The Food and Drug Administration (FDA) is just one agency out of the many that make up the United States Department of Health and Human Services and, from PharmacyChecker’s relatively small (non-regulatory) role of helping verify online pharmacies to protect public health, I’ve learned just how insanely massive its mandate is. I’ve also witnessed and participated in its criticism, and with good reason: the agency is not honest or forthcoming about personal drug importation; its drug approval process is “inherently biased”; due to the “revolving door,” the FDA is too cozy with Big Pharma; and many other things. Wikipedia has an extremely long page aptly called Criticism of the Food and Drug Administration, much of it having to do with its role with prescription drugs, and less so other sectors, such as food, tobacco and cosmetics.
Whily my advocacy initiatives implore the FDA to bring more balance, commonsense and fairness to regulating and providing consumer education about personal imports of prescription drugs, I’ve realized that I should practice the same in how I talk about the FDA. So, without further ado, a moment of praise amongst the criticism:
Despite its inability to please everyone, the FDA protects, lengthens, and improves the quality of hundreds of millions of lives through its work regulating the development, creation and distribution of medical products.
“It’s primarily the FDA’s role over drug safety and quality that captures my interest and admiration.”
The medications that we obtain in the U.S., whether in pharmacies, hospitals or other regulated settings, administered clinically or taken at home, are largely safe and reliable. The FDA’s capacity to evaluate new and generic drug applications and its oversight over drug manufacturing are why we have this degree of assurance. We can all take pride as Americans that we have created an agency of this magnitude. Support for the agency waxes and wanes among consumer groups, members of Congress and the public. Yet, more so than most federal agencies, experts in public health, medicine and science, and lawmakers from opposing political parties and ideologies generally come together in recognizing the FDA’s critical role in public health protection.
The Critique:
The 2019 publication of “Bottle of Lies: The Inside Story of the Generic Drug Boom” by investigative reporter Katherine Eban details not just many serious failures by the FDA to prevent poorly made generic drugs, especially those made in India, from coming to market, but outright corruption and illegality by some generic drug companies, with a focus on the Indian drug company Ranbaxy. While Ms. Eban’s greatest concern is with generic drugs, she hints at potential problems with brand name drugs as well, since the active pharmaceutical ingredients that go into many of these medications are made in India and China, where manufacturing problems are greater, relative to the U.S. and other high-income countries. This month, an investigative report by Kaiser Health News seemed to breathe life into the concerns over brand drug quality, showing instances where the FDA appeared to drop the ball and give brand name drug companies a pass on standards.
The Praise:
Despite everything, the FDA is not only one of the best drug regulatory authorities in the world (if not the best), its pioneering methodologies for drug reviews and approval and systems for drug manufacturing oversight effectively help ensure Americans can trust the medicines they purchase at local pharmacies. The FDA is also looked to by drug regulatory authorities in other countries for its strengths. The agency has a herculean task for which success and failure are often subjective metrics. Just as there is not a completely safe and effective drug, there is not an unequivocally foolproof system to make sure every single drug is manufactured at the highest quality. Perhaps that is the ideal, but if that was the standard, we would not have the dynamic systems of drug creation and manufacturing that we do today.
The FDA’s Role in Protecting Our Drug Supply
It’s primarily the FDA’s role over drug safety and quality that captures my interest and admiration. The whole scope of FDA’s practice is to minimize risks and maximize benefits from medical treatments to protect the public health. There have been glaring mistakes, system failures, and even corruption at the FDA, but the agency’s successes, which are more mundane, are not as loudly touted in the media and are sometimes taken for granted.
The overall work of the FDA, its mission, and, even more importantly, its many thousands of qualified personnel dedicated to safe and effective medical products, are incredible:
- Products regulated by the FDA account for about 20% of the entire economy.
- Of its annual budget in 2018, $5.4 billion, about 50% was dedicated to regulating medical products, including prescription drugs.
- Of the 17,468 people employed full time by the FDA, 6,571 are dedicated to evaluation and research of drugs and biologics (called “drugs” for the purposes of this post).
- Another 4,894 are with the Office of Regulatory Affairs (ORA), which carries out a multi-pronged, strategic effort to ensure that industries in the business of creating, making, selling and distributing drugs are following the rules.
There are 19,000 approved prescription drugs for marketing in the U.S. Just because those products have been approved doesn’t mean FDA’s work is done. Far from it. They must try to ensure that all approved products are manufactured in accordance with cGMP (current Good Manufacturing Practices). That entails inspections of the plants that make the medical products and even the active pharmaceutical ingredients (APIs) that go into the finished products. There are 267,000 FDA-registered facilities but the overwhelming majority of those involve food. There are 10,351 related to the manufacture and distribution of human drugs with perhaps the surprising majority of 7,147 facilities located outside the U.S.
See FDA Fact Sheet.
Of course, the faster a safe and effective medicine can come to market, the better. By evaluating new drugs to determine their safety and efficacy, the Center for Drug Evaluation and Research (CDER) is on the FDA front lines of protecting the public health from bad medicine and bringing to market medical treatments that cure, prevent and mitigate the effects of illness. This is the heart of FDA’s mission. Thousands of dedicated medical doctors, nurses, pharmacists, scientists, statisticians and other analysts are responsible for CEDR’s important work.
The ORA is the “eyes and ears” of the agency. For new or generic drugs to work in a patient, they must, of course, be made correctly by using Current Good Manufacturing Practices. ORA inspects manufacturing plants, issues warning letters and import alerts, and, more recently, has a major role regulating the distribution of prescription drugs.
Inspections mean that the plants manufacturing our drugs are more likely to do so under cGMP; investigations create a deterrent to illegal and dangerous behavior among regulated industries; and stop the importation of substandard or falsified medicines. Where people and companies are breaking U.S. laws, the ORA, through the Office of Criminal Investigation, brings nefarious actors to justice.
I have summarized the main FDA roles, as carried out by CEDR and ORA, in protecting the U.S. drug supply. But there is so much more. For example, the agency started the Office of Pharmaceutical Quality (OPQ) in 2015, which is entirely dedicated to making sure FDA-approved drugs are of high quality. Despite being relatively new, OPQ is the largest office housed within CEDR and its work dovetails with that of CEDR’s handling of drug applications and ORA’s manufacturing oversight. I believe that where the FDA has fallen short on consistent quality in the past, OPQ can turn that around. One way to understand OPQ’s work is to note that it’s the responsibility of ORA to make sure drugs are manufactured under cGMP, but OPQ’s responsibility to better ensure the products that are actually manufactured are free of contamination and defects.
Dissecting Criticism of the FDA: Inspections & Sovaldi’s Approval
Katherine Eban’s scathing criticism of the FDA’s failures contains the meat and potatoes for what journalists want to write about and members of Congress want to score points for criticizing. Notably, we are not doing a good enough job inspecting manufacturing plants in other countries that make pharmaceuticals for the U.S. market. Notwithstanding the importance of watchdogs shining a light on what’s wrong, the FDA has in some respects substantially improved its oversight over the inspection of foreign drug manufacturers. A report by the U.S. Government Accountability Office in 2007 showed that out of 3,249 foreign drug establishments subject to FDA inspection, the ones permitted to ship pharmaceuticals to the U.S., there is no record of an inspection at any time of 2,133 of them. Ten years later, a GAO report shows vast improvement by the FDA. The agency had improved its registration database, which cataloged fewer foreign establishments (3,000) permitted to export pharmaceuticals and 2,000 of those had been inspected. The report stated that the FDA “reduced its catalog of drug establishments with no inspection history to 33 percent of foreign establishments, compared to 64 percent in 2010.”
In looking at the recent Kaiser Health News exposé criticizing the FDA on brand name drug manufacturing, the agency’s tough balancing act of benefits and risks resonates loudly. According to Kaiser, when Gilead was seeking approval for its wonder drug sofosbuvir, sold under the brand name Sovaldi, problems were discovered at Sovaldi’s testing facility in Foster City, California. Kaiser describes the report by FDA inspectors:
“Their findings criticized aspects of the quality control process from start to finish: Samples were improperly stored and catalogued; failures were not adequately reviewed; and results were vulnerable to tampering that could hide problems.”
The eventual result was that Gilead was given an ultimatum: either use a different contract testing facility or bring in independent contractors to manage the Foster City plant. Gilead chose the former and its drug was approved quickly thereafter. Since approval, there have been adverse health reports about Sovaldi, some serious. Moreover, while Gilead claims a 90% cure rate, one survey shows that 20% say the drug did not work for them.
Was the FDA wrong in approving Sovaldi when it did?
Sovaldi was a major breakthrough. It cures hepatitis C and there had been nothing like it on the market. The FDA may have been able to do a better job, but it’s hard to say. The inspectors did their job. They found and reported the deficiencies at Foster City. The decision left to CEDR involved tradeoffs. The reporting really doesn’t tell us what they were exactly. Was the change to a new testing site sufficient? What exactly should the FDA have done? Each day off the market was another day someone would not be cured of hepatitis C. CEDR decided that, in line with Gilead’s corrective action, getting people cured sooner outweighed the risks of keeping Sovaldi off the market. Tens of thousands of people were cured of hepatitis C within weeks of the drug’s launch. The gray here is illuminating.
[None of the above forgives the unconscionable U.S. retail price of $1,000 per pill, even for a cure to hepatitis C.]
Within CEDR exists the FDA’s Office of Prescription Drug Promotion (OPDP). Its mission is to ensure that drug companies are telling the truth about their products when they market them to the public. Where CEDR’s overall mission to review the safety and efficacy of drugs before the come to market is the “heart” of the FDA’s work, OPDP is the “soul.” To prevent the medical quackery, which is fraudulent marketing and advertising of medical treatments, that was rampant in the late 19th and early 20th centuries, Congress passed the 1906 Pure Food and Drugs Act, legislation that formed the basis for the modern FDA. The Act required food and drug labeling to be truthful and that such products meet standards for purity and strength. It’s all about telling the truth to consumers.
I’m hoping the FDA brings some of this soul to the table on how to communicate the truth to Americans about personal drug importation and online pharmacies. But for today, I’m defending the FDA.
