On December 4, the U.S. Food and Drug Administration released draft guidance for the pharmaceutical industry entitled "How to Obtain a Letter from FDA Stating that Bioequivalence Study Protocols Contain Safety Protections Comparable to Applicable REMS for RLD." The draft guidance describes how abbreviated new drug application (ANDA) applicants may request a letter from the FDA stating that the applicant’s bioequivalence study contains safety measures comparable to the risk evaluation and mitigation strategy (REMS) applicable to the reference listed drug. The guidance provides that the FDA will not deem it a violation of the reference listed drug’s REMS if the drug sponsor provides a sufficient quantity of the reference listed drug to the ANDA applicant for testing purposes. The FDA may require a REMS for a reference listed drug to ensure that the benefits of the drug outweigh its risks. The REMS may include medication guides, patient package inserts, and communication plans.
When seeking approval to market a generic drug, ANDA applicants may rely on the FDA’s previous findings of safety and effectiveness for a reference listed drug; however, the ANDA applicant generally must demonstrate that the proposed generic drug is bioequivalent to the reference listed drug. Bioequivalence is generally demonstrated by studies in which the proposed generic drug is compared to the reference listed drug, which requires the ANDA applicant to have access to the reference listed drug to conduct the comparison.
In the draft guidance, the FDA noted its awareness that reference listed drug sponsors have refused to provide products to ANDA applicants to conduct bioequivalence studies, citing the reference listed drug’s REMS. To assist ANDA applicants, the FDA, upon request, may issue letters to reference listed drug sponsors, after reviewing the ANDA applicant’s study protocols, indicating that the bioequivalence study safety protections are comparable to the safety protocols listed in the REMS and that the FDA would not consider it a violation of the REMS for the reference listed drug sponsor to provide products to the applicant. The purpose of such letters is to encourage access to the reference listed drug so that ANDA applicants can conduct bioequivalence studies. ANDA applicants are not required to request or obtain a letter from the FDA. The draft guidance is intended to clarify the process for obtaining such a letter if an ANDA applicant desires to request one.
The draft guidance describes the process for submitting a request for a letter from the FDA, and the FDA’s procedure for reviewing such requests. The FDA is seeking public comments on the draft guidance by February 3, 2015. It is important to note that FDA guidance documents simply describe the FDA’s current approach and recommendations on an issue, and generally do not create legally enforceable obligations or responsibilities.