4.2.3.5.1 — Fertility and Early Embryonic Development

Fertility and early embryonic development study (Segment I) evaluating effects on male/female fertility

Requirements by Phase

IND Phase 2: conditional IND Phase 3: required NDA: required

Content Requirements

• Fertility and early embryonic development study summarized
• Brief methodology and important findings
• Effects on male and female fertility parameters
• Pre-mating through implantation endpoints
• GLP required, rat preferred species

Expected Deliverables

• Fertility study report (GLP, rat)
• Summary table of fertility parameters and findings

ICH Guidelines: S5(R3)

Regulatory Requirements (ICH M3R2)

• [Phase 1, Phase 2] Men can be included in Phase I and II trials before the male fertility study.
• [before Phase 3] A male fertility study should be completed before initiating large-scale or long-duration clinical trials (e.g., Phase III).
• [Phase 1, Phase 2] WOCBP can be included in repeated-dose Phase I and II trials before female fertility study if female reproductive organs are evaluated in repeated-dose toxicity studies.
• [before Phase 3] Nonclinical studies addressing female fertility should be completed to support WOCBP inclusion in large-scale or long-duration clinical trials (e.g., Phase III).

Note: P2: required if women of childbearing potential enrolled

Source: ICH S5(R3)