New Revised Bioequivalence Guidance Clarifies Requirements

FDA issued a newly revised Draft Guidance entitled Bioequivalence Studies with Pharmacokinetic Endpoints for Drug Submitted Under an ANDA (here).  The new Guidance document is specific to abbreviated new drug applications (ANDAs) and combines part of two previous guidance documents on general bioequivalence (BE) and BE for fed studies for ANDAs.  The document does not address bioavailability (BA) or BE for investigational new drug applications (INDs) or for studies required to support BE for new drug applications (NDAs).

This document deals with both BE and in vitro requirements for approval and post-approval changes to ANDAs and addresses many topics, including, but not limited to:

  • when fed studies are necessary
  • specific BE requirements for immediate-release products,  suspensions, solutions and modified-release and extended release dosage forms
  • sprinkle study requirements
  • when BE waivers are appropriate

Special topics covered include:

  • Moieties to be measured in the various studies
  • Fed studies
  • Alcohol studies
  • The issue of racemates and also how to handle evaluation of drugs containing endogenous compounds
  • Drugs with a Long half-life
  • First point Cmax and importance of Tmax
  • Partial AUCs
  • Orally administered drugs intended for local action
  • Narrow therapeutic range drugs
  • Parallel and replicate design studies

The Guidance also clarifies with certainty when and what products must be tested in vivo or in vitro when considering original ANDA approval or when making a post-approval change,which is an issue that has never really been spelled out before with as much clarity as in this document.  There are also specific instruction on how to handle the BE testing of chewable tablets.  There is also a section that deals with complex mixtures as the active ingredients that sheds some light on Office of Generic Drugs (OGD) expectations.

This ANDA-specific Guidance provides in one place information that has been scattered in various documents and some new direction for ANDA applicants in a manner that is straightforward and leaves no doubt as to OGD’s intention.