Toxicology in the Drug Discovery and Development Process

Michael A. Dorato1, Lorrene A. Buckley1

1 Lilly Research Laboratories, Greenfield, Indiana
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.3
DOI:  10.1002/0471141755.ph1003s32
Online Posting Date:  April, 2006
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The primary objective of toxicology studies in the drug development process is to evaluate the safety of potential drug candidates. This is accomplished using relevant animal models and validated procedures. The ultimate goal is to translate the animal model responses into an understanding of the risk for human subjects. To this end, the toxicologist must be aware of the international guidelines for safety evaluation, as well as traditional and nontraditional toxicology models. As described in this unit, the typical toxicology profile consists of safety pharmacology, genetic toxicology, acute and subchronic toxicology, chronic toxicology, absorption, distribution, metabolism, and excretion (ADME) studies, reproductive and developmental toxicology, and an evaluation of carcinogenic potential.

Keywords: Drug discovery and development process; International regulatory approaches; International Harmonization, Toxicology Profiles

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Table of Contents

  • New Chemical Entities (NCEs; Synthetic Organic Chemicals)
  • New Biological Entities (NBEs)
  • Models of Drug Effect
  • Incorporation of Toxicokinetics into the Toxicity Profile
  • Regulatory Guidelines for Toxicology Profiles
  • Special Issues for Biotechnology‐Derived NBEs
  • IND Safety Reports
  • Summary and Future Approaches
  • Literature Cited
  • Figures
  • Tables
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Key References
   Chengelis, C.P., Holson, J.F., and Gad, S.C. (eds.). 1995. Regulatory Toxicology. Raven Press, New York.
  Comprehensive overview of regulatory issue in toxicology.
   Dean, 2004. See above.
  Immunotoxicology in drug development.
   Dorato and Vodicnik, 2001. See above.
  Overview of the drug development process and the role of toxicology.
   Dorato and Engelhardt, 2005. See above.
  Overview of NOAEL in safety assessment.
   FDA. 2006. Guidance for industry, investigators, and reviewers: Exploratory IND studies. January.
  Important reference on exploratory IND studies.
   Hayes, A.W. (ed.) 2001. Principles and Methods of Toxicology. Taylor and Francis, New York.
  Comprehensive overview of toxicology principles and methods.
   Lewis et al., 2002. See above.
  Adverse effects in toxicology studies.
   Sipes, I.G., McQueen, C.A., and Gandolphi, J. (eds.) 1997. Comprehensive Toxicology Vol. 2: Toxicological Testing and Evaluation. Elsevier Science Publishing, New York.
  Comprehensive review of the toxicology profile for a potential drug.
   Findlay and Kermani, 2000. See above.
  Complete guide to research and development trends in the pharmaceutical industry.
Internet Resources
  Current information on consumer protection, regulatory guidelines, and FDA organization.
  Current information from The European Medicines Agency (EMEA).
  Current information on ICH Topics (regulatory guidelines) and the structure of ICH.
  U.S. Government Printing Office listings of available documents—e.g., Code of Federal Regulations.
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