CGMP guidance for Phase I Investigational Drugs

This guidance got approved in July , 2008

This Replaces guidance issued in 1991 “Preparation of Investigational New Drug Products for the manufacture of phase I investigational drugs” . However the 1991 guidance still applies to the manufacture of investigational new drugs(human and animal) used in phase II and phase III clinical trials
This guideline is intended to help in applying current good manufacturing practice (CGMP) required under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in the manufacture of most investigational new drugs (IND) used in phase I clinical trials.

This guidance describes an approach to
•Implementation of manufacturing controls that are appropriate for phase I clinical trial stage of development
•Product quality differences
−Between investigational drugs and commercial manufacture
–Among the various phases of clinical trials
•FDA's CGMP for the 21 Century initiative
– Where applicable, manufacturers are also expected to implement manufacturing controls that reflect product and manufacturing considerations, evolving process and product knowledge, and manufacturing experience .
Scope

This guidance applies to phase I investigational drugs for human use that are
•manufactured in small or large-scale environments
•typically designed to assess tolerability, or feasibility, for further development of a specific drug or biological product
•new drug and biological products including finished dosage forms used as placebos

- Investigational drugs used in phase I studies described in 21 C.F.R. § 312.21 of FDA’s IND regulations are EXEMPTED from the Current Good Manufacturing Practice (“CGMP”) requirements in 21 C.F.R. Part 211
- This exemption does not apply to an investigational drug for use in a phase I study once the investigational drug has been made available for use by or for the sponsor in a phase II or phase III study, or the drug has been lawfully marketed
- The exempted phase I drugs are, however, still required to meet statutory (as opposed to regulatory) requirements for CGMP

This guidance DOES NOT apply to phase I investigational drugs for human use that are
−Human cell or tissue products regulated solely under § 361 of the Public Health Service Act
−Clinical trials for products subject to the device approval or clearance provisions of the FD&C Act
−Investigational products manufactured for phase II and phase III clinical trials
−Previously approved products that are being used in phase I clinical trials (e.g. for a new indication)
−Positron Emission Topography (PET) drugs that are subject to § 501(a)(2)(C) of the FD&C Act and/or the new PET CGMP in 21 CFR part 212 when finalized