**Update, the NYT has an editorial in their Sunday edition recommending the passage of two bills in congress requiring advanced notice from drug manufacturers in event of likely shortage.
Health affairs discusses the increasingly frequent shortages of critical, life-saving, generic drugs. This is a serious problem that seems mostly limited to the U.S. healthcare system, and may adversely affect you or someone you know.
Many of the same drugs are not in such short and unpredictable supply in Europe, where in some cases they carry higher prices. This provides one major clue to the root cause: It’s the money.
Three of every four drugs on the US government’s shortage list were sterile injectable drugs, according to a report by HHS. For the most part, these are relatively low-cost generics. Simply put, most of those drugs are not very profitable to produce and sell, or supplies of them would not have dried up.
At an online presentation for journalists in November, Valerie Jensen, associate director of the FDA’s Drug Shortage Program, provided a casebook example. She mentioned the price of the tried-and-true sedative propofol, a lethal dose of which was found to have caused the death of singer Michael Jackson: The cost is forty-eight cents for a twenty-milliliter vial. “The older, sterile injectables are not economically attractive” for manufacturers to produce and market, Jensen said. Other generic drugs can have higher profit margins.
Propofol, one of the most frequently used drugs by anesthesiologists, is in increasingly short supply. I get emails from my hospital about which drugs are in short supply as physicians then try to ration these drugs for the most critical cases. In my own experience in the last year I’ve seen shortages of everything from injectable calcium gluconate (for electrolyte deficits), to levophed (a life-saving pressor used in critical care), metoclopramide (anti-nausea), and fentanyl (a powerful and useful short-acting narcotic). The FDA has a full list of recent shortages and it’s scary. Parents are having trouble finding drugs for their kids’ ADHD, vital chemotherapeutics like daunorubicin and doxorubicin are in short supply, dexamethasone (a powerful steroid), valium, digoxin (a staple of congestive heart failure and anti-arrhythmic treatment), diltiazem (hypertension and anti-arrhythmic), phenytoin (anti-epileptic also often used in acute brain injury), furosemide (an ubiquitous diuretic), haloperidol (anti-psychotic and sedative), isoniazid (a antibiotic used in TB), ketorolac (an excellent anti-inflammatory and analgesic), levofloxacin (a quinalone broad spectrum antibiotic), methotrexate (immune modulator), midazolam (a great short acting sedative), naltrexone (for reversing opioid overdose), vasopressin (another pressor) all are in short supply.
The drugs affected span all classes, what they have in common is they are all generic. Since there is too much competition in generics and too little profit margin, drug companies do not have a financial incentive to maintain adequate stocks to keep the drugs cheap and available. Shortages, if anything, increase profits because then the prices become artificially inflated.
Manufacturers, not surprisingly, blame the FDA, however the FDA hasn’t changed its standards despite increasing problems with shortages due to contamination or impurity. And that’s just for manufacturers in this country, fully 80% of the medications are produced, or active ingredients are produced, abroad. The main problem seems to be a concentration of production to a handful of companies that have adequate production capacity to compete in the generic market:
There is also a high level of concentration in US manufacturing for such drugs. That leaves little redundancy in the market as there would be for, say, generic statins. Three companies in particular–Hospira, Teva, and the Bedford Laboratories division of Boehringer Ingelheim–have been involved in selling 71 percent of the sterile injectable market by volume, the government says.7 All three have had manufacturing problems in the past two years.
With such consolidation as well as tight inventory management practices, the specialized manufacturers of injectable drugs lack the flexibility to adapt to manufacturing disruptions. If one plant shuts down, it may overburden the limited remaining competitors or choke off the supply entirely.
It’s hard to estimate the effects of these shortages, I don’t have good data on the damage done nationwide, only my personal experience. In particular, I remember during an ICU rotation running out of levophed, an incredibly important pressor that helps patients who are in shock from becoming fatally hypotensive.