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Design of Biological Equivalence Programs for Therapeutic Biotechnology Products in Clinical Development: A Perspective

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Abstract

The determination of biological equivalence requires that studies are conducted to establish that two molecules, two formulations, or two dosing regimens, for example, are indistinguishable with respect to safety and efficacy profiles that have been previously established. The criteria that are used to establish biological equivalence will depend on the nature of the change (e.g., molecular, process, formulation), the stage of the development program, the duration of treatment, and the intended clinical indications. Key components of an equivalence program include chemical characterization, in vitro and in vivo bioactivity against reference material, pharmacokinetics, and safety. Special considerations for patient populations, endogenous concentrations, environmental factors, immunogenicity, assay methodology, biochemical identity, pharmacodynamic equivalence, and statistical methodology are discussed. In addition, the role of preclinical in vivo assessments is addressed. Specific case studies provide insight into the varied nature of approaches that are currently employed.

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Authors and Affiliations

  1. Experimental Therapeutics, Genentech, Incorporated, 460 Point San Bruno Boulevard, South San Francisco, California

    Joyce Mordenti & James D. Green

  2. United States Food and Drug Administration, Center for Biologies Evaluation and Research, HFM-5, 1401 Rockville Pike, Rockville, Maryland

    Joy A. Cavagnaro

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  1. Joyce Mordenti
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Mordenti, J., Cavagnaro, J.A. & Green, J.D. Design of Biological Equivalence Programs for Therapeutic Biotechnology Products in Clinical Development: A Perspective. Pharm Res 13, 1427–1437 (1996). https://doi.org/10.1023/A:1016002823485

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