Teva Pharmaceutical Industries Ltd., one of the largest generic-drugmakers in the world, has recalled more than 2.5 million vials of drugs that the company said may not be sterile. The vials, many filled with medicine used to help treat cancer, may have contained mold contamination stemming from water leaks, U.S. inspectors discovered at a Teva production plant in California.

The company has temporarily stopped drug production at the Irvine, California, facility and is reviewing the concerns raised by the Food and Drug Administration, according to a Teva email response to Bloomberg. 

Teva recalled about a million of the vials in February, more than four months after it first detected mold in the air of manufacturing areas. The generic-drug giant yanked the rest of the drugs, almost 1.5 million vials, in July in the middle of an FDA inspection that found Teva left water damage unrepaired, likely creating mold in the walls. The inspection also found that the company hadn’t maintained procedures meant to keep factory workers from spreading mold and bacteria, according to inspection documents obtained by Bloomberg in response to a Freedom of Information request.

The discovery of water damage at the drug manufacturing facility comes amid a push from President Joe Biden to encourage the pharmaceutical industry to ramp up domestic drug production. Generic drugs, which make up 90% of the medications Americans take, are largely made in India. That country, in turn, imports almost 70% of the active ingredients it uses in drug manufacturing from China, according to a White House report. FDA inspectors have repeatedly found factories violating U.S. drug-making standards in those countries.

The problems at Teva’s California facilities, though, are the latest in a string of revelations that underscore the reality that U.S. factories also aren’t immune to quality problems. FDA inspectors have logged violations in recent years at several high-profile drugmakers, including Eli Lilly & Co. and Pfizer Inc.

Relaxed Standards

At the Teva facilities, FDA inspectors said benches in the room where factory workers changed into their scrubs showed signs of excessive use and were visibly dirty and that the company’s protocols didn’t include any procedure for sanitizing them. In addition, factory workers would wear their scrubs outside to take out the trash or to the restroom and not change them when they re-entered the building.

FDA inspectors also said Teva hadn’t made sure equipment used to ensure sterility and test for harmful organisms worked properly since it installed it 21 years ago, despite a change in how the test is performed, according to the documents.

Teva is "taking extensive actions to ensure the agency’s observations are fully addressed," Kelley Dougherty, a spokeswoman, said in an email to Bloomberg. The company is working closely with the FDA's staff to minimize patient impact, she added.

“We have been closely evaluating this event and will continue to monitor the marketplace and manufacturing efforts to help ensure the availability of safe products for U.S. Consumers,” Jeremy Kahn, a spokesman for the FDA, said.

In addition to drugs that help treat cancer, the recalled Teva vials include medications for arthritis and schizophrenia and a muscle relaxer used during intubation.

Teva’s violations appear related to a gradual relaxing of standards at the factory as opposed to deliberate wrongdoing, said John Gray, a professor of operations at the Ohio State University Fisher College of Business after reviewing the documents obtained by Bloomberg.

“It’s very easy to allow compliance to slip in any manufacturing plant anywhere in the world,” Gray, a pharmaceutical supply chain expert, said.

Still, it’s more likely the FDA will spot problems at a U.S. plant where agency inspectors can show up unannounced and spend weeks combing through data and walking factory floors. In India and China, an FDA inspection is almost always announced in advance and typically the duration of visits are limited due to visa restrictions.

Though the violations in India and China are egregious at times and have been found to include subterfuge like shredding key documents and covering up failed quality tests, those countries aren’t alone in their quality-control problems, as Teva and others show.

Quality Issues

Eli Lilly & Co. has also experienced major quality-control issues in the past year at a plant in New Jersey used to help produce its COVID-19 antibody therapy. Compliance officers at the FDA were so concerned about what they called “a major failure of quality assurance” in an internal memo dated Oct. 2, 2020, that they recommended the agency give Lilly a warning letter, one of its strongest enforcement measures. Lilly hasn’t received a warning letter for the plant.

Lilly continues to work with the FDA to address its concerns about the New Jersey site, Molly McCully, a company spokeswoman, said.

Pfizer Inc. also had quality-control issues of its own at a Kansas factory cited in 2020 for mold , a repeat offense at the plant, FDA inspectors said. Mylan NV’s now-shuttered West Virginia plant was warned by the FDA in 2018 for a host of quality violations, not the first time inspectors had raised concerns there.

Pfizer has completed the fixes it told the FDA it would make after the Kansas inspection, Eamonn Nolan, a company spokesman, said.

And Emergent BioSolutions Inc. had so many problems in its Baltimore facility earlier this year that it had to pause production after an FDA inspection in April following a mix up at the plant that resulted in throwing out 15 million doses of Johnson & Johnson's COVID-19 vaccine.

Emergent has worked diligently to address the FDA's concerns at the factory and the agency allowed manufacturing to resume in late July, said Matt Hartwig, a company spokesman.

Fears of U.S. drug supply exposure to manufacturing irregularities in other countries were heightened during the COVID-19 pandemic. India, some worried, could block U.S. access to needed drugs to save the treatments for its own citizens. At the Trump administration’s direction, the FDA published a list of essential medicines a year ago for domestic manufacturing efforts to ensure the drugs would always be available to Americans. The White House found that just half of the drugs on the essential medicines list had domestic sites where their active ingredients could be produced.

Even before the pandemic, U.S. defense officials had raised concerns that China could also seek to withhold necessary drugs or even deliberately contaminate products. Pentagon attention was driven by recalls in 2018 of millions of blood pressure pills made in India and China that were found to contain the chemical N-Nitrosodimethylamine, or NDMA, a carcinogen that was formed during the manufacturing process.

NDMA is part of a class of typically carcinogenic compounds called nitrosamines. The chemical has since been found in the heartburn medicine Zantac and a widely used diabetes drug metformin. The latest drug to contain nitrosamines is Pfizer’s smoking-cessation pill Chantix.

Pfizer said in September it would recall all lots of Chantix due to the contamination. While factories in India have largely been implicated in the string of nitrosamine recalls, Chantix has shown the problem can plague developed countries as well. The drug is made in Ireland, according to an FDA recall database.