Boston Scientific Endoscopy Comments on General Hospital & Personal Use Panel of Medical Devices Advisory Committee

WASHINGTON, Oct. 31 -- Brian J. Dunkin, vice president of medical affairs for the Boston Scientific Endoscopy, Marlborough, Massachusetts, has issued a public comment on the Food and Drug Administration's notice entitled "General Hospital and Personal Use Panel of the Medical Devices Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments". The comment was written on Oct. 21, 2019, and posted on Oct. 24, 2019:

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Executive Summary

Background: In September of 2013 the Center for Disease Control and Prevention alerted the Federal Drug Administration (FDA) about a duodenoscope-associated E. coli outbreak in the US. Since that time more outbreaks have been reported and the FDA has been diligent in its efforts to understand the etiology of duodenoscope contamination and to minimize risk to patients having endoscopic retrograde cholangiopancreatography. In response, medical device manufacturers are pursuing various technical solutions that focus either on better duodenoscope design or better reprocessing methods.

Some of these solutions are now being introduced into the healthcare community prompting questions about their utility, function, cost effectiveness, and availability. To address these questions, the FDA is convening a Committee to hear recommendations to reduce the risk of infection from reprocessed duodenoscopes. Boston Scientific is providing a written statement for consideration by the Committee and will have representation attending the in-person meeting.

Focus: Boston Scientific will focus its comments in this document on five perceived challenges to adoption of new duodenoscope technology.

Challenges:

1. A medical community that may not fully perceive a need for change. The reasons for this are multifactorial including the fact that endoscope associated infections are hard to detect and the symptoms they cause are variable, resulting in underreporting. Further, endoscopists believe that modifications in reprocessing made by their units mitigate the risk of infection despite a lack of evidence. Finally, the healthcare community may have information fatigue from multiple communications over time and the perception that recommendations offered are unproven or eventually shown to be ineffective.

2. Skepticism that a single-use duodenoscope can be used as effectively as a reusable one. Boston Scientific Endoscopy has deep experience making medical devices for endoscopists who perform ERCP and has been diligent in its development and testing of its single-use duodenoscope.

3. Cost. No matter what technologic solution is developed and utilized to eliminate duodenoscope contamination, it will add cost to the procedure. Current ERCP procedural payment does not account for this cost. To support patient access and safety while minimize costs for treating patients with endoscope acquired infections, a device-specific payment for single-use duodenoscopes, in addition to the ERCP procedural payment, is needed.

4. Limited supply. No medical device manufacturer with an effective solution will be able to serve the entire market immediately. Guidance is required on which patients benefit most from use of innovative technology so that clinicians may prioritize its use. The FDA is encouraged to support medical device manufacturers in their efforts to increase production rapidly and safely.

5. Uncertainty about the value of unproven solutions. Spending resources on unproven or ineffective solutions may not result in commensurate reduction in endoscope-associated infections. The FDA should clearly communicate the limitations of each solution proposed and require data to support the effectiveness of a new method or technology before it is endorsed.

The FDA has been diligent in investigating the cause for duodenoscope-related infections and fostering solutions to mitigate the risk. The Agency should continue to precisely and transparently educate the healthcare community about this topic, encourage early interaction with manufacturers in development of innovative models and methods, support the value proposition of new technology in this space, work with societies, government agencies, and industry to provide guidance to clinicians making decisions about use of technology not available to all, and use data to drive endorsements of technology.

Background:

In September of 2013 the Center for Disease Control and Prevention (CDC) alerted the Federal Drug Administration (FDA) about a duodenoscope-associated E. coli outbreak in the US. Since that time more outbreaks have been reported both within the US and without and the FDA has been diligent in its efforts to understand the etiology of duodenoscope contamination and to minimize risk to patients undergoing endoscopic retrograde cholangiopancreatography (ERCP)./1

That effort has revealed that, despite use of best practices in reprocessing, a patient undergoing ERCP has a better than 1 in 20 chance that their procedure will be performed with a duodenoscope contaminated with pathogenic bacteria./2

Clinical research has also revealed that the etiology of this problem does not reside solely in the complex and difficult to clean tip of the instrument but is a biofilm-related problem that affects the entire endoscope from biopsy channel valve to the distal tip./3

In response, medical device manufacturers are pursuing various technical solutions that focus either on better duodenoscope design or better reprocessing methods. Some of these solutions are now being introduced into the healthcare community prompting questions about their utility, function, cost effectiveness, and availability. In response, the FDA is convening a Committee to hear recommendations to reduce the risk of infection from reprocessed duodenoscopes. Boston Scientific is providing a written statement for consideration by the Committee and will have representation attending the in-person meeting.

Boston Scientific is one of the world's largest manufacturers of medical devices, serving over 30 million patients per year in 130 countries. The company's products serve the needs of patients across multiple disease states including diseases of the biliopancreatic system. Boston Scientific Endoscopy, one of six divisions in the company, provides the majority of devices used by US physicians to perform ERCP. In addition, the company is the world's largest manufacturer of single-use endoscopes for use in both urologic and biliopancreatic procedures. When the risks of duodenoscope-associated E. coli outbreaks became better understood, Boston Scientific Endoscopy embarked on an initiative to create a single-use duodenoscope.

Over 100 engineers have been working on this project during the last three years. With the expectation that multiple new devices will be developed to help mitigate the risk of endoscope acquired infections, Boston Scientific will focus its written comments on perceived challenges to adoption of new duodenoscope technology.

Challenge #1: A medical community that may not fully perceive a need for change

Despite the fact that it has been six years since reports of the first outbreak of duodenoscope-associated infections in the US and that there have been twelve FDA Safety Communications about this risk and six professional society guideline updates, a significant number of endoscopists do not seem to appreciate the significance of the problem and the need for change./4

The reasons for this are multifactorial. Endoscope associated infections (EAI) are hard to detect, the symptoms they cause in patients variable, and the timeline to development of symptoms potentially long (i.e. weeks to months after the procedure) making linkage to the procedure unclear to an examining clinician. As a result, the true incidence is under-reported and many endoscopists who have not experienced an outbreak in their unit may be skeptical about the magnitude of the risk./5

Further, even those clinicians who understand the risks of EAIs often believe that modifications in reprocessing made by their endoscopy units mitigate that risk. This is despite the fact that these enhanced methods (e.g. double high-level disinfection with or without ethylene oxide gas sterilization) have not been shown to be effective./6

Finally, the healthcare community may be experiencing an element of information fatigue on the topic of duodenoscope reprocessing with multiple communications over time from various organizations and societies. Some of the communications have been perceived as offering recommendations that are eventually shown to be ineffective or endorsing technologies that are unproven in their ability to reduce EAIs.

To mitigate this challenge, the FDA should continue its diligence in investigating the limitations of duodenoscope reprocessing and communicating clearly with the healthcare community. This includes precise reporting of data on the contamination/infection risks and the etiology of the problem (biofilm) while avoiding recommendation of solutions that are unproven and risk being found to be ineffective in their ability to reduce EAIs.

Challenge #2: Skepticism that a single-use endoscope can be used as effectively as a reusable one

Use of a single-use duodenoscope is a comprehensive solution that eliminates the possibility of any patient having an ERCP performed with an endoscope contaminated by bacteria from another patient because of inadequate reprocessing. It is a "stem-to-stern" solution that directly addresses the root cause of EAIs - biofilm. Despite the effectiveness of this solution, clinicians may be skeptical that a single-use device will be as safe and effective as a reusable one. ERCP is a nuanced procedure, requiring significant experience to master and precise control by the endoscopist in order to successfully cannulate the papilla and deliver devices for diagnosis and therapy. It is understandable that a clinician who has successfully performed thousands of cases with a particular reusable duodenoscope would be skeptical that a disposable version is as good. Boston Scientific Endoscopy has deep experience making medical devices for endoscopists who perform ERCP.

The requirements for success in the procedure are well understood by the company which is why the majority of endoscopists in the US perform ERCP using devices made by Boston Scientific. The company also has deep experience in developing and manufacturing high quality disposable endoscopes to be used in demanding procedures such as ureteroscopy and choledochoscopy. This expertise has been leveraged in the development of a single-use duodenoscope with a focus on minimizing barriers to adoption by endoscopists.

No two duodenoscope designs will be identical. However, to be legally marketed in the U.S., an innovative duodenoscope must either have the same technological characteristics as one already on the market or have different characteristics that do not raise different questions of safety or effectiveness, with information submitted to the FDA demonstrating that the innovative device is at least as safe and effective as the legally marketed device. Manufacturers of innovative technologies should be advised to utilize the FDA's mechanisms for early interaction with the agency to ensure such questions and information requirements are well understood prior to initiating the submission process.

Challenge #3: Cost

Given the complex design of a duodenoscope, there are costs required to manufacture one to a high standard, regardless of whether the scope is re-usable or disposable. For a single-use device, these costs may be perceived to be too high to be borne by typical payments to endoscopy facilities.

Adding to this perception is a failure to appreciate the costs incurred in maintaining a reusable duodenoscope inventory and managing a patient with an EAI. Enhanced reprocessing approaches lead to increased inventory numbers to maintain throughput, increased capital to transport, store, and possibly gas sterilize and/or quarantine devices, and increased training and labor. All of these factors increase per procedure costs for ERCPs performed using reusable scopes, costs which may be under-appreciated in the common calculus.

Interestingly, this investment is in a flawed system that results in 1 in 20 failures./2

Partial solutions like disposable caps are also associated with significant costs as they cannot be retrofitted to existing inventory, requiring purchase of new capital equipment. This too is an investment in an unproven technology that may need to be replaced before the end of its normal life cycle when data is available on its effectiveness in eliminating duodenoscope contamination from reprocessing. There are also the "hidden" costs of decreasing patient access to ERCP. Smaller volume endoscopy facilities unable to manage the burden of enhanced reprocessing requirements either because of cost or logistics may have to stop performing these procedures and refer patients to larger centers. This could reduce the availability of ERCP in some communities and increase the burden on referral centers to provide these procedures. Finally, there is significant cost of managing patients with EAIs./7

No matter what technologic solution is developed and utilized to eliminate duodenoscope contamination, it will add cost to the procedure. Current ERCP procedural payment does not take into account the added cost of safer technology including disposable duodenoscopes. To support patient access and safety, a device-specific payment for single-use duodenoscopes, in addition to the ERCP procedural payment, is needed. This will lessen the economic burden on individual hospital systems performing these critical procedures.

The Centers for Medicare and Medicaid Services (CMS) offer two mechanisms to secure device specific payment, specifically, the transitional pass-through (TPT) and new technology add-on payment (NTAP) programs. Under the TPT and NTAP programs, several criteria must be met, including demonstrating substantial clinical improvement of the device compared to the standard of care. Typically, CMS requires comparative study data to demonstrate this improvement. However, given that the FDA-mandated studies have demonstrated the high contamination rate associated with reprocessed scopes and that the disposable duodenoscope is sterile, eliminating the risk of patient-to-patient transmission from inadequate reprocessing, this criterion should be deemed to have been met.

Conducting a comparative study to demonstrate the benefits of disposable duodenoscopes versus reprocessed ones is not only unnecessary (there is no debate about the sterility of a single-use duodenoscope) but also unethical given that such a study would knowingly expose patients to potentially contaminated endoscopes and put them at risk of infection. This would contradict the intent of the FDA's recommendation to avoid unnecessary patient risk and to protect the public health. In this case, the avoidance of risk of infection by providing a sterile single-use duodenoscope should be considered to meet the criteria for significant clinical improvement.

Boston Scientific encourages the FDA to engage CMS to discuss the patient safety implications of reprocessed duodenoscopes, the FDA's recommendation to move to disposable duodenoscopes and caps, and how both agencies can work together to facilitate patient access to safer ERCPs.

Challenge #4: Limited supply

Over 700,000 ERCPs are done per year in the US alone./8

No medical device manufacturer with a comprehensive and effective solution for EAIs will be able to serve the entire market immediately. As a result, a scaling-up strategy is required to ensure that all patients continue to have access to ERCP when needed. One strategy is to stratify the risk of ERCP for certain groups of patients and prioritize the use of enhanced technology for their procedures. For instance, those at highest risk for harm if exposed to a contaminated duodenoscope (e.g. immune compromised or suppressed patients or those at risk of post-procedure cholangitis) would benefit the most from a sterile duodenoscope and thus this technology would be prioritized for their cases. In addition, patients undergoing ERCP who harbor active infection are more likely to cause contamination of existing reusable inventory and a single-use duodenoscope should be used for them as well.

The FDA should work with the CDC, professional societies, and industry to provide guidance to endoscopists on which patients benefit most from use of technology that eliminates the risk of exposure to a contaminated duodenoscope so they may prioritize use of that technology in their institution. In addition, the FDA is encouraged to support medical device manufacturers as they work to increase production as rapidly as possible while maintaining patient safety so that more of these devices can available for patient care.

Challenge #5: Uncertainty about the value of unproven solutions

The medical community strives to care for patients using evidence-based medicine and best practices and is willing to invest in technologies that help to achieve that aim. However, some options proposed to reduce the risk of EAIs are incomplete in their approach or unproven. Current enhanced methods of reprocessing (e.g. double high-level disinfection with or without ethylene oxide gas sterilization) are shown to be ineffective in eliminating the risk of duodenoscope contamination and variable in effectiveness./3

In fact, human factors analysis has revealed that technicians frequently have difficulty understanding and following manufacturers' reprocessing instructions and are not able to reliably and successfully complete all of the necessary reprocessing steps./2

New more effective reprocessing methodologies will be difficult to develop as they must eliminate the formation of biofilm and remove human error from the process. Disposable caps logically may reduce duodenoscope contamination rates but are unlikely to eliminate it as they are a partial solution that doesn't comprehensively address biofilm formation and remains heavily reliant on existing inefficient reprocessing approaches. They are also unproven in their ability to reduce EAIs.

Given these uncertainties, healthcare institutions are unsure of how to invest their resources to effectively address this important issue. Spending resources on unproven or ineffective solutions or doing nothing to reduce EAIs are both unacceptable approaches. It is important that the FDA clearly communicate the limitations of each solution proposed for reducing the risk of duodenoscope contamination and require data to support the effectiveness of a new technology before it is endorsed.

Summary

The FDA has been diligent in investigating the cause for duodenoscope-related infections and fostering solutions to mitigate the risk. The Agency should precisely and transparently educate the healthcare community about this topic, encourage early interaction with manufacturers in development of innovative models and methods, support the value proposition of new technology in this space, work with societies, government agencies, and industry to provide guidance to clinicians making decisions about use of technology not available to all, and use data to drive endorsements of technology.

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Footnotes:

1. FDA. Infections Associated with Duodenoscopes. https://www.fda.gov/medical-devices/reprocessing-reusable-medical-devices/infections-associated-reprocessed-duodenoscopes. Accessed October 19, 2019.

2. The FDA Continues to Remind Facilities of the Importance of Following Duodenoscope Reprocessing Instructions: FDA Safety Communication. April 12, 2019. https://www.fda.gov/medical-devices/safety-communications/fda-continues-remind-facilities-importance-following-duodenoscope-reprocessing-instructions-fda.

3. Thornhill G, David M. Endoscope-associated infections: A microbiologist's perspective on current technologies. Techniques in Gastrointestinal Endoscopy August 20, 2019 (epub ahead of print). https://doi.org/10.1016/j.tgie.2019.150625.

4. Boston Scientific voice of customer input

5. Ofstead CL, Langlay AMD, Mueller NJ, Tosh PK, Wetzler HP. Re-evaluating endoscopy-associated infection risk estimates and their implications. American Journal of Infection Control. 2013(41):734-6.

6. Rubin ZA, Kim S, Thaker AM, Muthusamy VR. Safely reprocessing duodenoscopes: current evidence and future directions. Lancet Gastroenterol Hepatol 2018; 3: 499-508.

7. Almario, C. V., May, F. P., Shaheen, N. J., Murthy, R., Gupta, K., Jamil, L. H.,... Spiegel, B. M. Cost Utility of Competing Strategies to Prevent Endoscopic Transmission of Carbapenem-Resistant Enterobacteriaceae. The American journal of gastroenterology 2015; 110(12): 1666-1674. doi:10.1038/ajg.2015.358

8. Boston Scientific internal estimate

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The notice can be viewed at: https://www.regulations.gov/document?D=FDA-2019-N-3793-0001

TARGETED NEWS SERVICE, Harwood Place, Springfield, Virginia, USA: Myron Struck, editor; 703/304-1897; [email protected]; https://targetednews.com