Weak drug regulation and patient tragedies: We’ve seen this story before

Plenty of new drugs, but few that are truly innovative. Growing costs from their use. Physicians deemed “Dupes of Big Pharma” for their interactions with the pharmaceutical industry. A call to produce better information on which drugs work best. Finally, shoddy drug manufacturing is injuring and even killing patients. These stories could be lifted from today’s headlines — but they’re actually from 1962. Problems with the behavior of the pharmaceutical manufacturing industry, and our relationship with it, are not new. Nor are they restricted to one country. Every developed country’s health-care system is different, but one feature is near-universal: none have a public pharmaceutical industry. Ever nation relies on for-profit, private companies to supply its population with drug products.

Blog posts here can get pretty wonkish about health policy, as many of the substantial challenges to science-based medicine have their roots in regulation — whether it’s DSHEA which implemented a regulatory double-standard for supplements, or the state-by-state legislative alchemy that Jann Bellamy has documented, which transforms magical thinking and pseudoscientific practices into registered and regulated health practitioners. Federal food and drug regulations have also come under some scrutiny (and praise). The FDA’s under fire again; this time over its responsibility to oversee pharmaceutical manufacturing. But in this case, it’s not Big Pharma that’s the villan — it’s pharmacies.

Pharmacies rarely makes the headlines, and that’s probably a good thing. Safe and effective is boring. But my Google Alert for pharmacy news has been pinging me nonstop. The catastrophe of fungal meningitis that continues to emerge across America may be the worst drug manufacturing disaster since the 1930’s when the S.E. Massengill company inadvertently mixed the antibiotic sulfanilamide with antifreeze, killing over 100 people. It was the Massengill fatalities that led to the Food, Drugs and Cosmetics Act (1938). They were a good first start, focusing on the requirement to for manufacturers to document that their products were safe. But they didn’t go far enough.

From today’s perspective, the FD&C Act (1938) was pretty basic.  There was no requirement for manufacturers to demonstrate good manufacturing practices. And if the FDA didn’t move to block a sale within 60 days, a product could be sold. By the 1950’s, it was clear that the Act wasn’t fully effective. Concerns of excessive pricing and questionable evidence statements from manufacturers eventually led to hearings led by Senator Estes Kefauver. Over 18 months an array of new amendments emerged: efficacy claims would be reviewed and approved. Side effects must be reported. Drugs must be approved for sale before any sales could begin. Good drug manufacturing standards would be mandatory, and would be FDA-inspected. Advertising would be monitored. Drugs would have clear generic names, in addition to trade names. All of these proposals made it into the final wording. What’s pretty interesting is what they cut:

  • Compulsory licensing of generics after 3 years to allow competitive markets
  • Banning so-called “me-too” drugs — new drugs which failed to offer substantial improvements over existing drugs — would be forbidden, as well as minor modifications to existing chemicals that didn’t offer any therapeutic improvements (hello, Nexium)
  • Patent approval only where a new drug offered advantages over the current standard treatment — not just demonstrating superiority over placebo

Why did they get cut? As expected, there was strong opposition from pharmaceutical companies. But the American Medical Association also objected, particularly against a greater role for the FDA in evaluating efficacy. The bill was on life support until the thalidomide disaster in 1962 that secured its passage, now called the Kefauver-Harris Amendments to the Federal Food, Drug and Cosmetics Act. It effectively set the template for modern-day regulation which has been subsequently emulated around the world. Without these amendments, the requirements for pre-licensing clinical trials probably would not exist. Nor would longer patents, granted in 1984 based on appeals for longer patent protection due to the barriers established before drugs can be sold.

So how did we end up with a meningitis outbreak this year? Through a loophole in the Act. The contamination of injectable steroids is one of a long string of medical harms caused by “compounding pharmacies” — pharmacies that skirt FDA regulations by acting as chameleons. To hospitals and physicians, they’re businesses selling drug products, just like any other pharmaceutical company. But to the FDA, they claim to be pharmacies, not pharmaceutical companies, which put them under the jurisdiction of state pharmacy regulators. Why the loophole? Until fairly recently, all pharmacies used to be compounding pharmacies. Each store made its own dosage forms like creams and capsules. Everything could be personalized. Today, compounding in the pharmacy has dwindled for most products, as Pharma can do it faster, cheaper, and more accurately.  But compounding is a legitimate part of pharmacy practice, and can fill real patient care needs. And in an era of regular drug shortages, they can manufacture drug product – but without any of the quality standards mandatory for pharmaceutical companies.  Unlike federal requirements which are uniform across the USA and around the world, regulations for pharmacies are determined at the state level, by pharmacy regulators. The same degree of oversight simply does not exist.

It should not be surprising that compounding pharmacies have fought all attempts by the FDA to impose more rigorous manufacturing standards, which would make it harder to sell products. To lawmakers, advocates position it as an access and “right to choose” argument especially for “natural” products like “bioidentical” hormones which are often made by compounding pharmacies. These are the same pharmacies preparing chelation infusions, and they used autistic children to argue for their right to continue to manufacture these products, despite the fact that they are clinically useless for autism. But they seem to work well as a lobbying tool. They’ve successfully killed legislation proposed in 1997, 2003 and again in 2007.  This lobbying success is remarkable given there have been no shortage of problems: Since 1990 the Institute for Safe Medication Practice has documented 22 significant pharmacy compounding errors involving 71 different drugs resulting in over 200 adverse events — some fatal.

But is FDA oversight required to keep fungal contamination out of injectable drugs? It shouldn’t be. The United States Pharmacopeia Chapter <797> establishes sterile manufacturing standards which are expected to be adhered to by pharmacies that make these products. Tightening of requirements <797> in 2008 had the effect of causing more outsourcing to larger pharmacies, as smaller centres could not meet the requirements.  Probably most concerning is that the requirement to follow <797> isn’t uniform across states — five boards don’t mandate it, and the others don’t audit consistently. That seems to be the case in Massachusetts , where the New England Compounding Center (NECC),  has now been closed permanently as it’s revealed that  basic safety and manufacturing standards, including <797> requirements were not being followed when it manufactured preservative-free methylprednisolone acetate. The two lots of drug contaminated with black mold have reached 14,000 patients in 23 states. This is no small operation. Furthermore, NECC was flouting state pharmacy law by failing to act as a pharmacy: it shipped product out without a prescription, or labelled for an individual patient.


Regulatory frameworks evolve over time. Regrettably, it sometimes takes a public health catastrophe to give lawmakers the motivation to ignore vested interests and act in the interest of public health. Like the Massengil deaths in the 1930’s, and the thalidomide birth defects in the 1960’s, the New England Compounding Centre may prove to be the impetus for the appropriate regulation of compounding pharmacies. Products manufactured by facilities like NECC should receive the same regulatory oversight, and meet the same manufacturing standards as any other bulk manufactured drug product. What’s clear is that this responsibility cannot be left to the pharmacy profession to manage itself. As I pointed out back in 2010, pharmacy regulators have repeatedly failed to act on the ethical and safety problems with compounding pharmacies. That their inertia has resulted in another public health tragedy is shameful to the profession of pharmacy, and patients across America are quite literally paying the price.

Posted in: Pharmaceuticals, Politics and Regulation

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