Bioequivalence and bioavailability (BABE) studies form the basis of a successful drug development endeavor. Depending on a particular drug development project, BABE studies can be placed at different positions in a drug discovery flowchart. However, to develop and manufacture a generic drug, sponsors should demonstrate pharmaceutical (having same dosage form, strength, the active ingredient, and route of administration), therapeutic (can be substituted with the reference listed drug), and bioequivalence (having a similar rate and extent of drug absorption) between a reference listed drug and the test drug product. 

The 21 CFR 320.24 guidelines recommend several approaches, including in vivo and in vitro studies for bioequivalence testing. However, the ideal method depends on the study purpose in a particular drug development process, the availability of bioanalytical methods, and the properties of the test drug product. Hence, bioequivalence services use the most appropriate, sensitive, accurate, and reproducible method for BE studies.

Moreover, to further support bioequivalence testing, the US FDA publishes product-specific guidelines describing its current philosophy and expectations regarding BE studies for specific reference listed drugs. Product-specific guidelines are the ultimate recommendations the FDA publishes to enhance drug development and ANDA approvals and eventually increase the availability of safe and affordable generic drug products. Let us understand more about these product-specific guidelines and the role FDA plays in keeping them updated for the public.

Product-specific guidelines for bioequivalence testing.

FDA publishes new and revised product-specific guidelines on a quarterly and also on a needed basis. These product-specific guidelines are the agency’s current thoughts and expectations for bioequivalence testing. Moreover, they also guide in selecting an ideal method and evidence necessary for the generic pharmaceutical industry. The published product-specific guidelines are available on the FDA’s website for the public.

Product-specific guidelines for complex generic products that are under development mentions the reference listed drug application number, dosage form, and route of administration. Besides, for complex generic products under revision, the FDA also provides planned revision categories. This section only mentions the plans FDA has for issuing new and revised product-specific guidelines.

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For revised product-specific guidelines, FDA briefly explains the characteristics of anticipated revisions. Planned revisions are of three types, major, minor and editorial revisions.

A brief of each of these revisions are as follows:

• Major revision: Major revisions include additional evidence or BE studies needed for FDA approval.
• Minor revision: They form a broad spectrum of rectifications. This revision comprises suggestions for removing specific studies, adding information on newly identified strengths of a reference listed drug, providing alternative approaches for the currently approved studies, or recommendations resulting in additional studies for ANDA submissions.
• Editorial revision: Editorial modifications include changes, such as rectifying grammatical issues, updating external references, and changing the format of current guidelines.

Moreover, FDA also provides information on when these planned versions will become available for the public. FDA updates the product-specific page each time on a new quarterly basis. Each update replaces the old guidelines with the new or under development revisions. These advance notifications keep the drug development companies informed about future outcomes in bioequivalence testing.