FDA Releases Guidance on Accelerated Approvals

FDA announced a draft guidance on Dec. 5, 2024 that explains the procedures and criteria for the agency’s accelerated drug approval for serious conditions. The guidance, Expedited Program for Serious Conditions–Accelerated Approval of Drugs and Biologics, also explains procedures for expedited withdrawal of approval (1). Revisions made by Congress through the Consolidated Appropriations Act, 2023 (Public Law 117-328) are also discussed.

FDA’s accelerated approval pathway is one of the agency’s expedited programs for the development and review of new drugs to meet unmet medical needs for serious or life-threatening conditions in a timely manner. Sponsors whose product is granted accelerated approval conduct confirmatory trials that are completed postapproval to verify and describe the anticipated effects and benefits of the drug. If these trials confirm the clinical benefit, FDA will then count the confirmatory requirement as met. However, if the sponsor fails to conduct the trial with due diligence or the trial fails to verify effects and benefits, FDA may withdraw approval.

Per the guidance document, conditions and requirements associated with accelerated approval include:

• The conducting of postapproval studies to verify and describe the anticipated clinical benefit of the drug.

• FDA must specify the conditions for postapproval studies, by the date of approval. These may include a deadline to submit the final study protocol, targets for enrollment progress, and other milestones such as the target date for study completion.
• The agency may require postapproval studies prior to the accelerated approval.
• A succinct description of limitations of usefulness and anticipated benefits must be included in the drug label’s Indications and Usage section with a reference to the Clinical Trials section.
• Copies of sponsor’s promotional materials must be submitted to FDA with specified time frames.
• Progress reports on the postapproval studies must be submitted to FDA approximately every 180 days.

“Accelerated approval should not be considered if the completion of an adequate and well-controlled clinical trial to verify and describe clinical benefit will be infeasible,” the agency states in the document (1).

The guidance document specifically provides considerations for the use of surrogate and intermediate clinical endpoints, evidentiary criteria for accelerated approval; requirements for confirmatory studies; and labeling, promotional materials, postmarketing recordkeeping, and safety reporting considerations. In regard to evidentiary criteria, the document states, “Drugs granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional approval. For effectiveness, the standard is substantial evidence based on adequate and well-controlled clinical investigations. For safety, the standard is having sufficient information to determine that the drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling. An application for accelerated approval should also include adequate evidence that a proposed surrogate endpoint or an intermediate clinical endpoint is reasonably likely to predict the intended clinical benefit of a drug.”

The document’s section on withdrawal of accelerated approval states, “The Agency generally expects that any proposal to withdraw approval of a drug that has been granted accelerated approval will be issued by the center or centers (hereafter, Center) that approved the drug. When the data or other information received by the Agency raises concerns that one or more of the criteria for withdrawing approval may have been met, responsible officials within the Center should discuss their concerns with the sponsor and seek an appropriate resolution. Such discussions may result in the sponsor’s voluntary request for withdrawal of approval under 21 CFR [Code of Federal Regulations] 314.150 or 21 CFR 601.5(a) or other regulatory actions, as appropriate, 552 depending on the circumstances” (1).

Reference

1. FDA. Expedited Program for Serious Conditions–Accelerated Approval of Drugs and Biologics, Guidance for Industry, Draft Guidance (CDER, CBER, December 2024).