By Rose Pagano and Suzanne M. Sensabaugh, MS, MBA


This guidance was recently released and serves to distribute information concerning the enactment of section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act). This section of the law allows FDA to require particular postmarketing studies and clinical trials for prescription drugs that fall under this law and biological products affiliated with the Public Health Service (PHS) Act of section 351.The FDA approves drugs on the basis that the drug has been proven to be safe and effective when administered under the instructions described in proper labeling. Sometimes, the FDA may be made aware of more necessary information or data related to the drug after approval.

The 505(o)(3) section of the FD&C Act allows the FDA to require that an applicant carry out postmarketing studies or clinical trials. The agency can also request that the applicant take these steps if they become aware of new safety information. For example, the FDA may be concerned over a potential risk associated with a drug because of the lack of knowledge surrounding the risk, which prevents them from fully understanding the effect of the drug. In a case like this, the FDA can require an applicant to carry out postmarketing studies or clinical trials addressing the risk.

Postmarketing studies and clinical trials can be conducted for the following purposes: assessing the serious risk related to using the drug of interest, analyzing the signals of serious risk for the drug, and to determine if there are any unexpected, serious risks related to the drug. This guidance goes on to explain that clinical trials are any prospective investigations in which the applicant determines the method of assigning the drug or other interventions to one or more human subjects. Studies are then classified as all other investigations.

It is important to note that before requiring a postmarketing study, the FDA needs to find that adverse event reporting under section 505(k)(1) of the FD&C Act and the active postmarketing risk identification and analysis system under section 505(k)(3) of the FD&C Act are not sufficient to meet their necessary purposes.

Generally, the postmarketing requirement (PMR) under section 505(o)(3) is related to serious risks. A serious risk is the risk of a serious adverse drug experience. This means that a postmarketing study or clinical trial can further analyze the potential pharmacological effect. Remember, applicants are required to annually report the status of particular PMRs and postmarketing commitments (PMCs) and the FDA will also track them annually in the Federal Register.

Additionally, when submitting PMRs under section 505(o)(3) of the FD&C Act, include a timetable (a set of milestone dates) for complete, periodic reports on the status of the study (any difficulties, etc.), periodic reports on the status of the clinical trial [if enrollment has started, number of participants enrolled, anticipated completion date, difficulties in completing the clinical trial, registration information related to section 402(j) of the PHS Act, etc.]. Also, applicants need to submit reports on any study or clinical trial investigating a safety issue that the FDA did not request themselves.

It is important to keep all of these factors in mind when submitting a drug application to the FDA. Some potential postmarketing requirements that would be a reasonable request for the FDA to make under the FD&C Act could include safety studies in animals investigating specific end-organ toxicities, assessing carcinogenic potential in appropriate species, or assessing reproductive toxicology.  Be prepared to conduct studies comparable to these if the FDA requests this.


At HartmannWillner LLC, we understand the regulatory requirements for development of biological products, biosimilars, and combination products through the BLA route. With our help, you can transition your biologic to a licensed biologic. Contact us today to learn more about our services and how we can help you. Suzanne is the President and Principal Consultant of HartmannWillner LLC. She is an FDA regulatory affairs consultant who assists companies in advancing biologics, biosimilars, and biologic/device combination products through the FDA.


Suzanne is the President and Principal Consultant of HartmannWillner LLC. She is an FDA regulatory affairs consultant who assists companies in advancing biologics, biosimilars, and biologic/device combination products through the FDA.

She formed HartmannWillner in 2009 as a regulatory affairs consultant. Since then, Suzanne has: 


  • Assisted in the development of over 130 biologics, biosimilars, and biologic/device combination products
  • Conducted over 30 FDA GMP audits, including preapproval inspections (PAI), which allowed for FDA approval
  • Provided GMP compliance consulting to successfully address Form FDA 483 observations and Warning Letters
  • Prepared expert witness opinions and testimony in the areas of FDA regulatory affairs and GMP compliance
  • Wrote and reviewed hundreds of original INDs and BLAs and amendments and supplements