FDA Reissues Exemption for Phase I Testing

July 24, 2008
Angie Drakulich

Angie Drakulich was editorial director of Pharmaceutical Technology.

ePT--the Electronic Newsletter of Pharmaceutical Technology

The US Food and Drug Administration issued a final rule on July 18 that exempts early Phase I investigational drugs from certain good manufacturing practice regulations.

Rockville, MD (July 24)-The US Food and Drug Administration issued a final rule on July 18, 2008 that exempts early Phase I investigational drugs from certain good manufacturing practice (GMP) regulations. The new regulation, Current Good Manufacturing Practice and Investigational New Drugs Intended for Use in Clinical Trials, adds paragraph (c) to 21 CFR 210.2, exempting certain investigational drugs (including biological drugs) for use in a Phase I clinical trial from compliance with Part 211. However, according to the rule, these drugs remain subject to the statutory requirements under section 501(a)(2)(B) of the act (i.e., current GMP or CGMP).

Exemption from compliance with Part 211 does not apply to an investigational drug that a manufacturer has made available for a Phase II or III clinical trial, or has lawfully marketed, and is being used for a Phase I trial. Such investigational drug products used for a Phase I trial must comply with Part 211. FDA will continue to oversee the manufacture of these drugs through its general statutory CGMP authority and review of investigational new drug (IND) applications. 

A companion guidance, CGMP for Phase I Investigational Drugs, recommends an approach for complying with CGMP statutory requirements such as standards for the manufacturing facility and equipment, the control of components, testing, stability, packaging, labeling, distribution, and record keeping.

“We are tailoring the CGMP requirements to make them appropriate to the earliest stages of drug development,” said US Health and Human Services Deputy Secretary Tevi Troy in an FDA news release. “This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection.”

In 1996, when FDA issued 21


Parts 210 and 211, which covered drugs and biologics, the agency stated that the regulations applied to all types of pharmaceutical production, but that it was considering proposing regulations more appropriate for the manufacture of drugs used in investigational clinical trials. According to the news release, certain requirements in Part 211 are directed at the commercial manufacture of products and may be inappropriate to the manufacture of investigational drugs used in Phase I clinical trials. The guidance describes an approach manufacturers can use to implement manufacturing controls that are appropriate for Phase I clinical trials.

Under the guidance, pharmaceutical manufacturers still must submit detailed information about relevant aspects of the manufacturing process as part of their IND applications. 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.

The rule takes effect 60 days after being published in the Federal Register.

Read the full guidance.

Read the full final rule.