Where Has All the Propofol Gone?

Propofol -- one of the drugs that led to Michael Jackson's untimely death -- is a short-acting, intravenously administered hypnotic agent. Known in some circles as "Milk of Amnesia," its uses include the induction and maintenance of general anesthesia, sedation for mechanically-ventilated patients, and procedural sedation. Propofol -- and its generic equivalents -- has been widely and successfully administered in hospital operating rooms around the world for nearly 30 years. And, as of June 4, 2010, Teva Pharmaceuticals, the Israeli-based firm that was the major supplier of Propofol, no longer manufactures it. Today, it is almost impossible to find.

Where has all the Propofol gone?

And while we're at it, where has all the Doxil, Adderall, Mitomycin, Morphine Sulphate, Avalide, Ondansetron, Succinylcholine, Dextrose, B-12 and more than 200 other important meds gone? Shockingly, between 2006 and 2010, drug shortages increased by more than 200% according to a Government Accountability Office Report released late last month. Many of the drugs declared "MIA" are critical chemotherapeutics; intravenously infused medicaments and "cocktails" that can often mean the difference between remission and metastasis -- between life and death. Some of the shorted meds -- though far less exotic -- are just as critical to the health and well-being of patients in need: things as basic as injectable cobalamin (vitamin B-12) and Tylenol 1 (the 325 mg version). Although a lack of injectable B-12 might not seem as critical as a dearth of Propofol or Doxil (a chemotherapeutic drug used in the treatment of breast cancer), it can be for the patient in need; severe B-12 deficiency can lead to irreversible damage, especially to the brain and nervous system. I know; I'm supposed to receive a weekly injection . . .

When and if a supply of these drugs can be located, it is at a cost; there are reports of drugs which distributors sold just two years ago for $25.00 per dose, now going for as much as $1,200 per dose on the "Grey Market." And this phenomenon is not confined to certain states or regions; it's happening all over the United States. Large, well-heeled establishments like the Mayo Clinic, Cleveland Clinic and Vanderbilt University Medical Center at least have the possibility of purchasing critical medications -- at monstrously inflated prices -- because they have both the ability and the resources to order in great quantity. But one should keep in mind that there are just as many -- if not more -- patients whose lives depend on receiving chemotherapeutic drug protocols who live in small towns and are served by small hospitals that don't buy in quantity and thus cannot afford to pay hyper-inflated prices. Sometimes, when a drug that a patient tolerates well can't be readily located, the physician will prescribe an alternative -- which frequently the patient cannot tolerate. With some medical conditions, an interruption in treatment of a month, even a week, can be disastrous . . . even deadly.

The question is not only "Where has all the Propofol gone?" but "What has led to its scarcity?"

It all depends on who you ask, what ones starting point might be . . . even what axe they may be grinding. Make no mistake about it: the scarcity of pharmaceuticals is an issue and a problem for both Democrats and Republicans, ultra-conservatives and ultra-progressives. Anyone, regardless of his or her political philosophy, can contract cancer or Crohn's Disease, require surgery or suffer from a thousand-and-one life-threatening ailments. And yet, when it comes to analyzing the current situation, politics and point of view do count for something.

At base, market forces have a lot to do with the scarcity of drugs. The prices we pay for pharmaceuticals in the United States are far higher than those paid by the citizens of any other country in the world. In large measure this is why the pharmaceutical industry has for years been the most profitable of all businesses in the U.S. According to the annual Forbes 500 survey, the American pharmaceutical industry tops the list of all industries with a return of 17% on investment. And although the cost of manufacturing a new drug is relatively low, the cost of inventing and then patenting a new drug is relatively high. Drug manufacturers have always claimed that the high cost of pharmaceuticals is due to this latter issue. Then too, a hefty part of the price for bringing a new drug to market can be found in advertising costs; ever notice all those commercials urging us -- the patient -- to tell our physician that we want them to prescribe drug "x" or "y" for condition "a" or "b?" Silly me; I thought it worked the other way around; that the doctor did the suggesting and prescribing to me, and not I to her . . .

Many, many pharmaceutical giants have seen their patents lapse and other companies manufacture, then market, generic versions of their creations. Generally speaking, when a drug goes off patent and becomes generic, the price drops precipitously; the companies making them are in the business of gaining as much market share as possible. This is a no-brainer. But then, the generic manufacturers cry, the price remains both low and flat; profits are minimal -- too minimual, many say, to warrent continued manufacturing of generic "a" or "b." Some place blame on the Medicare Prescription Drug Improvement and Modernization Act (H.R. 1) which Congress passed and President George W. Bush signed into law on December 8, 2003. This act limits Medicare payment for physician-administered drugs to the average sales price plus a 6% administrative fee, which manufacturers claim has limited profit margins and thus their ability to maintain and upgrade their facilities. And despite the fact that H.R. 1 provides for an analysis of average sales prices twice a year, it still means that the profit to be made on these generics is going to rise at a pretty slow pace. Many companies have concluded that if drug "a" or "b" can't bring in more than 6% profit above cost, they simply will discontinue its manufacture.

Another factor is the drug distribution system itself. Physicians face pressure from health insurers to obtain the best prices for prescription drugs through multiple distributors. However, as noted above, distributors tend to provide the best prices and most stable supply to high-volume purchasers. Then too, according to information provided by IMS Institute for Healthcare Informatics, most of the nearly 170 prescription drugs in a shortage status as of October 2011 were offered by a single supplier or a small number (under 4) of firms.

Some claim the problem has been exacerbated by tighter Food and Drug Administration (FDA) enforcement of drug manufacturing standards. (According to public records, over the past 2 years the FDA expedited more than 300 industry applications for new or updated manufacturing facilities. So much for the It's-the-fault-of-too-many-damned-regulatory-hoops-to-jump-through argument.) This past October, President Obama signed an executive order requiring the FDA to expedite regulatory review of drug manufacturers and investigate price gouging. At the same time, the White House announced that they would immediately begin requiring some drug manufacturers to report production interruptions to the FDA. The manufacturers that have to report to the FDA are those drug manufacturers that have no generic equivalent and are critical to maintaining life. There are currently two pieces of legislation making their way through Congress calling for advanced warning of impending drug shortages and more FDA action. But passage is both uncertain and a long way off. For now, drug distributors would appear to be in the driver's seat.

Today, a majority of the shorted meds are being manufactured overseas -- in China, South America, Eastern Europe and Israel. The FDA simply does not have the budget or the manpower to inspect these foreign manufacturing plants. As a result, there are a lot of pharmaceuticals on the market that do not meet American safety standards -- another cause of shortages.

That the country which prides itself on having "the best healthcare on the planet" should have these problems -- drugs shortages, an unscrupulous "grey market" charging sky-high prices for life-saving meds, and a fast-declining manufacturing base -- is unconscionable. That no other industrialized country suffers from a similar set of problems likely shows that we do not, in fact have "the best healthcare on the planet." To my way of thinking, many of these problems would be alleviated by going to a single-payer system; one that recognizes that although industries -- especially those that employ more lobbyists than any other on the planet -- have a constitutional right to make a reasonable profit, human beings have a God-given right to live.

If Michael Jackson's doctor could get his hands on Propofol why can't my doctor at the Cleveland Clinic?

And while we're at it, where in the hell is my B-12?

©2012 Kurt F. Stone

Comments

[Merrill]

If I was a young man today, and still in the pharmaceutical manufacturing business, I could make a fortune just concentrating on these shortages.

[Dr. Mike, MD]

Dr. Stone has the fundamentals correct.

The pressure to cut costs on drug spending has eroded profit margins to the point where it does not make business sense to manufacture and distribute many generic drugs. Since by definition, there is no patent coverage for a generic, the business model for generics is for manufacturers to manufacture at the lowest possible cost (generally means outside the US) and to make only those generics that generate a reasonable profit. Health care system (ie VA) shop around for the cheapest source of a given generic, so the manufacturers don't have any long-term stability in their business either. Since the profit margins for generic companies were slim to begin with there were not too many companies in the field to begin with and several of them have gone out of business.

The whole debate about drug costs is rather perverse because when you take a look at the actual percentage of the health care dollar spent on drugs, its relatively small compared to what is spent on terminal care or futile intensive care.

There is truth to the fact that the pharma sector was indeed a very profitable sector for many years, but as of 2008, pharma has shed over 60,000 jobs and as a whole pharma companies have lost $80 Billion in market value. This is partially due to the fact that many very profitable drugs are seeing their patents expire (i.e. Lipitor), that insurance companies are not reimbursing patients or hospitals for certain drugs and that the cost of getting a new drug on the market has gone up dramatically while the probability of getting an approval has dropped.

I am not sure what sorts of solutions could be implemented. Generic companies have very low regulatory hurdles to pass to get a generic compound approved..so this all comes down to a societal agreement on how much profit is reasonable for generic companies to make. The US government could potentially offer tax breaks to generic companies that demonstrate that they are manufacturing drugs designated as being in shortage. The FDA will need to receive additional funding to send more inspectors to India and China in order to monitor the quality of generics manufactured there, but am not Congress would agree to that given how partisan our politics have become. In the end, it means that patients who are affected need to raise hell with their congressional representatives, because as was mentioned in the article...for some patients this is really about life vs. death.

Ohh..and if you ask why do these companies need to make a profit...well at some point you need to pay for land, buildings, equipment, supplies, water, electricity, not to mention the salaries of people who work in these companies.We've experimented with regulated monopolies (ie phone system) and have some regulated businesses where profits are "managed" (ie electricity, water etc). These kinds of regulated businesses work because the increased costs can be passed onto everybody and therefore relatively small on an individual basis. I don't think you would get agreement to run generic companies are regulated monopolies since the vast majority of people are not affected by these drug shortages.

Interesting topic!

[Paul]

Thanks for spotlighting the current silent-crisis in drugs. You mention that generics should be cheaper, but here's my experience:

Using a mail-order house (Prescription Solutions), I re-ordered my Lipitor 10 mg. This RX was written before the release of the generic and marked 'brand' only. Prescription Solutions automatically switch me to the generic which is made by Pfizer for Watson. The bill for 90 days for the generic is $108.

My billing for Lipitor (90 days) was $111. Ok, $3 more, but Pfizer has a rebate program so that they sent me a check for $99. Net for 90 days is $12!

Fortunately, Prescription Solutions honored by original "brand" prescription and is exchanging the generic for the brand.

However, I sympathize with seniors who are not as aware of rebates and other manipulations available

[Alan Weiss]

I actually had a problem getting my B 12 shot too. And pot is still illegal.