Use of "Big Data" to Evaluate Responses to Changes in Regulatory Guidelines: Trends in Genotoxicity Testing Packages for New Pharmaceutical Products.

Background: In 2006, a concept paper (ICH S2(R1)) describing the need for revision of the ICH guidelines on genotoxicity testing for new "small molecule" pharmaceuticals (then ICH S2A and ICH S2B) was finalised. As a result, testing strategy has changed, and flexibility has been introduced in the form of two "equally suitable" options for completing the battery of genotoxicity studies required to support clinical development and marketing of new products.

Methods: The TIBCO Spotfire platform was used to create a specific view of available in-house data on genotoxicity studies conducted to support pharmaceutical product development over a period of approximately 12 years. The available in-house dataset comprised all reportable non-clinical data from Good Laboratory Practice (GLP) compliant and non-GLP/screening studies on regulated products (including pharmaceuticals, industrial chemicals, agrochemicals, and medical devices) across multiple testing sites, in different geographical locations.

Results: The analysis showed clear trends in the numbers and types of genotoxicity studies conducted on small molecule pharmaceutical products during development, which correlated with the changes in the available regulatory guidance over time. More interestingly, where two "equally suitable" options for genotoxicity testing are described in the international guidance, there is a clear preference for ICH S2(R1) Option 1 (70-80% of testing) compared to Option 2 (20-30%).

Conclusion: Use of 'Big Data' identified trends in the newer approach to genotoxicity testing by industry in the light of the updated regulatory guidance.