GMPs for Phase I Investigational Drugs
FDA has issued new Guidance regarding GMPs for Phase I Investigational Drugs. This guidance is intended to assist 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 1 clinical trials.2 These drugs, which include biological drugs, are exempt from complying with 21 CFR part 211 under 21 CFR 210.2(c) (referred to as phase 1 investigational drugs).
This guidance applies, as part of CGMP, quality control (QC) principles to the manufacture of phase 1 investigational drugs (i.e., interpreting and implementing CGMP consistent with good scientific methodology), which foster CGMP activities that are more appropriate for phase 1 clinical trials, improve the quality of phase 1 investigational drugs, and facilitate the initiation of investigational clinical trials in humans while continuing to protect trial subjects.
The guidance finalizes the draft guidance entitled “INDs—Approaches to Complying with CGMP During Phase 1” dated January 2006; and is being issued concurrently with a final rule that specifies that 21 CFR part 211 no longer applies for most investigational products (see section III), including certain exploratory products (Ref. 2) that are manufactured for use in phase 1 clinical trials.
During product development, the quality and safety of phase 1 investigational drugs are maintained, in part, by having appropriate QC procedures in effect. Using established or standardized QC procedures and following appropriate CGMP will also facilitate the manufacture of equivalent or comparable IND product for future clinical trials as needed.
Adherence to CGMP during manufacture of phase 1 investigational drugs occurs mostly through:
• Well-defined, written procedures
• Adequately controlled equipment and manufacturing environment
• Accurately and consistently recorded data from manufacturing (including testing)
Manufacturers may have acceptable alternatives to meet the objectives described in this guidance. It is the manufacturer’s responsibility to provide and use such methods, facilities, and manufacturing controls to ensure that the phase 1 investigational drug meets appropriate standards of safety, identity, strength, quality, and purity. Manufacturers of phase 1 investigational drugs should consider carefully how to best ensure the implementation of standards, practices, and procedures that conform to CGMP for their specific product and manufacturing operation.
FDA recommends the following steps to establish the appropriate manufacturing environment for phase 1 investigational drugs:
• A comprehensive and systematic evaluation of the manufacturing setting (i.e., product environment, equipment, process, personnel, materials) to identify potential hazards
• Appropriate actions prior to and during manufacturing to eliminate or mitigate potential hazards to safeguard the quality of the phase 1 investigational drug
Quality Systems has been leading startup firms and major research institutions into Phase I Investigational Trials by implementing many of the concepts presented in the new FDA Guidance. With more than 30 years experience and over 45 INDs we can facilitate the appropriate quality and development strategy to get your Phase I trial initiated.