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Drug Development of Therapeutic Monoclonal Antibodies

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Abstract

Monoclonal antibodies (MAbs) have become a substantial part of many pharmaceutical company portfolios. However, the development process of MAbs for clinical use is quite different than for small-molecule drugs. MAb development programs require careful interdisciplinary evaluations to ensure the pharmacology of both the MAb and the target antigen are well-understood. Selection of appropriate preclinical species must be carefully considered and the potential development of anti-drug antibodies (ADA) during these early studies can limit the value and complicate the performance and possible duration of preclinical studies. In human studies, many of the typical pharmacology studies such as renal or hepatic impairment evaluations may not be needed but the pharmacokinetics and pharmacodynamics of these agents is complex, often necessitating more comprehensive evaluation of clinical data and more complex bioanalytical assays than might be used for small molecules. This paper outlines concerns and strategies for development of MAbs from the early in vitro assessments needed through preclinical and clinical development. This review focuses on how to develop, submit, and comply with regulatory requirements for MAb therapeutics.

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(modified from Chirmule et al. [62]; reproduced with permission of Springer)

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Acknowledgments

The authors would like to thank the reviewers for their thoughtful consideration of this manuscript.

Author contributions

Drs. Mould and Meibohm contributed equally to the writing of this review article.

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Authors and Affiliations

  1. Projections Research Inc., Phoenixville, PA, 19046, USA

    Diane R. Mould

  2. College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA

    Bernd Meibohm

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Correspondence to Diane R. Mould.

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Conflict of interest

Dr Mould is president of Projections Research Inc., a consulting company for the pharmaceutical industry. Dr Meibohm provides consultancy services to multiple entities in the pharmaceutical industry.

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No sources of funding were used to assist in the preparation of this manuscript.

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Mould, D.R., Meibohm, B. Drug Development of Therapeutic Monoclonal Antibodies. BioDrugs 30, 275–293 (2016). https://doi.org/10.1007/s40259-016-0181-6

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