To bolster its resources, FDA has proposed a reinspection user fee that would collect $23 million to cover the cost of revisiting
manufacturing facilities cited for violations in initial good manufacturing practice (GMP) inspections. The agency would use
$13 million of that new fee revenue to support 100 additional ORA field staffers.
ORA's streamlining plan is scheduled to take effect on Oct. 1, 2007 unless it is sidetracked by opposition, which is surfacing
within the agency as well as among manufacturers. Agency staffers are nervous, and industry fears more difficulty in contacting
field officials and getting answers to specific questions. Members of Congress have opposed closing FDA laboratories at a
time of increased public concern about food contamination and medical-product safety.
New approaches to quality assurance
FDA officials would like to shift the focus from counting the number of plant inspections it conducts to evaluating how well
it can ensure medical-product quality and safety. This approach involves adopting more efficient strategies for targeting
inspections to high-risk operations likely to have the greatest impact on public health and safety.
FDA's risk-based approach to regulating GMPs fits ORA's need to do more with less to ensure drug quality. David Horowitz,
ORA deputy associate commissioner for compliance policy, noted at the pharmaceutical quality workshop that in addition to
a "significant decline in resources for inspections," more complex manufacturing processes require more expertise to evaluate.
And, the need to oversee a growing number of foreign drug-manufacturing facilities also stretches ORA resources.
Moreover, FDA regulatory operations suffer from industry efforts to sidestep the rules, Horowitz said. Industry compliance
with GMPs "is bad and getting worse," he remarked, observing that manufacturers are "studying for the test"—correcting specific
deficiencies but not investing in systems that can avoid problems and correct root causes. Modern manufacturing and technological
developments such as process analytical technology (PAT) provide opportunities for both FDA and industry to establish quality-oriented
approaches, Horowitz added, and risk management can better focus and target regulatory and manufacturing activities to "get
the most bang for the buck."
FDA is helping manufacturers adopt innovative approaches for ensuring that drugs meet quality standards, as seen in its Quality Systems Approach to Pharmaceutical CGMP Regulations guidance published in September 2006. Additional guidances from FDA will clarify approaches for aseptic processing, process
validation, investigating out-of-specification test results, and manufacturing standards for Phase I clinical supplies. The
anticipated Q10 standard from the International Conference on Harmonization will further describe approaches for harmonizing
quality systems on a global basis. FDA also plans to revise its rules governing Part 11 and GMPs. In approaching the long,
cumbersome rulemaking process, FDA envisions an "incremental approach" to adjusting specific policies, starting perhaps with
those governing potable water and aseptic processing.
In addition to providing advice to manufacturers, FDA is incorporating quality approaches into internal programs for training
field inspectors and for issuing Warning Letters. ORA's transformation initiative, said Horowitz, aims to embed risk-based
approaches in all its operations and to better coordinate the perspectives of field and Centers. This strategy, he hopes,
will lead to greater harmonization in management approaches internationally and enhanced integration of inspection with review
A key ORA initiative seeks to improve the knowledge and training of pharmaceutical field inspectors so that they better grasp
complicated quality-management systems and risk-management approaches they encounter at production sites. The centerpiece
is establishing the Pharmaceutical Inspectorate (PI), a group of highly trained individuals with the knowledge needed to evaluate
facilities that have adopted the latest scientific and technological innovations for ensuring 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 with about 25% for regular field
inspectors. But unlike the agency's centrally located Team Biologics cadre, which inspects biotechnology manufacturing facilities,
PI members work at district field offices and can inspect other facilities as needed.