Reprocessing has taken center stage in the medical device industry over the past two months, thanks to several high-profile “superbug” outbreaks that were linked to the use of contaminated duodenoscopes (type of endoscope) at two prominent U.S. hospitals.
First, UCLA's Ronald Reagan Medical Center reported that up to 179 of its patients may have been exposed to a drug-resistant bacterium called carbapenem-resistant Enterobacteriaceae (CRE) during procedures involving duodenoscopes — and two of those patients had died. Two weeks later, Cedars-Sinai Medical Center confirmed that at least four of its patients, and as many as 71 — had contracted CRE during the same procedure involving the same brand of endoscopes.
Much panic and finger-pointing ensued. The hospitals maintained that they had followed the manufacturer’s instructions to a “T” when cleaning the devices. Several of the victims and victims’ families promptly filed lawsuits against the manufacturer. The FDA issued a safety alert, which was followed almost immediately by final guidance on the reprocessing of reusable medical devices. Even the White House got involved, announcing a five-year roadmap to combat antibiotic-resistant bacteria in the United States.
How did we get to this point as an industry? What can we do to ensure this type of problem doesn’t occur with our medical device designs? And what will the future hold when it comes to the reprocessing of medical devices? Let’s explore these (and other) questions related to this significant and timely issue.
How We Got Here: The Regulatory Backdrop
The reprocessing of medical devices — or more specifically, the cleaning and sterilizing of devices that have been previously used (e.g., surgical instruments) — has been happening since the earliest days of medicine. However, the medical device industry has not been overly concerned about reprocessing, because it largely has been conducted by hospitals and therefore lies outside the FDA’s oversight. As everybody knows, FDA does not regulate the practice of medicine, and it can easily be argued that reprocessing (like usability, pharmaceutical compounding and 3D printing) is the practice of medicine.
Obviously, that position quickly erodes in the face of an issue like the one that occurred with the duodenoscopes. Believe it or not, back in 2011, FDA issued draft guidance on the reprocessing of medical devices in healthcare settings, including endoscopes. The guidance was very controversial at the time, because it was another example of regulatory expansion, or what I like to call the regulatory big bang, where FDA increases its reach into areas where, historically, it didn’t have jurisdiction.
(Regulatory expansion like this is not necessarily a bad thing. However, it is not something FDA should do unilaterally. Rather, what FDA regulates and what they do not is a matter of healthcare policy and therefore should be discussed and debated as a society.)
Unfortunately, it took four years for that guidance to be finalized. Coincidentally, the final guidance was released in March 2015, literally days after the UCLA story broke. For the sake of comparison, our friends in Ottawa, Health Canada, put out their final guidance on the same topic back in 2011.
Why the heck did it take so long? More importantly, what does the guidance — or, indeed, any regulation — really accomplish? One of my favorite adages is that we followed the regulation perfectly, but the patient died anyway. Unfortunately, that’s exactly what happened in the duodenoscope incidents, because the regulations were being followed, and yet people were infected and, in some cases, died as a result.
Not A New Problem
Endoscopic procedures like these have been around for decades. In fact, it’s likely that CRE and similar antigens (bacteria, viruses, etc.) have been transmitted from patient to patient via ineffectively — but not necessarily improperly — reprocessed endoscopes without clinical significance for years. Based on the number of procedures that take place, coupled with the ineffective and impractical cleaning processes that we’ve been using to this point, it’s naïve to think that cross-contamination hasn’t been happening with a frequency higher than many would like to think.
The difference is that in the past, these infections were either asymptomatic, meaning that we didn’t know that the patient had them, or they were symptomatic but easy to treat because the antibiotics would take care of them. Since these problems were not clinically significant in the past, few people really worried about it.
Now that CRE has reached superbug status, these problems can no longer be overlooked. These bacteria are resistant to even our strongest antibiotics, and according to the Centers for Disease Control and Prevention (CDC), they may kill up to half of the people that it infects.
A lot of people think that just because we don’t experience a problem that there isn’t one, and that’s not necessarily the case. The absence of evidence is not evidence of absence! Unfortunately, many use this “logic” as a justification to not look for problems. We can no longer ignore these issues because now, regrettably, we have evidence of them. In other words, we can no longer allow ourselves to be sloppy engineers.
The issue is not limited to duodenoscopes. This is a potential problem across the entire endoscopic community, and even more broadly, across the entire medical device universe, at least for medical devices that are reused in patients over and over again. After all, those who forget their history are doomed to repeat it.
Design For Reprocessing
So what can we, as medical device designers, do to prevent such problems from occurring with our products? Short answer: a lot!
The new FDA guidance includes a few recommendations. For example, one is that all reprocessing instructions should recommend thorough cleaning of a device. I think that’s a statement of the obvious. And what the heck does “thorough” mean? Although the guidance does include contamination limits, it is highly debatable what these limits should be.
We have known for a long time that cleaning is clearly the weakest link in the reprocessing chain. For the design engineers out there, it is important to take into account something I call “design for reprocessing,” from the very beginning of the product development cycle. In a sense, is this not what we should be doing already as part of usability testing? Where is it written that usability testing is limited to the clinical user? Shouldn’t it also include the reprocessor, especially if our device is labeled as such?
In other words, we need to do everything we can to ensure that if we’re working on a device that is intended to be reused and reprocessed, it is designed from the very beginning to allow that to happen. It could be something as simple as designing the device to be taken apart in several different pieces, so that it can be cleaned and sterilized more effectively, or choosing coating materials or surface modifications not only for biocompatibility but to optimize reprocessing as well.
Simply put: there are solutions to all of these problems. Some can be best addressed by better engineering, others by regulation. Of course there are advantages and disadvantages to each.
The unfortunate reality is that this tragedy could have been prevented through better design and more realistic regulation. Unfortunately, many regulatory solutions, while they sound good on paper, are simply not realistic. Perhaps a good thing will arise from it, though, that it will cause people to say, “Hey, how can we do a better job in the design and regulation of our devices?”
Collaborating With The Healthcare Community
Another thing that the guidance mentions is that instructions for reprocessable devices should be “technically feasible in the context of their intended locations and their intended users.” On one hand, this is common sense, an example of what I call “prudent engineering” — and do we need regulation to tell us what we all know should be done anyway? But on the other hand, exactly what does this statement mean?
Should the device manufacture design and validate the cleaning procedure if the manufacturer will not be doing the actual reprocessing? In my opinion, this makes no sense! And there have already been reports of endoscope manufacturers validating cleaning procedures that cannot be replicated in the hospital where the actual reprocessing takes place. In other words, reprocessing validation should not be conducted by the manufacturer in a vacuum, because the manufacturer is not the one that ultimately will be reprocessing the device.
Instead, the manufacturer should be working in conjunction with the hospital — or whatever user community will be reprocessing that particular device — to understand how it will be cleaned in a clinical setting and to make sure that the hospital cleans it in a satisfactory way. And now we are back to the issue of the FDA not regulating the practice of medicine. So in that sense, does the solution to this problem really involve the FDA?
Responsible design engineers should be testing their medical devices in the environment in which they are intended to be used (i.e., the OR, cath lab, etc.). When this doesn’t happen, problems occur. Over the years, several medical devices have been removed from the market because the physician did not use the device in the way the designer thought it should be used. In most cases, these problems are completely avoidable — and not by regulation, i.e., labeling. It is amazing how many regulatory professionals assume people read labels, directions for use (DFUs), etc. No responsible engineer would make such an assumption. The same regulatory logic should be applied to reprocessing.
Bottom line, this has to be a team effort. Manufacturers should be working hand-in-hand with all of the users of their devices. This includes the physicians who use their device on the patient and the technicians who reprocess the device in the hospital in between patients.
And, the cleaning procedures must be realistic. They need to be simple enough for the folks who are actually doing the reprocessing to understand. Most people are used to having standard operating procedures (SOPs), but where is it written that an SOP must be in writing? Why not have a cleaning SOP video? They say a picture is worth a thousand words, and a video is worth a thousand pictures!
And cleaning procedures should be validated in the hospital where the devices are being reprocessed, not in the controlled environment of the manufacturer.
Johns Hopkins reprocesses 37,000 instruments every day, including 500 instrument sets with about 75 instruments per set and 200 individual instruments. The hospital inventory of devices requiring reprocessing is more than 14,000. Referring to reprocessing in the real world, an AAMI report on reprocessing [PDF] states:
“There are complicated instructions with too many steps that are unreasonable, with too many variables.… Staff have to work from memory or hearsay. IFU [instructions for use] expect people to read an awful lot, in an environment that is not conducive to do such. Nobody reads. It is easier to just ask a neighbor or see what someone else is using.”
This is precisely what I mean when I say regulation should be realistic! Given the numbers of devices processed, the cleaning procedure needs to be accomplished in a ‘reasonable’ period of time. Some have suggested that any reprocessessing procedure taking more than about 17 minutes per device, no matter how good it may be, is simply not realistic! Device manufactures would be wise to include this in their design inputs as the design controls remind us to do. But have manufacturers done this? They are following the design controls but patients have died anyway.
Finally, manual cleaning of devices like endoscopes, although it has been done for decades, makes no sense for many reasons. Validating a manual cleaning procedure is difficult if not impossible. How do you validate the manual washing of dishes or the manual washing of cars? While not impossible, it is certainly not easy. And does anyone really think a special brush “labeled” to clean endoscopes will really solve this problem? So perhaps there is another way.
Maybe we need an automated dishwasher or any automated car wash? Automated endoscope cleaning machines already exist, but they are not commonly used. In fact, if such devices were used, the CRE infections and deaths leading to this debate may never have happened! Medical device manufactures would be wise to partner with such companies to make sure their devices are designed to be reprocessed.
At the end of the day, manufacturers and the FDA have to understand that it really doesn’t matter what they put on paper in terms of validation, or even what they validate in their own lab. What’s more important is what’s happening in the real world, and in this particular case, the real world is the hospital setting.
As I mentioned earlier, I think it would be a mistake to limit our thinking to just this particular type of endoscope, the duodenoscope. This scenario potentially can, and probably already is, affecting (infecting?) all medical devices that are reused over and over again. In that sense, this particular case — although it’s certainly a tragedy — could be just the tip of the iceberg. It could potentially affect all devices that are reused or reprocessed.
In fact, the new guidance indicates that a well-designed and properly validated cleaning procedure likely will be a requirement of most, if not all, regulatory submissions in the future: 510(k)s, premarket approvals (PMAs), etc. This will not only apply to endoscopes, but potentially to all reprocessable medical devices, across the board. Once again, this should be common sense, prudent engineering. Call me naïve, but I would like to think that responsible medical device manufactures do this anyway — because it’s the right thing to do — regardless of what the regulation may or may not require.
What are the future ramifications of the duodenoscope incidents? In one word: huge. They truly have the potential to impact most, if not all medical devices, and the problem might even get worse.
CRE is deadly, but even more importantly, cases of CRE infection already have been reported in nearly all of the 50 states in this country. This problem is actually much more common than a lot of people think, and the CRE case has the potential to have a huge impact on this industry, similar to the New England Compounding Center tragedy that happened in 2013, where contaminated products led to deaths from meningitis and resulted in additional FDA oversight and new regulation. The impact on industry has yet to be fully appreciated today.
In the medical device world, the breast implant fiasco that happened two decades ago led to sweeping changes in the requirements for biomaterials. More recently, the infusion pump problem that took place a few years ago was the single driver, the root cause, behind the adoption of usability or human factors testing for virtually all medical devices. Once again, I would like to think if you’re designing a device to be used in a patient, you would test the device for biocompatibility. And if you’re designing a device to be used by a physician, you would test the device for usability by the physician (i.e., the intended user) and not by the design engineer. Consider this: Sooner or later, each of us may be on the receiving end of one of these devices. When that time comes, what would we expect to have been done?
We have to always look for similarities where no similarities seem to exist. Don’t think of this case in isolation. Don’t think, “Gee, I don’t work with duodenoscopes, I don’t work with endoscopes. Therefore, these things are not important to me.” On the contrary, they have the potential to drastically impact the medical device industry, across the board.
And, with all the emphasis on cost savings in healthcare, why limit ourselves to the discussion of reusable medical devices? There’s been an ongoing debate for the last several years about the challenges associated with reprocessing single-use medical devices. The simple reality is that a medical device company can stamp in big letters on their label, “Only use this device once, and throw it away,” but again, I think it’s naïve for us to believe that everybody practices medicine that way. From a regulatory perspective, that is technically considered off-label use, but can we really be so naïve as to think that it doesn’t happen?
Here is another way to address the problem: Design the single-use device so it becomes disabled or falls apart after the first use. Then you won’t have to worry about single-use devices being reused. More importantly, you won’t have to worry about whether anyone reads or follows your label. There is more than one way to skin a cat.
And what of the reprocessing challenges surrounding reusing permanent implants? Yes, you heard me right — reusing permanent implants Think this couldn’t possible happen? It already has! Pacemakers, for example, have been harvested from patients post mortem, “reprocessed,” and implanted into the next patient. Granted, this would likely never happen in the United States, primarily for liability reasons, but in other parts of the world it is already occurring. And liability aside, if a patient in a third-world country could not afford a pacemaker, would it be ethical to withhold a device that could save their life simply because it has already been used?
To its credit FDA is hosting a two-day Gastroenterology and Urology Devices Panel meeting on May 14 to 15, 2015, to address reprocessing issues. I will be one of several presenters at this meeting, and I hope it provides a forum for an open, honest, and candid debate, where all stakeholders can express their concerns and come up with practical solutions to prevent similar tragedies from occurring again in the future.
Medical devices, not just endoscopes, are becoming more complex, and similar problems will occur with other types of devices in the future. It is incumbent on all of us — not just in the medical device industry, but in the regulatory community, the healthcare community, and the lay public — to be not just reactive but proactive. We need to be thinking ahead to similar problems and what can we do in the future to try to prevent them.
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