Expensive brands may not be manufactured by name firms, and instead, may be cranked out in dirty and risky secondary facilities. And the research that leads to expensive products may have been ripped off from federal scientists funded by taxpayers who aren’t getting paid back.
Sydney Lupkin of the independent, nonpartisan Kaiser Health News service deserves credit for expanding public attention on growing concerns over the safety and quality in drug manufacturing beyond generics and on to costly, blue chip branded prescription medications. As she reported of the Federal Food and Drug Administration:
“The FDA has repeatedly found a way to approve brand-name drugs despite safety concerns at manufacturing facilities that had prompted inspectors to push to reject those drugs’ approval … This happened in 2018 with drugs for cancer, migraines, HIV and a rare disease, and 10 other times in recent years, federal records show … For example, inspectors found that facilities making immunotherapies and migraine treatments didn’t follow up when drug products showed evidence of bacteria, glass or other contaminants. At a Chinese plant making the new HIV drug Trogarzo, employees dismissed ‘black residue’ found to be ‘non-dissolvable metal oxides,’ assuming it ‘did not pose a significant risk,’ federal records show. Without a follow-up inspection to confirm drug makers corrected the problems inspectors found, these medicines eventually were approved for sale, and at list prices as high as $189,000 a month for an average patient.”
Issues cropped up in plants making both generic and branded drugs, here and offshore, KHN reported:
“In January 2018, FDA inspectors hit a Korean manufacturing plant that makes Ajovy, a migraine drug, with a warning letter. With the problems still unresolved in April, an agency reviewer recommended withholding approval. When they returned in July, inspectors wanted to give the plant the worst possible classification: ‘Official Actions Indicated.’ Among other problems, inspectors found that glass vials sometimes broke during the manufacturing process and that the facility lacked protocols to prevent the particles from getting into drug products. The FDA’s Office of Manufacturing Quality eventually downgraded the inspection to just ‘Voluntary Actions Indicated.’ The drug was approved in September 2018 and priced at $690 a month. FDA records indicate no further disciplinary action was taken. Teva, the maker of Ajovy, did not respond to requests for comment. Similarly, when FDA inspectors visited a contract manufacturing facility in Indiana used to make Revcovi, which treats an autoimmune disease, they noted that a redacted drug lot had failed a sterility test because the vials tested positive for a bacterium called Delftia acidovorans, which can be detrimental even in people with healthy immune systems, studies show. But the drug-filling machine stayed in use after the contaminant was discovered, the FDA determined. Inspectors recommended withholding approval. The drug was approved in October 2018 even after another inspection turned up problems, with a list price of $95,000 to $189,000 per month for an average patient …”
When serious safety or quality issues arise in plants making branded pharmaceuticals, why don’t inspectors move fast to shut them down and to ensure all concerns get resolved in the most public fashion as possible? As Lupkin reported, that’s not the FDA way these days. The agency, prodded by pro-business lawmakers (most of the GOP variety), expedites its work on prescription drugs, in the belief that beneficial innovations should get to patients as quickly as possible. Congress has put added incentives on the agency to do this, for example, allowing drug makers to pay more and special fees that are a larger part of the overall FDA budget for speeding up oversight.
Lupkin, with reason, zings the drug maker Gilead for flogging the FDA to hurry its products. That’s because the company has campaigned that its drugs can save and change lives, notably with Truvada as a key prevention against HIV-AIDS (more about this in a bit) and Solvadi to wipe out detectable Hepatitis C infection.
Those are admirable aspects of Gilead’s enterprise. But, at the same time, Lupkin reported this about the facility where the company tested products:
“Gilead’s Foster City facility has been cited for an array of problems over the years. In 2012, FDA inspectors said the facility had failed to properly review how the HIV drugs Truvada and Atripla became contaminated with ‘blue glass’ particles; some of that tainted batch was distributed. The company ‘made no attempt to recover’ the contaminated drugs, according to FDA inspection records. Gilead had just filed its application for Sovaldi’s approval when FDA inspectors arrived at Foster City for an unrelated inspection in April 2013. Inspectors slapped the facility with nine violations … and said that the reliability of the site’s methods for testing things like purity were unproven and that its records were incomplete and disorganized, according to FDA inspection documents. As a result, the FDA initially rejected two HIV drugs, Vitekta and Tybost. Gilead had to resubmit those applications, and it would take 18 months before the FDA approved them in late 2014.”
After further tussling, the firm negotiated with the FDA, so its drug testing would be conducted by outside contractors. Gilead shut its disputed testing site.
Although Gilead may have shown what politely might be called chutzpah in its dealings with FDA inspectors, the sprawling and powerful federal Health and Human Services agency apparently decided it had had it with the firm and what the government asserted was its profiteering of U.S. scientists research that led to the PrEP therapy to prevent HIV-AIDS infection. The federal government has sued Gilead for infringing on U.S. patents on anti-viral drugs. As the New York Times explained of the treatment at the heart of the case:
“PrEP is a drug regimen: A person at risk of contracting HIV is prescribed one of two drugs to be taken in pill form once daily to prevent the infection. Both of the drugs approved for use in this regimen, Truvada and Descovy, are made by Gilead. If taken daily, the drugs cut the risk of HIV infection by more than 99%. Public health officials are eager to get more people on PrEP. About one million Americans are at high risk of getting HIV through sex or shared needles and would benefit from PrEP, according to the CDC. But just 270,000 Americans are on PrEP, and there are about 40,000 new infections each year. The price has been an obstacle, critics say. Truvada, which will come off patent next year, has cost about $20,000 per patient per year in recent years; Descovy currently costs about the same. In other countries, generic versions of Truvada sell for as little as $60 a year.”
Gilead has negotiated with the federal government over the price and supply of its HIV drugs, contending it would donate what it calls significant amounts of them and work to ensure that they would stay affordable to assist in the reduction of a once deadly and still potentially debilitating disease. Still, the company’s sparring over price and supplies has infuriated those with or at risk of HIV infection and their allies. It also appears finally to have angered the Trump Administration, which has made one of its key health policy goals an even greater reduction in the harms of HIV-AIDS.
The battle over patents has gone on for a while now, as the New York Times reported:
“The basis of the government’s patent claim is that, in the early 2000s, scientists at the CDC did many experiments on monkeys to see if antiretroviral drugs … would protect them against infection with the simian version of HIV. Government scientists ultimately found that a combination of tenofovir and emtricitabine was the most effective at stopping the virus… Although the government started applying for patents in 2006, some were not granted until 2015 and one was granted only in July. (The CDC patents were recognized in Europe, and generic companies that sell the drug in Europe, Canada and Australia are paying royalties to the agency.) Gilead, the government contends, relied on those CDC experiments in its application to the FDA for approval to use Truvada for prophylaxis. The crucial 2010 study proving that Truvada prevented HIV, called iPrEx, was conducted by Dr. Robert M. Grant of the University of California, San Francisco, and paid for by the National Institutes of Health and the Bill and Melinda Gates Foundation. Gilead’s only role, Dr. Grant said, was to provide Truvada free of charge … Gilead first released Truvada for HIV treatment in 2004, charging less than $10,000 a year. After it was approved for prevention in 2012, however, Gilead slowly raised the price to about $20,000. The company also sued every generic maker that tried to enter the market, and then reached out-of-court settlements with each one. The details were kept secret, but activists believe that Gilead paid each company millions of dollars to stay out of the market — ‘pay-for-delay’ deals.”
In my practice, I see not only the harms that patients suffer while seeking medical services, but also their struggles to access and afford safe, efficient, and excellent medical care. This has become an ordeal due to the skyrocketing cost, complexity, and uncertainty of medical therapies and prescription medications, too many of which turn out to be dangerous drugs.
If retailers voluntarily are pulling drugs off shelves, and generics are under question for their quality and safety, and, now, pricey branded meds have a shadow over them, what should the public conclude? Maybe that Big Pharma and its allies, while promoting innovation and patient benefits while relentlessly seeking profits, really have only skidded closer to the line of putting lives at risk?
Yes, the HIV-AIDS crisis showed that urgency by the FDA could matter and be beneficial. But recent research on cancer drugs — so costly that they’re almost bankrupting to many patients from the instant doctors suggest them — is far from making the case for speedy agency reviews of prescription medications. Here’s what Drew Smith, a molecular biology Ph.D. and onetime research and development director in biotech, reported online recently:
“The real-world record of cancer drugs approved by expedited review is not impressive. Of ten new cancer drugs reviewed after receiving expedited approval, only six showed significant benefit in actual clinical practice. Another study of 29 cancer drugs receiving expedited approval found that only six increased survival. Of 53 new cancer drugs approved between 2003 and 2013 (both expedited and regular approvals), only 23 showed survival improvement of more than 3 months over existing drugs, and 16 showed no benefit whatsoever. Twenty-four of these drugs were also found to reduce patient safety compared to conventional treatment. Despite the claims of the big cancer treatment centers, we are not outsmarting or defeating cancer. We are making slow, steady progress, but at an enormous cost. Even with lowered barriers, only 3% of cancer drug candidates make it to approval. The false narrative promoted by the cancer industrial complex leads the public to believe in miracle cures … The overall result is a steady corruption of our medical and regulatory establishments, and diversion of resources that could be put to better use … Cancer is not being outsmarted but the public is.”
For many drugs and their makers, an abundance of caution and slow and steady to market makes more sense — maybe not for their revenue streams but for safety and quality and the protection of the public.
It also would be helpful to debunk Big Pharma’s myth about the need for speed, so firms can recover what they claim are onerous research and development costs. The left-leaning Center for American Progress recently posted about how taxpayers prop up pharmaceutical companies, with tax benefits and by spending for crucial, basic research that firms then plunder and exploit:
“Billions of taxpayer dollars go into the creation and marketing of new drugs. The Los Angeles Times reports that, ‘Since the 1930s, the National Institutes of Health has invested close to $900 billion in the basic and applied research that formed both the pharmaceutical and biotechnology sectors.’ Despite taxpayers’ crucial investment, U.S. consumers are increasingly paying more for their prescription drugs. A 2018 study on the National Institute of Health’s (NIH) financial contributions to new drug approvals found that the agency ‘contributed to published research associated with every one of the 210 new drugs approved by the [FDA] from 2010–2016.’ More than $100 billion in NIH funding went toward research that contributed directly or indirectly to the 210 drugs approved during that six-year period … Pharmaceutical companies also benefit from research and development tax credits. The federal R&D tax credit was first introduced in 1981 to encourage private sector investment in pioneering research … Pharmaceutical industries also receive a tax deduction for their marketing and advertising expenses. According to a report in the Journal of the American Medical Association, ‘From 1997 through 2016, medical marketing expanded substantially, and spending increased from $17.7 to $29.9 billion, with direct-to-consumer advertising for prescription drugs and health services accounting for the most rapid growth, and pharmaceutical marketing to health professionals accounting for most promotional spending.’ The report also found that from 1997 through 2016, ‘the number of advertisements … increased from 79,000 (including 72,000 television commercials) in 1997 to 4.6 million (663,000 television commercials) in 2016.’”
We’ve got a long way to go to ensure the safety, quality, and affordability of prescription drugs — and that federal officials and agencies that are supposed to serve the public and be watchdogs over Big Pharma do their jobs.