In silico toxicology models and databases as FDA Critical Path Initiative toolkits

In silico toxicology methods are practical, evidence-based and high throughput, with varying accuracy. In silico approaches are of keen interest, not only to scientists in the private sector and to academic researchers worldwide, but also to the public. They are being increasingly evaluated and applied by regulators. Although there are foreseeable beneficial aspects -- including maximising use of prior test data and the potential for minimising animal use for future toxicity testing -- the primary use of in silico toxicology methods in the pharmaceutical sciences are as decision support information. It is possible for in silico toxicology methods to complement and strengthen the evidence for certain regulatory review processes, and to enhance risk management by supporting a more informed decision regarding priority setting for additional toxicological testing in research and product development. There are also several challenges with these continually evolving methods which clearly must be considered. This mini-review describes in silico methods that have been researched as Critical Path Initiative toolkits for predicting toxicities early in drug development based on prior knowledge derived from preclinical and clinical data at the US Food and Drug Administration, Center for Drug Evaluation and Research.