A key element in this streamlined approach to early clinical testing is to facilitate production of small quantities of test compounds needed for early clinical trials. To this end, FDA issued a new rule exempting manufacturers and research organizations from compliance with Good Manufacturing Practices (GMPs) when producing drugs for all phase 1 studies. A companion 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 lab to the clinic, said Janet Woodcock, FDA deputy commissioner for operations when she announced the new policy in January of this year. These innovations aim to establish more efficient clinical study plans and improve the success rates of the current drug development process, a primary goal of FDA's Critical Path Initiative.
MODERNIZING GMPSThe new rule reflects FDA's belief that manufacturers can establish a controlled process for reproducing a test product, even if they don't fully comply with GMP requirements. The regulation explains how researchers and manufacturers can adopt modified approaches for producing small quantities of test materials for phase 1 studies [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, according to FDA, because limited production operations have no need for rules regarding stock rotation for drug product containers or for repackaging and relabeling drug products. Small-scale production may involve just a few steps within a single facility, and operations may use disposable equipment and prepackaged water to accomplish this.
FDA specifies that the phase 1 exemption applies to investigational biological products normally subject to GMPs. These include recombinant therapeutics, vaccines, allergenic products, in vivo diagnostics, plasma derivative products, blood and blood products, gene therapies and somatic cellular therapies. The rule modification does not pertain to previously approved products now in phase 1 studies, or to phase 2 and 3 trials.
Consequently, pharma and biotech companies are likely to continue manufacturing clinical supplies in GMP-compliant facilities to avoid complications with later scale-up activities. At the same time, the new policy provides an option for biotech manufacturers to modify their operating procedures and validation requirements for producing early test products. The rule may also enable some companies to produce investigational agents in-house instead of contracting them out.
Even without full GMP compliance, FDA expects manufacturers to document processes for ensuring the safety and quality of an investigational drug as part of an IND filing. This involves providing sufficient chemistry, manufacturing, and control (CMC) information to describe the composition, manufacture, and control of the investigational drug product. FDA emphasizes that it still retains the authority to terminate a study, seize an investigational drug, or halt production if the manufacturer does not provide sufficient risk information in the IND, or fails to "establish and maintain appropriate standards of identity, strength, quality, and purity as needed for subject safety."