Genzyme Drugs Contain Bits Of Trash
33 CommentsBy Ed Silverman // November 13th, 2009 // 7:05 pm
A case of garbage in, garbage out? Not to be taken lightly, the beleaguered biotech has enough problems with contamination. But now the FDA, which has been inspecting Genzyme facilities of late, has found stainless steel fragments, non-latex rubber from vial stoppers and fiber-like material from the manufacturing process, all of which may cause serious adverse events (the FDA statement).
The affected products include Cerezyme, Fabrazyme, Myozyme, Aldurazyme and Thyrogen. On the bright side, less than 1 percent of these drugs contained any junk and there were no adverse events reports. And given these meet rare medical disorders, the drugs will remain available. But Genzyme has been struggling most of the year to convince regulators, doctors and patients that it has its act together. The troubles began when its Allston Landing, Ma., plant was shut down for several weeks this summer to remediate viral contamination.
The plant makes Cerezyme, which is the only approved therapy for Gaucher disease, and Fabrazyme, the only approved treatment for Fabry disease. Consequently, rationing plans were put into effect, and the FDA asked Shire Pharmaceuticals and Protalix to quickly ready their own experimental drugs for Gaucher patients. The same plant also makes another of the contaminated meds and finishes the packaging process for the other two containing bits of trash.
“…We do not believe this is a wide-scale problem, but we do not have information that fully defines the scope of the problem,” says Jason Woo, associated director for medical and scientific affairs in the FDA’s CDER Office of Compliance, The Pink Sheet writes. “…because of the medical necessity of these drugs, Genzyme is not (recalling the drugs) and FDA concurs with this decision based on the overall risk-benefit information that is known at this time.”
Not surprisingly, Wall Street battered Genzyme shares, sending them down 7 percent. And the latest episode only further undermines the biotech’s credibility. For instance, Genzyme senior vp Geoff McDonough in September told The Pink Sheet that the biotech was ready for the FDA to return to inspect everything. “We have indicated to FDA that we are ready for them to come into the plant at any moment,” he boasted. Or so he thought.
Thx to Miss Heidi B/Flickr Creative Commons for the cans
Full disclosure: Ed Silverman is an editor at The Pink Sheet
James Corn
I’d just love to see their validation of “only 1%”. Was a 100% audit of entire batches performed? If so, how many? What assurance has the company given that batches produced “under the microscope” accurately represents future batches produced, in it’s normal state of cut-corner, warp speed, “get as many batches out the door as possible” state?
Sterility studies, while intended to ensure a contination free product, are currently performed in a useless manner, given the fact that such a statistically insignificant amount per batch is actually tested.
Just one more problem to solve…
James
Pickle Toes
I’ve worked in a liquid vile filling manufacturing site, and heard a contractor say verbatim to a manufacturing supervisor: “Everyone knows there are aluminum shards in vaccines. The trick is to get them small enough to not be detected by the human eye”.
People actually get paid for this.
Whether the shards are controlled by a 22 micron filter does nothing. Liquid metal would pass thru that. Would you want that injected into you just because it passed thru a filter?
JaT
I know someone that works in a food production plant. The product is run through a metal detector and will be kicked off the line if it contains any of a few different metals. Not so with drugs? Why not?
Pickle Toes
No, not so with drugs. Why? A few reasons:
1. It would be another characteristic tested for Quality (other than some lab rat shaking a vial and putting his or her signature to “no particles detected”
2. Apparatus as you described sounds like something costly, and again, another point of failure.
3. It is commonly known to “those that know” that this is a regular occurrence. Why? Could be a number of reasons. Improper validation of production equipment, the usage of old production equipment with refusal to upgrade and revalidate.
From my experience, as of today at least, particulates including metal particulates, is understood to be common among “those that know”.
Unless I’m in the process of dying, and an injection is the only thing that would save me, I avoid vaccines as if they were the plague. Not far off… I NEVER get flu shots, and there is no way in he’ll I’d get the H1N1 vaccine. Vaccines are of poor quality when they ARE “regulated”. The government granted immunity of liability to makers of swine flu vaccine. There is no way IN HELL I’d receive that vaccine.
Compliance Analyst
Actually many pharma companies use metal detectors on line. My company does not handle sterile fills, but I would probably think that the finished product is not run through a metal detector since the cap would be metal…..they may do it before the fill….
Pickle Toes
Running a liquid product would raise more questions of contamination than not. And the bottom line is, that this is assumed to be the case (metal particles), and is verified visually.
Compliance Analyst - which companies use metal detectors on line???
What is the sensitivity are these set at? Will they pick up trace amounts of potentially harmful metals, or larger quantities? Is this variable adjustable, and who monitors the rats guarding the cheese?
Pickle Toes
Compliance Analyst,
How many pharmaceutical manufacturing processes have you
overseen? If any, how many of these were for vial or syringe fill?
Have you ever been trained in Class 3 gowninf, and have you ever been inside a Class 100 cleanroom while a live manufacturing process was occurring.
Forgive me for my questions, but you seem to “guess” and “assume” too much.
laura
“Genzyme is not (recalling the drugs) and FDA concurs with this decision based on the overall risk-benefit information that is known at this time.”
Excluding Thyrogen, the yearly annual dosage cost of the drugs involved is between $150,000 and $430,000. Consequently, there is another risk-cost benefit that Genzyme might consider when deciding not to recall the drugs…
Hailey Tosis
Look, if the plant has manufacturing issues, more times than not, it is equipment or facility related. Do you have any idea how devastating revamping a facility or revalidating equipment is? Pharma companies will pay reknownef experts to work with their staff at the hundreds-per-hour in order to make themselves look like good little people for when they get audited. All of this BS with 1%, etc is number fudging. It is far too easy to do, and I’ve seen it happen, more than once.
Martina Brodiva
Compliance Analyst,
Do you know what a sterility suite is? Do you have any idea how they are controlled and run?
It sounds like your talking through your #2 place.
Martina
Compliance Analyst
Martina/Pickle,
If you actually read what I said, the company I work for does not run sterile liquids….we only run nonsterile operations for tablets, powders, nonsolids, and other odds and ends. We actually have a capsule fill area that meets Class 100,000, but have not qualified it as such.
I am familiar with sterility suites, but am in no way an expert, as my background is not in parenteral drugs. I was mainly responding to JaT who was insinuating that drug companies do not use metal checks (he/she never stated which type of drug company), which is entirely false. We run metal detectors at the end of the compression process on all of our tablet presses, and they will catch metal should machinery start rubbing.
It is funny that people mention that food companies have metal detectors (which is the exact equipment that most pharma companies have), but then fail to mention that they are also allowed to have a certain amount of animal hair and bug parts in food…
I am a little sad to see that people on here can’t have intelligent conversations without starting to get snippity…
JaT
I wasn’t insinuating anything, Compliance Analyst. I was only asking out of curiosity based on what one food producer does. Seemed relevant to the topic. nvm.
Compliance Analyst
You were asking why pharma companies don’t use metal checks, thus making the assumption that they don’t use them. I was just correcting that assumption. Definitely relevant to the topic, since general GMPs cover food and drugs.
Rooster
And Genzyme also produces medical devices, the form of pharmaceuticals protected from examination and accountability provided by the rule of FDA preemption.
In other words if these products had been medical devices the harm that may come from them would not be subject to product liability responsibility.
Or - Garbage in, garbage out…. enjoy your garbage, approved for consumption by the FDA.
laura
Rooster,
Cockadoodle doo! Wake up, America! Our rights are being sold out to medical device companies so that they can profit at our expense.
Martina Brodiva
Compliance Analyst,
Please dispose of your soapbox, and put a sock in it. You’ve wasted my time.
Martina
Compliance Analyst
ROFL…soapbox, that’s rich. Sorry to have added some insight and facts. Quit playing martyr.
Pat Sailo
Why do horses wear shoes?
Are there horse socks?
Is anybody listening to me?
I think I’m going to construct a crossword puzzle now so that I feel pertinent.
-Pat Sailo
Martina Brodiva
CA,
Your gaseous emmissions are rich.
Martyr? Please explain. In detail, if you will (if capable)
Martina Brodiva
Rooster
Furthermore, Genzyme has not been able to produce other products due to a viral infection at another of their plants. It has been shut down for months in a clean up effort, and is just now coming on line.
Here is a company that should spend a little more of their time and money on quality assurance and less on profit assurance.
Compliance Analyst
Martina,
Let me recap/paraphrase for you:
JaT asked why pharma companies don’t use metal checks. I say a lot of companies do in non-sterile operations. You guys question my experience in sterility and I explain that is not my background, though I have general familiarity with the subject. Pickle and JaT were speaking in generalities…as was I…
You start being rude instead of clarifying and reading what I said. Instead of refuting anything that I said with facts, you instead chose to attack me and then turn it around that I am wasting your time. Add the irony that your time must be so precious since you are posting anonymously on an internet website. To me that is playing the victim.
So yeah, I am capable of explaining it to you, but you have to be willing to listen.
laura
All of the noise on this thread is masking some very important issues that could be raised by this story. (If you want to divert attention, what’s the best way to do it? Pick a fight.)
Rooster brought up the point that Genzyme also manufactures class 3 medical devices. These devices are totally immune from lawsuits because of the Supreme Court’s decision in Riegel v Medtronic. On the other hand, Wyeth v Levine maintained accountability through lawsuits for drug companies. Genzyme is a company that walks on both sides of this fence. If impurities were found in Genzyme’s Seprafilm. a class 3 medical device, and someone was harmed, I believe that there would be no chance that a lawsuit would be able to proceed. Conversely, if ultimately someone is harmed by one of the drugs mentioned in this story, Genzyme could face a lawsuit…What’s the difference, other than the fact that one is a medical device and the other is a drug? Also, does the threat of a lawsuit put Genzyme in a more defensive mode and encourage them to produce safer drugs? I believe that it does and it is a huge injustice that, just because someone is injured or killed be a medical device, they can’t seek redress in a court of law.
Compliance Analyst
Does anyone know how combination products (drug/device or biologic/device) would fit into the preemption world?
laura
Compliance Analyst,
If a product has gone through the FDA’s premarket approval process, it is a class 3 medical device. All class 3 medical devices are preempted. So, using the example I gave previously, Genzyme’s Seprafilm, even though it is a biologic because it is made with man-made hyaluronic acid, it is also a class 3 medical device and, therefore, Genzyme enjoys total preemption from any product liability lawsuit involving Seprafilm. That’s a great thing for Genzyme, but probably not for anyone else.
Compliance Analyst
So what about Class 1 and 2?
JaT
I sincerely do not wish to move away from this topic. It is important. However, for my own purposes, it is also important that I am not misrepresented. My integrity is valuable to me. So to clarify.
I did not simply ask why drug makers do not use metal detectors, as Compliance Analyst suggests. That would indeed be an assumption that they do not. My intent was this…
“Not so with drugs?”
(translation: do drug makers not use metal detectors as food producers do?)
“Why not?”
(translation: If they do not use metal detectors, why not?)
My intent holds no assumptions, but rather, was genuine curiosity. Curiosity based on metal being found in the Genzyme product and my small bit of knowledge of how food production avoids the same problem.
There is a difference, CA, which I hoped could be cleared up without having to write an essay. I definately could have formatted my questions in a better manner.
Sorry to have interrupted the conversation.
Rooster
Compliance Analyst - Best ask your boss at Genzyme what a Class 1 and 2 medical device is and then get back to work. Better yet, for our sakes, find another job.
Compliance Analyst
Rooster,
I know what Class 1 and 2 medical devices are, but was asking a more complex question in regards to preemption and the effect on combination products that include class 1 and 2 medical devices.
And again….I work for a non-sterile solid dosage and nonsolid dosage company. We used to have a medical device back in the day, but decided to stick to drugs (and I am familiar with 820).
JaT, not a problem, I apologize for reading your question incorrectly.
laura
JaT,
I think we all understood your intention and there is no need to clarify or apologize. Your question was a good one and I was interested in hearing the answer, as well.
Compiance Analyst,
In case your question was genuine (although it seems questionable since you are a compliance analyist and should probably know the answer), class 1 medical devices are unlikely to harm a user. They include tongue depressors, bedpans, and bandages. Class 2 medical devices are usually noninvasive and might require special labeling and postmarket surveillance. Examples of these are x-ray machines, powered wheelchairs and surgical needles. These two classes make up the majority of medical devices and are not preempted from lawsuits. They also are not nearly as likely to cause injury or death to their recipients. So, when you hear an advocate of medical device preemption state that most medical devices are not preempted from lawsuits, keep in mind that those devices are probably not likely to cause harm and, therefore, the chance of a lawsuit being brought against them is minimal.
According to the FDA, “Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of class III devices.” Therefore, the FDA requires premarket approval of these medical devices and postmarket reporting. The problem with this system is that clinical trials and adverse event reporting is dependent upon the good will of the medical device manufacturer. It is they who conduct the clinical trials and report adverse events to the FDA. If their data is inaccurate, the FDA generally is unaware. If they report improperly, again, the FDA is generally unaware. And yet, the FDA’s knowledge of the safety and efficacy of a given device is dependent upon the medical device company’s reporting. And in most cases, I hope, that trust is not broken. But the naive belief that it can never be broken is incomprehensible. And if you believe that there is even one manufacturer out there who might by fudging data, under reporting adverse events or hiding results, then you have to believe that victims of this company’s medical device should be given the chance to state their case in court and somehow obtain justice. Unfortunately, this right has been absolutely taken away from any person who has been harmed by a medical device. Is that right? You tell me.
Compliance Analyst
I understand the regulations as it pertains to medical devices alone, but when they are combined with drugs in the case of inhalers, patches, etc. (combination products), does preemption still pertain? The new guidance for combination products doesn’t address issues like preemption and piqued my curiosity. I am not sure that the FDA has ever addressed preemption and combination products.
I am a compliance analyst in terms of manufacturing GMPs for drugs/dietary supplements and not law. I handle internal audits, supplier audits, and interface with the FDA when they come onsite for inspections.
And personally, I disagree with preemption.
Sue
I’ve read everyone’s comments, and I must say that most of it is above my head as I’m just the housewife of a Gaucher’s patient who has been receiving Cerezyme for many years. Now they are saying the drug is available again, and they’ll use a filter. My poor husband is so freaked out by all that has happened, and is holding off on ordering the stuff. Personally, I’d like to sue them just for the stress they have caused him. Could anyone advise whether a pill form would be safer?
Thanks,
Sue
Jaynesday
Genzyme Drugs Contain Bits of Trash - Another reason to be included on The List of Shame.
seema
nice……!