Draft Guidance Tackles Crossover Risk of Male API Use to Potential Offspring

The FDA wants drugmakers to assess the risks of active pharmaceutical ingredients taken by men on the development of embryos and fetuses of their female partners.

While guidance exists on the risk of pharmaceuticals administered to pregnant or potentially reproductive females, there’s a lack of consistency in clinical trial designs regarding the risk for sexual partners of men being given an API, the agency says in draft guidance.

The guidance focuses on two main risks when an API has been shown to be genotoxic or a potent developmental toxicant — developmental risk caused by the effects of the API on the germ cell before conception and developmental toxicity in the fetus when the API is transferred to a pregnant partner via semen.

The guidance also applies to new molecular entities for which risk has not been determined, the FDA notes.

Before administering a drug, sponsors should conduct in vitro studies such as genotoxicity assays and general toxicity in vivo studies with histopathology and/or semen analysis. They should also clinically determine the amount of drug or biologic secreted into semen or perform pharmacokinetic modeling.Until the developmental or reproductive risk of an API is known, precautions such as contraceptives should be taken to prevent pregnancy or exposure to a potential embryo.

When an API is shown to have developmental risk, contraceptives should be used until the potential for male-mediated effects has been fully assessed, the draft guidance says.

The risks associated with transfer of a drug or biologic via seminal fluid also apply to men who have had a vasectomy, the FDA says.

Comments on the draft guidance are due Aug. 11. Read it at www.fdanews.com/06-12-15-MaleMediated.pdf. To read the Federal Register notice, go to www.fdanews.com/06-12-15-Notice.pdf. — Kellen Owings