When it comes to drug inspections, the Food and Drug Administration hasn’t always had the best reputation.
The issue has been on the U.S. Government Accountability Office’s High Risk List since 2009, meaning the watchdog agency has long had concerns about the FDA’s ability to maintain quality inspections of global drug manufacturing. Now, the COVID-19 pandemic has added an additional layer of complexity to the problem.
According to a new GAO report, the FDA has postponed hundreds of drug inspections in the last year, citing health and safety concerns related to the virus. This has created a significant drop in the number of inspections and an even longer inspection backlog, which could have long-lasting consequences for consumers and the pharmaceutical industry alike.
“These on-site inspections are probably one of the most critical tools the FDA has in ensuring the safety and quality of medications after approval,” said Dr. Michael Carome, director of the Health Research Group at advocacy organization Public Citizen. “The great worry is because of this significant drop-off of inspections, the FDA is not implementing its usual tool for ensuring the safety and quality of prescription and over-the-counter drugs.”
The FDA did not complete its planned 1,000 inspections for 2020. To put that figure in context, the FDA conducted 400 domestic inspections between March and October 2019. That sum dropped to 52 inspections during that same time frame in 2020, after the FDA announced it was postponing most of its inspections due to travel advisories and health risks.
Moreover, between March 13, 2020 and the end of the year, the FDA completed a mere three foreign inspections deemed mission-critical: one each in Canada, Germany and India. By comparison, in each of the two preceding years, it conducted more than 600 overseas inspections in that same time frame.
Before a drug is approved, the agency must weigh in at several different moments. It must conduct a pre-approval of manufacturing facilities and periodic routine surveillance on a rotating basis, as well as for-cause inspections when there’s a complaint or a problem at a facility. Carome characterizes these check-ins as “critical.”
The issue has proven challenging to address. As the GAO has tracked the number of drug inspections both in the U.S. and abroad, it has consistently argued that the FDA has struggled to maintain an acceptable schedule – and that was before COVID-19 hit.
Foreign inspections continue to vex the agency. After the GAO flagged the issue in 2009, the agency boosted the number of overseas inspections; it conducted more than 1,900 in 2016. But in December 2019, the GAO reported that the FDA was struggling to fill staff vacancies, resulting in a decline in its foreign inspections that year to 977.
The even more significant decline in 2020 could lead to a slowdown in drug approvals – and, possibly, contribute to drug shortages down the road.
“The longer that the inspections are paused, the more the FDA will be challenged to bring more drugs to market,” said Mary Denigan-Macauley, GAO director of health care, public health and private markets. “A lot of the inspections were done months in advance, so you didn’t see an initial backlog. But now that it’s been over a year, companies are now not being able to get drugs approved.”
A recent Johns Hopkins Bloomberg School of Public Health report noted that “the COVID-19 pandemic has revealed the fragility of the U.S. drug supply in a public health crisis.” Furthermore, it added that “these shortages point to serious vulnerabilities in the pharmaceutical supply chain that can compromise the response to future crises.” The authors of the report listed the FDA’s regulatory delays as one of the major contributing factors.
Some pharma companies have called on the FDA to find a solution. In a December letter, drug lobby PhRMA wrote that the current delay “will increase the risk of drug shortages in the global supply chain… and could delay availability of new therapies.”
To that point, certain drugmakers have already experienced delays in drug approvals due to the issue, including Spectrum (on its application for cancer treatment Rolontis) and Bristol Myers Squibb (for lymphoma treatment Breyanzi).
A solution has, so far, proven elusive. For its part, the FDA has said it is employing alternative methods to accomplish its regulatory goals, including using foreign regulators to conduct on-site visits.
“In situations where physical inspections are not feasible due to travel and quarantine restrictions, the agency continues to be successful in its oversight of regulated industry and in making regulatory decisions by using additional tools such as remote interactive evaluations, record requests and leveraging information from trusted regulatory partners,” the FDA said in a statement.
Carome countered that record reviews, though they may yield useful information, aren’t a foolproof substitute for on-site inspections. “Company manufacturing records can be altered, they can be withheld, they can be destroyed,” he explained. “The companies could easily hide things if the FDA is solely relying on these remote record reviews.”
Meanwhile, the FDA has yet to embrace virtual video inspections in any significant way, and continues to evaluate the idea. And even if the agency suddenly reversed course, Carome doesn’t believe that remote inspections would prove a worthy substitute. He said many potential issues wouldn’t be detected unless an inspector is on site, including ones related to cleanliness.
“There have been inspections where they’ve found filthy conditions and rodents, which could lead to contamination of drug products,” Carome said. “Does that mean there’s imminent danger? No, but this could ultimately lead to a serious problem going undetected, which could lead to harm to patients.”
Denigan-Macauley echoes these concerns, noting that foreign inspections assume an outsized importance because many drugs sold in the U.S. are manufactured overseas. Problems typically detected when an inspector physically enters a facility, like employee hygiene or broken pipes, could be overlooked.
“It’s an increasingly global environment,” she explained. “When drugs are manufactured overseas, the issue takes on another level, because they don’t have the same laws and procedures that we have here. The FDA is in a tough spot and that’s why it’s on our High Risk List. They need to find solutions to these problems.”
Carome, meanwhile, finds it hard to believe that FDA inspectors haven’t been deemed essential workers during the pandemic.
“It’s important that they ramp up these inspections as soon as possible – and because there’s now an enormous backlog, they’re probably going to need to hire and train additional inspectors to make sure that these inspections can happen safely,” he said. “These are mission-critical staff that need to be vaccinated, and they need to be provided with appropriate protective gear.”