Drug Regulators, New Draft FDA Guidance

The FDA has published new draft guidance, Postmarketing Studies and Clinical Trials — Implementation of Section 505(o) of the Federal Food, Drug, and Cosmetic Act

Introduction

This guidance provides information on the implementation of new section 505(o) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 355(o)), added by section 901 of the Food, and Drug Administration Amendments Act of 2007 (FDAAA). Section 505(o) authorizes FDA to require certain post marketing studies and clinical trials2 for prescription drug and biological products approved under section 505 of the Act or section 351 of the Public Health Service Act (the PHS Act) (42 U.S.C. 262). This guidance provides information about the requirements for postmarketing studies and clinical trials under section 505(o) of the Act. The guidance also describes the types of postmarketing studies and clinical trials that:

• will generally be required under the new legislation (postmarketing requirements (PMRs)) and
• will generally be agreed-upon commitments (postmarketing commitments (PMCs)) because they do not meet the new statutory criteria for required postmarketing studies and clinical trials

Background

On September 27, 2007, the President signed FDAAA (Public Law 110-85). Section 901 of  Title IX of FDAAA amended the Act by adding new section 505(o). Section 505(o) authorizes  FDA to require certain postmarketing studies and clinical trials for prescription drug and biological products approved under section 505 of the Act or section 351 of the PHS Act.

Past Practice

In the past, FDA has used the term postmarketing commitment (PMC) to refer to studies (including clinical trials), conducted by an applicant after FDA has approved a drug for  marketing or licensing, that were intended to further refine the safety, efficacy, or optimal use of a product or to ensure consistency and reliability of product quality. These PMCs were either agreed upon by FDA and the applicant or, under certain circumstances, required by FDA. Prior to the passage of FDAAA, FDA required PMCs in the following situations:

• 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);
• Deferred pediatric studies, where studies are required under the Pediatric Research Equity Act (PREA) (21 CFR 314.55(b) and 601.27(b)); and
• 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)).

New FDAAA Authority and Requirements

Section 505(o) of the Act authorizes FDA to require postmarketing studies or clinical trials at the time of approval or after approval if FDA becomes aware of new safety information. Section 89 505(o)(3)(A) states that postmarketing studies and clinical trials may be required for any or all of  three purposes listed in section 505(o)(3)(B):

• To assess a known serious risk related to the use of the drug
• To assess signals of serious risk related to the use of the drug
• To identify an unexpected serious risk when available data indicate the potential for a serious risk

Applicants Are Required to Report on the Status of Studies and Clinical Trials.

The applicant is required to provide certain information to FDA with regard to required postmarketing studies and clinical trials (section 505(o)(3)(E)(ii)). Under section 505(o)(3)(E)(ii), this information must include:

• For all required postmarketing studies and clinical trials, a timetable for completion
• For each study required under section 505(o), periodic reports on the status of the study, including whether any difficulties in completing the study have been encountered
• For each clinical trial required under section 505(o), periodic reports on the status of the 128 clinical trial, including:
  • whether enrollment has begun,
  • the number of participants enrolled,
  • the expected completion date,
  • whether any difficulties completing the clinical trial have been encountered, and
  • registration information with respect to the clinical trial under section 402(j) of the PHS Act (42 U.S.C. 282(j))

Implementation of postmarkeing study and clinical trial requirements under FDAAA

Under section 505(o)(3) of the Act, FDA will require applicants to conduct a postmarketing study or studies or clinical trial(s) when the following conditions are met:

1. When the decision to require a postmarketing study or clinical trial is based on scientific data deemed appropriate by FDA, including information regarding chemically-related or pharmacologically-related drugs; and
2. When FDA has found —
   1. before requiring a postmarketing study, that adverse event reporting under section 505(k)(1) of the Act and the new pharmacovigilance system that will be established under section 505(k)(3) will not be sufficient to meet the purposes described in condition 3 below; and
   2. before requiring a postmarketing clinical trial, that a postmarketing study will not be sufficient to meet the purposes in condition 3 below; and
3. When the purposes of the study or clinical trial, as described in section 505(o)(3)(B), are one or more of the following
   1. To assess a known serious risk related to the use of the drug
   2. To assess signals of serious risk related to the use of the drug
   3. To identify an unexpected serious risk when available data indicates the potential for a serious risk

When these conditions are met, the Agency intends to require the study or clinical trial as a postmarketing requirement (PMR).

the draft regulations continue in more detail, Postmarketing Requiremtns (PMRs), Postmarketing Commitments (PMCs), Procedures, Reporting, Dispute Resultion, and Enformcement of Requiremtns for Postmarketing Studies and Clinical Trails.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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