Comment Requested: Assessment of Male-Mediated Developmental Risk for Pharmaceuticals Draft Guidance

The Food and Drug Administration (FDA) announced the availability of a draft guidance for industry entitled “Assessment of Male-Mediated Developmental Risk for Pharmaceuticals.” This draft guidance provides recommendations to sponsors for assessing risks to embryo/fetal development resulting from administration of an active pharmaceutical ingredient (API) to males either through an effect on the male germ cell or from fetal exposure following seminal transfer of a potentially developmental toxicant to pregnant females. The need for measures to mitigate the risk to embryo/fetal development posed by males participating in clinical trials is also addressed.

The Teratology Society will be preparing comments on the draft guidance. This will be done through the Public Affairs Committee (PAC) with input from individual members and approval by Council.

Please add your comments on the draft guidance below using the Comment function (you must be logged in to BDR Connection). The final date for comments to be submitted for consideration/inclusion is July 17.

If you would like to participate in the PAC's discussion about the draft guidance and the development of the Society's comments, please contact PAC Chair Chris Lau as soon as possible.

More details may be found on the Federal Register.


1 Comment

Assessment of Male-Mediated Developmental Risk for Pharmaceuticals Draft Guidance

July 2, 2015 02:29 PM by Dinesh J. Stanislaus, PhD

Page 4: lines 124 to 127 : Based on what is written here, a clinical trial with a non-genotoxic API that doesn’t have a concern for developmental toxicity based on pharmacology and without any DART studies will require precautions to prevent pregnancy of a partner
or exposure to a conceptus. By this definition all typical Phase I clinical trials
will require contraception use.  FDA guidance is not well substantiated by scientific evidence.  It is accepted that using the most generous assumptions exposure in women
via semen is 3 or more orders of magnitude lower than the blood concentration
in man, whose semen is supposed to be transferring the API (Birth Defects
Research (Part B) 74:119, 2005). Recommend reconsidering this statement
to state what is known about seminal exposure to women, and taking
precautions if the drug target dictates need for caution for non-genotoxic API

Page 5:  For clarity request providing literature references for various assumptions made when calculating drug exposure in women via semen. For example, human blood volume assumptions, ejaculate volume etc.

Page 8 Line 28: More clarity is needed on the recommendation for contraception use for one full spermatogenic cycle. Is it warranted for situations where there is concern only on seminal transfer or more relevant in situations where male germ-line mediated developmental toxicity is of concern?

Recent Stories
CERSI-FDA Workshop on Prenatal Somatic Cell Gene Therapies, October 26, 2021

Call for Nominations: F. Clarke Fraser New Investigator Award, Patricia Rodier Mid-Career Award, and Edward W. Carney Distinguished Service Award

Register Today for the Virtual Human Teratogens Course, November 2-4, 2021