Overall impact of the regulatory requirements for genotoxic impurities on the drug development process

Eur J Pharm Sci. 2011 May 18;43(1-2):1-15. doi: 10.1016/j.ejps.2011.03.004. Epub 2011 Mar 21.

Abstract

In the last decade a considerable effort has been made both by the regulators and the pharmaceutical industry to assess genotoxic impurities (GTI) in pharmaceutical products. Though the control of impurities in drug substances and products is a well established and consolidated procedure, its extension to GTI has given rise to a number of problems, both in terms of setting the limits and detecting these impurities in pharmaceutical products. Several papers have dealt with this issue, discussing available regulations, providing strategies to evaluate the genotoxic potential of chemical substances, and trying to address the analytical challenge of detecting GTI at trace levels. In this review we would like to discuss the available regulations, the toxicological background for establishing limits, as well as the analytical approaches used for GTI assessment. The final aim is that of providing a complete overview of the topic with updated available information, to address the overall GTI issue during the development of new drug substances.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical
  • DNA Damage
  • Drug Contamination* / legislation & jurisprudence
  • Drug Contamination* / prevention & control
  • Drug Industry / standards
  • Europe
  • Guidelines as Topic
  • Humans
  • International Cooperation
  • Mice
  • Mutagens* / analysis
  • Mutagens* / toxicity
  • Pharmaceutical Preparations / analysis*
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / standards
  • Quality Control
  • Risk Assessment
  • Toxicity Tests / standards
  • United States
  • United States Food and Drug Administration

Substances

  • Mutagens
  • Pharmaceutical Preparations