Testing for the potential for drugs to cause damage to DNA is an essential
component of any pre-clinical testing program. Genotoxic findings can halt further
development or cause problems and delays during pre-clinical work and product
registration. It is therefore advisable to screen for genotoxic effects as early
as possible.
ICH guidelines require that at least one in vivo assay is performed
prior to entry into phase II clinical trials. If this in vivo test
had been performed prior to entry into phase I, and all in vitro and in vivo tests were negative, then no further testing is required.
If any positive findings are found, then at least one more in vivo assay will
be required. Furthermore, additional mechanistic investigations may be helpful
to elucidate the mechanisms by which genotoxic effects are seen.
The in vivo assays available include:
- Rodent micronucleus
- Unscheduled DNA synthesis
- Comet assay
Huntingdon Life Sciences has extensive experience in all the necessary regulatory
studies, across many compound classes, and can additionally provide an expert
review or consultancy service on request.
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