32 deaths. 461 cases...and counting. Unless you live under a rock, you probably know about the nationwide outbreak of an unusual fungal meningitis caused by Exserohilum rostratum, a plant fungus. The outbreak is now linked to a single pharmacy in Massachusetts, New England Compounding Center (NECC), which compounded a variety of drugs used for injection, including the implicated steroid.
Almost daily, we learn sordid new details, without any of the irony or salaciousness of the Petraeus affair. This week’s shockers included:
- Barry Cadden, president, co-owner and director of NECC, pleading the fifth amendment to avoid self-incrimination at today’s House Energy and Commerce oversight subcommittee hearings. Cadden then shamelessly left, carefully avoiding any contact with Joyce Lovelace, widow of the first victim.
- More conflicts of interest unearthed, with Cadden having been “chosen to serve on a state pharmacy board task force to write new rules for compounding pharmacies” in 2002, the same time the FDA began reviewing complaints about his company, NECC.
-According to the Boston Globe, although three top pharmacy board administrators knew that the “Illinois company chosen to monitor NECC was led by a man convicted of fraud involving a product blamed for blinding people…they did not tell board members before they voted the following month to accept the Illinois firm’s findings that New England Compounding had made satisfactory improvements.”
-The director of the state’s pharmacy board was fired for failing to alert the board that NECC was making and distributing drugs in mass quantities even though it wasn’t licensed to do so
So why are we relying on compounding pharmacies?
Compounded drugs used to be mixed by a relatively small and generally local pharmacy and are intended for a specific patient. The law regulating compounding pharmacies, in fact requires that each compounded drug be prepared based upon a prescription from a physician for a specific patient. They are custom produced to meet specific allergies, for example, or to mask flavor. However, New England Compounding Center (NECC), was were essentially acting as a small pharmaceutical company, mass producing the steroids for injection.
Such broader production of compounded drugs was originally intended to be a response to shortages of raw materials. Due to the wide-scale shortages that have become commonplace in the last few years, a marketing opportunity has appeared that compounding pharmacies have been quick to fill. Some compounding companies have also been allowed to also continue production as less-expensive alternatives to brand name drugs.
Let’s play pin the blame on…the FDA
There’s one thing there is no shortage of in this tragic meningitis outbreak—finger-pointing. The first point of attack was, appropriately, on the pharmacy. Rather than compounding drug for an individual patient, they became a major supplier across the country. In fact, they sold large quantities of the implicated steroid product to the government itself, for the Veterans Administration. Further, while she reportedly recused herself, Sophia Pasedis was an executive for a NECC-affiliate as well as board member and former president of the Massachusetts Board of Registration in Pharmacy. This obviously raises the question as to whether a cozy relationship might have led to averted gazes.
But, as in keeping with tradition, the main question has been, “Why doesn't the FDA regulate compounding pharmacies?” The answers are quite peculiar. First, the FDA actually doesn’t appear to have the authority to do so, according to Kevin Outterson, director of the health law program at Boston University. As collateral damage in a 2002 suit, (Thompson vs. Western States Medical Center), in a Supreme Court ruling regarding a pharmaceutical company’s advertising and free speech, the FDA lost much of its regulatory oversight of compounding pharmacies.
While the FDA is being criticized for not providing more oversight, according to Regulatory Focus, “In a case involving Franck's Pharmacy—the same company whose products were involved in the May 2012 recall—a judge ruled FDA could "not assume it had authority to regulate compounding pharmacies." Professor Outterson further details how the 2002 Supreme Court ruling hobbled the FDA in a recent New England Journal of Medicine article, concluding, “It's possible that if the Supreme Court hadn't struck down Section 503A, the tragedy at NECC could have been averted.”
So now the FDA has to wait until there is a problem before they can intervene in production by a compounding pharmacy. According to the NY Times, the International Academy of Compounding Pharmacists actually “tutored pharmacists on how to sidestep requests” for information or samples from inspectors.
Adverse reactions are not easy to detect. This outbreak was picked up early because of an astute Infectious Diseases physician at Vanderbilt, Dr. April Pettitt, who took a careful history, prompting her suspicion that her patient’s unusual fungal meningitis was related to the injections he had received.
There is no well-organized procedure for detecting adverse outcomes. Side effects are reported during clinical trials, but include relatively small numbers of patients. Post-marketing or for compounded drugs, there is only a voluntary reporting system through MedWatch. Frankly, many physicians either don’t think of this, nor will they find it very gratifying activity to complete yet more forms. And while the number of FDA analysts has held steady, the number of adverse event reports has steadily grown, along with the number of drugs available. Even when there are drug recalls, detecting lots is cumbersome and not everyone adheres to the recalls.
The FDA is in an unenviable position. While they were aware of some problems at NECC and, in fact, issued a warning in 2006, the FDA has deferred to “states’ rights”: “so long as a pharmacy’s operations fall within the scope of the practice of pharmacy (as outlined in FDA’s Compliance Policy Guide 460.200), FDA will generally continue to defer to state authorities for regulatory oversight.”
Once again, the FDA is in a no-win position. If they try to be tough enforcers, they are damned by pro-business forces, like Congressman Darrell Issa’s witchhunt report, the FDA’s Contribution to the Drug Shortage Crisis, where he criticizes the FDA warnings to manufacturers about production problems before actual outbreaks occurred, as being unnecessary. Would Issa have preferred the FDA to wait for outbreaks? Then the FDA would have been damned for not being proactive enough, which is what the consumer watchdog group, Public Citizen, has just done.
“Corporations are people, my friend,” and as such, exercised that in the Supreme course free speech case that limited FDA’s authority over compounding pharmacies. These pharmacies also have vociferous lobbyists who spend millions of dollars trying to prevent regulation; the International Academy of Compounding Pharmacists boasted of its success defeating such legislation. Previously, FDAMA prevented them from advertising their services: “The restrictions included that the prescription be unsolicited and that the providers not advertise or promote the compounding of any particular drug, class of drug, or type of drug.” Through the Thompson vs. Western States Medical Center suit challenging The Food and Drug Administration Modernization Act of 1997 (FDAMA)’s restrictions on commercial free speech, compounding pharma lobbyists were quite successful in widening their reach.
Partisan attacks occurred today targeting Dr. Margaret Hamburg, FDA commissioner, led by Rep. Joe Barton, of Texas. He forgot to mention that many compounding pharmacies and their lobbyists are also based in Texas. According to the NYTimes, Barton “is a top recipient of political donations from the industry” and is described by the compounding academy as a “dedicated” industry advocate…and been outspoken in praising compounding.” The NYTimes also notes that in 2003 ex-Rep. Tom DeLay, also from Texas, helped kill a Medicare bill regulating compounding, saying that regulating them should be left to the states.
Efforts have been made to regulate the industry, including the Safe Drug Compound Act of 2007, proposed by Senator Edward M. Kennedy, but they have consistently been defeated by compounding pharmacy lobbyists.
The more that we learn about NECC, the role of cronyism, and lax regulatory oversight, the more sickening this web of deceit becomes. NECC knew that their so-called clean rooms, for sterile preparations, “contained bacteria or mold at levels requiring corrective action to remove contamination, according to company records,” yet they willfully ignored their findings, jeopardizing patients’ lives. Pharmacy workers turned off air conditioners at night, fostering conditions favoring growth of fungi and bacteria, and there was visible discoloration and growth on surfaces.
A scathing article in Slate notes that NECC had been repeatedly cited for failing to meet acceptable standards, and was to have received a 3-year probation and public reprimand in 2004. Craig Unger reports that the “reprimand was withdrawn by the [then Governor] Romney administration in apparent deference to the company’s business interests.” Thus, the probation was decreased to 1 year and the reprimand became “a non-disciplinary agreement that would not be reported to the National Association of State Boards of Pharmacy or other outside agencies.” According to Philip Johnston, former Massachusetts secretary of health and human services (pre-Romney), this was in keeping with the Romney administration philosophy “to have lax regulations across the board.”
The FDA has been attempting to reduce drug shortages by “fast-tracking” approval of manufacturing plants after remediation. The FDA also issued a pointed response to the House Oversight Committee’s report, squarely laying much of the blame for drug shortages on profit motives.
Now the FDA is being scapegoated by many, especially Republicans, for failure to oversee the compounding pharmacy industry, even though it appears to lack the authority to do so.
While I suspect there is plenty of blame to share, perhaps it might be more productive if the oversight group and “small government” representatives targeted lobbyists as well as the FDA for admonishment…but then they might not be re-elected.
As it stands now, even with fast-tracking, predictions are for serious drug shortages to continue at least through 2014, so we are likely stuck with needing compounding pharmacies.
I, for one, am a strong supporter of protecting the defenseless. As such, I believe that compounding should be limited to pharmacies producing drugs for individual patients, as was intended, and that large production centers, like NECC, should be eliminated or strictly regulated.
This outbreak surfaced just before the elections. Though they are mostly over (except in incompetent Arizona), this tragedy still illustrates stark differences in politics and approaches to governing. Do we want a laissez faire government that puts profits before people and believes in the superiority of privatization to such an extent that it waives any thought of regulatory oversight? Do we want a strong government and disaster preparedness agency through Federal Emergency Management Agency (FEMA), which is showing an exemplary response to Hurricane Sandy’s destruction, or “Heckofajob Brownie’s” pathetic and reckless response to the smaller Hurricane Katrina? Do we want an FDA with the authority and funding to protect us, or do we want to continue with a hodge-podge of individual state regulations?
The fungal meningitis outbreak is a microcosm of the decisions facing us and the opposing paths we might take. While it's fine to want to encourage business, we need to be sure to do so without simultaneously endangering the public's health. I hope that Congress and the Supreme Court will stop playing politics and finally give the FDA the tools it needs to protect us.
(This post has been adapted and updated from my guest post on Ed Silverman's Pharmalot: The Op-Ed: Compounding & Laissez Faire Rules last week.)
Suggested Readings: for ongoing coverage
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