PMRs and PMCs: Which Obligations Are Enforceable

Most approval letters impose postmarketing studies. Each is either a requirement or a commitment, and the difference is enforceability.

Postmarketing requirement (PMR). A study or trial you are required to conduct, under a statutory authority. Missing one is a violation.

Postmarketing commitment (PMC). A study you have agreed to conduct that is not required by statute. Not enforceable in the same way, but you still report on it and FDA still tracks it.

Both appear in the approval letter.

Statutory sources of PMRs

FDAAA section 505(o)(3). FDA can require studies to assess a known serious risk, to assess signals of a serious risk, or to identify an unexpected serious risk when available data indicate the potential for one. This is the broadest authority and the most common source.

Accelerated approval, 21 CFR 314.510 and 601.41. Approval based on a surrogate endpoint carries a requirement to verify clinical benefit in a confirmatory trial. Failure to conduct it with due diligence is grounds for withdrawal, and FDA has withdrawn approvals on this basis.

Pediatric Research Equity Act. Required pediatric assessments.

Animal Rule, for products approved on animal efficacy data.

Milestones and reporting

Beyond the study itself, each PMR and PMC carries:

• A milestone schedule: protocol submission, study completion, final report submission. These dates are in the approval letter and FDA holds you to them.
• Annual status reporting on progress against those milestones.
• Public visibility. FDA publishes PMR and PMC status, so a delayed commitment is visible to anyone who looks.

Common failures

The obligations arrive as the team moves on to the next program, and land with whoever inherits the file. The failures are ordinary:

• The milestone dates were negotiated by people who have left.
• The obligation sits in the approval letter and nowhere else, so no system tracks it.
• A PMC is assumed to be optional because it is not enforceable, and the annual report then has nothing to say about it.
• Nobody notices a slipping schedule until the annual status report forces the question.