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Higher-Order Structure and Protein Aggregate Characterization of Protein Therapeutics: Perspectives from Good Manufacturing Practices and Regulatory Guidance

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Biophysics for Therapeutic Protein Development

Part of the book series: Biophysics for the Life Sciences ((BIOPHYS,volume 4))

Abstract

The complex three-dimensional structure of therapeutic proteins may be affected by the conditions used for production, purification, handling, and storage. Changes to this structure affect product quality and could impact product safety and effectiveness; thus, adequate product quality control and tight control of manufacturing process is necessary. In this chapter we consider some important factors and parameters that, if not well controlled, may result in protein structural changes and aggregation. We also provide a discussion of current and emerging methods that can be used for characterization of protein therapeutics during the production process and upon release. Lastly, we describe the framework of regulatory and good manufacturing principles, as stipulated in various guidances and other pertinent publications.

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Notes

  1. 1.

    FDA guidance documents contain recommendations that reflect FDA’s current thinking on given issues and are intended to assist the industry in carrying out its obligations under statutes and regulations. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. They are publically available on the FDA website. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

  2. 2.

    ICH is an organization that brings together regulators and pharmaceutical industry representatives from Europe, Japan, and the USA. The ICH mission is to facilitate development of safe, effective, and high-quality drugs in the most resource-efficient manner by harmonization of guidelines and requirements for product registration.

  3. 3.

    USP is a standard setting organization that can aid in ensuring the quality and safety of drugs, dietary supplements, and food ingredients.

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Authors and Affiliations

  1. Division of Hematology, Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), 29 Lincoln Drive, Bethesda, MD, 20892, USA

    Evi B. Struble, Chava Kimchi-Sarfaty, Zuben E. Sauna & Ewa Marszal

  2. Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccine Research and Review, CBER, FDA, 29 Lincoln Drive, Bethesda, MD, 20892, USA

    John F. Cipollo

  3. Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, FDA, 29B Lincoln Drive, Bethesda, MD, 20892, USA

    Jack A. Ragheb

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  1. Evi B. Struble
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  2. John F. Cipollo
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  3. Chava Kimchi-Sarfaty
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  4. Zuben E. Sauna
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  5. Jack A. Ragheb
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  6. Ewa Marszal
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Correspondence to Ewa Marszal .

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  1. , Research & Development, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, 91320, California, USA

    Linda O. Narhi

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The findings and conclusions in this chapter have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy.

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Struble, E.B., Cipollo, J.F., Kimchi-Sarfaty, C., Sauna, Z.E., Ragheb, J.A., Marszal, E. (2013). Higher-Order Structure and Protein Aggregate Characterization of Protein Therapeutics: Perspectives from Good Manufacturing Practices and Regulatory Guidance. In: Narhi, L. (eds) Biophysics for Therapeutic Protein Development. Biophysics for the Life Sciences, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4316-2_11

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