USFDA still struggling to conduct pending drug inspections after Covid

Federal regulators responsible for the safety of the US drug supply are still struggling to get back to where they were in 2019, before the Covid-19 pandemic upended factory inspections in the US and across the world, The Associated Press has found.

An AP analysis of Food and Drug Administration data shows that agency staffers have not returned to roughly 2,000 pharmaceutical manufacturing firms to conduct surveillance inspections since before the pandemic.

The firms that are overdue for safety and quality inspections represent about 42 per cent of the 4,700 plants that are currently registered to produce drugs for the US and previously underwent FDA review before May 2019, the AP found.

 

Most of the overdue plants are in the US, but more than 340 are in India and China, countries that together make up the largest source of drug ingredients used in low-cost US prescriptions.

Generic drugmakers are under intense pressure to cut their costs and some will do that by cutting quality, said David Ridley of Duke University, who studies the pharmaceutical industry.

Last year, tainted eyedrops from an Indian factory led to an outbreak of antibiotic-resistant bacteria that sickened more than 80 Americans, killing four of them and blinding more than a dozen others. The plant never registered with the FDA.

The US drug supply is the safest on the planet and no other regulator conducts more inspections than the FDA, said FDA Associate Commissioner Michael Rogers, noting that the agency has increased drug inspections each year since 2021 while prioritising foreign factories.

But last year's inspection numbers were still down almost 40 per cent from the pre-pandemic period, when the FDA averaged around 4,300 annual inspections.

The FDA halted all but the most mission critical inspections in March 2020. It gradually restarted prioritised inspections later that year, but regular international visits did not resume until 2022.

Beginning in the 1990s, drugmakers began shifting manufacturing overseas, first to Puerto Rico, and then to Asia in search of cheaper labour and materials. The FDA has largely been playing catch-up ever since.

We have to recognise that this is the world we live in and we have to adapt to it, said Dr. Stephen Ostroff, FDA's former chief scientist. That has to include being able to get into these facilities and take a look at what they're doing, particularly in India and China.

Cascade of failure

The FDA keeps a confidential list of drug facilities to inspect, prioritising them based on potential risks. The AP created its own list by compiling public records of FDA inspections from before Covid-19 and tracking which firms haven't received a follow-up within five years.

FDA's internal list of sites for inspection has increased 14 per cent over the past five years, the agency noted last year. On a global basis, FDA says only 6 per cent of sites inspected last year had serious problems. But rates are higher in India, where 11 per cent of plants were cited for violations, the most of any country.

Nearly 90 per cent of FDA's foreign inspections in fiscal 2023 were announced in advance, according to FDA correspondence with Congress obtained via public records requests. The GAO and other government watchdogs have long raised concerns about the practice, which typically gives companies up to 12 weeks to correct or conceal potential problems.

Even with the advanced warnings, the FDA has found egregious violations in overseas factories.

When agency staffers visited Intas Pharmaceuticals' plant in northwest India for the first time in nearly three years they found what they called a cascade of failure. Among the violations, inspectors saw an employee pouring acetic acid in a trash bin to destroy company documents used for drug testing. Elsewhere inspectors found plastic bags filled with torn and discarded documents relating to quality control measures.

This kind of behaviour has been pointed out to the FDA time and time again by people like me for the last 10 years, said Dinesh Thakur, a former pharmaceutical industry executive who became a whistleblower for the US government. In 2013, his work led to a USD 500 million settlement with Indian drugmaker Ranbaxy for falsifying generic drug data.

If you do not prosecute people who do this kind of wrongdoing, it gives the implicit signal that the FDA will give companies a pass, Thakur said.

In the case of Intas, FDA issued a warning letter which has no legal repercussions and blocked some of the company's exports to the US, while attempting to maintain shipments of the critical chemotherapy drug cisplatin. That strategy backfired in June 2023 when Intas abruptly shuttered the plant, triggering a nationwide shortage of cisplatin, which is used in more than a half-dozen cancers.

FDA inspections in India have been accelerating, but 160 plants are overdue, including some which haven't been inspected since 2015 yet continue shipping pain pills, antibiotics and other medications to the US, according to AP's analysis.

Mexico, France and Spain also have over 100 overdue firms between them.

In China, political tensions have made inspections even more challenging. Just two fulltime FDA inspectors are based in the country, where about 185 factories are overdue. Former FDA officials say the Chinese government has withheld visas from inspectors unless the US reciprocates for Chinese nationals seeking to enter the US.

Help wanted

The FDA could seemingly address its inspection backlog by hiring more investigators or assigning extra work to current staffers. But the agency is struggling to hold onto inspectors who can often earn far more working for the companies they now regulate.

The FDA currently has 225 vacancies on its inspection workforce, nearly four times as many as before Covid-19, according to agency records.

New inspectors generally start at an annual salary of about USD 40,000 and can eventually rise to over USD 100,000. Job postings alert applicants they may have to travel up to 50 per cent of the time.

Testing for quality

The slowdown in inspections has attracted scrutiny from lawmakers and raised new questions about whether FDA's decades-old approach is working.

House Republicans have peppered the agency with dozens of inquiries about the programme since 2023. In their most recent letter, members of the Energy and Commerce Committee ask regulators to explain why FDA staffers making high-priority inspections in Asia are reporting less than half as many violations today compared with pre-Covid-19.

The committee is concerned that FDA's fear of triggering additional drug shortages is driving the decreased rate that FDA issues warning letters, states the June letter.

FDA's Rogers rejected the argument, saying inspectors follow strict guidelines when conducting inspections and that decisions about managing drug shortages are handled separately by other parts of the agency.