During the pandemic, the U.S. Food and Drug Administration stopped most of their foreign inspections of drug manufacturers.
“It was understandable,” said Professor David Ridley of Duke University’s Fuqua School of Business, as lockdowns and travel restrictions brought disruptions both globally and at home.
But in a paper published in the journal, Health Affairs, Ridley and co-authors Emily Cuddy of Duke’s Economics Department and Yun Peng Lu of the University of Maryland, say that foreign inspections for drug quality haven’t returned to pre-pandemic levels. In fact, they found that as of the end of 2022, while the FDA’s domestic inspections were slowly returning to previous volumes, inspections of foreign establishments were still 79% lower than pre-pandemic rates.
“That’s alarming,” Ridley said, “because we rely on a global supply of drugs and active ingredients.”
The Global Supply
Half of the prescription drugs consumed in the U.S. market are manufactured by foreign establishments, and the same happens for two-thirds of the generic active ingredients. India, China, and Italy account for more than half of the manufacturing facilities that supply U.S. drugs.
Ridley said the FDA had ramped up foreign inspections in the years before 2019, often by opening offices in strategic locations abroad.
“It was a good trend, the FDA had finally figured out how to get their people to go abroad,” he said. “And then the trend reversed with COVID.”
In their research, Ridley and colleagues examined data about FDA drug inspections between 2012 and 2022. They also looked at available data for 2023.
They found that the number of inspections the FDA conducted abroad never returned to the 2019 levels.
“It’s hard to justify such a prolonged drop, considering that most of the logistical disruptions of the pandemic were lifted years ago,” Ridley said. “Mexico, for example, reopened for travel in 2020, and yet the FDA did not inspect any of Mexico’s drug-making sites until 2022.”
The researchers also found that there was not a budget or personnel reduction during the same period. In fact, the researchers say data show that the number of days spent inspecting has recovered, but the inspectors are visiting fewer establishments, especially abroad.
The Risks
Fewer inspections on foreign establishments is a big concern, Ridley said, because it often leads to a decrease of regulatory adherence.
“The generic drug market is intensely competitive,” said Ridley, “so there is an incentive to cut costs by cutting quality, especially if no one is watching.”
As an example, Ridley mentioned an incident earlier this year in which four people died after using imported eyedrops. He also mentioned a 2008 incident, a year in which FDA inspections abroad were also lacking. Adulterated heparin, a blood thinner manufactured abroad, caused 81 deaths in the U.S.
Achieving Safety
The FDA, U.S. Congress, companies and patients, all have a role to play to ensure drug quality, Ridley said.
The FDA should prioritize foreign inspections again, and hire the talent to support those efforts, Ridley said.
It’s also important that the U.S. keeps working on the mutual agreements with foreign countries, to make sure that the FDA facilities abroad can operate with minimal frictions, Ridley said.
The FDA warns establishments weeks in advance of an inspection for manufacturers abroad, as well as for U.S. establishments since the start of COVID-19. “But historically, bad-actor firms have abused such notices to hide quality issues,” Ridley said.
Another concern is that inspections are not a panacea to achieve drug quality, he said.
“The FDA only conducts inspections, they don’t test the drugs,” Ridley said. “But increasing testing is one of the best ways to enforce manufacturers’ accountability.”
Buyers like the U.S. Department of Defense and some private health providers are already using third-party lab testing to select suppliers based on quality.
“Pharmacies and insurers should do the same,” Ridley said.
The public should also be made aware of quality differences across manufacturers, inspection issues found in foreign facilities, and possibly the origin of certain ingredients, he said.
“If Americans start paying attention to the drugs they ingest, then they will force retailers and hospitals to pay attention too,” Ridley said. “The retailers and hospitals who have a reputation for caring about drug quality will get more business, and they in turn will give more business to the highest-quality generic drug makers.”