Vivotecnia

Genotoxicity

Genotoxicity

Registration of pharmaceuticals requires a comprehensive genotoxicity evaluation. Genotoxicity is assessed following the advice on study timing relative to clinical development given in the ICH guidance M3(R2) Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals. According to this guideline, in vitro tests to evaluate mutations and chromosome damage are required prior to first human exposure. If findings are positive or equivocal, additional testing must be performed. The standard battery of genotoxicity tests (ICH Topic S2) must be completed prior to initiating Phase II studies.

Besides ICH M3(R2), ICH guidance S2(R1) provides drug sponsors with recommendations on which tests should be performed to assess potential genotoxicity of new pharmaceuticals throughout their preclinical development. Vivotecnia provides a full genotoxicity testing service in compliance with these guidelines and also offers advice on testing conditions, data interpretation, and follow-up strategies should an in vitro assay give a positive response. Our services ensure that your compound’s potential to cause genetic damage is suitably tested in compliance with regulatory requirements.

Genotoxicity testing of pharmaceuticals

Test battery Option 1:

• Gene mutation test in bacteria.
• Cytogenetic test for chromosomal damage (in vitro metaphase chromosome aberration test or in vitro micronucleus test), or an in vitro mouse lymphoma Tk gene mutation assay.
• In vivo genotoxicity test, generally a test for chromosomal damage using rodent hematopoietic cells, either for micronuclei or for chromosomal aberrations in metaphase cells. (Can be integrated into repeat tox studies if a suitable dose is used.)

Testing battery Option 2:

• Gene mutation test in bacteria.
• In vivo genotoxicity assessment with two different tissues, usually an assay for micronuclei using rodent hematopoietic cells and a second in vivo assay. Typically, this would be a DNA strand breakage assay in liver, unless otherwise justified. (Can be integrated into repeat tox studies if a suitable dose is used.)