This guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both development and post approval phases for orally administered immediate-release (IR) solid oral dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules/powders for oral suspension.
Deviations from the recommendations in this guideline may be acceptable if appropriate scientific justification is provided. Applicants are encouraged to consult the regulatory authority(ies) when an alternate approach is proposed or taken.
M13A is the first guideline in the series to describe the scientific and technical aspects of study design and data analysis to support BE assessment for orally administered IR solid oral dosage forms. How regulatory decisions may be made based on BE assessment is out of the scope of this guideline.
Acceptance of comparator products across regulatory jurisdictions could reduce the burden of multiple clinical trials demonstrating BE against local comparator products. However, in many regions this is governed by local laws rather than scientific guidelines. Therefore, the acceptance of comparator products across regions is not in the scope of M13A. However, study designs containing multiple comparator products or test products are included in M13A to take some initial steps to reduce the associated burden without prejudice to regional legal requirements.
The second guideline in the series, M13B, will describe biowaiver considerations for additional strengths not investigated in BE studies.
The third guideline in the series, M13C, will include data analysis and BE assessment for 1) highly variable drugs, 2) drugs with narrow therapeutic index, and 3) complex BE study design and data analysis considerations, e.g., adaptive BE study design.
These guidelines do not cover PK study design or data analysis to support BA assessment for new drug development in support of intended use or dosing recommendations in drug labelling, e.g., relative BA assessment, food effect, drug-drug interactions, special population studies, bridging formulations without the necessity to demonstrate BE, and studies to support changes in dosing regimens or routes of administration. In such cases, study design and decision criteria may be
based on the objective of the study and availability of other information including exposure58 response and proposed labelling.