When you get on an airplane or an elevator you assume someone inspected the equipment. That is the implicit understanding between customers and companies. The goal is safety. But who inspects pharmaceutical manufacturers? It’s supposed to be the FDA. The agency is responsible for ensuring drug quality and safety. But ever since the start of the pandemic, FDA inspectors have not been doing that job in foreign countries where most drug manufacturers make your medicines. Even before the pandemic, the FDA relied on drug companies to tell the truth. Was that a mistake?
There Is a Reason to Trust but Verify!
We love the old Russian proverb “Doveryay, no proveryay.” It has been loosely translated as “Trust but verify.” Ronald Reagan was fond of repeating this saying when negotiating with the former Soviet Union.
Most of us intuitively get the meaning of this phrase. When we cash a check at the bank, we trust the teller to get it right, but we still count our money before we leave. The Food and Drug Administration is far too trusting when it comes to drug company data.
Relying on the Honor System:
What’s your take the honor system? This is an idea that has been adopted by many institutions. Take the United States Military Academy West Point’s Cadet Honor Code:
“A Cadet will not lie, cheat, steal, or tolerate those who do.”
The idea of an honor system dates back to 1776 when General George Washington required a “proper sense of honor” in his officer corps. The honor system is not reserved exclusively for military institutions, though.
Many colleges and universities require students to sign a pledge that they will not cheat and that they will report any classmates who violate this code of honor. The idea only works when everyone in the community is trustworthy. Sadly, there are many examples where the honor system has failed.
Take Princeton, for example. The honor code was established there in 1893. According to an article in the Daily Princetonian (March 28, 2021), however, when 85 students witnessed cheating, only four reported it.
Middlebury college states unequivocally:
“The College has an Honor Code and takes it seriously. Before students enter Middlebury College, they are required to sign a document stating that they have read the code and understand it, and they are given a multi-step orientation to the Honor Code upon their arrival.”
How well does it work? According to an article in the New York Times (April 11, 2014):
“Last spring, a student, Craig Thompson, conducted a survey for an economics course, and his findings shook the campus. Of 377 student respondents, 35 percent admitted to violating the honor code at least once in the 2012-13 academic year.
“Most honor codes rely on students to report witnessed cheating; Middlebury’s calls them ‘morally obligated’ to do so. But the students who are supposed to be proctoring one another aren’t. In a February student-government survey, 63 percent of students said they would feel neutral about, or not report, witnessed exam cheating.”
The FDA, Drug Quality and the Honor System:
The honor system doesn’t work any better when it comes to pharmaceutical companies and the FDA. Most people assume that the Food and Drug Administration does a lot of testing, especially of foreign-made medications. This would be a good way to ensure quality and root out cheating.
In truth, though, the FDA does very little testing. For the most part, it relies on companies to do their own testing and submit their data for review.
Over the last decade or two, there have been repeated problems with pharmaceutical testing and manufacturing. We have been documenting contamination with carcinogens, corruption and falsification of documents for years.
Katherine Eban is an investigative reporter. We have interviewed her on The People’s Pharmacy syndicated public radio show several times. In her 2019 book, Bottle of Lies: The Inside Story of the Generic Drug Boom, Ms. Eban documents case after case of fraud and malfeasance within the generic drug industry.
Even before Bottle of Lies, though, Katherine Eban wrote a scathing critique of generic drug company abuse. In her article for Fortune titled “Dirty Medicine” (May 15, 2013) she described the scandal surrounding Ranbaxy, an Indian generic drug company.
She wrote:
“On May 13, Ranbaxy pleaded guilty to seven federal criminal counts of selling adulterated drugs with intent to defraud, failing to report that its drugs didn’t meet specifications, and making intentionally false statements to the government. Ranbaxy agreed to pay $500 million in fines, forfeitures, and penalties — the most ever levied against a generic-drug company.”
Drug Company Cheating:
Katherine Eban critiqued the FDA’s ability to oversee and catch drug company cheating:
“As the Ranbaxy story makes vividly clear, generic-drug makers intent on breaking the rules — especially those operating abroad — can easily do so. Drug applications work on the honor system: The FDA relies on data provided by the companies themselves. ‘We depend on that information to be truthful,’ Gary Buehler, who headed the FDA’s office of generic drugs for 10 years, said in December 2009. (Buehler has since taken a position at the U.S. unit of the Israeli generic-drug company Teva.) The approval system ‘requires the ethical behavior of the applicant,’ he said. Otherwise, ‘the whole house of cards will fall down.’
The FDA’s House of Cards:
We had numerous conversations with Gary Buehler ourselves. When we discovered problems with the generic form of the antidepressant bupropion (Wellbutrin), we informed Mr. Buehler that something smelled very bad, literally and figuratively! That’s because many of the samples readers sent us smelled terrible. He pretty much dismissed our concerns. Eventually, the FDA did require tests that showed a number of generic bupropion products were not bioequivalent to the brand name.
In 2013 investigative journalists at ProPublica reported on the FDA’s missteps. A whistle blower at a large research laboratory tipped the agency off to fraudulent data manipulation. Over 100 drugs were involved, many of them generics. This lab fudged data between 2005 and 2009; according to the FDA, its actions were egregious.
Since the agency could not trust the data for many of the medications that had been approved, it required retesting, but it did not tell physicians, pharmacists or the public which medications were under scrutiny. Most remain on the market and no list of affected drugs is available. We still do not know how the FDA verified drug quality for these frequently prescribed medications.
COVID-19 Has Halted Foreign Inspections:
The pandemic has only made matters worse. Because so many of our medications are now made in foreign countries, inspections are more important than ever. The FDA finds it challenging to inspect these plants even under the best of conditions.
Before COVID, the agency actually inspected domestic and foreign plants. In the US, they would often show up unannounced. In countries like India and China, however, they had to make appointments well ahead of time. That could allow manufacturers time to clean up their acts.
Would you trust drug quality reports from a company that was notified weeks or months ahead of time that someone would be coming to inspect? It would be like telling restaurant owners that the local health department will be coming in six weeks to inspect the kitchen. By the time the inspectors arrive, someone will have cleaned up all the mouse droppings and dirty cabinets and made the premises spotless.
When the pandemic started, the FDA suspended both foreign and domestic inspections. Travel was considered too dangerous for FDA personnel.
Inspectors are still avoiding countries like India and China where many drug companies manufacture our medicines. Some “Mission-Critical” inspections are going on, but they appear to be few and far between.
Drug Quality and FDA Oversight:
Over the last several years, we have reported numerous instances of drugs contaminated with probable carcinogens. They include some popular blood pressure medications such as certain lots of losartan and valsartan. Other manufacturers also produced the diabetes drug metformin with unacceptably high levels of nitrosamines. You can read about these drug quality issues at this link.
With the pandemic still killing people, the agency is:
“limiting unnecessary contact by only conducting prioritized domestic facility inspections and those that are deemed mission-critical.”
In practical terms, that likely means that you are now swallowing medicines for blood pressure regulation, diabetes management, epilepsy regulation or cholesterol control that the FDA did not oversee during their manufacturing process.
What’s Happening in India?
India has been on a roller coaster with COVID-19. In May of 2021, the country was a disaster. Over 400,000 people were contracting COVID each day. Then cases came down. By the fall of 2021, it seemed India had almost recovered. Then along came the Omicron variant. Cases surged to a peak in January. Although cases are now down again, it is unlikely that the FDA will send inspectors abroad any time soon.
Where do you think a great many of our generic drugs come from? India! Here is just a partial list of Indian drug manufacturers:
Aurobindo
Dr.Reddy’s
Glenmark
Hetero
Lupin
Macleods
Sun Pharma
Torrent
Wockhardt
Zydus Cadila
How is the FDA guaranteeing drug quality in India?
The GAO Inspects the FDA!
The Government Accountability Office (GAO) reported that FDA:
“has paused most inspections since March 2020.”
In fact:
“FDA was unable to complete more than 1,000 of its planned fiscal year 2020 inspections and will likely face a backlog of inspections in future years.”
The countries most affected are China and India.
In a typical year, the FDA would carry out at least 600 inspections of foreign manufacturing facilities. The GAO reports that “FDA conducted three foreign inspections in fiscal year 2020 following the pause” due to the pandemic.
Why did the GAO conduct its review of FDA inspections? The United States increasingly relies on foreign companies for the drugs Americans take. Three fourths of the active ingredient manufacturers are located outside our national boundaries.
The GAO report notes:
“FDA is responsible for overseeing the safety and effectiveness of all drugs marketed in the United States, regardless of where they are produced, and it conducts inspections of both foreign and domestic manufacturing establishments.
“GAO has had long-standing concerns about FDA’s ability to oversee the increasingly global pharmaceutical supply chain, an issue on our High Risk List since 2009.”
What is the FDA Doing About Drug Quality?
How is the FDA responding to worries about its lack of drug company inspections? The agency has issued a guidance for “voluntary remote interactive evaluations.” Essentially, these are video visits.
Anyone who has been meeting on Zoom during the pandemic knows that it’s better than nothing, but certainly not the same as being there in person. For remote evaluation, the facility must have adequate internet connection throughout to support live-streaming video and audio during the “walkthrough.” Inspectors may also need translators to help with communication during interviews.
What About Clinical Trials?
The latest controversy involves a Chinese partner to US drug company Eli Lilly. The FDA is questioning a new lung cancer drug, sintilimab, because of concerns about the clinical trial. Pharmaceutical researchers conducted the study entirely in China and the FDA has criticized the methodology.
Perhaps it is time for the Food and Drug Administration to reconsider its policy of relying on the honor system for data about drug quality. Trust is admirable, but President Ronald Reagan had a point when he said:
“Trust but Verify.”
We describe our own investigation into the FDA’s generic drug approval process in our eGuide to Saving Money on Medicines. It can be found under the Health eGuides tab at www.PeoplesPharmacy.com.
In it, we reveal the inside story on the house of cards that the agency created around the generic antidepressant bupropion (Wellbutrin).
To learn more about the shocking state of global drug manufacturing, you might want to listen to our free interview with Katherine Eban, author of Bottle of Lies: The Inside Story of the Generic Drug Boom. It is Show 1169: What Are the Problems with Generic Drugs at this link. Click on the arrow inside the green circle to hear Katherine Eban explain what she uncovered about drug quality problems.
