Global Manufacturing Challenges Industry Regulators

The FDA is increasing foreign inspections and adopting new initiatives to ensure the quality of imported medicines.
Sep 01, 2008
Volume 21, Issue 9

Jill Wechsler
The heparin debacle and other crises involving imported drugs and biologics has put pressure on the US Food and Drug Administration to step up its oversight of foreign drug manufacturing. Congress is giving the FDA additional funds to expand foreign inspections and overseas operations. Legislative leaders also are developing new bills to strengthen FDA authority to block suspect imports and to crack down on fraudulent foreign operators.

Global Enterprise
At the same time, there is broad agreement that the current approach for monitoring drug quality is obsolete as more active pharmaceutical ingredients (APIs) and drug products are produced and imported from overseas (see sidebar: Global Enterprise). Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, told the House Energy and Commerce Committee in May that inspections alone cannot fully evaluate the capability of manufacturing facilities to generate safe and high-quality products. FDA Commissioner Andrew von Eschenbach similarly acknowledges that the FDA will never have enough resources to inspect all facilities frequently enough to catch all safety and quality problems.


To better assess the quality of foreign products, the FDA is establishing on-the-ground regulatory offices in critical parts of the world as part of the FDA's "Beyond our Borders Initiative." The first in-country operation will be in China, followed by similar programs in India, Europe, Latin America, and the Middle East (most likely in Amman, Jordan). An additional $20 million from a supplemental budget appropriation approved in June will enable the FDA to staff the first four operations by the end of next year with 35 US employees and 13 foreign nationals.

The FDA plans to open offices in Beijing, Shanghai, and Guangzhou, China by year-end. A staff of 13 will conduct some site inspections, but primarily work with Chinese regulatory authorities to better track local enforcement activities, become more informed of legal and political issues affecting drug regulation, and further acquaint Chinese officials and manufacturers with US drug quality standards and enforcement policies.

India is next in line, and the FDA is negotiating to establish offices in New Delhi and Mumbai to oversee the vast volume of drugs and APIs exported to the US. FDA facilities in Europe will monitor sites that produce drugs and medical products for export, while a Central American operation will focus on the large amounts of fruits and vegetables shipped to the US.

In addition, the FDA is expanding overseas inspections of drug and biotech manufacturing facilities. The agency conducted 322 foreign inspections in FY 2007—a big jump from 212 in 2006, 266 in 2005, and 260 in 2004. The plan is to carry out 500 foreign inspections in 2009, which will be supported by increased appropriations. Most of these visits involve pre-approval inspections (PAIs), which are required for every facility listed on a new drug application, biologics license application, or supplement before the product can be distributed in the US.

In addition to more PAIs, the FDA plans to boost routine surveillance of overseas manufacturers. Similar to its risk-based approach for targeting US good manufacturing practices (GMP) inspections, the agency will set priorities for inspecting foreign plants based on dosage form, date of last inspection, shipping volume, and the firm's compliance history with both the FDA and local regulatory authorities. The FDA's Office of Regulatory Affairs, which operates the agency's field inspection force in the US and abroad, is establishing an international cadre of inspectors to conduct site visits around the world. And whenever the FDA receives information that raises doubts about the safety of a regulated product, it will rapidly conduct a for-cause inspection, whether foreign or domestic.

The FDA also is making internal changes to better cope with the globalization of the pharmaceutical supply chain and the need to deal with an ever-growing number of brokers, traders, distributors, repackagers, and manufacturers. A top priority is to build an interoperable data system for facility registration and product listing. This would more accurately identify who is manufacturing which medical products and what is being distributed in the US. The FDA has launched a pilot to encourage manufacturers to shift from paper registration to electronic filing of establishment registration and drug listing information in advance of required e-filing by June 2009. A July draft guidance explains the registration and listing information manufacturers should submit and provides technical information on the e-filing process.

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