Compounding, fungal meningitis, and the future effects on pharmacy...

[psychoandy]

CDC main page on fungal meningitis updates, treatment, ppx, etc http://www.cdc.gov/HAI/outbreaks/meningitis.html

Surprised there's nothing on the front page regarding the New England Compounding Center and the litany of issues stemming from intrathecal methylpred. 214 cases of fungal meningitis from aspergillus & 15 resulting deaths is serious business. And now FDA is saying that ANY patient who got injectable or ophthalmic products should be warned (if they haven't figured it out already), as there are new cases of meningitis with triamcinolone inj and cardioplegic solution. Transplant patients getting aspergillus could be from a ton of other things, but it's still a little worrying if there's the slightest possibility their heart could have been getting cardioplegia with a touch of aspergillus. And the idea of prophylactic/treatment Vori/AmB on a wide scale is really really expensive.

If you look at the list of recalled drugs, almost all of the parenteral products are preservative free (since they're epidural/intrathecal). I'm not an IV RPh but when you're compounding things that aren't commercially available for injection into the CSF, it seems pretty high risk to me, 797 or not. Obviously there's a huge niche for intrathecal meds with chronic pain patients, but if a real manufacturer won't take on the cost/risk of making them, and a smaller compounding pharmacy has issues like this...what are we gonna do?

And the blame...obviously someone at NECC screwed up big time, but i'm sure there are some good pharmacists and techs who did no wrong and are now sending out resumes and/or playing CYA and lawyering up. And in terms of compounding for injections and intrathecal use...while we can compound crazy dilaudid/clonidine/baclofen IT mixes from scratch, should we?

Not only that but now the legislators want to regulate compounding pharmacies. Injections, maybe, but all compounding? That might be a bit much. And we all know the FDA is fully funded and equipped to regulate the actual manufacturers since the Chinese Heparin event... 🙄

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[Sparda29]

Just started a patient on Voriconazole loading dose, 1 week IV, then 14 days PO recently. I wonder if they are in the hospital this specific issue. My hospital does a lot of spinal surgeries so I wonder if one of those patients got the contaminated injection.

 

[rxlea]

The FDA has wanted to fight this battle for some time, I think. Now they have the evidence they need and there are already a couple pieces of legislation in the works.

We all have a responsibility for the patient but I'm not sure the physicians would have been able to tell there was contamination. Finding the source of that contamination is essential. IMO, and from experience preparing intrathecal medications, my guess is that proper aseptic technique was not used or the wrong filter was used or something else was prepared at the same time in the same hood or something similar. In that case, it would be the fault of the employee and supervising pharmacist. This is another cautionary tale of why proper technique is essential.

Furthermore, I've never seen a drug with preservative used for intrathecal administration. Ever. Preparation guidelines, from what I've seen, mandate preservative free only.

 

[BidingMyTime]

Very good questions, and no easy answers. The problem isn't that the pharmacy was making "unapproved drugs", as many of the major news outlets are basically saying....nobody thinks there is a problem with the drug methylprednisolone. The problem is with the compounding technique--which as I gather, the FDA already has the oversight to inspect compouding pharmacies. From what I read, they had inspected this pharmacy in 2006, found problems, and then never reinspected??? I know people try to claim this as evidence that the FDA isn't funded well enough, but c'mon, a pharmacy with known problems and they can't reinspect it at any point within 5 years? The FDA has more funding then that, for whatever reason the FDA was adequately regulating this pharmacy, so I fail to see how additional regulations would help this situation at all. It sounds like the compounding pharmacy also broke the law by not getting individual prescriptions for each compound, instead they were selling in bulk.

The drugs being manufactured were legitimate drugs that were legitmately needed. These drugs weren't available elsewhere. I don't think telling the compounding pharmacy they can't compound needed drugs is the answer, and I don't think the FDA needs to be "approving" everything that is compounded.

I think to start with, there needs to be more patient approval--patients have the right to know they are getting technically "unapproved" drugs and the risks associated with that. Patients also need to know the risks of getting any intrathecal preservative-free drug. Granted, many patients aren't going to really understand or appreciate the risks, but regardless, they have the right to know, so they can make more informed decisions on their medical care.

Certainly the cause of the outbreak needs to be found, if it was a system screw-up (like the pharmacy with chemo hood that vents back into the chemo room!) then the pharmacy should be cited. If it was human error, or some unexpected source, than that needs to be known, so other pharmacists & pharmacies can try to take steps to minimize the chances of that happening again.

Nothing in medicine will ever be risk-free. I get so many patients asking me if such and such a drug is "safe" or they will say "this drug doesn't have any side effects does it?" or "the flu shot can't do anything worse than give me a sore arm, right?" On one hand, I don't want to scare people out of getting a drug, when its known the vast majority of users will have minimal problems from that drug, on the other hand, any drug could extremely rarely cause an anaphylatic reaction leading to death, and most drugs have extremely rare very serious adverse affects. People need to know that any medicine or treatment carries risk, including death, and that the risk isn't hypothetical, real people have died or been serious injured from that treatment/medicine. Problem is most people have no understanding of statistics, they can't comprehend that a 1 in a million chance is extremely unlikely to affect them personally, but that it really actually could affect them personally.

Risk happens, human errors happen, and while possibly the FDA could have done a better job of checking up on the NECC, the FDA can't prevent all medication tragedies. Whi

 

[KARM12]

The majority of the cases were not due to aspergillus. The mold causing these is an environmental pathogen called Exserohilum rostratum.

 

[All4MyDaughter]

I was under the impression (but can't recall my source right now) that the methylprednisolone solution that the pharmacy was compounding IS commercially available, but is expensive. If that's true, that seems to violate regulations about compounding commercially available products. Not only that, but the pharmacy was making huge batches and reselling it in multiple states. Also against the rules. Compounding is supposed to be for a specific patient in response to a specific RX from a prescriber. You can make extra doses in anticipation of need or based on typical prescribing patterns, but it seems like what the NECC was doing was far beyond that, and more consistent with manufacturing.

 

[npage148]

That's what I was thinking but many of these big compounding pharmacies are doing stuff like this and straddling some poorly defined/enforced line between manufacturing and compounding and when they end up hurting people (it seems like they do a lot) it makes us look bad.

 

[All4MyDaughter]

That's what I was thinking but many of these big compounding pharmacies are doing stuff like this and straddling some poorly defined/enforced line between manufacturing and compounding and when they end up hurting people (it seems like they do a lot) it makes us look bad.

I think it's because they are only routinely inspected by the BOP and not the FDA. The BOP inspectors may not be proficient in sterile compounding or may be willing to look the other way on certain issues or may just not have the time to REALLY delve into what is being done and whether proper procedures are being followed. IMO this really makes all of us look bad/incompetent/greedy/unethical, even though most compounding pharmacists are none of those things and DO follow the rules.

 

[Socrates25]

But do MDs have responsibility because they're prescribing/injecting high-risk off label compounded medications? Do pharmacists have a role in enabling this prescribing to happen or dispensing/keeping on formulary? While we can compound crazy dilaudid/clonidine/baclofen IT mixes from scratch, should we?
:

You seem to be implying that the off label use of these injections was partly responsible for the bad outcomes. I dont see any evidence to support that -- so far all I see is bad compounding resulting in many injuries/deaths to an otherwise fairly safe procedure.

Compounding should be solely in the purview of the pharmacist, and therefore, solely the pharmacist's responsibility. Are pharmacists independent professionals who we can trust to do the compounding in a safe way for patients? Or are MDs now responsible for looking over your shoulder to make sure your compounding is sound?

The only thing "high risk" about these injections is that the compounding was obviously shoddy. No way are the MDs responsible for this UNLESS THEY KNEW IN ADVANCE that the compounding pharmacy was a sham.

 

[Doctor M]

You seem to be implying that the off label use of these injections was partly responsible for the bad outcomes. I dont see any evidence to support that -- so far all I see is bad compounding resulting in many injuries/deaths to an otherwise fairly safe procedure.

Compounding should be solely in the purview of the pharmacist, and therefore, solely the pharmacist's responsibility. Are pharmacists independent professionals who we can trust to do the compounding in a safe way for patients? Or are MDs now responsible for looking over your shoulder to make sure your compounding is sound?

The only thing "high risk" about these injections is that the compounding was obviously shoddy. No way are the MDs responsible for this UNLESS THEY KNEW IN ADVANCE that the compounding pharmacy was a sham.

Agreed. The pharmacist has 110% responsibility to ensure the product is safe to use. Why would an MD be responsible for any part of the compounding process?

 

[psychoandy]

post #420...damn, wishing this was relating to marinol or something and not one of the largest safety events since the tylenol recall in the 1980s.

Furthermore, I've never seen a drug with preservative used for intrathecal administration. Ever. Preparation guidelines, from what I've seen, mandate preservative free only.

right, i assume preservatives like benzyl alcohol are not appropriate for injection into the CSF (otherwise we'd just use normal methylpred vials). all of the intrathecal pain meds i personally saw had to be ordered in advance and i assume were compounded and delivered/used within a day or two. but this methylpred was stockpiled and sent everywhere; i guess i feel uneasy compounding nonsterile drugs into IT formulations and then having them sit around across the country. but like i said earlier i do NOT do compounding of sterile products so maybe i'm outside of my lane.

I was under the impression (but can't recall my source right now) that the methylprednisolone solution that the pharmacy was compounding IS commercially available, but is expensive. If that's true, that seems to violate regulations about compounding commercially available products. Not only that, but the pharmacy was making huge batches and reselling it in multiple states. Also against the rules. Compounding is supposed to be for a specific patient in response to a specific RX from a prescriber. You can make extra doses in anticipation of need or based on typical prescribing patterns, but it seems like what the NECC was doing was far beyond that, and more consistent with manufacturing.

compounding commercially available products is something that pharmacists apparently don't grasp; i saw this in the community and in certain practice settings. while i am all about saving money sometimes, the law is the law. even pharmacy directors on ASHP messageboard have no idea.

You seem to be implying that the off label use of these injections was partly responsible for the bad outcomes. I dont see any evidence to support that -- so far all I see is bad compounding resulting in many injuries/deaths to an otherwise fairly safe procedure.

Compounding should be solely in the purview of the pharmacist, and therefore, solely the pharmacist's responsibility. Are pharmacists independent professionals who we can trust to do the compounding in a safe way for patients? Or are MDs now responsible for looking over your shoulder to make sure your compounding is sound?

The only thing "high risk" about these injections is that the compounding was obviously shoddy. No way are the MDs responsible for this UNLESS THEY KNEW IN ADVANCE that the compounding pharmacy was a sham.

i had a little too many beers after work and apologize for the implication that MDs are completely responsible and will edit my initial post appropriately. I was trying to illustrate issues with the off-label medication use; if this was some weird cream or suppository or PO suspension for a kid or for a G-tube or something, whatever, but this was with intrathecal injections.

In response to "looking over [the pharmacist's] shoulder"...
based on the fact pattern most everyone had no idea that NECC was making bulk batches of preservative free mixes and shipping them nationwide (which breaks a ton of FDA and board of pharmacy regulations on compounding). however, i have seen some anecdotal information (retrospective now of course so not high quality) from hospital pharmacy purchasing people who said that they requested sterility/beyond use dating reports and NECC was reluctant and ultimately refused to provide it. obviously an MD would assume that a specialty pharmacy can deliver what they promise (otherwise the pharmacy wouldn't be licensed, etc); and retrospectively trying to see an MD perspective, you wouldn't really think of contamination if it came from a big producer advertising these products. but now i think a lot of these physicians will be doing more than their full share of due diligence in terms of determining sterility information and site conditions than they otherwise thought to.

you say this is an "otherwise fairly safe procedure" but as a pharmacist i partially agree. I would consider IT injections of commercially available products (like MTX, hydromorphone, etc) to be a "fairly safe procedure". but with compounded products where a small pharmacy is taking bulk unsterile methylpred powder, making a solution, "sterilizing" it by filtering the solution, unit dosing, and then shipping them across the country with unknown expiration dating, and then an MD is injecting them into the CSF...i can't think of a higher risk way of using and administering a medication (in terms of contamination risk, infection risk, complications, etc).

i understand many of these patients suffer from debilitating chronic pain issues and that IT agents aren't 1st, 2nd, or even 3rd line treatment options, but at the same time, maybe there's a reason there isn't a commercially available product - because it's either too expensive or too high risk (or both) to produce.

 

[npage148]

What I don't understand is that THERE IS a commercial available preservative medrol as Novaplus (NDC: 00009-0039-xx). So i'm even more confused why there were compounding it.

It's probably the same BS where pharmacies were continuing to compound Alpha-Hydroxy Progesterone Caproate after KV Pharmaceuticals obtained exclusivity

 

[ethyl]

So it's being reported that other drugs that were compounded by this facility are resulting in infections in immunocompromised patients. There's really no telling what else might be contaminated. If they were banking on the electrolyte shortage, we could see a spike in TPN related infections too.

 

[WhiteSnows]

This can be an act of terrorism. Who knows if these people will turn into zombies tomorrow.

 

[MountainPharmD]

I was under the impression (but can't recall my source right now) that the methylprednisolone solution that the pharmacy was compounding IS commercially available, but is expensive. If that's true, that seems to violate regulations about compounding commercially available products. Not only that, but the pharmacy was making huge batches and reselling it in multiple states. Also against the rules. Compounding is supposed to be for a specific patient in response to a specific RX from a prescriber. You can make extra doses in anticipation of need or based on typical prescribing patterns, but it seems like what the NECC was doing was far beyond that, and more consistent with manufacturing.

Yep. What they are doing is called manufacturing. They are going to get slammed down hard. Jail time I am sure.

 

[MountainPharmD]

Say goodbye to compounding. The FDA has been after pharmacist compounding for years. Like all pharmacy legislation in the last 100 years it takes a sentinel event like this to bring about change.

Very similar to a famous incident involving Elixir of Sulfanilamide. It brought about a small change in pharmacy laws called the Food, Drug and Cosmetic Act of 1938.

If I owned or worked at a compounding pharmacy I would be ****ting my pants right now.

 

[Its Z]

Say goodbye to compounding. The FDA has been after pharmacist compounding for years. Like all pharmacy legislation in the last 100 years it takes a sentinel event like this to bring about change.

Very similar to a famous incident involving Elixir of Sulfanilamide. It brought about a small change in pharmacy laws called the Food, Drug and Cosmetic Act of 1938.

If I owned or worked at a compounding pharmacy I would be ****ting my pants right now.

Nah, the issue is sterile compounding.... taking raw material and making injections.

The FDA isn't targeting Pharmacist only. They have targeted "ALL" manufacturers which has been a contributing factor to medication shortage we face today.

But it's for a good reason.

Non sterile compounding such as oral and topical medications should be fine.

Now go suck it LOSER!!

 

[All4MyDaughter]

I'm not worried about our compounding operation. We only make things that aren't available commercially and that patients can't get anywhere else. Nothing sterile.

I hope the FDA will go after pharmacies who are manufacturing and mass producing things that are already available in the marketplace. Clearly the policy of having that policed by the BOPs isn't working.

 

[MountainPharmD]

Nah, the issue is sterile compounding.... taking raw material and making injections.

The FDA isn't targeting Pharmacist only. They have targeted "ALL" manufacturers which has been a contributing factor to medication shortage we face today.

But it's for a good reason.

Non sterile compounding such as oral and topical medications should be fine.

Now go suck it LOSER!!

Do you think Joe Public or your Congressman knows or cares if there is a difference? In their eyes compounding is compounding....

 

[deleted129840]

It sounds like they got too greedy. The pharmacist in charge as well as a lot of his family members have several million+ dollar houses from this and other businesses. They were manufacturing large lots and selling them without prescriptions, which is illegal for compounding pharmacies in Massachusetts.

 

[BidingMyTime]

If these allegations are true, then this is really a reprehensible situation, and I can see why they are asking the pharmacists involved to volutarily give up their licenses. It sounds like they weren't even making basic attempts at sterility (they couldn't even scrub down their hoods!?!?!

http://drugtopics.modernmedicine.co...id=793984&sk=1991a435392d0d1825c46e1603f6a623

Mass. DPH finds multiple health, safety violations at NECC

NECC also had shipped medications from the suspected lots before they had confirmed that the medications were sterile. Some medication was shipped more than a week (11 days) before results were available, Dr. Biondolillo reported.

Sterilization processes at NECC did not conform to accepted standards, she said. "Examination of NECC records indicated a failure of the facility to sterilize products for even the minimum amount of time necessary to ensure sterility. NECC did not conduct proper validation of the equipment used to sterilize product, for example, failing to test their autoclaves on a regular basis to ensure proper function.”

The pharmacy also did not follow basic standards of pharmacy operations. Powder hoods in the sterile compounding areas were covered with residual powders and had not been thoroughly cleaned. Mats outside of the sterile areas were covered with dirt and debris, and a leaking boiler adjacent to the clean room created unsanitary conditions.

 

[hereticmnk]

Step 1: Loophole
Step 2: Exploit loophole
Step 3: **** happens
Step 4: Regulations happen
Step 5: Back to Step 1

 

[Ducttape]

An update of sorts:

it looks like the situation in compounding pharmacies in New England has not changed.

http://www.outpatientsurgery.net/news/2013/02/8-33-of-37-Mass-Compounding-Pharmacies-Cited-in-Surprise-Inspections

In case you cant view it:

32 of 40 Mass. Compounding Pharmacies Cited in Surprise Inspections
Report gives more reason to worry about drug contamination.

Published:February 12, 2013

Categories:
Infection Control Legal/Regulatory Safety News

You'd think compounding pharmacies in Massachusetts would have cleaned up their acts in the wake of the fatal outbreak of fungal meningitis last year, but surprise health inspections found that just 8 of 40 specialty pharmacies are fully complying with industry safety standards, officials said.

The sterile compounding facilities were inspected as part of Governor Deval Patrick's edict to strengthen oversight of the commonwealth's compounding pharmacy industry in the wake of the fungal meningitis outbreak caused by New England Compounding Center.

Of the 40 inspected pharmacies, 11 were issued cease-and-desist orders for a range of violations and another 21 were cited for "minor deficiencies that have since been corrected or are currently being addressed through corrective measures," according to the Massachusetts Department of Public Health.

Cease-and-desist-related violations uncovered by the expanded efforts included non-compliant storage of hazardous medications, non-compliant preparation and dispensing of sterile medications, non-compliant clean-room engineering controls and structure, and insufficient personnel training and environmental monitoring. One pharmacy was cited "after inspectors found evidence the pharmacy was engaged in sterile compounding despite an earlier statement that it was not."

Orders to stop operations have been issued to Apothecare South Shore in Brockton; Baystate Home Infusion, Springfield; Home Infusion Solutions, Falmouth; Lenox Village Pharmacy, Lenox; OncoMed Pharmaceuticals, Waltham; PalliMed Solutions Pharmacy, Woburn (partial); PharmaHealth Pharmacy, New Bedford; PharMerica, Brockton; Western MA Compounding Center, West Springfield; and West River Pharmacy, Marlborough. Whittier Pharmacist in Bradford was issued a full cease-and-desist on November 28. Upon inspection, board staff noted significant deficiencies in the structure and engineering of the clean room.