Jill Wechsler

These developments require major changes to how FDA does business. Instead of sending out inspectors to scrutinize foreign facilities, agency officials seek to collaborate more with other regulatory authorities to make greater use of third-party auditors and to establish global information networks that can better alert officials to potential safety hazards.

The call for a new approach to food and drug regulation will have a notable impact on FDA field inspections and compliance operations, as seen in changes at the Office of Compliance (OC) in FDA's Center for Drug Evaluation and Research (CDER) that increase its focus on imports and supply chain issues. At the same time, pharma companies are supporting new collaborative efforts to ensure the quality of supplies and to prevent drug theft, diversion, and distribution of counterfeit products around the world. Increasingly tight resources at FDA and other government agencies and healthcare organizations, moreover, necessitate new approaches, as FDA faces sizeable cuts in its budget for fiscal year 2012.

Major difficulties in ensuring the safety and quality of imported food and medical products in a world of increasingly blurred lines between domestic and foreign production are outlined in the "Pathway to Global Product Safety and Quality," which Commissioner Margaret Hamburg unveiled in June. While the report contains few really new proposals for overseeing food and drug imports and outsourced production, the document is noteworthy for providing a comprehensive overview of the forces reshaping the global economy and biopharmaceutical product development.

To cut costs and increase productivity, FDA documents how pharma companies are shifting manufacturing and clinical testing to new locations. US pharma companies now import 80 percent of active ingredients, and contract manufacturing has more than doubled over the past decade to an estimated $46 billion business in 2010. More complex, high-risk biologics and vaccines are coming from emerging nations, instead of Western Europe. In addition, more R&D is shifting overseas; India and China already have more than 30% of the world's drug master files, and more clinical trials are taking place outside the United States and Europe. These developments make it "difficult to identify the 'source' of a product and to ensure that all players along the supply chain meet safety and quality responsibilities," the report states.

With more foreign operators to monitor, FDA concedes that it's not viable to scale up its current regulatory model, even if it had the resources to do so. The average cost of a foreign inspection is $52,000, more than twice the $23,000 outlay for a domestic site visit. More than 54 percent of foreign drug facilities went uninspected from 2002 to 2007, and the record is even worse for medical device operations overseas. Clinical site inspections dropped in 2010, compared to the previous year, particularly for foreign investigators and for drugs and biologics.

These developments also raise the specter of encouraging economically-motivated abuse, such as drug counterfeiting, fraud, and intentional adulteration. For many novice operators, the "temptation of economic gain is greater than any concern for risk to human and animal health," the FDA report observes. Americans feed these actions by purchasing more pharmaceuticals online, often from unknown sources and without appropriate oversight and safeguards. The nation already has suffered the consequences of adulterated heparin and counterfeit glucose monitoring strips, and low-quality counterfeit medicines are widely available, particularly in developing countries.