FDA Rule and Companion Guidance Make Early Stage Clinical Drug Development Safe and Efficient

The U.S. Food and Drug Administration today issued a final regulation that makes early phase 1 clinical drug development safe and efficient by enabling a phased approach to complying with current good manufacturing practice (CGMP) statutes and FDA investigational requirements.

To facilitate this new approach, the regulation exempts most phase 1 investigational drugs from the requirements in 21 CFR part 211 — FDA will continue to exercise oversight of the manufacture of these drugs under FDA’s general statutory CGMP authority and through review of investigational new drug (IND) applications. A companion guidance recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, as well as testing, stability, packaging, labeling, distribution, and recordkeeping.

“With this action, we are tailoring the CGMP requirements to make them appropriate to the earliest stages of drug development. This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection" said U.S. Health and Human Services Deputy Secretary Tevi Troy.

When FDA originally issued CGMP regulations for drug and biological products (21 CFR parts 210 and 211), the agency stated that the regulations applied to all types of pharmaceutical production, but explained in the preamble to the regulations that FDA was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials. The reason for this is that certain requirements in part 211 are directed at the commercial manufacture of products — such as repackaging and relabeling of drug products, rotation of stock, and maintaining separate facilities for manufacturing and packaging. These types of requirements may be inappropriate to the manufacture of investigational drugs used in phase 1 clinical trials, many of which are carried out in small-scale, academic environments, typically involving fewer than 80 subjects.

“The new rule and guidance are intended to assure that manufacturers meet high standards for the safety of phase 1 drugs and biologics while removing unnecessary barriers that can slow the development of these potentially life-saving products,” said Rachel Behrman, M.D., associate commissioner for clinical programs and director of FDA’s Office of Critical Path Programs.

The guidance, CGMP for Phase 1 Investigational Drugs, describes an approach manufacturers can use to implement manufacturing controls that are appropriate for the phase 1 clinical trial stage of development. The approach described in this guidance reflects the fact that some manufacturing controls and the extent of manufacturing controls needed to achieve appropriate product quality differ among the various phases of clinical trials.

Manufacturers will continue to submit detailed information about relevant aspects of the manufacturing process as part of the IND application. The FDA may inspect the manufacturing operation, suspend a clinical trial by placing it on “clinical hold,” or terminate the IND if there is evidence of inadequate quality control procedures that would compromise the safety of an investigational product.