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Differentiating biosimilarity and comparability in biotherapeutics

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Abstract

The manufacture of biologics is a complex process involving numerous steps. Over time, differences may arise as a result of planned changes to the manufacturing processes of a biologic from the same manufacturer. Comparability is the regulatory process that outlines the scope of an assessment required of an already licensed biologic after a manufacturing process change made by the same manufacturer. The aim of a comparability assessment is to demonstrate that any pre-manufacturing and post-manufacturing changes have no adverse impact on quality, safety, and efficacy of the biologic. A comparability assessment is distinct from a biosimilarity assessment, which involves extensive assessment of a biologic that is highly similar to the originator (reference product) in terms of quality, safety, and efficacy. The US Food and Drug Administration, European Medicines Agency, and World Health Organization have applied the fundamental comparability concepts into their respective biosimilarity guidance documents. In this review, we examine the rationale behind the distinct, highly regulated approval processes governing changes that may occur over time to an originator biologic due to planned manufacturing changes (as described by a comparability exercise) and those that outline the approval of a proposed biosimilar drug, based on its relationship with the reference product (biosimilarity evaluations).

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Acknowledgments

Medical writing support was provided by Neel Misra, MSc, CMPP, of Engage Scientific Solutions and was funded by Pfizer. The authors would like to thank Chee-Keng Ng of Pfizer for his contributions to the manuscript. The authors also wish to thank Shivanthy Arnold, Beverly Ingram, and Judith Macdonald, all of Pfizer, for their contributions to the regulatory sections of the manuscript.

Author information

Authors and Affiliations

  1. Federal University of Paraná, Curitiba, PR, Brazil

    Valderilio Azevedo

  2. Pfizer Biotech, Dublin, Ireland

    Brian Hassett & Brian Fitzpatrick

  3. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa and Hospital de Santa Maria, Lisbon Medical Academic Medical Centre, Lisbon, Portugal

    João Eurico Fonseca

  4. Division of Rheumatology, Hokkaido University, Sapporo, Hokkaido, Japan

    Tatsuya Atsumi

  5. Pfizer Inc., New York, NY, USA

    Javier Coindreau & Ira Jacobs

  6. Pfizer Inc., Collegeville, PA, USA

    Ehab Mahgoub & Ena Singh

  7. Pfizer Worldwide Safety and Regulatory, EU and International Regulatory Policy, Dublin, Ireland

    Julie O’Brien

  8. Pfizer Biotech, Andover, MA, USA

    Steven Vicik

  9. Pfizer Biotech, Global Supply, Grange Castle, Dublin 22, Ireland

    Brian Fitzpatrick

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  1. Valderilio Azevedo
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Corresponding author

Correspondence to Brian Fitzpatrick.

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Conflicts of interest

Authors had control of all primary data. Valderilio Azevedo has received unrestricted grants or served on speakers bureaus for AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, Celltrion, UCB, and AstraZeneca. João Eurico Fonseca has received unrestricted research grants or served on speakers bureaus for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Servier, and UCB. Tatsuya Atsumi has accepted honoraria for educational meetings from Mitsubishi Tanabe Pharma, Chugai Pharmaceutical Co., Astellas Pharma Inc., Takeda Pharmaceutical Co., Pfizer Inc., AbbVie Inc., and Eisai and has received a research grant from Astellas Pharma Inc., Takeda Pharmaceutical Co., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Daiichi-Sankyo, Otsuka Pharmaceutical, and Pfizer Inc. Brian Hassett, Javier Coindreau, Ira Jacobs, Ehab Mahgoub, Julie O’Brien, Ena Singh, Steven Vicik, and Brian Fitzpatrick are full-time employees of Pfizer.

Funding

This report is supported by Pfizer Inc.

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Azevedo, V., Hassett, B., Fonseca, J.E. et al. Differentiating biosimilarity and comparability in biotherapeutics. Clin Rheumatol 35, 2877–2886 (2016). https://doi.org/10.1007/s10067-016-3427-2

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