SOCMA and EFCG issued a joint position paper in October 2006 to highlight the lack of inspections occurring in foreign-drug
manufacturing facilities, a situation particularly affecting APIs in generic and OTC drugs. "In 2005, FDA conducted 163 inspections
of foreign API manufacturers, of which 14 (9%) of the API inspections were in China, 23 (14%) were in India, which is not
proportional to the quantity of API being imported," said the SOCMA-EFCG position paper (2). The groups estimate that more
than 80% of APIs used by US manufacturers are imported, with about half of the imported volume originating from India and
Government Accountability Office.
The US Government Accountability Office (GAO) issued reports in November 2007 and April 2008 to evaluate FDA's program for
inspecting foreign drug-manufacturing facilities (3, 4). GAO is an independent agency that works on behalf of Congress. GAO
earlier reported on this issue in 1998, when it cited problems with the frequency, number, and rigor of foreign inspections
by FDA (5).
In its November 2007 report, GAO reported that using a list of 3249 foreign facilities that FDA had prioritized for inspection,
FDA may inspect about 7% of foreign establishments per year. Of these 3249 foreign facilities, there were 2133 foreign facilities
for which FDA could not identify a previous inspection. Of the remaining 1116 foreign facilities on FDA's priority list, 242
had received at least one inspection, but had not received a GMP surveillance inspection since FY 2000 (3).
GAO found that most of FDA's inspections of foreign facilities are conducted as part of the preapproval process (i.e., when
processing a new drug application or an abbreviated new drug application), rather than as GMP surveillance inspections, which
are used to monitor the quality of marketed drugs. "Although FDA used a risk-based process to develop a prioritized list of
foreign establishments for GMP surveillance inspections in FY 2007, few such inspections are completed in a given year," specified
Marcia Crosse, GAO's health care director, to the House Subcommittee on Oversight and Investigations of the Committee on Energy
and Commerce. (3). According to GAO, FDA conducted 332 inspection of foreign drug-manufacturing facilities in FY 2007, which
was an improvement compared with FY 2006, when FDA conducted 212 inspections of foreign drug facilities, and with FY 2005,
when FDA conducted 266 inspections (3).
GAO provided additional data to illustrate the disparity in the number and type of inspections (preapproval or GMP surveillance)
between domestic and foreign drug-manufacturing facilities. From FY 2002 through FY 2007, FDA conducted 1445 foreign inspections:
1177 of these inspections included a GMP component, of which 998 were conducted in conjunction with a preapproval inspection.
In contrast, FDA conducted 9694 inspections of domestic facilities that included a GMP component, of which 7742 were not conducted
with a preapproval inspection (3).
GAO cited other problems in FDA's inspection process:
- A lack of dedicated staff for foreign inspections
- Making announced rather than unannounced GMP surveillance inspections of foreign drug manufacturers. Domestic manufacturers
are subject to announced inspections.
- A lack of flexibility to extend foreign inspections if problems arise
- A lack of translators for inspection teams (3).
GAO also relayed concerns over FDA's information technology infrastructure and databases of manufacturing facilities in being
able to provide an accurate count of foreign establishments subject to inspection (4).
Responding to these issues, federal agencies initiated reforms, and Congress developed a discussion draft and held hearings
this spring for purposes of considering legislation to improve FDA's inspection process.