COVID-19 complicates already challenged FDA foreign inspection program

June 3, 2020

The outbreak of COVID-19 has called greater attention to the United States' reliance on foreign drug manufacturers and further highlighted the importance of ensuring a safe pharmaceutical supply chain. 

Much of the manufacturing of drugs for treating COVID-19 occurs overseas, which is also true of the majority of other drugs marketed in the U.S. While the volume of drugs manufactured overseas for the U.S. market is not fully known, the U.S. Food and Drug Administration (FDA) reports that about 70 percent of establishments manufacturing active ingredients and more than 50 percent of establishments manufacturing finished drugs for the U.S. market were located overseas, as of August 2019. 

The FDA is responsible for overseeing the safety and effectiveness of all drugs marketed in the U.S., regardless of where they are produced, and conducts inspections of both foreign and domestic drug manufacturing establishments. 

In December 2019, the Government Accountability Office (GAO) found that a growing number of foreign drug manufacturing inspections conducted by the FDA were in China and India (43 percent in 2018), where most establishments that manufacture drugs for the U.S. were located. 

But the FDA began to postpone almost all inspections of foreign manufacturing establishments in March 2020 due to COVID-19. GAO testified that this lack of foreign inspections removes a critical source of information about the quality of drugs manufactured for the U.S. market. 

In fiscal year 2015, the FDA, for the first time, conducted more foreign inspections than domestic inspections. However, from fiscal year 2016 through 2018, both foreign and domestic inspections decreased—by about 10 percent and 13 percent, respectively. FDA officials attributed the decline, in part, to vacancies among investigators available to conduct inspections. 

In March 2020, the FDA announced that, due to COVID-19, it was postponing almost all inspections of foreign manufacturing establishments. While the FDA has indicated it has other tools to ensure the safety of the U.S. drug supply, the lack of foreign inspections removes a critical source of information about the quality of drugs manufactured for the U.S. market. 

GAO also found that FDA had vacancies among each of the groups of investigators who conduct foreign inspections. The FDA had 190 investigators in the U.S. who conduct the majority of foreign inspections, but an additional 58 positions were vacant. At the time of GAO's December 2019 testimony, the FDA was in the process filling 26 of these vacancies, with 32 remaining. However, according to FDA officials, it could be two to three years before new staff are experienced enough to conduct foreign inspections. The FDA also faced persistent vacancies among investigators in its foreign offices. 

GAO further found in December 2019 that FDA investigators identified persistent challenges conducting foreign inspections, raising questions about the equivalence of foreign to domestic inspections. Specifically, GAO found: 

·       While FDA inspections performed in the U.S. were almost always unannounced, the FDA's practice of preannouncing foreign inspections up to 12 weeks in advance may have given manufacturers the opportunity to fix problems ahead of the inspection.

·        Investigators from the FDA's China and India offices had conducted some unannounced inspections, but these staff do not perform most of the inspections in these countries (27 percent and 10 percent, respectively).

·        The FDA was not generally providing translators on foreign inspections. Rather, the FDA continued to rely on translators provided by the foreign establishments being inspected, which investigators said raised questions about the accuracy of information FDA investigators collected. For example, one investigator said there was more risk of conflict of interest if the establishment used its own employees to translate. In addition, the establishment representative providing the translation may be someone who does not have the technical language needed, which can make it harder to communicate with establishment staff and facilitate the inspection.

·        The overseas travel schedule can present challenges for FDA's domestically-based investigators, who conduct the majority of foreign inspections.

Domestically-based investigators told GAO there is little flexibility for them to extend foreign inspections during an overseas trip. The inspections they conduct on an overseas trip are scheduled back-to-back in three-week trips and may involve three different countries. Therefore, extending one inspection would limit the amount of time the investigator has to complete their other scheduled inspections. 

FDA officials said that inspections conducted by investigators based in China or India (and domestic inspections in the U.S.) are generally scheduled one at a time and can thus more easily be extended if the investigator needs additional time to pursue potential deficiencies. However, these in-country investigators are not involved in the majority of FDA inspections conducted in China or India. 

GAO has had long-standing concerns about the FDA's ability to oversee the increasingly global pharmaceutical supply chain, an issue highlighted in GAO's High Risk Series since 2009. In particular: 

·        GAO recommended in 2008 (GAO-08-970) that the FDA increase the number of inspections of foreign drug establishments.

·        GAO found in 2010 (GAO-10-961) that the FDA continued to conduct relatively few foreign inspections than domestic inspections.

·        GAO found in 2016 (GAO-17-143) that the FDA was conducting more of these foreign drug inspections, and GAO closed its 2008 recommendation to conduct more foreign inspections. However, GAO also reported that the FDA may have never inspected many foreign establishments manufacturing drugs for the U.S. market.

·        In addition, in the summer of 2018, the FDA began announcing recalls of blood pressure medications manufactured overseas that were tainted with a potential carcinogen, raising further questions about the FDA’s oversight of foreign-manufactured drugs.

GAO has the report.  

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