Over the past two years, compounded medications have figured in two highly controversial episodes. In one instance, Roche attempted to prevent ophthalmologists from using its older Avastin med for treating wet macular degeneration when its newer and more expensive Lucentis is the only approved treatment. The drugmaker has claimed that rejiggered vials of Avastin pose a safety risk (read
here and here).In another, KV Pharmaceutical caused a huge ruckus by initially charging $1,500 for its Makena premature birth drug and trying to use its FDA approval under the Orphan Drug Act to prevent compounding pharmacies, which charged a fraction of the price, from competing. The move outraged physicians, among others, who maintained the compounded versions were safe and kept a lid on rising healthcare costs.
Now, an outbreak of meningitis that has been traced to a compounding pharmacy in Massachusetts has, once again, placed compounding in the spotlight, and renewed debate about the extent to which oversight is sufficient. The outbreak, which has left five people dead and another 30 in various stages of illness across six states, appears to have been caused by a compounded steroid drug contaminated by a fungus.
The drug has been recalled, but so far the pharmacy has shipped more than 17,000 to 75 clinics in 23 states, according to the FDA. More than 7,500 compounding pharmacies operate in the US, up from 5,000 in 2009, and account for $3 billion in sales and 3 percent of all prescriptions filled, the Associated Press writes, citing data from the International Academy of Compounding Pharmacies.
"There's not a lot of oversight of compounding pharmacies" compared with drugmakers, Allen Vaida, executive vp of the Institute for Safe Medication Practices, tells the AP. And William Schaffner, an infectious-disease specialist at Vanderbilt University, adds that compounded meds "fall into this gray area and no one supervises in a rigorous fashion their manufacturing processes. The state pharmacy boards don't have the resources or the knowledge or experience, and the FDA does not get involved unless a problem occurs."
In the Makena flap, for instance, the FDA repeatedly stated that enforcement actions against compounded versions would not be pursued unless there was a safety risk, a stance that infuriated KV Pharmaceutical. The drugmaker, in fact, sued the agency for purportedly abdicating its responsibilities, but last month, a federal judge tossed the lawsuit, ruling that the FDA acted appropriately in exercising its discretion in whether to pursue enforcement actions against compounders (back story).
The FDA has, however, warned the New England Compounding Center, which has been blamed for the meningitis outbreak, in the past over its practices. In 2006, the agency sent a warning letter that, among other things, cited concerns about marketing anesthetic creams and potential microbial contamination associated with splitting and repackaging Avastin, here). And Massachusetts health officials have also investigated complaints over the past decade against the company, according to The Boston Globe.
This latest episode underscores the difficulties that both state pharmacy boards and the FDA have encountered in attempting to regulate compounders. Only 162 compounders have applied for voluntary industry accreditation of the 3,000 or so compounding pharmacies around the country, according to the International Academy of Compounding Pharmacies. The New England Compounding Center is not among them, The New York Times writes. Meanwhile, the company shipped across state lines, which further opened the door for the FDA to take action.
But the FDA's authority to pursue compounders has been questioned. Last year, for instance, a federal judge ruled the agency overstepped its bounds in attempting to prevent compounders from using bulk ingredients to compound prescription meds for non-food producing animals. The case involved a compounder called Franck's that made veterinary meds.
The issue, as we noted at the time, involved the basic premise that state-regulated compounding pharmacies should have the right to mix bulk ingredients in order to fill a prescription from a veterinarian. The FDA, however, worried such activity may offer the potential to blur the line between valid compounding and mass manufacturing of a new drug – and sought to exercise long-dormant authority over the practice (back story).
Of course, compounding serves an important purpose. Compounders provide meds for individual patients with special needs and prepare drugs that are not available commercially. The meningitis outbreak, however, may renew calls for stricter regulation, or at least to clarify the extent to which state pharmacy boards and the FDA should have clearly defined - and possibly enhanced - responsibilities to pursue enforcement. What do you think?
Should FDA Have More Oversight Responsibility For Compounders?
- Yes (82%, 108 Votes)
- No (18%, 24 Votes)
Total Voters: 131
12 Comments
http://www.ajo.com/article/S0002-9394(11)00931-7/abstract
Any of this investment in billion dollar technology gonna help the tech doing the mixing...?
Two asides; the commercial product was/is on the shortage lists and there is little evidence to support the use of this product as a meaningful remedy for lower back pain.
About all the government does these days is levy fines for off-label marketing ...no prison terms. Nada. Zilch.
As reported here, Bernie Sanders introduced a bill that would get around the "no business with gov." if felony conviction by limiting exclusivity on a drug illicitly promoting. That went nowhere.
So I'd say most of the cowards are in Congress.
"Most of the cowards are in Congress."
You got That one right.
http://psychroaches.blogspot.com/2012/05/us-18c95-sec-1958-skull-at-banquet.html
As for the DOJ being a "weak sister", it's the Direction of what's to actually Be enforced that's the "weak sister", and that's a Political Call from above that's keeping the DOJ from enforcing a whole raft of enforceables they're not currently interested in.
Lots this large that are being shipped throughout the country make this sound like the compounding pharmacy is manufacturing, not compounding. It certainly seems to put them in the realm of commercial compounding, boardering on manufacturing.
Reimbursement amounts for drug that are on short do not necessarily reflect the shortage. In addition, reimbursement may not fully reflect the actual cost of shipping and handling.
Adulterated drug dispenses are not allowed under state pharmacy board regulations in every state. Depending on the circumstances and state, fines and penalties range from monetary penalties to felony penalties with a minimum 8 year sentence.
In addition, while I am not an attorney, there was a counterfeit drug case in New York 10 or so years ago and the case was framed on implied warrantees of merchantability and fitness. So, perhaps these specific circumstances also violate state implied warrantee regs?
RV meth labs are safe, also.
A fungus is pretty disgusting basic housekeeping habits...
Compounding according to the traditional practice fills and essential role in healthcare. But the traditional role has transformed into a chemical/API supplier driven industry, which essentially franchises pharmacies that, if added up across the country, rival medium to large, global manufacturing firms in terms of dollars and/or population exposures.
Of note, as a pharmacy student, one such chemical supply company came to a class at my college and described how compounding could lead to a 7-figure salary for pharmacists. At the time, I looked forward to an annual income of roughly $50k.
For approved products, prescribers rely on population- level benefit risk determinations made by FDA and they also rely on FDA's oversight of manufacturing to ensure products in the marketplace adhere to federal standards. For traditional compounding, there is no population-level benefit-risk assessment for prescribers to rely on, and, FDA is not responsible for enforcing federal standards at the pharmacy level for the traditional practice. In this unique setting, physicians fill in as surrogates for making benefit-risk determinations at the individual level. But, this assessment is confounded by a lack of transparency to material facts essential for weighing individual benefits and risks. For example, pharmacies may not discuss with physicians the differences between practical standards and federal standards for assuring sterility. Many pharmacies will not label their products "sterile" and "a pyrogenic" because they don't meet a federal standard, yet, they won't explain this to physicians when they proffer their products.
Keep in mind, under the traditional model, the physician's benefit risk assessment supports a "triad" decision making process involving patient, prescriber, and pharmacist. But this individual benefit-risk assessment and joint decision-making is pre-empted for facilities that purchase unapproved drug for use at population levels. This is an untenable situation for prescribers and patients, and one which the professional practices of pharmacy and medicine have failed to mitigate.
As serious as this outbreak is, it does not address the larger issue. Epidural Steroid Injections (ESI’s) that are used to treat back pain are NOT FDA APPROVED for that use! They are administered off-license (off-label) by doctors and Pain Centers who rarely tell their patients the truth about the risks involved.
Secondly, Pharmacia/Pfizer has repeatedly warned doctors and Pain Centers for many years that the "epidural administration of Methylprednisolone Acetate (Depo-Medrol) is Not Recommended” due to hundreds of serious adverse event reports, including death. But doctors have ignored these warnings. The evidence is clear that Depo-Medrol's ESI (or any steroid for that matter) safety and efficacy record is littered with thousands of severe injuries, from paraplegia, paralysis, meningitis, heart attack, stroke, Arachnoiditis, and death, etc. There is ample evidence that any benefit is usually short term at best in those lucky enough to tolerate the treatment.
Contaminated or not, the real thing or a copy, it doesn't matter, ESI's are dangerous. When doctors and Pain Centers obtain steroids made by a third party it adds even more risk to the receiving patient. However, please keep in mind that no injectable steroid is indicated for epidural or intrathecal administration which is specifically contraindicated by the FDA. In fact there are no steroid compounds made by any company that are FDA approved for this use. When doctors use it, it’s at their risk and those of the patient who most likely signed a consent waiver before their ESI procedure. Google "ARACHNOIDITIS" and see the horror these injections are causing those that survive.