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Bacterial mutagenicity screening in the pharmaceutical industry
P A Escobar1, R A Kemper1, J Tarca1
1Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877-0368, USA.
Mutation Research
|December 25, 2012
Summary
This review examines bacterial mutagenicity assays used in pharmaceutical drug discovery. It highlights strategies for early hazard identification to minimize late-stage attrition and optimize candidate selection.
Area of Science:
- Pharmacology and Toxicology
- Drug Discovery and Development
- Genetics and Genomics
Background:
- Genetic toxicity testing serves as an early indicator for carcinogenicity and is a regulatory requirement for pharmaceutical development.
- Pharmaceutical companies aim to identify mutagenic candidates early to reduce late-stage attrition and resource expenditure.
- Current consensus is lacking on optimal mutagenicity testing platforms and timing for drug candidate selection.
Purpose of the Study:
- To review current applications of bacterial mutagenicity assays in pharmaceutical discovery programs.
- To summarize the advantages and disadvantages of various mutagenicity screening platforms and strategies.
- To discuss the sensitivity, specificity, and predictivity of early screening assays compared to regulatory tests.
Main Methods:
- Review of current literature and industry practices regarding bacterial mutagenicity assays.
- Analysis of data from pharmaceutical companies on early and late-stage drug discovery programs.
- Discussion of assay interpretation, testing strategies, and best practices.
Main Results:
- Most companies employ a tiered approach, starting with small-scale screening assays followed by more robust testing.
- Various mutagenicity screening platforms have distinct advantages and liabilities.
- The sensitivity, specificity, and concordance of early screening assays with regulatory tests are crucial for effective candidate selection.
Conclusions:
- Bacterial mutagenicity assays are vital tools in pharmaceutical discovery for early hazard identification.
- Optimized testing strategies are essential for maximizing resource efficiency and minimizing the risk of advancing mutagenic compounds.
- Continued evaluation and refinement of mutagenicity testing platforms are necessary to improve drug development success rates.
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