The Standard

FDA's January 2025 draft guidance on accelerated-approval confirmatory trials defines how the agency generally intends to interpret when a confirmatory trial is "underway" under section 506(c) of the Federal Food, Drug, and Cosmetic Act.

The guidance is still draft and nonbinding. But it is directionally important because it shows how FDA intends to operationalise its FDORA-amended authority to require confirmatory trials to be underway before approval or within a specified period after approval.

FDA says it generally intends to consider a confirmatory trial underway before accelerated approval if three conditions are met:

  1. The trial has a target completion date consistent with diligent and timely conduct of the trial, considering the design and objectives.
  2. The sponsor's progress and plans for postapproval conduct provide sufficient assurance that the trial will be completed on time.
  3. Enrollment of the confirmatory trial has been initiated.

Industry coverage from OncLive, Targeted Oncology, and the FDA's own oncology announcement framed this as a procedural clarification. For a regulatory writing organisation, the implication is more direct: the confirmatory-trial plan has become a primary submission argument. Sponsors now need to show, not merely state, that the trial is operationally credible.

FDA also acknowledges that there may be limited circumstances where a confirmatory trial is not underway before approval — for example, where the confirmatory study is contingent on a future event. That caveat matters. But the default writing posture should assume the sponsor must justify the timing, feasibility, and operational credibility of the confirmatory trial before approval.

What Each Criterion Asks of the Writing

Each criterion translates into a writing requirement.

A credible target completion date. This cannot be just a date in the protocol. The sponsor needs to justify why the date is credible: disease natural history, recruitment assumptions, site activation plan, availability of alternative treatments, endpoint follow-up duration, projected efficacy-analysis timeline, and database-lock-to-readout assumptions. FDA specifically notes that sponsors should provide a clear and sound justification of the proposed target completion date. A protocol that says "expected primary completion Q4 2028" without the supporting narrative is going to draw a question. A package that walks the reviewer through the assumption stack underlying the date will defuse the question before it gets asked.

Sponsor progress and plans that provide sufficient assurance. "Sufficient assurance" is not a single metric. It is a constructed operational argument. The package should show that the sponsor understands the trial's complexity, has resourced it appropriately, has identified foreseeable recruitment and retention risks, and has a plan to keep the trial moving after accelerated approval. This is essentially a project-management narrative inside a regulatory artifact. It has to be specific without being defensive.

Enrollment has been initiated. Enrollment initiation is the floor. The stronger package explains what initiation means operationally: first patient enrolled, active sites, country rollout, expected recruitment ramp, and how the current pace supports the target completion date. FDA does not require a particular number of sites or a particular pace in every case — but the dossier that just claims enrollment is open, without the operational specifics, is leaving the assurance argument under-built.

The cumulative writing burden is substantial. A confirmatory-trial commitment can no longer be treated as a paragraph at the end of an accelerated-approval briefing document. It needs its own argument structure.

Where the Argument Has to Live

These three criteria need to be made visible across the accelerated-approval package — especially in briefing documents, confirmatory-trial plans, and the clinical-overview narrative.

In practice, a sponsor should expect the underway argument to appear in the briefing document and to remain consistent with the Module 2 clinical summaries and overview. The sponsor does not want the confirmatory-trial rationale to live in only one place. A briefing document that constructs the argument carefully, but is undermined by an inconsistent treatment in the clinical overview, creates the kind of seam an attentive reviewer will surface.

The guidance also makes timing a pre-submission writing issue. FDA says the confirmatory-trial timeline, including the expected completion date, should be discussed before submission of the accelerated-approval application. That means the underway argument cannot be drafted at the end of the BLA/NDA package — it has to be built during pre-submission interaction planning, validated in Type B or Type C meetings, and then carried forward into the submission with the agency-facing language already aligned.

What This Asks of the Writing Organisation

Three practical adjustments are worth making now for any sponsor planning an accelerated-approval submission over the next 12–18 months.

Add an "Underway Confirmatory Trial" section to briefing-document templates. The section should map directly to FDA's three criteria: target completion date, sufficient assurance, and initiated enrollment. The goal is not to add volume. The goal is to make the agency's decision framework easy to review against. Most current templates address the confirmatory trial commitment in passing, often as a single paragraph or table. The post-guidance version needs its own section, with subsections mapping to the three criteria, and with reviewer-facing narrative that anticipates the assurance question rather than minimising it.

Build explicit traceability between the briefing document, protocol, and operational plan. The underway argument should cite the protocol's design choices, sample-size assumptions, primary endpoint, follow-up period, statistical assumptions, recruitment model, and site-activation plan. If the briefing document says one thing and the protocol or operational plan says another, the reviewer will find the seam. The cross-reference has to be explicit and traceable — not just present, but visibly threaded.

Co-author the assurance argument with operations. The writing team cannot invent "sufficient assurance" from the protocol alone. Clinical operations, site management, biometrics, safety, finance, and regulatory strategy should all feed the argument. The best version is not a polished narrative layered on top of weak facts; it is a structured intake from the teams that actually own trial delivery. The writing organisation that has a structured intake from operations into the briefing-doc drafting will produce a stronger document than one that drafts in isolation and asks operations to review at the end.

The Broader Direction

The underway-trial guidance is part of a broader FDA shift toward tighter post-approval accountability in accelerated approval. FDORA gave FDA additional authority to require confirmatory trials to be underway before approval or within a specified period after approval. The draft guidance shows how FDA intends to think about whether that requirement is satisfied.

For regulatory writing organisations, this changes the architecture of accelerated-approval packages. The confirmatory trial is not just a post-approval commitment. It is part of the front-end benefit-risk and credibility story.

The agency has named a documentation surface that reviewers are likely to check more consistently in accelerated-approval submissions. The briefing documents that hold up under this scrutiny will be the ones that treat the underway standard as a primary writing surface. They will explain the completion date, operational assumptions, enrollment status, and risk controls before FDA has to ask.

The weaker packages will spend the review cycle answering questions that should have been pre-answered in the original submission.

We wrote previously about why the writer's draft has to hold up under agent-assisted review. The underway-trial guidance is a specific instance of the same pattern: the agency has named a documentation surface that will be checked, and the writing organisations that internalise this early will move through the review cycle cleanly.

What This Asks of Sponsors Pursuing Accelerated Approval

For any sponsor with an accelerated approval in flight or planned over the next 18 months:

  • The confirmatory trial is now a documentation artifact as much as a clinical artifact.
  • The briefing document should construct the underway-trial argument directly against FDA's three criteria.
  • The cross-reference from briefing document to protocol, statistical plan, and operational plan needs to be tight.
  • The assurance argument should be co-authored with operations, not drafted from operational summaries at the end.
  • The sponsor should discuss the proposed completion timeline with FDA before the accelerated-approval application is submitted.

Accelerated approval is still a powerful pathway for therapies addressing serious or life-threatening diseases. But the pathway now asks for more proof of execution readiness upfront.

The science may earn the accelerated-approval case. The writing has to show that the confirmatory trial can actually finish.