4.2.2.5 — Excretion

Mass balance and routes of excretion studies

Requirements by Phase

IND Phase 1: basic IND Phase 2: full IND Phase 3: required NDA: required

Content Requirements

• Routes and extent of excretion (urine, feces, bile, expired air)
• Mass balance study results
• Excretion in milk (if performed)
• Renal clearance estimates

Expected Deliverables

• Mass balance / excretion study report
• Excretion summary table by route

ICH Guidelines: M3(R2)

Regulatory Requirements (FDA IND PHASE 1)

• [All phases] If known, this section should contain: 1) a description of the pharmacologic effects and mechanism(s) of actions of the drug in animals, and 2) information on the absorption, distribution, metabolism, and excretions of the drug.

Regulatory Requirements (ICH M3R2)

• [before Phase 3] Further PK information (absorption, distribution, metabolism, excretion) and in vitro biochemical information relevant to potential drug interactions should be available before exposing large numbers of human subjects or treating for long duration (generally before Phase III).

Regulatory Requirements (ICH S5R3)

• [All] A specific risk assessment for breastfeeding should be based on hazards identified in PPND/ePPND studies, considering offspring growth/development effects attributed to milk excretion and systemic exposure data in pups.

Regulatory Requirements (ICH S9)

• [Nonclinical/Clinical] Further information on absorption, distribution, metabolism and excretion of the pharmaceutical in animals should normally be generated in parallel with clinical development.

Source: ICH M3(R2)