Postmarketing Studies and Clinical Trials – Implementation of Section 505(o) of the Federal Food, Drug, and Cosmetic Act

Status: Draft

Date: July 2009

Target Audience: Applicants of new prescription drugs or biological products

Laws and Regulations:

Authorization for the FDA to require certain postmarketing studies and clincial trials for prescription drugs including biological products approved under the new section 505(0) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(0)), which was added by section 901 of the Food and Drug Administration Amendments Act of 2007, or under section 351 of the Public Health Service Act (PHS Act, 42 U.S.C. 262).


The new section 505(0) authorizes the FDA to require postmarketing studies or clinical trials to access a known/potential new serious risk associated with a prescription drug or biological product at or after approval if the FDA is aware of such a risk. Under the same section, applicants required to conduct postmarketing studies or clinical trials must also provide periodic status reports with specific required information on these studies, trials, or any other studies or trials undertaken to investigate a safety issue.


This guidance describes the requirements for postmarketing studies and clinical trials under 21 U.S.C. 355(0) and the types of postmarketing studies and clinical trials that will generally either be:

  1. required (i.e., a postmarketing requirement) under the new law
  2. agreed-upon as a commitment (i.e., a postmarketing commitment)


The FDA requires a postmarketing study or clinical trial as a postmarketing requirement if the following conditions are met:

  1. the FDA has appropriate scientific data (including data on chemically- or pharmacologically-related drugs) as evidence
  2. before requiring a postmarketing study, the FDA has found (a) adverse event reporting under section 505(k)(1) and the new pharmacovigilance system to be established under section 505(k)(3) of 21 U.S.C. 355(0); or (b) a postmarketing study will be insufficient to meet condition 3 below
  3. when a study or clinical trial proposes to:
    1. access a known serious risk related to the drug,
    2. access signals of (3.1), and/or (3.2) identify unexpected serious risk when available data suggests a potential serious risk

Postmarketing requirements may include but are not limited to:

  1. observational pharmacoepidemiology studies evaluating a serious risk related to drug exposure or to access/quantify factors (e.g., drug dose, time of exposure, or patient characteristics) that may influence the risk of serious toxicity
  2. clinical trials with a safety primary endpoint with prespecified assessments
  3. animal safety studies accessing specific end-organ toxicities (e.g., carcinogenicity, reproductive toxicity)
  4. in vitro laboratory safety studies
  5. pharmacokinetic studies or clinical trials in the patient population specified in the drug label or in a subpopulation potentially at risk for toxicity from high drug exposure
  6. drug interaction or bioavailability studies or clinical trials when scientific data indicate a potential serious safety risk

A postmarketing study or clinical trial that an applicant of a prescription drug or biological product agrees to undertake without a postmarketing requirement from the FDA is a postmarketing commitment.

Postmarketing commitments may include:

  1. drug and biologic quality studies (e.g., manufacturing, stability, immunogenecity) without a safety endpoint
  2. pharmacoepidemiology studies accessing the natural disease history or background adverse event rates
  3. clinical trials with a primary efficacy endpoint


Whenever a marketing application for a new prescription drug (including biological products) is filed to the FDA, the FDA will send to the applicant a list of possible postmarketing requirements and commitments to be discussed and finalized with the FDA review team. Once the applicant agrees to conduct the postmarketing requirements and/or commitments under an agreed upon timetable, the applicant must periodically report on the status of these studies or clinical trials. If an applicant does not comply with the timetable, periodic reporting, or other requirements in section 505(o)(3)(E)(ii), the FDA will enforce these requirements by issuing an unapproved drug charge, a misbranding charge (21 U.S.C. 332(z)), or civil monetary penalties (21 U.S.C. 333(f)(4)(A)).

With applicants of new prescription drugs being required to conduct postmarketing safety studies and clinical trials, the FDA will have more data to identify and access potential safety risks, and consequently the patient population taking these new prescription drugs will be better protected from these potential safety risks.

For more information on this issue, contact the Kulkarni Law Firm.