Accelerated approval gets a drug to market faster, but it leaves an open regulatory obligation: a postmarketing requirement (PMR) to verify clinical benefit through a confirmatory trial. If that trial fails, stalls, or misses its deadline, FDA has statutory authority to withdraw the indication. After the Food and Drug Omnibus Reform Act of 2022 (FDORA), the stakes are higher and the reporting cadence is tighter.
This article is for regulatory affairs leads, commercial launch teams, and medical affairs professionals who need to understand how FDA tracks PMRs, what FDORA changed, and what to monitor after an accelerated-approval launch.
How FDA tracks postmarketing requirements
FDA maintains a searchable Postmarketing Requirements and Commitments Database, updated quarterly (January, April, July, October). The database includes all open PMRs and postmarketing commitments (PMCs), plus those closed within the last year.
PMRs are studies or clinical trials that sponsors are required to conduct under statute or regulation. PMCs are studies sponsors have agreed to conduct but that are not legally mandated. The distinction matters: PMR non-compliance can trigger enforcement action; PMC non-compliance is a reporting gap.
PMR/PMC status categories
FDA classifies each PMR/PMC into one of the following statuses:
| Status | Meaning |
|---|---|
| Pending | Study not initiated; original projected start date has not passed |
| Ongoing | Study has started (subjects enrolled or animals dosed) |
| Delayed | Original milestone date has passed without meeting the milestone |
| Submitted | Final study report submitted to FDA |
| Terminated | Study ended before completion |
| Fulfilled | FDA reviewed the final report and determined the requirement is met |
| Released | FDA determined the requirement is no longer needed or feasible |
FDA also classifies each PMR/PMC as "on schedule" or "off schedule" based on whether the applicant has missed a milestone date in the original schedule. The annual Federal Register report tracks these metrics for all NDAs and BLAs.
The annual status report requirement
Under Section 506B of the FD&C Act (21 U.S.C. 356b) and 21 CFR 314.81 and 601.70, sponsors must submit an Annual Status Report (ASR) on every open PMR and PMC within 60 days of the approval anniversary. In FY 2024, 537 NDAs and 213 BLAs required an ASR, per FDA's most recent report.
FDA's FY 2024 data show that 70% of open PMRs (1,147 of 1,636) were on schedule, and 80% of PMCs (307 of 386) were on schedule. But the tail of delayed requirements is the operational risk.
What FDORA changed for accelerated-approval PMRs
The Food and Drug Omnibus Reform Act (FDORA), enacted in December 2022 as part of the Consolidated Appropriations Act of 2023, added several provisions that tighten PMR oversight specifically for accelerated approvals.
Mandatory 180-day progress reports
Before FDORA, accelerated-approval sponsors reported on PMR progress once a year in the ASR. FDORA added a requirement for two reports per year:
- One 180-day progress report due 180 days after the original approval date (with a 60-day grace period).
- A second 180-day report submitted together with the annual 506B status report.
Each report must address enrollment targets, milestones, and study progress. Per FDA SOPP 8413 (CBER) and corresponding CDER procedures, if any open AA PMR exists, the 180-day cadence continues until the PMR is fulfilled or released.
Confirmatory trial must be "underway"
FDORA gave FDA the authority to require that confirmatory trials be underway prior to approval or within a specified timeframe after approval. In January 2025, FDA released draft guidance "Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway" defining what "underway" means.
Factors FDA considers when determining whether a trial is underway include:
- Whether the protocol has been submitted to FDA
- Whether sites are activated and screening patients
- Whether enrollment has begun
- The feasibility of completing the trial on schedule
- Whether the sponsor has sufficient financial resources
FDA's stated default is that confirmatory trials should be underway before accelerated approval is granted.
Expedited withdrawal procedures
FDORA provides FDA with a streamlined withdrawal process. If the confirmatory trial fails to verify clinical benefit, FDA can issue a formal notice of proposal to withdraw. The sponsor can appeal, request an advisory committee review, or meet with FDA. But the law shifts the burden: the sponsor must demonstrate why the approval should stand, rather than FDA having to prove it should not.
The confirmatory-trial failure record
The historical record shows that confirmatory trial failure is not rare, particularly in oncology.
Oncology withdrawal data
FDA's Oncology Center of Excellence has published data showing that approximately 15% of oncology accelerated approvals have been withdrawn because of failed or incomplete confirmatory trials. About 60% of all accelerated approvals are for oncology indications.
As of May 2026, FDA maintains separate public tables for:
- Ongoing cancer accelerated approvals (active AA indications awaiting confirmatory data)
- Verified cancer accelerated approvals (confirmatory trial verified clinical benefit)
- Withdrawn cancer accelerated approvals (indications withdrawn after failure or non-completion)
Recent high-profile withdrawals include:
- Xpovio (selinexor) for DLBCL, withdrawn April 2026
- Trodelvy (sacituzumab govitecan-hziy) for metastatic urothelial cancer, withdrawn November 2024
- Bavencio (avelumab) for gastric cancer indication withdrawn in 2024
- Keytruda (pembrolizumab) for several accelerated-approval indications in gastric and cervical cancer that were voluntarily withdrawn after confirmatory trial failures
The Aduhelm (aducanumab) case
Aduhelm (aducanumab-avwa), Biogen's Alzheimer's drug, received accelerated approval in June 2021 based on reduction in amyloid beta plaques. The confirmatory trial requirement had a deadline of 2030. The approval was controversial enough that three FDA advisory committee members resigned. A 2022 HHS Office of Inspector General report found that 35 of 104 drugs with open accelerated-approval confirmatory trials had fallen behind their original completion dates. The product was later discontinued in its original IV formulation, though the regulatory PMR framework it illustrates remains relevant.
The Makena (hydroxyprogesterone caproate) case
Makena received accelerated approval in 2011 for prevention of preterm birth. The confirmatory trial failed to show benefit. FDA proposed withdrawal in 2020, but the sponsor contested it. More than two years passed before a public hearing was held. The case illustrated that even when confirmatory data are negative, withdrawal can be procedurally slow, creating an extended period where an unverified indication remains on the market.
Building a post-launch PMR tracker: operational checkpoints
For a product that received accelerated approval, the following checkpoints should be tracked by regulatory affairs in coordination with commercial and medical affairs teams.
Pre-approval
- Confirm the PMR language in the approval letter is precise: endpoint, patient population, sample size, primary analysis, final report date
- Ensure the confirmatory trial protocol is aligned with the PMR description before the trial starts
- Verify that the confirmatory trial's timeline is feasible given the patient population and competitive landscape
First 180 days after approval
- Submit the first 180-day AA PMR progress report
- Confirm trial enrollment has started or will start within the agreed timeframe
- Assess whether the original milestones remain realistic
Every 180 days ongoing
- Submit the required progress report (FDA SOPP 8413)
- Track enrollment rate against the planned trajectory
- Document any protocol amendments and assess whether they affect the PMR commitment
- If milestones are slipping, prepare a revised schedule with justification; FDA will still assess against the original schedule for its own tracking
Annual
- Submit the 506B Annual Status Report (combined with the second 180-day report)
- Cross-check the PMR status in FDA's public database against internal records
- Review any FDA correspondence (fulfillment letters, release letters, requests for information)
When the confirmatory trial completes
- Submit the final study report to FDA
- If the trial confirms clinical benefit, FDA will convert to traditional approval
- If the trial fails, prepare for potential withdrawal: assess impact on other indications, labeling, NCCN guidelines, and payer coverage
- If the trial produces ambiguous results, engage FDA early; the agency has discretion
What happens to commercial operations when a PMR fails
A failed confirmatory trial creates cascading commercial risk:
Indication withdrawal. FDA issues a Federal Register notice, and the indication is removed from the label. Product labeling, promotional materials, and sales training must be updated immediately.
NCCN guideline lag. A 2024 analysis in the Journal of Clinical Oncology found that NCCN guidelines only removed or weakened recommendations for 42% of indications where confirmatory trials failed. This means payers and prescribers may continue using the drug off-label or under outdated guideline language even after withdrawal.
Payer coverage retraction. Medicare and commercial payers will typically remove coverage for the withdrawn indication, but the timeline is inconsistent. Prior authorization criteria may not update in sync with FDA action.
Revenue impact. If the withdrawn indication represents a meaningful share of total prescriptions, the commercial impact is immediate. For oncology products with multiple accelerated-approval indications, the impact may be partial.
Investor and analyst communication. Confirmatory trial failure is material information. The company must disclose results and the expected regulatory outcome.
Key FDA sources for PMR tracking
| Resource | Location | Update frequency |
|---|---|---|
| PMR/PMC Searchable Database | FDA.gov, Drug Approvals and Databases | Quarterly |
| PMR/PMC Downloadable Database File | FDA.gov | Quarterly |
| Ongoing Cancer Accelerated Approvals table | FDA.gov, Oncology Center of Excellence | Periodic |
| Withdrawn Cancer Accelerated Approvals table | FDA.gov, Oncology Center of Excellence | Periodic |
| Annual PMR/PMC Federal Register Report | Federal Register | Annually |
| Drugs@FDA approval letters | FDA.gov, Drugs@FDA | At approval |
| 180-day AA PMR progress reports | Submitted by sponsor to FDA | Twice yearly |
The regulatory framework references
- Section 506 of the FD&C Act (21 U.S.C. 356), as amended by FDORA Section 3210: accelerated approval authority, confirmatory trial requirements, expedited withdrawal
- Section 506B of the FD&C Act (21 U.S.C. 356b): annual postmarketing study status reports
- 21 CFR 314.81 (NDAs) and 21 CFR 601.70 (BLAs): postmarketing reporting requirements
- FDA SOPP 8413 (CBER): procedures for PMR/PMC-related submissions, including 180-day reporting
- FDA SOPP 8415 (CBER): procedures for developing postmarketing requirements
- FDA Draft Guidance, January 2025: "Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway"
- FDA Draft Guidance, December 2024: "Expedited Program for Serious Conditions — Accelerated Approval of Drugs and Biologics"
Sources
- FDA, Accelerated Approval Program. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program. Updated 05/15/2026.
- FDA, Ongoing Cancer Accelerated Approvals. https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals. Updated 05/13/2026.
- FDA, Withdrawn Cancer Accelerated Approvals. https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-cancer-accelerated-approvals. Updated 05/01/2026.
- FDA, Postmarketing Requirements and Commitments: Reports. https://www.fda.gov/drugs/postmarketing-requirements-and-commitments-introduction/postmarketing-requirements-and-commitments-reports.
- FDA, About the Postmarketing Requirements and Commitments Searchable Database. https://www.fda.gov/drugs/drug-approvals-and-databases/about-postmarketing-requirements-and-commitments-searchable-database.
- FDA, Postmarketing Requirements and Commitments: Downloadable Database File. https://www.fda.gov/drugs/postmarketing-requirements-and-commitments-introduction/postmarketing-requirements-and-commitments-downloadable-database-file.
- FDA, SOPP 8413: Postmarketing Commitment Related Submissions. https://www.fda.gov/media/90205/download.
- FDA, SOPP 8415: Procedures for Developing Postmarketing Requirements. https://www.fda.gov/media/90591/download.
- Federal Register, "Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway; Draft Guidance," January 7, 2025. https://www.federalregister.gov/documents/2025/01/07/2024-31527.
- HHS Office of Inspector General, "Delays in Confirmatory Trials for Drug Applications Granted FDA's Accelerated Approval Raise Concerns," 2022. https://oig.hhs.gov/reports/all/2022/delays-in-confirmatory-trials-for-drug-applications-granted-fdas-accelerated-approval-raise-concerns.
- Mehta GU, Pazdur R. "Oncology Accelerated Approval Confirmatory Trials: When A 'Failed' Trial Is Not a 'Failed' Drug." J Clin Oncol. 2024;42(32):3778. PMC 11540715.
- RAPS, "FDA finds most postmarketing requirements, commitments progressing on schedule," April 27, 2026. https://www.raps.org/resource/fda-finds-most-postmarketing-requirements-commitments-progressing-on-schedule.html.
- ICER, "Strengthening the FDA's Accelerated Approval Pathway: Progress and Unfinished Business," April 2026. https://icer.org/wp-content/uploads/2026/04/Strengthening-the-FDAs-Accelerated-Approval-Pathway-_-ICER-White-Paper-_-April-2026.pdf.
- White & Case, "Accelerated Approval confirmatory trials requirement may further complicate life." https://www.whitecase.com/insight-alert/accelerated-approval-confirmatory-trials-requirement-may-further-complicate-life.
- Arnold & Porter, "FDA Issues New Draft Guidance on Getting Confirmatory Trials 'Underway' for Accelerated Approvals," January 2025. https://www.arnoldporter.com/en/perspectives/advisories/2025/01/fda-guidance-confirmatory-trials-for-accelerated-approval.
- PMC, "Flexibility over rigor: stakeholder acceptance of the limitations of confirmatory studies following accelerated approval." PMC 12617412.
