The US Food and Drug Administration (FDA) on Wednesday finalized guidance for drugmakers on identifying and evaluating early signals that could indicate whether a drug might have adverse effects on the testes and when clinical trials are necessary to assess those risks.
Specifically, the 14-page guidance lays out recommendations for identifying nonclinical signals that suggest risk of testicular toxicity; conducting nonclinical assessments to further evaluate the risk; clinical monitoring; and study design for clinical trials primarily aimed at evaluating drugs for testicular toxicity.
The guidance, which finalizes a draft version released in 2015, includes revised recommendations for nonclinical study design, including species selection, chronic study design, histopathology assessment, sperm quality and what findings increase concerns for impaired fertility.
The guidance has also been revised to stress that “to the extent possible, subjects enrolled in the dedicated clinical safety trial represent the intended population.”
According to the guidance, evaluating a drug for testicular toxicity is challenging as there are only a few clinical markers that can track potential changes in testicular function and because there is a latency period of several months between the time a drug-related injury occurs and when it can be detected using semen analysis.
As such, FDA says it is standard for drugmakers to conduct nonclinical studies to look for evidence of adverse effects on the male reproductive system in animals…