The Anatomy of the Changing Supply Chain - Pharmaceutical Technology

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The Anatomy of the Changing Supply Chain
The high-profile case of contaminated heparin from a Chinese supplier has intensified the debate on the effectiveness of FDA's process for inspecting foreign drug-manufacturing facilities. The article examines proposed legislative and regulatory reforms and actions taken by the agency to improve drug-import safety.

Pharmaceutical Technology

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 China (2).

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.


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