The highly publicized recall of heparin resulting from adulterated product from a Chinese supplier earlier this year is helping to galvanize industry and political forces to seek reform in the US Food and Drug Administration's process for inspecting foreign drug-manufacturing facilities. The introduction of a discussion draft and Congressional hearings on the "Food and Drug Administration Globalization Act of 2008" in April and May of this year is taking that debate to the next level by examining the funding, resources, and implementation of FDA's inspection process.
Planting the seed
Although recent Congressional and public focus has raised the level of scrutiny for FDA's process for inspecting drug-manufacturing facilities, a myriad of industry and governmental groups have weighed in on the debate during the last several years.
. In September 2006, the Bulk Pharmaceuticals Task Force (BPTF), an affiliate of the Synthetic Organic Chemical Manufacturers Association (SOCMA), submitted a citizen petition to FDA requesting that the agency increase inspections of drug-manufacturing facilities located outside of the United States. SOCMA is the US-based trade association representing batch and custom manufacturers. SOCMA's BPTF is an industry-trade organization of US manufacturers of active pharmaceutical ingredients (APIs), pharmaceutical intermediates, and excipients.
The petition offered data to show the disparity in inspections of domestic and foreign drug-manufacturing facilities. In 2004, 3300 domestic and 2700 foreign drug-manufacturing facilities were registered with FDA. (These figures exclude 4500 domestic sites registered solely for the production of medical gases). China and India led in the number of registered sites with 440 and 300 sites, respectively. Approximately 51% of the registered foreign sites were API manufacturing sites. The remaining sites were other establishment types such as finished-dosage plants and control laboratories. The petition also cited that 87% of the 510 drug master files filed with FDA in fiscal year (FY) 2004 were for products and APIs manufactured outside the US (1).
The petition outlined recommendations for improving FDA's ability to reduce the risks from drug products imported into the US. These recommendations, as outlined below, were also presented in Congressional hearings in November 2007:
- Ranking foreign and domestic drug-manufacturing firms together to determine inspections. FDA maintains two lists: one foreign and one domestic, and mainly inspects domestic firms. By merging the lists, foreign firms that have a higher risk profile would be inspected before a US firm with a much lower profile.
- Listing "foreign facility" as a significant risk factor for determining facility inspections
- Creating a program to monitor the impurity profiles of imported over-the-counter (OTC) drugs for patterns creating the appearance of underlying problems in complying with current good manufacturing practices (CGMPs) to allow FDA to refuse entry to products appearing adulterated. This would allow FDA to see if impurity profiles for a facility change over time, which would show that a facility does not have control processes in place and would warrant an inspection (1).
. The European Fine Chemicals Group (EFCG) joined SOCMA in its efforts in seeking to reform FDA's inspection process. EFCG was formed in 2004 to address the competitiveness of European fine-chemical companies. EFCG is part of the European Chemical Industry Council, the Brussels-based trade association representing European chemical manufacturers.
Inspection fees and country-of-origin labeling