FDA is working to help manufacturers adopt innovative approaches for assuring that drugs meet quality standards, as seen in
its final guidance on quality systems approaches published last September. Additional guidances will clarify approaches for
aseptic processing, process validation, investigating out-of-specification test results, and manufacturing standards for Phase
1 clinical supplies. The anticipated Q-10 standard from the International Conference on Harmonization (ICH) will further describe
approaches for harmonizing quality systems on a global basis. FDA also plans to revise its regulations governing Part 11 and
A key ORA initiative is to improve the knowledge and training of pharmaceutical field inspectors so that they better understand
sophisticated quality management systems and risk management approaches they encounter at production sites. FDA has improved
the operation of its Team Biologics cadre that inspects biotech manufacturing facilities, with an eye to implementing quality
management systems approaches. This includes establishing metrics to better assess team performance and to determine the need
for improved training and qualification of team members. FDA is working with the Pharmaceutical Quality Research Institute
(PQRI) to evaluate Team Biologics operations and its impact on manufacturers, according to Mary Malarkey, director of the
Office of Compliance and Biologics Quality in the Center for Biologics Evaluation and Research (CBER).
Similarly, FDA is establishing a Pharmaceutical Inspectorate (PI) to handle inspections of drug manufacturing facilities.
Following the Team Biologics model, this group of highly trained individuals will have the knowledge needed to evaluate facilities
that have adopted the latest scientific and technological innovations for assuring drug quality. ORA and the Center for Drug
Evaluation and Research (CDER) are working hard to build a cadre of 50 certified PI members by 2007. PI members would spend
80% of their time conducting drug quality inspections, compared to about 25% for regular field inspectors.
A main approach for utilizing FDA resources more efficiently is to target inspections and oversight to industry operations
most in need of FDA scrutiny. CDER has established a risk-based site selection program for identifying those drug manufacturing
facilities to schedule for GMP inspection, based on a range of risk factors associated with products, processes, and facility
characteristics. ORA now plans to extend this risk-based model to better target Team Biologics inspections to high priority
situations. The long-term goal, says Horowitz, is to develop more outcomes-oriented metrics for evaluating risk.
Another important component of FDA's more science-based inspection process is for field staff to collaborate more closely
with Center product specialists and technical experts in evaluating a firm's risk management programs, product and process
knowledge, process capability, and quality system robustness. This approach for drugs builds on long-standing procedures in
CBER. Postapproval GMP inspections of biotech manufacturers have been performed by Team Biologics together with CBER product
specialists for the past decade, Malarkey commented. Such integration begins as early as the investigational new drug application
(IND) stage, and is particularly important for dealing with complex and innovative technologies.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634. firstname.lastname@example.org