Guidance Breakdown: FDA Sets New Expedited Withdrawal Procedures for Accelerated Approvals
The FDA just released new details on how it plans to expedite the withdrawal of certain accelerated approvals when drugs fail to show clinical benefit in confirmatory trials.
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The FDA released new details on Thursday regarding its plan to expedite the withdrawal of certain accelerated approvals for drugs that fail to demonstrate clinical benefit in confirmatory trials, as mandated by Congress.
This new 22-page draft guidance replaces a final guidance issued in 2014. The updates, found in Section V, outline the FDA’s current approach to swiftly withdraw "dangling accelerated approvals," which occur when treatments remain on the market despite a failed confirmatory trial. The agency indicates that it "should generally" convene an advisory committee to discuss such withdrawals.
Recently, the FDA has held several advisory committee meetings to review these dangling accelerated approvals, particularly in oncology. About a year ago, the agency published a table listing 12 oncology accelerated approvals for which confirmatory trials had surpassed their original completion dates.
The FDA noted that, in oncology, the median time to completion of confirmatory trials that have verified clinical benefit is 3.1 years. Therefore, an appropriate target completion date for oncology products would ideally be within 2 to 4 years after the accelerated approval is granted.
The expedited procedures for withdrawing an accelerated approval, as outlined in the 2023 legislation, require the FDA to provide the sponsor with:
Due notice of the withdrawal
A detailed explanation
An opportunity to meet with the commissioner or their designee
A chance to submit a written appeal, and
An opportunity for an advisory committee meeting to review the withdrawal
“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” or other regulatory actions.
As part of the new expedited withdrawal process, there will be more transparency in the withdrawal proceedings. The guidance states that a summary of communications between the FDA and the sponsor must be developed by the Commissioner or their designee and placed in the public docket for the proceeding.
Additionally, the FDA is required to provide an opportunity for public comment on the proposal to withdraw an approval. They must also publish an online summary of the public comments received along with the agency's responses to those comments.
In 2023, Congress granted the FDA the authority to require that a confirmatory trial be underway before granting accelerated approval. The FDA has begun to implement this authority and plans to address it further in a separate guidance document.
A closer look at Section V: Withdrawal of Accelerated Approval
Section V outlines the procedures for expedited withdrawal of FDA approval for drugs approved under accelerated approval — where we see the changes here.
The FDA can initiate withdrawal of accelerated approval under four key circumstances:
Sponsors failing to conduct required postapproval studies diligently
Confirmatory studies failing to verify clinical benefits
Evidence showing the product isn't safe or effective
Sponsors distributing misleading promotional materials