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Characterizing biological products and assessing comparability following manufacturing changes

Nature Biotechnology volume 22, pages 1383–1391 (2004)Cite this article

Abstract

Changes in production methods of a biological product may necessitate an assessment of comparability to ensure that these manufacturing changes have not affected the safety, identity, purity, or efficacy of the product. Depending on the nature of the protein or the change, this assessment consists of a hierarchy of sequential tests in analytical testing, preclinical animal studies and clinical studies. Differences in analytical test results between pre- and post-change products may require functional testing to establish the biological or clinical significance of the observed difference. An underlying principle of comparability is that under certain conditions, protein products may be considered comparable on the basis of analytical testing results alone. However, the ability to compare biological materials is solely dependent on the tests used, since no single analytical method is able to compare every aspect of protein structure or function. The advantages and disadvantages of any given method depends on the protein property being characterized.

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Figure 1: Typical forms of protein heterogeneity.

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Acknowledgements

Members of international regulatory authorities, industry and academia met at an FDA-sponsored meeting held at the National Institutes of Health, Bethesda, MD, June 10–13, 2003 to discuss how current analytical technologies are able to characterize biological products and contribute to the comparability process. The authors would like to thank fellow meeting participants Laura Bass, Marta Czupryn, William Egan, Darón Freedberg, Mike Grace, Martin Green, Reed Harris, Steven Indelicato, Eugene Koren, Stacey Ma, Mike Mulkerrin, Leland Paul, John Philo, Zorina Pitkin, Vytas Reipa, Amy Rosenberg, Joseph Siemiatkoski, Stephanie Simek, Steve Swanson, Guillermo Tous and Meenu Wadhwa for advice. The authors would also like to thank Bassil Dahiyat, John Desjarlais, Joyce Morrison and David Szymkowski for critical reading of the manuscript, and Marie Ary for valuable editorial advice.

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  1. Xencor Inc., 111 West Lemon Avenue, Monrovia, 91016, Calfornia, USA

    Arthur J Chirino

  2. Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, 1451 Rockville Pike, 20852, Maryland, USA

    Anthony Mire-Sluis

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Correspondence to Arthur J Chirino.

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Chirino, A., Mire-Sluis, A. Characterizing biological products and assessing comparability following manufacturing changes. Nat Biotechnol 22, 1383–1391 (2004). https://doi.org/10.1038/nbt1030

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