Risky plants get priority
The risk-based approach for selecting sites for GMP inspections was launched this year under a program developed by Gardner's
compliance division. Of roughly 1400 sites that FDA inspected this year, about 500 appeared on CDER's tier-one list for priority
inspection during fiscal year 2006. OC is issuing an updated white paper that describes the program's first year of operation
and refines the methods for making priority inspection assignments for 2007, based on the office's 2006 experiences. FDA will
inspect high-risk facilities every two years. The agency concedes that low-risk plants may be visited only every five or six
years unless a manufacturer experiences production problems or difficulties in maintaining product quality.
The 500 facilities in the 2006 tier-one group included those that had not been inspected in the past six years and were long
overdue for a visit. The others were plants that had earned high risk scores because of facility characteristics (e.g., size, operations, inspection history), product (e.g., drugs or packaging), process control, and contamination potential. Manufacturers continue to maintain that large, high-volume
plants are not necessarily riskier and that facilities' age and operations are more valid risk measures. But FDA officials
maintain that a quality problem at a plant producing blockbuster drugs would put more patients at risk and therefore warrants
more frequent inspections. Although FDA currently calculates facility size based on product sales, the agency acknowledges
that production-volume data for each drug product would be a more valid measure, but says it does not have access to that
CDER also is using risk models to select some 1000 product samples to test annually in FDA field laboratories. During the
past year, the list included all transdermal patches, the top 100 drugs, the top 30 generics, and products from companies
with past compliance problems, field alerts, and difficult manufacturing processes. As in most years, only a very small percentage
of samples indicated quality problems.
In addition, OC has begun using risk factors to identify those company adverse drug event (ADE) reporting systems it should
inspect. These include firms producing drugs that pose a potentially significant health risk to consumers such as newly approved
drugs, new indications, products with a narrow therapeutic range, and treatments for vulnerable patients. ADE inspections
assess the quality of the firm's reporting program as evidenced by its written procedures, data processing, and overall performance.
Challenges for biologics
Although risk-based models are proving useful in identifying those drug manufacturers and products that warrant closer and
more frequent regulatory scrutiny, this approach may be less useful for biotechnology products because almost all therapies
regulated by CBER are fairly high risk, explained Mary Malarkey, director of CBER's Office of Compliance and Biologics Quality,
at the PDA–FDA conference. In fact, CBER recently decided to inspect vaccine makers annually (instead of every two years)
because of recent concerns about vaccine quality and supply. CBER also is continuing its practice of integrating preapproval
and GMP inspections and using a systems-based approach for blood and source plasma establishments, which is a program that
Malarkey's office plans to update during the coming year.