Despite greater emphasis on safety as a result of attrition, the application of toxicology (~6% of the total R&D budget) to the preclinical drug development process has remained largely unchanged for over 30 years!  For this reason, the impetus to reduce safety risks early has been slow to evolve, with limited resources specifically dedicated to this endeavor. Revolutionizing  the way that toxicology is applied, such as moving from a hazard  identification and risk assessment preclinical paradigm to one that reduces or  eliminates risk prior to major expenditures,  may provide a means of narrowing the productivity gap within the biopharmaceutical industry.  This paper suggests a strategy for the integration of toxicology into early drug development (discovery phase) through identification of potential safety issues related to therapeutic use, target selection, and compound selection, with a primary emphasis on new chemical entities. Information gained may also guide the appropriate selection of the toxicological species used to support clinical trials.  Assays predictive of target organ effects (insufficiently discussed, in my opinion, in the present article) vs. assays designed to look at specific mechanisms of drug-induced toxicities at the intracellular level are presented relative to the need for development of high throughput safety screens.

In conclusion, the preclinical toxicology strategy needs to accommodate the unique attributes of the target, the compound, and the therapeutic application, along with assays that are “fit-for-purpose” for that specific project. This paper provides an overview of safety issues for initial exploration and cites possible techniques available to address them in the preclinical space.

Source:  Pharmaceutical Outsourcing

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