4.2.2.2 — Absorption

Absorption studies including bioavailability, rate and extent of absorption

Requirements by Phase

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

Content Requirements

• Absorption extent and rate from in vivo and in situ studies
• Kinetic parameters (Cmax, Tmax, AUC, bioavailability)
• Bioequivalence and bioavailability (serum/plasma/blood PK studies)
• Absorption mechanism studies if performed

Expected Deliverables

• PK study reports with kinetic parameter tables
• Absorption summary by species and 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 Q6A)

• [Marketing Approval] Water content: A test for water content should be included when the new drug substance is hygroscopic, degraded by moisture, or a stoichiometric hydrate, with acceptance criteria justified by data on hydration/moisture absorption effects.
• [Marketing Approval] Water content: A test for water content should be included when appropriate, with acceptance criteria justified by data on hydration or water absorption effects.

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)