In fiscal year 1996, FDA reviewed the results of 287 inspections of foreign pharmaceutical manufacturers conducted by its investigators in 35 countries (see figure 1). Timeliness of Inspection Reports Has Improved, but Delays in Taking Prompt Enforcement Actions Continue

FDA’s 1988 internal evaluation found that delays in the submission of final inspection reports by investigators made it difficult for FDA to take prompt enforcement action against foreign manufacturers that did not comply with federal regulations that ensure the safety, purity, and quality of pharmaceutical products. For domestic manufacturers with a history of serious GMP manufacturing problems, FDA typically conducts a reinspection to verify that promised corrective actions have been implemented. As a result of downgrading, FDA conducted far fewer reinspections of foreign manufacturers than was recommended by its investigators. However, CDER officials downgraded the inspection classifications and recommendations for enforcement action in 41 of these inspections, based on foreign manufacturers’ promises to implement corrective actions. The OAI classification is the most serious and requires FDA to reinspect the manufacturer to verify that it has improved its production processes to comply with GMPs. FDA Conducts Infrequent Routine Inspections of Foreign Pharmaceutical Manufacturers

FDA’s 1988 and 1993 internal evaluations found that while FDA routinely conducted surveillance inspections of domestic pharmaceutical manufacturers, foreign manufacturers were typically inspected only when they were listed in new drug applications. Enforcing GMP compliance through routine surveillance inspections is FDA’s most comprehensive program for monitoring the quality of marketed pharmaceutical products. FDA Plans to Conduct More Routine Inspections of Foreign Pharmaceutical Manufacturers

In June 1997, FDA’s foreign inspection working group proposed a strategy for scheduling more routine surveillance inspections of accepted foreign pharmaceutical manufacturers. Serious Problems Persist in Managing Foreign Inspection Data

Although both FDA’s 1988 and 1993 internal evaluations identified serious problems in its foreign inspection data systems, the agency still lacks a comprehensive, automated system for managing its foreign inspection program. As a result, essential foreign inspection information is not readily accessible to the different FDA units that are responsible for planning, conducting, and reviewing inspections and taking enforcement actions against foreign manufacturers. As a result, foreign inspection data are not readily accessible to the different FDA units responsible for conducting foreign inspections and reviewing inspection results. FDA has taken some action to address these problems. Recommendations to the Commissioner of the Food and Drug Administration

To improve the effectiveness of FDA’s foreign inspection program to ensure that only safe, pure, and high quality drugs are imported into the United States, we recommend that the Commissioner of FDA ensure that serious manufacturing deficiencies are promptly identified and enforcement actions are initiated by requiring investigators to prepare inspection reports and CDER to issue warning letters within established time periods and reexamine and revise FDA’s foreign inspection strategy to provide adequate assurance that all foreign manufacturers exporting approved pharmaceutical products to the United States comply with U.S. standards.
Why GAO Did This Study

Pursuant to a congressional request, GAO reviewed the Food and Drug Administration's (FDA) efforts to correct problems identified in earlier evaluations of its foreign drug inspection program, focusing on FDA's efforts to: (1) prepare inspection reports and take enforcement actions against foreign pharmaceutical manufacturers in a timely manner; (2) improve the consistency with which FDA evaluates the results of foreign inspections and conducts reinspections to verify that foreign pharmaceutical manufacturers have corrected serious deficiencies; (3) conduct routine inspections of foreign pharmaceutical manufacturers to monitor their compliance with U.S. quality standards; and (4) improve the management of data needed for planning inspections, monitoring inspection results, and taking enforcement actions.

What GAO Found

GAO noted that: (1) FDA has taken several actions to address problems with its foreign inspection program that were identified in two previous internal evaluations; (2) although FDA has improved the timeliness with which investigators submit inspection reports, in fiscal year (FY) 1996, almost 60 percent were still submitted later than called for by agency standards, including half the reports that identified the most serious deficiencies in manufacturing quality; (3) during FY 1996 and FY 1997, headquarters review personnel continued to downgrade the classifications of inspections recommended by its field investigators who conducted the inspections; (4) most of the decisions to downgrade the classifications were based on foreign manufacturers' promises to implement corrective actions; (5) as a result, FDA conducted fewer reinspections of these facilities to verify that foreign manufacturers had corrected serious manufacturing deficiencies; (6) FDA conducts infrequent routine inspections of foreign manufacturers to ensure that they continue to comply with U.S. quality standards, although routine surveillance inspections constitute FDA's most comprehensive program for monitoring the quality of marketed pharmaceutical products; (7) most inspections of foreign pharmaceutical manufacturers are performed to approve the marketing of new products; (8) routine surveillance inspections of manufacturers producing approved pharmaceutical products already marketed in the United States accounted for only 20 percent of FDA's foreign inspections during FY 1995; (9) as a result, routine inspections of foreign pharmaceutical manufacturers occur with far less frequency than the 2-year interval required for domestic manufacturers; (10) FDA has been striving to improve its management of data needed for planning inspections, monitoring inspection results, and taking enforcement actions; (11) at present, FDA relies on 15 separate systems to identify foreign pharmaceutical manufacturers, plan foreign inspection travel, track inspection results, and monitor enforcement actions; (12) as a result, essential foreign inspection data are not readily accessible to the different FDA units that are responsible for planning, conducting, and reviewing inspections and taking enforcement actions against foreign manufacturers; and (13) FDA is developing a comprehensive, agencywide automated system to provide better data for managing its foreign inspection program.