FDA Fails in Lab Inspections of Thousands of Drug Manufacturers

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In early September 2024, an Associated Press (AP) investigation revealed that the FDA has struggled to keep up with lab inspections, especially those based overseas. The agency faces a backlog of about 2,000 labs that haven’t been inspected in more than five years, even as they continue to produce medications taken daily by millions of Americans.

This lack of regulatory inspections can lead to serious risks, as the prescription and over-the-counter drugs you take could be ineffective, sold in incorrect doses or contaminated with dangerous chemicals or bacteria. Here’s what to know and what experts say you can do to minimize the risks for you and your family.

The FDA Has Struggled with  Lab Inspections Since 2009

The Government Accountability Office (GAO), a non-partisan agency that examines how tax dollars are spent and makes suggestions to improve the efficiency of government agencies, has considered the FDA’s inability to regulate overseas labs a “high risk” issue since 2009, and has released several reports on the crisis, the most recent of which came out in February 2024.

The AP’s analysis found that 42% of registered labs remain uninspected after five years. While the 2024 GAO report points out that the backlog was exacerbated by a pause in foreign inspections early in the COVID-19 pandemic, it also highlights the fact that the quality of these inspections—when they do occur—can be questionable due to a variety of factors. As of 2019, 72% of drug manufacturing laboratories were located overseas, with nearly a third in China and India. Foreign inspections by regulators typically involve advance notice to help manage travel visas and translation needs. In contrast, inspections of U.S. laboratories are often conducted without prior warning.

Experts point out that this can compromise the integrity of lab inspection. “Investigators may be less likely to see the true day-to-day operating environment of foreign establishments as compared to domestic,” notes the GAO report. “Further, FDA has relied on translators provided by the foreign establishments being inspected, which investigators noted can raise questions about the accuracy of information FDA investigators collect.”

Up until 2012, the agency intended to inspect each U.S. lab every two years. But, as labs began to move overseas—typically as a cost-saving measure—the agency realized it couldn’t keep up with that goal, and it created a risk-based system. The new system requires the FDA  to attempt to inspect each lab at least once every five years, prioritizing those that it deems “high risk” based on a confidential internal assessment.

Despite an increase in foreign inspections (from 242 in 2000 to a peak of 1,041 in 2016), the FDA was still unable to meet its revised five-year target, and to this day says it doesn’t have enough inspectors to reach its goal.

The GAO reports describe the challenges in conducting inspections, including difficulties in hiring and retaining enough inspectors, and occasionally the reports provide the number of inspections completed in a given year. However, they don’t specify exactly how many labs have gone uninspected for five years or more—the threshold at which the FDA deems an inspection urgently needed.

Matt Perrone, an award-winning health writer who MedShadow interviewed for this article, and data journalist Nicky Forster—authors of the AP article—set out to uncover that crucial figure.

Thousands of Labs Uninspected for Over 5 Years Due to Lax Lab Inspections

At first, Perrone says, he thought it would be easy to figure out how many labs hadn’t been inspected for five years or more, but he quickly ran into a wall. The FDA publishes the results of all inspections done, but it doesn’t publish the list of laboratories it intends to inspect. Perrone suspects that if the risk score that the FDA assigns to each lab prior to an inspection were ever published, it could damage the laboratory’s reputation or business.

“So the FDA decides, ‘how important is this plant? How important are the drugs [it makes]? What are the potential risks if something goes wrong?’ and it’s really, really at their discretion how often they’re supposed to be there,” says Perrone. This could depend on how common the drugs it makes are, and how many other manufacturers make the same drugs, for example. “But for consumers, it does seem like it’s a bit problematic, because we have very little transparency into how FDA is making these decisions.”

When asked for a comment on this story, Michael Rogers, associate commissioner for regulatory affairs at the FDA, told MedShadow, “We select facilities for inspection that prioritize medical product surveillance inspections deemed high-risk based on a variety of specific criteria, such as the facility type or its compliance history, the inherent risk of the product manufactured there, and more. It is the obligation of drug manufacturers to produce medical products that are safe, effective, and meet quality standards. The FDA takes its oversight of these facilities seriously to protect public health.”

The agency also pointed out that it collaborates with international regulators to oversee drug manufacturers, and that it lacks the resources to inspect each individual lab frequently, and thus is required to take a risk-based approach to inspections.

Because they couldn’t access the list of intended inspections, Perrone and Forster compared inspection records from labs inspected prior to May 2019 and those inspected more recently. They found that the FDA had yet to return to about 2000 of the labs it had last inspected more than five years ago.

“I thought that there would have been many plants that they wouldn’t have revisited,” says Perrone, “but I don’t think if you had told me that it was about 2,000… that’s a very big number that even I was surprised by.”

What Happens When Drug Manufacturing Labs Go Uninspected?

Of course, uninspected labs can and do manufacture medications that work exactly as they should. But in the absence of routine and comprehensive inspections, it’s impossible to know which labs are doing quality work and which are not. When a lab is poorly run, it can produce drugs that are contaminated due to inadequate quality control or sanitation practices that would have been flagged during an inspection.

For example, in 2023, at least 81 people were infected, including 14 who lost vision and four who died as a result of over-the-counter eye drops tainted with a drug-resistant strain of Pseudomonas aeruginosa bacteria. The eye drops, EzriCare Artificial Tears and Delsam Pharma’s Artificial Tears, were manufactured by Global Pharma, a company located in Tamil Nadu, India. After the outbreak, inspectors visited the lab and recorded a variety of issues, including improper packaging and a lack of testing for microbes, among other issues. The FDA issued a warning letter detailing the pervasiveness of the contamination and describing testing the agency had done to establish this. In that letter, which was sent to the company and posted online, the FDA stated the plant’s drugs were placed on an import alert, and that if the plant couldn’t prove it had improved practices, the agency may withhold approval of any new drugs that are manufactured at the plant.

The company issued a voluntary recall. No additional inspections show up in the FDA’s dashboard, but the EzriCare and Deslam Pharma websites host recall notices, and the drops have not returned to the market.

In another instance in 2016, a commonly prescribed stool softener for hospitalized patients was contaminated with a dangerous bacterium, Burkholderia cepacia, later found in the water used to clean equipment at PharmaTech’s Florida manufacturing plant. The drug, liquid docusate, was made by PharmaTech and distributed by six different companies: Rugby, Major, Bayshore, Metron, Centurion, and Virtus. The plant had passed an FDA inspection months prior.

According to the FDA and Centers for Disease Control and Prevention (CDC), the drug may have made at least 64 people sick. One young patient who was in need of a heart transplant had to have his surgery postponed because of the illness, which worsened his condition. He was later reinfected with the same bacterium when recovering from surgery. Drugs made at PharmaTech were recalled in 2016. They were recalled again in 2018 due to contamination with the same bacterium. The FDA issued a series of recalls on the company’s products, including the stool softener and several vitamins and supplements.

All of those recalls have since been terminated, meaning the FDA now deems the products safe.

When inspectors visit labs, they not only check to make sure processing areas are free of dirt and pests, but they also check for accurate packaging, labeling and detailed records that show how the company is ensuring and tracking the quality of the drugs in its facility. According to the FDA, when they tried to inspect a plant owned by Intas Pharmaceuticals in Gujarat, India, the makers of a variety of medications, in late 2022, inspectors found employees destroying documents related to testing and quality control by pouring acid on them. Those types of documents are essential for understanding the safety of a medication, and if it ever is contaminated, determining how and when.

One Doctor’s Personal Encounter with Potentially Contaminated Medications

Harry Lever, M.D., a retired cardiologist who was the medical director at the Hypertrophic Cardiomyopathy Center at the Cleveland Clinic, and who is currently an advocate for drug testing reform, has had personal experiences with what he believes are consequences of drugs made by unscrupulous manufacturers.

Dr. Lever recalls treating a patient with hypertrophic cardiomyopathy at the Cleveland Clinic. After surgery, the patient did well for three years, then suddenly entered heart failure. Dr. Lever says that he had been prescribed a diuretic called torsemide. The patient went home, but three days later, his symptoms returned. After reviewing all of the drugs his patient was taking, Dr. Lever realized that his patient’s pharmacy had initially been giving him torsemide manufactured by Hikma, a London-based company. But at some point, the pharmacy switched him to torsemide manufactured by Hetero, a company in India, and repackaged in the U.S. by a company called Camber. 

On a hunch, Dr. Lever had the pharmacy switch his patient’s prescription from Hetero’s torsemide to torsemide made by a different manufacturer. The patient’s health improved after the switch, though he never fully recovered and died a short while later. 

Dr. Lever says he can’t know for sure if the medication was tainted or ineffective because it was never tested, but the patient’s symptoms and subsequent recovery corresponded with his switching to a drug from a different manufacturer, he says.

Products made by Hetero and Camber have been the subjects of several recalls, five of which took place between 2017 and 2018, though none were for the drug Dr. Lever’s patient took.

Studies of common generic drugs, like the generic torsemide Dr. Lever’s patient was on, have found that these generics can vary widely in efficacy. For example, a study from 2010 notes that people who took generic anti-epilepsy drugs were more likely to require additional medical care, such as hospital visits, than those who used the brand name drugs.

Addressing the FDA’s Inspection Backlog: Possible Solutions and Next Steps

Since writing his AP article, Perrone says he’s received positive feedback from the FDA. “The general feedback from [the FDA] has been, you know, ‘we’re really glad that you highlighted this. This is 100% accurate and true, and it’s something that we’ve been talking about, and frankly not too happy about for some time,’” he says.

Still, the agency has a long way to go to close the gap—and it’s hard to know if it ever will. “Because of the massive backlog that they’re facing, it would be very difficult to catch up,” says Eunjoo Pacifici, PharmD, Ph.D., an associate professor of regulatory and quality sciences at the University of Southern California. “It’s like a moving train. We can’t pause and catch up.”

To do so, the agency would need to significantly increase its inspector workforce and offer more competitive salaries, as many FDA inspectors often leave for higher-paying work for the companies they used to inspect. According to AP, inspectors often start at salaries of around $40,000, working up to about $100,000 annually. They also often spend half their working lives traveling. One former inspector quoted in the AP’s article says he was making $100,000 a year with the FDA, but once he became a private consultant, now reportedly makes $250,000 a year, along with a significantly more relaxed work schedule.

The GAO has recommended some options for stepping up investigator recruitment and retention, and in 2022 and 2023, the FDA described six strategies it would be using to bulk up its investigator workforce, such as raising the minimum salary and adding incentives for inspectors willing to do foreign inspections. Still, the GAO writes that as of July 2024, the FDA had not yet formed a detailed time frame for its foreign office recruitment.

Testing Drugs Instead of Lab Inspection

Waiting for the FDA to hire more lab inspectors is not the only option. Another possible solution would be to conduct chemical analysis on medications, rather than visit the labs where they’re made.

Contrary to popular belief, testing drugs for quality or contamination is not currently part of the FDA’s responsibilities.

Dr. Lever is advocating for the government to support chemical analysis of all drugs within the U.S.—whether they’re manufactured here or abroad. Dr. Lever emphasizes that he doesn’t want people to panic and stop taking their medications but that “if you’re going to swallow medication, you’ve got to know that it’s safe.” Dr. Pacifici agrees that this could be an effective option to ensure safety.

A rollout of such a testing plan is already underway. A company called Valisure is currently partnering with the Department of Defense and the Uniformed Services University for Health Sciences to evaluate the quality of essential medications made by different manufacturers. Doing so, the team hopes, will allow buyers in the U.S. to differentiate between labs that consistently produce safer and higher-quality medications and those that don’t. Once an evaluation is done, researchers assign a rating to each drug and manufacturer based on the testing results over time. For example, if tests show that a drug made by a particular company consistently contains the appropriate dose of ingredients and no contaminants, it would receive a green rating. Like a traffic light, yellow suggests purchase with caution and a red rating would suggest that the medication and company were unreliable. This would incentivize high-quality manufacturing.

“The end goal we want is to ensure the safety of drugs that enter the U.S. supply chain for our citizens,” says Dr. Pacifici.

How You Can Protect Yourself and Your Loved Ones

Whether or not the FDA clears its years-long backlog or implements new plans, you can still take proactive steps to protect your and your family’s health.

No matter what kind of medication you take, from over-the-counter eye drops to prescription corticosteroids, the label is required to state the name and address of its manufacturer, packer, or distributor. You can type the name of the company on the label into this FDA search to see how recently it was inspected and whether it received any citations at that time. Unfortunately, this method isn’t completely fool-proof, as, for example, the PharmaTech plant in Florida had passed an inspection shortly before its drugs were discovered to contain dangerous bacteria. Additionally, since the label can contain the name of the manufacturer, packer, or distributor, but not necessarily all three, you may not know for sure where the drug or its ingredients were made.

For instance, if you search “Intas Pharmaceuticals” you’ll find a litany of issues including a lack of training for employees involved in manufacturing, insufficient or nonexistent protocols for preventing contamination, lack of documentation and more.

If it looks like your manufacturer has not been inspected in several years or you see citations that concern you, you can consider asking your pharmacist about getting the medication you need from a different manufacturer.

See a demo here.

@medshadow_foundation What can you do when the FDA fails to inspect thousands of drug manufacturing labs? @Health Journo Emma #fda #medicine #health #healthcare #inspection #medication #otc #prescriptionmeds #drugsafety ♬ original sound – MedShadow Foundation

“There is no question that the FDA is finding egregious results from their inspections,” says Dr. Pacifici. “That information is open and accessible on the FDA website. You can see warning letters, you can see inspection reports.”

If you want to tell the FDA that it’s time to reform its laboratory inspections program, send an email to the FDA’s Office of Pharmaceutical Quality at CDER-OPQ-Inquiries@fda.hhs.gov