Accelerated approval: FDA revises guidance to reflect revised withdrawal procedures

The US Food and Drug Administration (FDA) on Thursday issued draft guidance that would replace the accelerated approval portion of its broader guidance covering its various expedited pathways to reflect changes to the accelerated approval program brought on by recent legislation.

Under the Consolidated Appropriations Act of 2023 (CAA), Congress mandated changes to the program, giving FDA new authorities for setting conditions for confirmatory trials and establishing new procedures for withdrawing products if they fail to demonstrate clinical benefit.

“This draft guidance addresses the accelerated approval process, including granting accelerated approval (e.g., discussion of endpoints, evidentiary criteria, confirmatory trials and other conditions of accelerated approval), and withdrawal of accelerated approval,” said FDA. “Changes from the 2014 final guidance include early consultation on novel endpoints, timely conduct of confirmatory trials, other aspects of confirmatory trials, and the expedited withdrawal of accelerated approval.”

“Other changes include a revised title and editorial changes for clarity, as well as updated references and contact information for FDA,” the agency added.

Under the CAA, FDA is required to update conditions that sponsors who use the pathway must follow, including requiring confirmatory trials by the date that the drug is granted accelerated approval. The agency may also set conditions on the confirmatory trials, such as enrollment targets, an agreed-upon study protocol, and certain milestones, such as the target date on which the trial must be completed.

The agency added it would stipulate conditions for postapproval studies no later than the date the drug is granted accelerated approval, which may include details such as the final study protocol deadline, enrollment targets, and other certain milestones.

While it has the authority under the CAA to require confirmatory trials begin before the drug is granted accelerated approval, FDA said it would address that authority in a separate guidance. The agency also added that it would not consider granting accelerated approval to a drug if completing an adequate and well-controlled trial to determine its clinical benefits isn’t feasible.

"FDA may require that postapproval studies be underway prior to accelerated approval or within a specified time from the date of accelerated approval," said FDA. "The INDICATIONS AND USAGE section of drug labeling must include a succinct description of the limitations of usefulness of the drug and any uncertainty about anticipated clinical benefits, with reference to the CLINICAL STUDIES section for a discussion of this available evidence."

Congress also required FDA to revise its process for withdrawing accelerated approval to ensure that drugs that fail to meet postapproval expectations can be quickly removed from the market. The agency noted that it might withdraw accelerated approval using expedited procedures if the sponsor fails to meet its postapproval study requirements, the confirmatory study fails to show clinical benefit, additional evidence shows the drug fails to meet safety and efficacy requirements, or the sponsor uses false or misleading information to promote the drug.

FDA said sponsors must submit copies of all their promotional materials to the agency within certain time frames and provide reports of the progress of their postapproval studies approximately every 180 days, which the agency must publish.

FDA recommended that sponsors talk to regulators early in their drug development to evaluate if they are eligible for accelerated approval, to discuss their surrogate endpoints or intermediate clinical endpoints, clinical trial design, and planning for their confirmatory trials.

“FDA will strive to provide a timely response to a sponsor’s inquiry regarding a development program intending to seek accelerated approval, and it is equally important that a sponsor responds promptly to FDA’s inquiries,” said the agency. “This applies particularly to formal meetings and related inquiries, written correspondence, and other interactions.”

Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2024-D-2033 until 4 February.

Draft guidance

Accelerated approval: FDA revises guidance to reflect revised withdrawal procedures

Related topics

Recommended content

Welcome to the new RAPS Digital Experience