A key element in this streamlined approach to early clinical testing is to make it easier for study sponsors to produce the small quantities of test compounds needed for early clinical trials. To this end, FDA is exempting manufacturers and research organizations from compliance with good manufacturing practices (GMPs) when producing drugs for all Phase I studies. A guidance offers advice for ensuring that test products meet quality standards and that study sponsors document production processes and procedures, particularly for sterile products and biologics. A major bottleneck in drug development is moving from the laboratory to the clinic, pointed out FDA Deputy Commissioner for Operations Janet Woodcock in announcing the new policy at the beginning of the year. These innovations aim to spur faster clinical development.
When FDA officials wrapped up the first two years of its effort to modernize "GMPs for the 21st Century" in September 2004, one of the items on the list of unfinished business was the need to streamline GMPs for clinical supplies. The original 1978 GMP regulations specified that the rules applied to investigational drug products, but the regulators left the door open to future modifications. They recognized that a prime objective of setting manufacturing standards for clinical supply production is to establish a framework for the manufacturer to operate a well-documented and controlled process for reproducing a product for further testing and ultimate commercial production. The new policy reflects FDA's current belief that manufacturers can meet these objectives without fully complying with GMP requirements; this approach, according to Woodcock, fits FDA's initiative to end a "one-size-fits-all approach to manufacturing."
The new rule explains that researchers and manufacturers may adopt modified approaches for producing small quantities of test products for use in Phase I studies, which usually involve less than 80 participants (see "Current Good Manufacturing Practice Regulation and Investigational New Drugs," Federal Register, Dec. 17, 2006, found at http://www.fda.gov/OHRMS/DOCKETS/98/fr/06.353.pdf). This approach is appropriate, FDA explains, because investigational production does not raise many of the issues related to manufacturing products for later clinical studies or for commercial marketing. Limited production operations have no need for rules about rotating stock for drug product containers, for example, or repackaging and relabeling drug products or maintaining separate packaging and production areas. Small-scale production may involve just a few steps within a single facility, and operations may use disposable equipment and prepackaged water.
FDA specifies that the Phase I exemption policy also applies to investigational biological products subject to GMPs. Such products include recombinant therapeutics, vaccines, allergenic products, in vivo diagnostics, plasma derivative products, blood and blood products, gene therapies, and somatic cellular therapies.