Testicular Toxicity. An International Consortium for Innovation and Quality in Pharmaceutical Development (IQ)...

The International Consortium for Innovation & Quality in Pharmaceutical Development (IQ) Preclinical Safety Leadership Group (DruSafe) sponsored the formation of a Testicular Toxicology Working Group (TTWG) which conducted an industry-wide survey to gather information and gain insight into the process by which companies evaluate, interpret and modify drug development programs in response to testicular toxicity in nonclinical toxicology studies. Nineteen (19) IQ member companies participated, providing information on 127 test items reported to be associated with testicular toxicity during drug development. The majority of test items were small molecules, with nearly half of test items being developed for oncology indications. Evidence of testicular toxicity in human clinical trials was rare (1.6%); however, most test items lacked sufficient clinical data. When exposure multiples at the no observed adverse effect level (NOAEL) were known, >80% of responses received reported that testicular toxicity had no negative effect on clinical development. Use of in vitro or ex vivo assays were utilized on a case-by-case basis, with assays being used to answer specific questions and/or evaluate specific mechanisms and/or manifestations of testicular toxicity. Biomarkers, utilized when cause for concern occurred on specific programs and primarily for investigational purposes, predominantly included assessment of serum hormones.