Guiding a Single-Use Duodenoscope Toward FDA Approval

 Rajesh Krishnamoorthi, MD, and Hayley Helm, RN, perform an ERCP.
Rajesh Krishnamoorthi, MD, and Hayley Helm, RN, perform an ERCP.

Endoscopic retrograde cholangiopancreatography (ERCP) has become an indispensable way to assess and treat patients with a wide variety of pancreaticobiliary conditions, from benign pancreaticobiliary disease to pancreas cancer and cholangiocarcinoma. Endoscopists at Virginia Mason perform a high-volume of ERCPs annually, and, as a regional referral center, care for patients with pancreaticobiliary disorders ranging from straightforward to complex. While ERCP has always been associated with a risk of infection, it was historically thought that infection was related to endogenous bacteria already colonizing the patient at the time the procedure was performed. Over the past six years, it has become evident that ERCP is also associated with a risk of transmission of exogenous bacteria from inadequately reprocessed endoscopes. A post-market surveillance study mandated by the United States Food and Drug Administration revealed a 5.4 percent rate of endoscope contamination with high concern organisms following reprocessing performed according to manufacturers’ instructions.

In response to an outbreak of multi-drug resistant E. coli infection in patients who had undergone ERCP, team members at Virginia Mason developed a “culture and quarantine process” that provided a quality check on the duodenoscope cleaning process that had previously lacked this important safety feature. In addition, over the past three years, Virginia Mason’s Andrew Ross, MD, has been part of a group of physicians working with industry partners in the development of the world’s first disposable duodenoscope.

“Virginia Mason has been at the forefront of developing solutions to the cross-contamination issue since it was first detected,” Dr. Ross says. “The single-use scope is the latest chapter in that effort, and we think it has the potential to solve this problem once and for all.”

Contamination Concerns

Berni Delisle, Endoscopy Technician, uses culture and quarantine equipment during the duodenoscope cleaning process.
Berni Delisle, Endoscopy Technician, uses culture and quarantine equipment during the duodenoscope cleaning process.

Several years ago, centers worldwide reported a number of outbreaks of infections with multidrug resistant organisms in patients who had undergone ERCP. Investigations revealed that these infections were transmitted between patients by inadequately reprocessed duodenoscopes. Whereas previous reports of endoscope-mediated patient cross contamination had been associated with major systemic failures in endoscope reprocessing, the recent reported outbreaks associated with duodenoscopes failed to identify significant lapses in cleaning protocols.

With time, it has become evident that the recently reported outbreaks represent the culmination of multiple factors. The duodenoscope is one of the most complex medical instruments to undergo reprocessing for reuse in patients. Unlike straight-channel endoscopes, the duodenoscope has an elevator mechanism which poses significant challenges to reprocessing. In addition, existing reprocessing protocols are lengthy, complex and lack a final quality check to verify that the endoscope is clean and ready for use in the next patient. Finally, the emergence of multidrug resistant organisms has allowed medical centers to more easily identify clusters of infections which point to a common source of infection.

Virginia Mason has been at the forefront of developing solutions to the cross-contamination issue since it was first detected. The single-use scope is the latest chapter in that effort, and we think it has the potential to solve this problem once and for all.”Andrew Ross, MD

“It’s likely that there have always been ERCP-related infections, but they probably involved bacteria that were susceptible to antibiotics, making them unlikely to be detected or linked to duodenoscopes,” Dr. Ross says.

“Obviously, these bacteria are dangerous and activate hospital surveillance alarms,” Dr. Ross says. “Antibiotic-resistant infections were the canary in the coal mine that tipped us off that there is a larger problem of potential scope contamination.”

Improved Reprocessing Protocols

Cleaning Process

The Therapeutic Endoscopy Center of Excellence took a first step toward a solution in 2014, when Dr. Ross and his colleagues implemented a quality check on the duodenoscope cleaning process — called culture and quarantine — that required reprocessed endoscopes to be cultured and held out of clinical use until the cultures returned negative for high-concern organisms. This method, however, was expensive to implement and imperfect, as the sensitivity of endoscope cultures remains an unknown.

“The ultimate question is ‘How do I know this endoscope is clean and ready for use on the next patient?’” Dr. Ross says. “Defects in endoscope cleaning should be identified upstream, before the devices are put into patients. Infection as a marker of a defective cleaning is too far too down the line and poses a safety risk to patients. We started to think that the best solution might be to avoid the cleaning challenge altogether.”

Developing a Single-Use Duodenoscope

In 2017, the Therapeutic Endoscopy Center of Excellence entered into a research and design collaboration with an industry partner and leading physicians from the University of California, Los Angeles; the Mayo Clinic; the University of Pittsburgh Medical Center; Beth Israel Deaconess Medical Center; and Long Island Jewish Medical Center. The goal was to create a 100 percent disposable duodenoscope.

“It’s a wonderful synergy,” Dr. Ross says. “The clinical team has unparalleled expertise in therapeutic endoscopy and ERCP, and our industry partner has the ability to engineer, manufacture and market a potentially game-changing new scope.”

Satisfaction GraphDr. Ross and his colleagues provided design feedback and animal-model testing for initial prototypes ultimately leading to the production of the first generation, single-use duodenoscope. Early testing hinted that the scope could be used for its intended purpose, as published in 2019 in Gastrointestinal Endoscopy: the scope performed comparably to three models of reusable duodenoscopes for basic ERCP-related maneuvers. Despite this success, the endoscope had never been used in humans.

First-In-Human Trial

Following rapidly after pre-clinical testing, Dr. Ross and investigators from medical centers around the United States performed the first-in-human trial of the new duodenoscope. The results, published in 2019 in Clinical Gastroenterology and Hepatology, were overwhelmingly positive. Out of 60 ERCP procedures, 58 were completed using only the disposable scope. Median overall satisfaction among physicians using the scope was 9 out of 10. There were no adverse events associated with use of the duodenoscope per se, although post-ERCP pancreatitis was observed in three patients.

In two instances, physicians switched from the single-use scope to a traditional scope. One instance involved cannulation that was unsuccessful with either scope. The other entailed balloon dilation of a biliary stricture and was completed with the reusable scope. The operating physician attributed the failure to dilate the tight intrahepatic stricture to diffculties torqueing and maneuvering the single-use scope, possibly due to the relative stiffness of the shaft compared to traditional scopes.

Median performance ratings of 5 (on a scale of 1 to 5) were recorded for the scope for 17 of the 23 ERCP maneuvers tested, including placement or removal of stents, balloon dilation of strictures, clearance of bile duct stones, cannulation and sphincterotomy. Scope performance characteristics that received at least one “1” rating included the following: positioning, elevator function, ease of passing ancillary devices through the channel of the scope and into the papilla, visualization and image quality/brightness.

“The first-generation single-use scope has slightly different performance characteristics than a conventional scope,” Dr. Ross says. “There were some handling issues related to the stiffness of the wheels and the actuation of the elevator itself.”

Refining the Design

In response to physician feedback from the first clinical trial, the scope’s design was altered and an updated version produced. These improvements are proprietary and cannot be disclosed at this time.

A clinical trial of the latest version of the disposable duodenoscope launched in early 2020 and is recruiting patients from around the world. It is also enlisting a larger number of physicians, with a wider array of expertise than those who participated in the earlier study.

“The first study was performed only by expert endoscopists. A broader range of users with varying levels of experience is imperative to understand whether this device can be massmarketed,” says Dr. Ross, who will be the study’s site principal investigator at Virginia Mason Medical Center. “We’re optimistic that the new design will be even easier to use and more effctive in patients.”

A Future Without Cross-Contamination

Reported ERCP-related outbreaks of infection declined nationally to fewer than 100 per year in 2018 after peaking at 250 in 2015, but recent data underscore the importance of developing an alternative to conventional duodenoscopes. In 2019, FDA-mandated post-market surveillance studies documented higher-than-expected contamination rates — up to 5.4 percent for high-concern organisms — in reusable scopes despite full compliance with manufacturer reprocessing instructions.

“That’s simply too high,” Dr. Ross says. “Our goal is for that number to be zero, and we think the single-use scope could be one way to get there.”