitigate that issue, the 11-pages draft guidance says FDA “will initiate discussions about the formation of a shared system REMS” under certain circumstances:

• "When the FDA has received an abbreviated new drug application (ANDA) that references a reference listed drug (RLD) that has a REMS with elements to assure safe use (ETASU);
• When the FDA has received a new drug application (NDA) or a biologic license application (BLA) for a product that references an NDA or a BLA that is subject to REMS with ETASU, and has determined that the proposed product also would require the same ETASU;
• When the FDA has determined for drugs and biologics in a class with similar, serious risks that a shared system REMS may minimize the burden of having multiple unique REMS programs."

The agency said it will “request that applicants of the pending applications submit an authorization for disclosure that will allow the Agency to hold meetings between multiple applicants. FDA will provide contact information for the product being referenced by the pending applications to facilitate the development of a shared system REMS”.

The FDA noted that it “does not advise on the business arrangements being negotiated or arbitrate substantive disputes about the terms of contracts”. However, the agency “will set forth expectations of the applicants for the development of the shared system REMS, which may include suggested timeframes for various milestones in the process of developing the shared system, and the process for submission of the proposed REMS. FDA may facilitate collaborations between applicants when necessary to achieve a shared system REMS. For example, FDA may host teleconferences to encourage communications between applicants”.

Applicants developing a shared system REMS also “should submit their REMS by application midpoint for pending applications, or another time frame specified by the Agency. To facilitate submission tracking, FDA recommends that shared system REMS applicants work together to coordinate their submissions on the same day, if possible,” the draft adds.

In addition, FDA advises applicants to refer to other relevant FDA resources, such as the following:

• Draft guidance on Format and Content of a REMS Document,
• Draft guidance on Factors in Determining When a REMS Is Necessary,
• Guidance on REMS: Modifications and Revisions,
• Draft guidance on Providing Regulatory Submissions in Electronic Format – Content of the REMS Document Using Structured Product Labeling.

Waivers
The 10-pages draft guidance "Waivers of the Single, Shared System REMS Requirement" describes how and when FDA will consider waiving a single, shared system requirement, and how generic drug applicants can request a waiver.

The guidance makes clear that while the FDA encourages companies to work together to form a single, shared system (SSS), the agency will consider each waiver request on a case-by-case basis (either upon request of the applicant, or on the agency’s own initiative). The FDA may waive the single, shared system REMS requirement and permit the generic company to use a “different, comparable” aspect of the ETASU if the agency finds that

• the burden of creating a SSS outweighs the benefits of having one, or
• an aspect of the REMS is protected by a patent or is a trade secret and the generic applicant certifies that it sought a license for use of that aspect and was unable to obtain one.

The draft guidance also provides recommendations to generic drug applicants regarding how to submit and what should be included in waiver requests.