Jill Wechsler
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The global expansion of pharmaceutical manufacturing and recent crises involving unsafe drug imports has put pressure on the
US Food and Drug Administration to step up its oversight of foreign drug manufacturing. Congress is giving FDA additional
funds to expand overseas inspections and operations, and legislative proposals aim to strengthen the agency's authority to
block suspect imports and to crack down on fraudulent foreign operators.
At the same time, the current approach for monitoring drug quality is generally considered to be obsolete because more active
pharmaceutical ingredients (APIs) and drug products are produced and imported from overseas (see sidebar, "Global enterprise").
Janet Woodcock, director of FDA's Center for Drug Evaluation and Research (CDER), told the US House of Representatives' Energy
and Commerce Committee (E&C) in May 2008 that inspections alone cannot fully evaluate the capability of manufacturing facilities
to generate safe, high-quality products. And "borders can no longer be the first line of defense," said Murray Lumpkin, FDA
deputy commissioner for international and special programs, at the Drug Information Association (DIA) annual meeting in June
2008. He explained that US authorities can't "inspect out" bad products at the border, they can only check that quality has
been built in to a product during manufacturing.
FDA Commissioner Andrew von Eschenbach acknowledges that the agency will never have enough resources to inspect all facilities
frequently enough to catch all safety and quality problems. The commissioner is traveling around the world to promote regulatory
cooperation and capacity building and to establish FDA foreign offices better able to monitor local drug production and export
activities.
Seeking standards
These developments are spurring more collaborative inspection initiatives by regulatory authorities and broader support for
systems to ensure the quality and safety of medical products. International standards for good manufacturing practices (GMPs)
are in the works, along with risk-based approaches that focus resources on monitoring products that are more likely to harm
patients if they are contaminated or compromised. Regulatory authorities are collaborating and sharing information about domestic
manufacturers and inspection findings to better target resources at high-risk areas and reduce redundant oversight activities
that waste resources. The regulators also want drugmakers to take full responsibility for component and product failures and
to increase investments in controls and oversight of foreign suppliers.
In Washington This Month
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The heparin debacle of the past year demonstrates many of the challenges and opportunities created by the globalization of
pharmaceutical manufacturing. FDA's failure to conduct the required preapproval inspection of the Chinese API producer allegedly
involved in the contamination was a major embarrassment for the agency. But the incident highlighted how inadequate funding
has undermined FDA enforcement capability. And the problem demonstrated the need for better information systems to track manufacturers,
imports, inspection activity, and companies' compliance status. Difficulties in identifying the source of product contamination,
moreover, illustrate the need for broader approaches to ensure drug quality and for cooperation from Chinese and other regulatory
authorities to detect and prevent similar problems.
The heparin case also has put drug-importation issues high on FDA's priority list. Ranbaxy (Gurgaon, India) recently was hit
with charges of fraudulent conduct, fabrication of stability and bioequivalence information, and attempts to conceal GMP violations,
stemming from a 2006 inspection of the firm's Paonta Sahib, India, plant. FDA sent the company a Warning Letter, and the US
government is suing Ranbaxy to gain access to a full audit report by consultant Parexel. Officials believe the report will
document the distribution of adulterated and misbranded products, including antiretrovirals for US international AIDS-treatment
programs.
