The Society of Chemical Manufacturers and Affiliates (SOCMA) reported last week that the US Food and Drug Administration responded to the association’s citizen petition relating to the inspection process of foreign drug-manufacturing facilities. SOCMA is the US-trade association representing custom and batch manufacturers, including contract manufacturers of active pharmaceutical ingredients and intermediates. The association had filed the petition in 2006.

We are pleased that the FDA has responded to our petition,” said SOCMA’s Government Relations Manager Lynne Jones Batshon, who filed the petition on behalf of SOCMA’s Bulk Pharmaceuticals Task Force. “The agency has rolled out several initiatives since our request was submitted, and we hope that some of them resulted from the concerns we highlighted in 2006,” she said in the SOCMA statement.

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 numbered 440 sites in China and 330 in India. 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 (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 which should be inspected. FDA maintains two lists of firms: 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 drugs for patterns that might indicate underlying problems in complying with current good manufacturing practices (CGMPs) to allow FDA to refuse entry to products that appear to be 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).

In SOCMA’s announcement, Batshon added that while SOCMA supports all the efforts being made by FDA, the majority of the initiatives cited in the agency’s response were announced in April 2008 and thereafter. “Right now we’re taking a wait-and-see approach to evaluating the effectiveness of FDA’s new initiatives, particularly their ability to conduct more foreign inspections,” she added.

SOCMA says FDA has only made nominal increases in foreign inspections since 2007 and that more needs to be done. “There will always be an unlevel playing field unless the FDA considers risk-ranking foreign and domestic facilities together,” said Batshon.  “The agency has cited a lack of resources for its decision to not risk-rank facilities together, which in our view, is not an adequate justification.”

Regarding monitoring impurity profiles, SOCMA disagrees with FDA’s assertion that conducting such surveillance would not be meaningful and suggests the agency expand its existing impurity- profile surveillance to identify patterns that might indicate manufacturing processes that do not meet CGMP standards.

Reference
1. P. Van Arnum, “The Anatomy of the Changing Supply Chain,” Pharm. Technol. 32 (8), Outsourcing Resources supp., s56–62 (2008).