For decades experts questioned safety of U.S. drugs made overseas. The pandemic made it worse.
By: Megan Luther and Lee Zurik
Originally Published: May 6, 2020
(InvestigateTV) – Nearly 80% of drug ingredients used in the United States originate overseas, but the Food and Drug Administration has struggled to oversee the manufacturers’ factories, raising red flags about safety.
That was before COVID-19.
The pandemic has delivered a one-two punch to the United States’ drug supply and highlighted the country’s long-time dependence on medicines made overseas.
It caused drug shortages and suspension of safety protocols of the medicines manufactured overseas—the majority in China and India.
Some countries slowed production of certain pharmaceuticals or stopped exporting them at the beginning of the pandemic. In order to protect investigators from the virus, the FDA stopped inspecting all foreign and domestic drug manufacturers, further shaking confidence in the safety of the U.S. drug supply- a concern that has existed for more than two decades.
“We are flying blind right now,” said Dinesh Thakur, a former Indian pharmaceutical executive turned public health activist.
As pharmaceutical companies have moved much of their manufacturing overseas to boost the bottom line, the FDA has struggled to keep up.
And consumers are left in the dark. To find out where prescriptions are made, U.S. consumers must do their own sleuthing because the U.S. lacks a federal mandate required by other countries, to disclose that information. India requires pharmaceutical packaging to identify the facility and its location.
A combination of high demand of medication to treat COVID-19 patients and slower production of drug manufacturing has meant fewer drugs available in the U.S.
In early May, the FDA listed a shortage of more than 100 drugs made by multiple manufacturers. Not all are due to COVID-19. In one recent analysis of drug shortages over five years, the FDA found that drug quality and manufacturing problems were responsible for the shortages nearly two-thirds of the time.
But the virus is adding stress to the system.
Three of the injectable drugs commonly used for intubation and ventilation of COVID patients were on the shortage list in early May. Manufacturers of the drugs – etomidate, ketamine and propofol – blame “demand increase.”
U.S. military members also rely on foreign-made drugs. Before the pandemic, Congress was warned that the U.S. dependence on drugs and ingredients from China “presents economic and national security risks,” the Department of Defense reported in November.
Because of this reliance, the FDA uses what it calls “regulatory discretion” to balance punishing manufacturers for violations with America’s need for medication. For example, refusing an import from a foreign facility could trigger a shortage of one or multiple drugs.
When Doug Campbell was the FDA-lead foreign drug investigator eight years ago, he saw maybe one shortage a year.
“You had to make a certain decision to use your regulatory discretion because if we don’t have this product on the market it will cause a shortage. Now, it’s a daily event and there are teams of people at the FDA who are managing it and this pandemic has exacerbated the condition immensely,” Campbell told InvestigateTV.
Check the FDA’s website to see if there’s a shortage on your medication.
For more than two decades, the Government Accountability Office has been questioning the FDA’s ability to properly regulate foreign drug makers. In 1998, the agency was inspecting just a fraction of oversea facilities. Little had changed nearly a decade later, when GAO found just 8% of foreign drug manufacturers had been inspected, according to the 2008 report.
Nearly a third of the 3,000 foreign facilities may have eluded inspection altogether, according to a 2016 GAO report. The report said the FDA could not produce documents of inspections.
By mid-2019, the FDA had finally inspected half of those missing facilities and found that 359 no longer needed to be inspected for legitimate reasons such as business closure or that the facility no longer supplied drugs to the U.S.
While FDA has made some progress, significant challenges remain, according to Mary Denigan-Macauley director of GAO’s Health Care division.
“Many of the concerns that we saw starting back in 1998 with the oversight of the safety and efficacy of the drugs coming from overseas are still here today,” she told InvestigateTV.
Unannounced inspections – the standard for U.S. drug manufacturers – aren’t always possible overseas. Foreign inspections require making traveling arrangements, giving the facility as much as 12 weeks’ notice before inspectors arrive, according to the GAO.
Now the pandemic has forced the FDA to suspend inspections and officials have not said when they will resume. The agency declined an interview request.
In March, FDA Commissioner Dr. Stephen M. Hahn released a statement about the suspension of foreign and domestic drug inspections. He cautioned that the quality of drugs should not solely rely on FDA inspections, but also should rest with the manufacturers.
“Safety and quality need to be owned by the industry and firms have the primary responsibility to reliably produce quality products,” he said at the time.
But history shows bad actors produce subpar drugs.
Thakur, the former pharmaceutical executive, knows first-hand. He worked for the largest generic drug maker in India when he discovered the company was lying to the FDA and violating manufacturing regulations resulting in substandard drugs.
The company made several types of generic medications including antibiotics and anti-virals. Thakur became a whistleblower and the company, Ranbaxy Laboratories. pleaded guilty in 2013 in U.S. federal court and paid a $500 million fine. Ranbaxy was sold in 2014.
Thakur, now working to improve pharmaceuticals in the U.S. and India, said the bad behavior continues.
“A lot of these facilities that are located overseas they try and beat the system,” he said. “There has been systematic documentation now from the FDA itself of people trying to fool the inspectors. People trying to take advantage of this honor-based system where they try to cut corners and supply substandard drugs.”
The FDA dealt with a massive recall in 2018 and 2019 of blood pressure medication made overseas tainted with cancer-causing ingredients. The cause was faulty manufacturing, according to the FDA.
During Campbell’s tenure with the FDA, he watched as the pharmaceutical industry moved overseas.
“I always say that the bottom line is the bottom line,” he said.
The FDA followed the industry. In 2006, the agency was doing around 100 foreign inspections. By the time Campbell left in 2012, the FDA was doing more than 700.
The agency conducted more than 1,000 inspections last year.
“Could it be better? Absolutely. It’s all about resources. Once it became a global mission, it’s a big world out there. It’s harder to do than people might think,” Campbell said. He now works with foreign manufacturers as a consultant, teaching them good manufacturing practices and how to comply with FDA regulations.
The FDA also has struggled with inspector vacancies. The agency had 190 inspectors in the U.S. who did foreign inspections and an additional 58 vacancies as of November. The agency was in the process of filling 26 openings at the time but noted that training the inspectors could take up to three years, according to GAO’s latest report.
Where are your drugs made?
It’s difficult for U.S. consumers to find out where their prescriptions come from. The federal government doesn’t require it.
But you can check the label on your shirt or see “Made in China” stamped on a child’s toy.
“Even dog food is labeled where it’s made,” Thakur said.
Other countries, including India, Thailand and Bangladesh require the manufacturing location to be listed.
There’s no website where American consumers can check the source of their prescription drugs. They can call the companies directly, if they can get through. Some customer service lines require an international call.
InvestigateTV called drug makers of more than 150 popular prescriptions in April. Some didn’t answer. Others put us on hold for 30 minutes without picking up. In some cases, the customer service representative was unable to say where a drug was made.
But even if consumers are able to find out where their medications are manufactured, it’s almost impossible to know the source of the raw materials.
For example, some drugs made in the U.S. get the ingredients from other countries. One reason India halted exports of 26 drugs and ingredients at the beginning of March was because of that country’s reliance on China for active pharmaceutical ingredients. India rescinded those restrictions a month later.
“Not a sustainable policy”
Republicans and Democrats have called for a change to the country’s dependence on foreign drugs.
Senate Minority Leader Chuck Schumer, D-New York asked the GAO to investigate the United States’ ability to manufacturer drugs and active ingredients currently made in China.
Rep. Jeff Fortenberry from Nebraska, a Republican on the House Appropriations Committee, believes pharmaceuticals need to be manufactured like military equipment: “Made in America.”
“CEOs of these big pharma companies need to be on notice. This is not a sustainable policy and it’s going to be addressed aggressively by Congress,” he said.
Thakur recommends U.S. consumers talk to their doctors and educate themselves about the medications they are taking. They should ask where the drugs are made and if the physician has heard of any issues with their effectiveness.
“Unless we as patients start to engage our providers and start asking these questions, we just don’t get more information about it,” he said.
Campbell has cancelled all overseas consulting trips for the rest of the year.
Ultimately, he said, consumers need to know that the FDA inspects only a small sample of foreign-made drugs.
“So the rest of the time we are crossing our fingers.”
Additional research conducted by: Peter Buffo, John Canicosa, Cody Downey, Laura Jayne, Anum Siddiqui, and Erin Snodgrass from Loyola University New Orleans.
InvestigateTV News Content Specialists Tess Rowland and Emma Ruby contributed to this report.