The FDA still has a ways to go to ensure the safety and quality of the U.S. drug supply chain, as it has yet to inspect nearly 1,000 foreign plants that manufacture drug substances for the market.
While one out of every three foreign plants shipping active pharmaceutical ingredients (APIs) and finished drugs to the U.S. has never been inspected by the FDA, the agency is making progress, according to the Government Accountability Office (GAO), and it plans to send investigators to each of those plants over the next three years. But personnel could be an issue. Nearly half of the agency’s approved positions at its foreign offices are vacant.
Given that 40 percent of the finished drugs sold in the U.S. and 80 percent of the APIs are produced overseas, the dearth of inspections is a safety concern. “The rapid pace of globalization has complicated the agency’s efforts to ensure the safety of our drug supply,” the GAO said in its latest report on the status of the FDA’s foreign drug inspections. Released this week, the report noted that the GAO’s concerns with the FDA’s response to globalization go back two decades.
In that time, the FDA has gained expanded authorities, opened foreign offices, increased the number of foreign drug inspections and adopted a risk-based approach to inspections of establishments manufacturing drugs for the U.S. market. While the agency has made progress on some fronts, it has been incremental on others, the GAO said.
When it comes to inspections, it’s doing better in some countries than in others. For instance, 59 percent of the uninspected facilities are in three countries – China, India and South Korea. Although the FDA has established foreign offices in both China and India, the number of manufacturing facilities in those countries creates a heavy load for inspectors. Of the 572 facilities manufacturing drug substances for the U.S. market in India, 189 – or 33 percent – have yet to be inspected. The numbers are worse in China, which has 535 establishments listed in the FDA catalog of facilities subject to inspection. Of those, 243 – or 45 percent – haven’t been inspected.
With 171, South Korea has fewer listed establishments, but it has the worst inspection rate. Only 17 of the listed drug manufacturing facilities located in South Korea have been inspected by the FDA, leaving 90 percent uninspected. As for other countries, the agency has yet to inspect 27 percent of the listed plants in Canada and the U.K., 24 percent in France, 22 percent in Japan, 16 percent in Italy, 13 percent in Germany and 11 percent in Switzerland.
Looking at the situation as a glass half full, the GAO noted that the FDA’s oversight of foreign facilities is much stronger today than it was 10 years ago. From 2007 through 2013, the agency inspected more than 1,000 drug facilities in the U.S. each year, but the number of foreign plants it inspected lagged far behind. That changed in 2015 when the FDA, for the first time, inspected more foreign facilities than it did domestic. (See FDA Inspections of Domestic and Foreign Drug Establishments, below.)
In addition, the FDA has improved the accuracy and completeness of information in its catalog of drug establishments subject to inspection, the GAO said. As a result of those improvements and the stepped-up foreign inspections, the agency has reduced the number of foreign drug establishments with no inspection history to 33 percent, compared with 64 percent in 2010.
While the GAO report focused on the deficiencies in foreign inspections, it revealed that the country with the largest number of uninspected facilities is the U.S., which has 291 drug facilities with no inspection history. That’s 14 percent of the 2,026 drug manufacturing plants listed in the U.S.
When the U.S. facilities are added to the foreign establishments, the global picture shows the FDA has not inspected 25 percent of the plants that produce the country’s drugs. That means the agency may not have inspected one of every four plants producing APIs and drugs for the U.S. market.