Post-Marketing Requirement (PMR) versus Post-Marketing Commitment (PMC)

Following the NDA or BLA approval, the sponsors may be required to conduct post-marketing studies. The phrase post marketing requirements and commitments refers to studies and clinical trials that sponsors conduct after approval to gather additional information about a product's safety, efficacy, or optimal use. Some of the studies and clinical trials may be required; others may be studies or clinical trials a sponsor has committed to conduct.

Post-approval studies can be classified by FDA as a postmarketing requirement (PMR) or a postmarketing commitment (PMC). 

A PMR is a study or clinical trial that an applicant (or sponsor) is required by statute or regulation to conduct postapproval. A PMC is a study or clinical trial that an applicant (or sponsor) agrees in writing to conduct postapproval, but that is not required by statute or regulation. PMRs and PMCs can be issued upon approval of a drug or postapproval, if warranted.

As a result, failure to conduct a PMR would be a violation of the Federal Food, Drug, and Cosmetic Act (FDCA) and/or implementing regulations, subject to enforcement action.  Potential enforcement actions can include an FDA Warning Letter, charges under section 505(o)(1) of the FDCA, misbranding charges under section 502(z), or civil monetary penalties.  In contrast, failure to conduct a PMC would not be a violation of the FDCA or regulations, and therefore not subject to enforcement action.

The table below compares the features of the PMR versus PMC:

Feature	Post-Marketing Requirements (PMR)	Post-Marketing Commitments (PMC)
Definition	Regulatory obligations imposed by authorities	Voluntary commitments made by the sponsor
Purpose	Gather additional data on safety, efficacy, etc.	Obtain more information post-approval
Enforcement	Mandatory; non-compliance may lead to penalties	Voluntary, but sponsors are expected to fulfill
Imposition	Imposed by health regulatory agencies	Made voluntarily by the sponsor during approval
Consequences of Non-compliance	Regulatory actions, fines, or product withdrawal	Regulatory actions; may impact marketing authorization
Flexibility	Typically less flexible; regulatory mandates	Voluntary, but commitment should be honored
Origin	External (regulatory agency)	Internal (sponsor during regulatory approval)
Examples	Post-approval safety studies, surveillance	Additional clinical trials, long-term safety studies

According to FDA's guidance "Guidance for Industry Postmarketing Studies and Clinical Trials — Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act", PMR may be required in the following situations:

PMC may be required in the following situations: 

These PMCs were generally agreed upon by FDA and the applicant. Prior to the passage of FDAAA, FDA required postmarketing studies or clinical trials only in the situations described below:

• Subpart H and subpart E accelerated approvals for products approved under 505(b) of the Act or section 351 of the PHS Act, respectively, which require postmarketing studies to demonstrate clinical benefit (21 CFR 314.510 and 601.41, respectively);

• Deferred pediatric studies, where studies are required under section 505B of the Act (21 CFR 314.55(b) and 601.27(b)); 6 and

• Subpart I and subpart H Animal Efficacy Rule approvals, where studies to demonstrate safety and efficacy in humans are required at the time of use (21 CFR 314.610(b)(1) and 601.91(b)(1), respectively). 7

Is the confirmatory trial after the accelerated approval PMR or PMC?  

As a condition of accelerated approval, the applicant should conduct confirmatory trials to verify the clinical benefit of the drug or demonstrate an effect on irreversible morbidity or mortality. If these trials completed post-approval verify the clinical benefit of an indication granted accelerated approval, the indication is granted traditional approval.

Per regulatory guidance, the confirmatory trial after the accelerated approval can be PMC, not PMR. However, without the results from the confirmatory trial to verify the clinical benefit, the approval will remain as 'conditional' and benefits will remain on the surrogate endpoint or biomarkers. A traditional approval (or full approval) can be obtained after the confirmatory trial verifies the benefit of clinical benefit. A drug with full approval will have advantages in the marketing and reimbursement positions. 

Searching the FDA's Postmarket Requirements and Commitments Database, almost all confirmatory trials after accelerated approval are PMRs, not PMCs. 

Is Post-Approval Pregnancy Study PMR or PMC?

TheFDAlawblog.com had a blog article "Why are Post-Approval Pregnancy Studies Post-Marketing Requirements Rather Than Post-Marketing Commitments?". It said the following: 

"Notably, of the 99 postmarketing pregnancy studies in the 10-year period, all but one were PMRs. The only example of a pregnancy PMC is for Paxlovid, for treatment of COVID-19, which is a distinguishable example because the sponsor committed to this study while the drug was still under an Emergency Use Authorization (EUA), not an NDA."

In general, the post-approval pregnancy's studies are PMR, not PMC.

What are examples of the PMR versus PMC?

Large pharmaceutical companies posted their PMRs and PMCs only for the purpose of transparency. For example, here are the lists of PMRs and PMCs for Amgen and Janssen. These PMRs and PMCs provide great examples what kind of studies they are. 

• Amgen United States Clinical Postmarketing Commitments/Requirements
• Janssen Pharmaceutical CompaniesU.S. Post-Marketing Requirements and Commitments