History

Between 2012 and 2015, duodenoscopes were linked to at least 25 outbreaks of carbapenem-resistant Enterobacteriaceae. ⁵ The actual toll was likely far higher but remained unknown given gaps in reporting and surveillance. ⁵ By early 2013, the manufacturer Olympus knew of 2 independent lab reports finding that a model of their duodenoscopes featuring a difficult-to-access elevator channel could harbor bacteria even after cleaning according to the manufacturer’s instructions. ⁵

Even though the FDA began investigating elevator channels in 2013 in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), Olympus did not forward the laboratory reports to the FDA or alert US hospitals, physicians, or patients to the risk of infection until February 2015. ^2,5 Further investigation revealed that 2 major duodenoscope manufacturers failed to pursue “FDA clearance” prior to bringing their devices with elevator channels to market. The FDA was also not aware of manufacturer warnings to European regulators that had occurred as early as 2013. ⁵

These events highlighted various inadequacies in manufacturer reporting, hospital investigation, and regulator action, prompting the CDC and FDA to re-examine reprocessing IFUs. In March 2015, the CDC released an interim duodenoscope surveillance protocol for healthcare facilities in cooperation with the FDA and American Society for Microbiology (ASM). ² In October the same year, the FDA ordered 3 major duodenoscope manufacturers to conduct postmarket surveillance studies to better understand duodenoscope-transmitted infections. ² Two years later, in June 2017, the FDA promulgated regulations to require manufacturers of certain “high-risk” reusable medical devices to include in their premarket notification 510(k) validated IFUs regarding cleaning, disinfection, and sterilization. ^5,6

Over the next 4 years, the FDA released 6 general updates of reprocessing instructions, 12 general communications on duodenoscopes, and 16 public correspondences to duodenoscope manufacturers. ² In February 2018, the FDA, the CDC, and the ASM released voluntary standardized protocols for duodenoscope surveillance culturing. ⁷ Yet in an August 2019 safety communication, the FDA noted in its postmarket surveillance report continued “elevated rates of contamination, including the presence of high concern organisms” such as Escherichia coli and Pseudomonas aeruginosa, highlighting persisting concerns of HLD and complex endoscope design. ²

These concerns have helped fuel a growing market for single-use equipment; manufacturers of varying scopes and probes have developed completely disposable designs. In November 2019, the FDA recommended transitioning to duodenoscopes with disposable components and cleared for marketing the first fully disposable duodenoscope 1 month later. ^8,9

Challenges

Amid this backdrop, several practical difficulties and regulatory challenges remain. First, although IFUs for reprocessing higher-risk medical devices must now be validated in accordance with FDA regulation, processes for validation are not standardized and are often unclear. Current FDA guidance refers manufacturers to technical information reports (TIRs) developed by the Association for the Advancement of Medical Instrumentation (AAMI), specifically AAMI TIR 2 (“labeling instructions for reusable medical device”) and TIR 30 (“compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices”). ¹⁰ However, most AAMI TIRs were last published in 2010 and are in critical need of updating.

In 2015, the AAMI published the more rigorous “Standard 91: Flexible and semi-rigid endoscope processing in health care facilities,” which outlines facility-level quality-control practices, addresses human-factors issues related to reprocessing, and comments on the design and flow of reprocessing departments. ¹¹ Yet full implementation of this standard, including cleaning verification processes, schedules, and tracking and tracing of all related endoscope equipment, remains challenging. ^{12,Reference Bringhurst13} Additionally, given rapid advances in disinfection and sterilization science and changes in regulation, this guidance also requires updating. ^11,12 Work on this update has been ongoing since early 2019, but a new draft document has not been released. ¹²

Over the past decade, manufacturers have largely been left to author IFUs without clear guidance as to what is an acceptable or standard cleaning protocol, ^{Reference Basile14} resulting in widespread variation in how IFUs are structured and written, the methods used to demonstrate that effective disinfection has occurred, and storage and handling practices. ^{Reference Basile14,15} For example, there are no uniform methodologies to assess whether proper cleaning (eg, detection of protein vs blood vs microbial DNA) has occurred, ^7,10 and there are no agreed-upon standards regarding when older equipment should be sent for maintenance, repair, or replacement—or whether, how, and when borescopes should be used to detect rips or tears. ^{7,11,Reference Bringhurst13}

Particularly critical to the disinfection process are manual precleaning steps. Although the FDA requires that reprocessing instructions “should be understandable,” ^{6,Reference Basile14} many consumer-facing IFUs are dense and difficult to follow (eg, some IFUs exceed 100 pages). In mandated human-factors postmarketing surveillance studies conducted by Fujifilm and Olympus, “most participants expressed some difficulty adhering to the reprocessing manual,” and one study concluded that the materials “are not sufficient to consistently ensure user adherence in these core reprocessing areas: precleaning, manual cleaning, manual high-level disinfection, rinsing, and storage and disposal.” ^8,15,16

IFUs can also contradict guidance from professional societies, which can conflict with each other. For example, the Society of Gastroenterology Nurses, the Association for Professionals in Infection Control and Epidemiology, and the Association of Perioperative Registered Nurses all have different recommendations on storage and “hang time”—the maximum duration of storage time before the endoscope is processed for next use. ¹¹ Recognizing such variability, The Joint Commission recently released its own clarification for hospitals, outlining that the IFU remains paramount to professional society guidance and consensus documents. However, gaps remain when IFUs are nonspecific or do not address key concerns, leaving hospitals in the position of having to reach out to manufacturers directly. ^17,18

The interplay of IFUs can also be a challenge. Although device manufacturers create their own IFUs, they typically do so separately from the manufacturers of automated reprocessors and high-level disinfectants. ^{Reference Bringhurst13,19} This situation creates another layer of complexity for end users in healthcare facilities, particularly those that use manual methods of disinfection. In reconciling IFUs, a hospital’s ability to swiftly recognize concerns and call attention to appropriate leadership can be hampered. ^{6,Reference Bringhurst13} Some device manufacturers of scopes create their own reprocessing equipment exclusively for their own devices, ²⁰ which can mitigate the burden of IFU coordination but can also result in undue contractual leverage, limiting the ability of hospitals to diversify their inventories.

More broadly, concern exists that HLD may be insufficient for scopes. ^{Reference Rutala and Weber21,Reference Rutala and Kanamori22} The decades-old Spaulding criteria outlines the use of HLD for semicritical devices such as scopes and sterilization for critical devices such as surgical instruments. ^{Reference Spaulding, Lawrence and Block23} HLD typically results in a 6-log₁₀ reduction of microorganisms, whereas sterilization results in at least a 12-log₁₀ reduction. ^{Reference Rutala and Kanamori22} However, flexible endoscopes acquire high levels of microbial contamination or bioburden during each use and may contain 10 different enteric microorganisms after use, ^7-10 with particular build-up around closed channels. ^{Reference Rutala and Kanamori22} Accordingly, some infection prevention experts refer to HLD as creating a “nonexistent margin of safety” that is unable to achieve disinfection consistently. ^{Reference Rutala and Kanamori22,Reference Rutala and Weber24}

Challenges also exist with sterilization. Typical scope materials cannot handle the high temperatures required for the most commonly available and robust methods of sterilization (ie, steam).^{Reference Rutala and Weber24,25} Additionally, existing sterilants have notable drawbacks. Ethylene oxide, a sterilant for rigid scopes, requires lengthy processing and aeration time. ^{Reference Rutala and Weber24} In high quantities, it also poses health hazards, including carcinogen risk. ^{Reference Rutala and Weber24–Reference Rabin26} Because of this risk, ethylene oxide is unavailable in many US hospitals. In 2019, 2 large device facilities were closed by state EPA agencies in response higher then acceptable levels of ethylene oxide in the air, creating abrupt shortages of sterilized devices. ²⁷

Finally, while the market for single-use equipment may be viewed as a clear path forward, inadequate attention has been given to associated waste streams. Use of disposable duodenoscopes ^{Reference Muthusamy, Bruno and Kozarek28} would contribute to the market growth of disposable designs for other scopes and probes, but the environmental footprint of single-use equipment has yet to be modeled nationally and internationally. ^{Reference Sherman and Raibley29–Reference Sorenson and Gruttner31} For example, in one study, single-use laryngoscope handles generated an estimated 16–18 times more lifecycle carbon dioxide equivalents (CO₂-eq) than traditional low-level disinfection of the reusable steel handle, and single-use plastic tongue blades generated an estimated 5–6 times more CO₂-eq than the reusable steel blade treated with high-level disinfection. ^{Reference Sherman and Raibley29} However, some studies suggest that the higher emissions of CO₂-eq may be offset by the cost of personal protective equipment (PPE) that are required to be worn during reprocessing, and that the energy consumption of reprocessing equipment also needs to be considered. ^{Reference Sorenson and Gruttner31} These comments underscore the need for further data with which to build comprehensive models.

Solutions and future directions

Addressing these challenges requires engagement among manufacturers, clinicians, regulators, central processing departments, infection prevention and control leadership, and healthcare administrators. Inconsistencies of IFUs and the lack of transparency and standardization around validation in all domains—precleaning, disinfection, storage, maintenance and repair—should be key priorities for the FDA and AAMI. Encouragingly, updates to key AAMI documents are in progress. ^{12,Reference Basile14} Working groups developing these documents include diverse stakeholders, including key manufacturers, regulators, and infection prevention experts. Making drafts of current TIRs or standards currently under review publicly available for comment may present opportunities for improvement and promote swifter uptake by manufacturers and healthcare facilities. ^{Reference Bringhurst13,Reference Basile14}

Even with updated AAMI standards, however, implementation will remain challenging. To facilitate optimal execution, healthcare administrators should seek to invest in competency and training programs for reprocessing staff, and they should consider including them in contracted services with manufacturers and vendors. ^{Reference Basile14} Coordination of IFUs across vendors requires close coordination of healthcare facility infection prevention and control, biomedical/clinical engineering, supply chain, and contracting departments. Although committees comprised of representatives from these groups may be found at many large, acute-care inpatient centers, they may not exist in ambulatory settings or surgical centers, where procedures are common. ^{Reference Bringhurst13} The absence of such committees should be considered in a facility’s gap analysis and should be examined as part of regulatory and reaccreditation requirements. ^{Reference Bringhurst13,Reference Seavey32}

Many experts, meanwhile, have called for the reclassification of scopes as critical devices that require sterilization. ^{Reference Rutala and Weber21,Reference Rutala and Kanamori22,Reference Rutala and Weber24} There is regulatory precedent for such action. In 1992, the FDA mandated a shift from disinfection to sterilization for dental hand pieces, even though there were no documented cases of disease transmission associated with dental hand pieces. ^{Reference Rutala and Kanamori22} Professional societies should support this transition, and accreditation agencies should start developing standards to facilitate institutional accountability. ^{Reference Rutala and Kanamori22}

Incentives will likely be needed to encourage further development of sterilization options, including low-temperature sterilization technologies (LTSTs). The FDA recently started this process, announcing in November 2019 4 participants in an “innovation challenge” to identify disinfection and sterilization alternatives that can be implemented at a large scale and maintain high throughput. ³³ Two of these participants will focus on the use of vaporized hydrogen peroxide technology that is currently being used on a large scale to disinfect respirators during the COVID-19 pandemic. ³⁴ Although participation does not constitute “regulatory acceptance,” manufacturers should expect that the FDA remains committed to expeditiously clearing LTSTs as they are developed if safety and effectiveness standards are met. ³³ In turn, manufacturers should commit to the FDA endorsement of creating scopes with innovative designs, including manufacturing scopes with materials that are compatible with LTSTs. ^{9,Reference Rutala and Kanamori22}

More recently, the FDA announced a second innovation challenge to decrease ethylene oxide emissions. ³⁵ In parallel with and in light of closures of sterilization facilities due to high ethylene oxide emissions, the US Environmental Protection Agency (EPA) issued a notice of proposed rule making to solicit information from industry and the public on strategies to further reduce ethylene oxide emissions in commercial sterilization and fumigation operations. This effort has included reviewing and updating regulations for sources that emit ethylene oxide and better understanding and addressing ethylene oxide emissions at facilities. ³⁶ Such interagency coordination will be needed to more identify the optimal role of ethylene oxide in medical device sterilization, the effects of endoscope sterilization, and the impact on the supply chain and transportation operations. ^35,36

Finally, hospitals and clinics will need to consider the far-reaching impacts of incorporating disposable equipment, especially as pathogens of high consequence, such as CRE, take hold. ^{Reference Muthusamy, Bruno and Kozarek28,Reference Bang37} Hospitals and clinics will need to partner and engage early with major biomedical waste companies and recycling vendors both in the United States and globally to create a regulated, functional waste stream. ^{Reference Rabin26,38,39} These groups will need to understand large throughput hospital- and clinic-based workflows, to calculate new labor costs, and to consider implications for their supply chains. Corporate social responsibility platforms should expand to account for the impact of such activities and should integrate this work into ongoing sustainability efforts, including tracking fleet and incinerator emissions. ^38,39 To more fully weigh complete environmental impact, cradle-to-grave life-cycle assessment and life-cycle cost estimating methods should be used. ^{Reference Sherman and Raibley29-Reference Sorenson and Gruttner31} For example, the EPA’s Tool for the Reduction and Assessment of Chemical and other Environmental Impacts (TRACI) can be used to model environmental impacts of greenhouse gases and other pollutant emissions. ^{Reference Sherman and Raibley29} As is required to examine ethylene oxide impacts, a sustained FDA and EPA partnership should additionally initiate detailed data gathering to inform national and international economic and environmental analyses. Such efforts should include how to weigh energy consumption of reprocessing departments and facilities, human labor costs, and PPE use.

High-level disinfection and sterilization of medical equipment has slowly evolved over the past 30 years. The outbreaks of drug-resistant bacteria traced to contaminated duodenoscopes earlier this decade exposed large gaps in medical device regulation. Although the FDA has made strides in closing these gaps, important and critical problems persist. A coordinated, public–private partnership will be required not only to minimize disease transmission but also to realistically consider environmental harms that may lie ahead. Without continued innovation in device management and regulation, the progress we have made will be lost.