The US Food and Drug Administration (FDA) on Thursday released a draft guidance for consultation on a revision to the International Council for Harmonization (ICH) guideline on reproductive toxicity testing.

The draft ICH guideline, S5(R3) Detection of Toxicity to Reproduction for Human Pharmaceuticals, was endorsed by the ICH Assembly in August and is currently in Step 3 of the formal ICH procedure as participating regulators hold public consultations on the guideline.

Specifically, the draft guideline discusses considerations for drugmakers when developing a testing strategy for identifying and characterizing the reproductive risk posed by a drug.

The guideline says that drugmakers should generally provide data from adult animals exposed to a drug and assess the drug's impact on "all stages of development from conception to sexual maturity."

But the guideline notes that "flexibility in testing strategy is warranted" as it is impossible to cover all possible scenarios in a single guideline.

That said, the guideline says that drugmakers should consider the following key factors when developing their reproductive toxicity testing strategy:

• The anticipated pharmaceutical use in the target population (especially in relation to reproductive potential and severity of disease);
• The formulation of the pharmaceutical and route(s) of administration intended for humans;
• The use of any existing data on toxicity, pharmacodynamics, pharmacokinetics, and similarity to other compounds in structure or activity;
• Selection of specific studies, test species/test system and dose levels.

According to FDA, the revised guideline is "intended to align with other ICH guidances, elaborate on concepts to consider when designing studies, and identify potential circumstances in which a risk assessment can be made based on preliminary studies."

FDA also says the draft guideline includes additional clarifications on the qualification and potential use of alternative assays to test for reproductive toxicity.

"To support using alternative assays, compounds that are either positive or negative in their ability to induce embryolethality or malformations are used in the process of qualifying assays," FDA writes.

But as FDA notes in the Federal Register notice announcing the consultation, the list of compounds identified in the draft guideline is not complete, and as such the agency says it is specifically looking for comments on additional compounds that could be added.

FDA, Federal Register Notice