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New FDA Guidance Seeks to Protect Unborn from Fathers’ Drug Toxicities

Posted 12 June 2015 | By Alexander Gaffney, RAC

New FDA Guidance Seeks to Protect Unborn from Fathers’ Drug Toxicities

When the US Food and Drug Administration (FDA) evaluates a drug, it's not just concerned about the drug's effect on the intended patient; it's also concerned about the drug's potential effect on other patients as well.

That's the take-home message of a new draft guidance issued by FDA, Assessment of Male-Mediated Developmental Risk for Pharmaceuticals.


The guidance concerns a long-standing concern for regulators: that a drug might affect an unborn child.

For women, such risks have been a matter of concern for decades. The 1962 passage of the Kefhauver-Harris Amendments—the law which gave FDA much of its present-day authority to regulate the safety and efficacy of drugs on the basis of clinical data—were in part a response to birth defects caused by the morning sickness drug Thalidomide. Though the drug was never introduced in the US, lawmakers were concerned that FDA didn't have the authority to require drugmakers to provide evidence of the safety and effectiveness of their drugs.

FDA now requires drugmakers to evaluate the potential for their products to cause birth defects under a handful of guidance documents: Evaluating the Risks of Drug Exposure in Human Pregnancies, Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products — Content and Format, and Establishing Pregnancy Exposure Registries.

In addition, specific controls have been added to certain drugs under authority given to FDA by the 2007 Food and Drug Administration Amendments Act (FDAAA). Under the law, FDA is able to control the use of certain drugs using what are known as Risk Evaluation and Mitigation Strategies (REMS). For example, Thalomid—brand name Thalidomide, the same drug which caused birth defects in the early 1960s—is subject to a strict REMS plan which seeks to prevent its use in pregnant women or women who might become pregnant.

But women aren't the only focus of Thalidomide's REMS plan. In fact, the plan also requires men receiving the drug to not donate sperm during treatment, and for four weeks following the termination of treatment.

New Guidance

The issue of how drugs affect men, and in turn their offspring (and partners), is the focus of FDA's latest guidance on male-mediated development risks.

The guidance, FDA explains, "presents an overview" of regulators' approach to assessing how drugs affect sperm and seminal fluid, which can both affect fetal development and offspring.

FDA said that at present, "there is a lack of consistency in clinical trial protocol designs regarding pregnancy risk for sexual partners of men being administered an API."

"The conceptus of a female sexual partner may be subject to developmental risk associated with pre- or postconception exposure of a male to an API," FDA wrote. "Such male-mediated developmental toxicity may result from an effect of the API on the male germ cell before conception or occur as a result of direct exposure of the conceptus to the pharmaceutical following seminal transfer and vaginal uptake in a pregnant partner."

To assess the potential risks of a drug, FDA recommends companies first consider what is known about drugs similar to the one under development, any pharmacologic properties "that suggest risk," the properties of the drug and how it is absorbed and metabolized by the body, and the reproductive and developmental toxicity of the drug.

Drugs with unknown risks or known risks should be accompanied with measures to reduce exposure, such as contraception, FDA explained. The guidance also contains recommendations on which tests to use to investigate potential fetal toxicity.

Comments on the guidance will be accepted until 11 August 2015.


Assessment of Male-Mediated Developmental Risk for Pharmaceuticals (FR)

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