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Carcinogenicity Testing Strategies for Small Molecules

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Genotoxicity and Carcinogenicity Testing of Pharmaceuticals

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Abstract

This chapter provides an overview of the current state of carcinogenicity testing strategies used to support marketing approvals of human small molecule pharmaceuticals. Testing strategies for biologic molecules is beyond the scope and the reader is referred to Chap. 8 by Dempster et al. In this chapter a brief history of pharmaceutical carcinogenicity testing is summarized that describes the path of evolution to our current state. The current state of pharmaceutical carcinogenicity testing strategy as defined by internationally agreed upon ICH guidelines is reviewed, including the use of transgenic mouse models in pharmaceutical carcinogenicity testing strategies. Limitations of these current testing approaches are summarized and examples are used to describe and explain the implications and impact of such limitations on practical aspects of pharmaceutical development. Often times, approaches are successfully deployed by industry scientists to support conclusions that positive rodent carcinogenicity study outcomes are related to compound class effects and are not human relevant, and examples are provided where product marketing has been enabled. Finally based on decades of such repeated experiences, a vision for a near future state pharmaceutical carcinogenicity testing strategy is described where the burdens of carcinogenicity testing may be reduced without compromising human safety, and the steps in progress to realize that vision are summarized.

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Author information

Authors and Affiliations

  1. US Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA

    Abigail Jacobs

  2. Safety Assessment and Laboratory Animal Resources, Merck and Co., Inc., West Point, PA, USA

    Frank D. Sistare

Authors
  1. Abigail Jacobs
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  2. Frank D. Sistare
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Corresponding author

Correspondence to Frank D. Sistare .

Editor information

Editors and Affiliations

  1. Vice- President of Drug Safety Evaluation, Bristol-Myers Squibb, Princeton, New Jersey, USA

    Michael J. Graziano

  2. ToxRox Consulting, McLean VA 22101, Virginia, USA

    David Jacobson-Kram

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© 2015 Springer International Publishing Switzerland

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Jacobs, A., Sistare, F.D. (2015). Carcinogenicity Testing Strategies for Small Molecules. In: Graziano, M., Jacobson-Kram, D. (eds) Genotoxicity and Carcinogenicity Testing of Pharmaceuticals. Springer, Cham. https://doi.org/10.1007/978-3-319-22084-0_7

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