Most biotech manufacturing operations fall into the high-risk category because they involve sterile injectables and production
methods susceptible to contamination. CDER is adopting this model to identify 500 domestic production facilities that fall
into the high-risk tier and should be inspected by ORA this year. This group will account for about half of ORA's drug inspections
for 2006, with the rest based on the need for a pre-approval inspection, a recall or complaint, or follow-up to a previously
unsatisfactory inspection. District inspectors more familiar with specific plant operations have discretion to add or remove
certain facilities on the priority list.
TEAM APPROACH
In addition to targeting inspections to high-risk operations, ORA is implementing other strategies to streamline the inspection
process. FDA's Good Manufacturing Practices (GMPs) for the 21st Century Initiative, launched to encourage risk-based approaches
to compliance and adoption of quality production technologies, has established several new approaches for GMP inspections.
One initiative has given Centers more input in issuing warning letters for GMP violations identified during inspections; another
seeks to better integrate pre-approval and GMP inspections.
An important development has been to extend the team inspection approach pioneered by Team Biologics to drugs and other medical
products. ORA is establishing a Pharmaceutical Inspectorate of specially trained experts able to audit complex drug products
and facilities. However, Team Biologics retains responsibility for inspecting manufacturers producing biotech therapeutics
now regulated by CDER, as well as for biologics and blood establishments in the Center for Biologics Evaluation and Research
(CBER).
For pre-approval inspections, CBER compliance staffers continue to take the lead in this area. And now a similar approach
has been adopted by CDER for biotech products, explained Brenda Uratani of CDER's Office of Compliance (OC) at a recent conference
on biotech regulation sponsored by Pharma Conference. Product specialists from OC's branch overseeing biotech therapeutic
facilities and from CDER's Office of Biotechnology Products who review biotech process manufacturing controls now have lead
responsibility for conducting pre-approval inspections for biotech therapeutics in CDER. FDA is incorporating this model of
more ORA–Center shared responsibility in revising inspection approaches for drugs. Team Biologics and the Pharmaceutical Inspectorate
are "the future" of federal GMP inspections, Glavin comments.
ACTION OVERSEAS
While FDA seeks to streamline the frequency and scope of its field inspection program at home, it is struggling to cope with
a rising number of foreign-based inspections. FDA conducts about 1,000 foreign inspections for drugs and biologics each year,
but this program, unfortunately, now is only the tip of the iceberg. More than 30 foreign regulatory agencies now want to
inspect pharmaceutical manufacturing plants, and the number continues to increase, according to Malcolm Holmes, director of
global quality assurance at GlaxoSmithKline. Industry is building large, sophisticated production facilities that may export
products to more than 80 different markets, and inspectors from all over the world are showing up to conduct their own audits.
This kind of "industrial tourism" does little to enhance public health and safety, Holmes stated, noting that industry now
spends some 35,000 person-hours coping with multiple foreign inspectors from Mexico, Argentina, Africa, and Asia.
International adoption of risk-based inspection models and more sharing of information offer prospects for relief. Although
no one is looking for mutual recognition of inspection decisions by foreign agencies, there is growing interest in bilateral
agreements for sharing inspection information among regulatory authorities. US membership in the Pharmaceutical Inspection
Cooperation Scheme (PIC/S), which is moving forward, could expand acceptance of PIC/S certificates to include that a plant
also meets GMP standards. Foreign regulators could save resources by first examining what inspection report information is
available from PIC/S, from FDA's inspections database, and from an EU database currently under development. Clarification
by the World Health Organization of its recommendations for when plant inspections are needed would be helpful. Manufacturers
with sound GMP compliance histories and corporate integrity programs also may gain some regulatory relief if foreign regulatory
authorities accept such quality assurance policies as indications of compliance.
Jill Wechsler is BioPharm International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634, jwechsler@advanstar.com
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