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Advances in Large-Scale Biopharmaceutical Manufacturing
and Scale-Up Production*, 2nd Edition

    The Science for Biogenerics: Are We There Already?

    The obstacles to the development of biogenerics may be more political than scientific. The manufacturers of innovator biotech products used to claim that their products could be characterized chemically so that manufacturing changes could be implemented without new clinical data. With biogenerics looming, some have now reversed their position on the ease of characterization of these products even though there have been advances in analytical capabilities. It may be time to move beyond the question of whether biogenerics are possible to determining a pathway for the development of biogenerics. There are some examples where we have biogenerics in all but name only. Some biotech products have been sold to other companies such as when InterMune acquired Actimmune and Infergen. Enbrel, which is a complex glycoprotein, has been manufactured in at least five different sites. Biogen made significant manufacturing changes after the completion of the phase 3 trial but before the approval of Avonex. Sponsors can change contract manufacturers at any time during product development or after approval. The scientific principles used to develop comparability policies would seem applicable to biogenerics. Comparability should be the standard in comparing a biogeneric with an innovator protein with the amino acid sequence, tertiary structure and bioactivity the same. Minor differences in impurities would be acceptable but any other product differences should be investigated further in preclinical or even clinical studies. Minor differences in glycosylation would be acceptable if there was no effect on PK. Analytical characterization and comparisons should be done by today’s standards. Often the test methods, specifications and reagents used by the innovator are outdated. While innovators often cite the history of the product as a argument against biogenerics there is no guarantee of this with corporate mergers, personnel changes and products being sold. Any need for clinical or immunogenicity data for biogenerics should be based on sound scientific reasoning but regulatory authorities may want some clinical data for the first biogenerics. Interchangeability may not be an option immediately but with increased analytical capability and comfort with biogenerics this could be a possibility. A case-by-case approach may allow the consideration of product history, complexity and clinical indication as a first step in the development of biogenerics.

    About the Author

    Theresa L. Gerrard, Ph.D.
    TLG Consulting Inc., Midlothian, VA

    Dr. Gerrard is president of TLG Consulting Inc., and has both FDA and industry experience. Dr. Gerrard was with the FDA for 11 years and was the Director of the Division of Cytokine Biology (now the Division of Protein Therapeutics). In this capacity she worked with many manufacturers in the review of IND and license applications for a variety of protein therapeutics and was involved in development of FDA policies on manufacturing changes and demonstration of comparability. After leaving FDA she was Director of Development for Amgen, Inc. in Boulder, Colorado where she oversaw the development of several products. Since establishing TLG Consulting Inc. eight years ago Dr. Gerrard has worked with many biotech and pharmaceutical companies in product development and regulatory strategy. She has assisted clients with CMC issues for recombinant products, scale up and manufacturing changes for protein therapeutics, immunogenicity of therapeutic proteins, and in clinical development.

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