The new regulations, which acknowledge that manufacturing controls should be appropriate to each stage of development, apply specifically to the section of the Code of Federal Regulations (Title 21 CFR Part 211) that refers to drug product manufacturing; they extend, by implication, to the production of active pharmaceutical ingredient (API), i.e., bulk drug substance. The new regulations apply to phase 1 clinical trials for all drug and biological products not previously tested in a later phase of clinical testing, but do not apply to certain cell-based products.
In lieu of full GMP compliance, FDA will require manufacturers to maintain proper safety controls in the form of tentative release criteria. The FDA will also require manufacturers to maintain a series of written procedures for all manufacturing processes and controls; to ensure that facilities and equipment are used properly; and to maintain an accurate production record of all phase 1 clinical supplies. FDA has issued a guidance to describe this. When limited resources exist, contract vendors are generally best suited to support phase 1 manufacturing.
Manufacturers should not presume that FDA will permit manufacturing of phase 1 clinical supplies outside the guiding principles of GMP regulations. Manufacturers should assume that FDA will question or audit manufacturing operations when safety concerns arise. Consultation with FDA will still be beneficial in certain situations and perhaps can be best handled through a pre-IND meeting.
The new GMP regulations for drugs in phase1 clinical trials are based on common sense, adherence to good scientific practices, and continuing concern for patient safety. In this setting, contract manufacturers and sponsors should do the following:
James A. Taylor, PhD, Partner,
Merchant-Taylor International, 162 S. Rancho Santa Fe Rd., Encinitas, CA 92024, (tel) 858.675.0808. (fax) 858 675.1047, [email protected]