Evaluating Reproductive Toxicity in Oncology Drugs: FDA Finalizes Guidance

Regulatory NewsRegulatory News | 09 May 2019 |  By 

The US Food and Drug Administration (FDA) on Thursday finalized guidance to help sponsors of oncology drugs evaluate reproductive toxicity, with recommendations for labeling on duration of contraception following cessation of therapy.

The 10-page guidance finalizes a draft from September 2017 and is meant to complement ICH’s S9 guideline on Nonclinical Evaluation for Anticancer Pharmaceuticals and a question and answer document on S9.

The guidance deals with evaluating embryo-fetal development (EFD) and assessing the need for an EFD study with a weight of evidence (WOE) approach, which is further explained in detail in the guidance.

“For small molecules, EFD studies, when needed, are typically conducted in two species; and when the study is positive for teratogenicity or embryo-fetal lethality in one species, generally a study in the second species is not warranted,” the guidance says. “For biotechnology-derived pharmaceuticals, when an EFD study is needed, generally a study in one pharmacologically relevant species should be sufficient. In general, a definitive study is not warranted if a dose-range finding study (including non-good laboratory practice) shows clear evidence of embryo-fetal lethality or teratogenicity.”

As far as pre- and postnatal development (PPND) studies, the guidance says a PPND study is not warranted for pharmaceuticals intended to treat patients with advanced cancer, but a PPND study may be warranted on a case-by-case basis when the cancer is not advanced.

In terms of assessing the risk for specific populations, the guidance addresses pharmaceuticals used only in men, those used only in postmenopausal woman and those used in pediatric populations.

And on the topic of labeling regarding the use of contraception following cessation of therapy to minimize embryo or fetal risks, the guidance says for men: “Use of contraception for a period of 3 months after cessation of therapy will minimize the risk of adverse embryo-fetal effects from genotoxic pharmaceuticals.”

Women are recommended to use contraception for a period of six months after cessation of therapy.

“The 6-month contraception labeling recommendation for genotoxic pharmaceuticals after cessation of therapy (see Table 1) covers the growth and maturation phase of folliculogenesis and is expected to allow elimination of most damaged follicles and oocytes,” the guidance says.

Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations: Guidance for Industry


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