Dosage form bioequivalence evaluations

Regarding drug formulation and development, the safety and efficacy studies should be evaluated to check if they were performed using the formulation for the proposed dosage form. Bioequivalency should be demonstrated if a different dosage form or formulation was used to conduct the study. Proposed changes should be critically evaluated for their impact on product quality, integrity, purity, safety, efficacy, bioactivity, uniformity, and stability. One should ensure... 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. 2000. 

Establishing in vitro in vivo correlation (IVIVC) for modified release dosage form provides a justification for waiving in vivo bioequivalence evaluation only for certain specified post approval changes. Since a correlation is dependent on the mechanism of drug release, it is not used in situations that could potentially alter its mechanism (16). 

A report from a 1990 ASCPT/DIA/APS/FDA-sponsored workshop entitled 7n vitro/In vivo Testing and Correlation for Oral Controlled/Modified Release Dosage Forms (1990) concluded that, while the science and technology may not always permit meaningful IVIVC, the development of an IVIVC was an important objective on a product-by-product basis. Procedures for development, evaluation, and application of an IVIVC were described. Validation of dissolution specifications by a bioequivalence study involving two batches of product with dissolution profiles at the upper and lower dissolution specifications was suggested. 

EU CPMP (1999) Note for Guidance on Modified Release Oral and Transdermal Dosage Forms Section II (Pharmacokinetic and Clinical Evaluation) July 1999 EU CPMP (2001) Note for Guidance on the Investigation of Bioavailability and Bioequivalence. July 2001 ICH-E5 (1998) Ethnic Factors in the Acceptability of Foreign Clinical Data. March 1998... 

Clinical (PK, PD, Safety and Efficacy) Human clinical studies can range in complexity from standard-design PK studies to complicated, long-term efficacy trials evaluating one or more indications in multiple populations. Human PK studies are used as the benchmark for establishing bioequivalence of conventional dosage forms. For traditional pharmaceuticals for which reliance on systemic exposure may not be suitable, PD or clinical safety and efficacy may be performed to show equivalence. 

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