Reprocessing of Flexible Endoscopes: From Liquid Sterilization to Terminal Sterilization

INTRODUCTION

Over the last 50 years, significant changes have reshaped the landscape of reuseable medical devices, including  the consolidation of prevacuum steam sterilization, the introduction of low-temperature sterilization agents, and the use of advanced materials like metal alloys and polymers. These advancements have enabled the development of innovative devices tailored to a wide range of therapeutic needs. One particular area is related to minimally invasive procedures, with endoscopic devices enabling multiple diagnostic and therapeutic solutions, which have increased in adoption due to the multiple benefits they bring.

Among the most impactful advances, endoscopic applications have increased both the variety and volume of procedures, requiring smaller, more intricate devices with multiple channels and complex mechanisms such as camera controls, wire loop, forceps, and injection needles. Although a wide range of endoscopic devices exist, two main categories predominate: rigid endoscopes (e.g., laparoscopes, arthroscope, bronchoscope), and flexible endoscopes (e.g. colonoscope, gastroscope, duodenoscope, enteroscope, sigmoidoscope). Specific applications, such as paediatric endoscopy, further require devices with narrower channels.

In 2019, an estimated 75 million flexible endoscopy procedures were conducted in the United States alone. Though this figure varies across sources, millions of patients undergo these procedures annually, with an expected increase due to the prevalence of gastrointestinal diseases.

Despite the tremendous advantages that flexible endoscopes offer to clinicians, there has been extensive debate over the last two decades, about their potential to spread infections between patients. Documented outbreaks have frequently been linked to reprocessing issues, the complexity of these devices and their high frequency of use make them particularly vulnerable to reprocessing breaches which can result in negative outcomes.

Flexible endoscope reprocessing has been a challenge since these devices were first introduced in medical practice, primarily due to factors such as their length, residual bioburden and water, and the difficulty of ensuring adequate exposure of lumens to detergents and chemical agents. The infrastructure required for proper reprocessing is another contributing factor.

Currently, the most common reprocessing methods uses automatic endoscope reprocessors (AERs), which flush cleaning and disinfectant agents through endoscope channels, followed by rinse and storage. Although this approach achieves high-level disinfection, there is ongoing debate about whether flexible endoscopes should be considered semi-critical devices (thus requiring only high-level disinfection) or critical devices that should undergo terminal sterilization.

CURRENT TECHNOLOGIES

The challenges in reprocessing flexible endoscopes stem from two primary needs: the growing number of procedures per device daily and the increased safety requirements for these devices, either through high-level disinfection or terminal sterilization, a trend increasingly supported by regulatory bodies, scientific societies, and standards organizations.

Three main trends affect endoscope reprocessing:

1) endoscopes are used in multiple procedures each day,

2) the number of endoscopes available in each facility is limited

3) reprocessing time remains a significant hurdle often taking 30 minutes or more depending on endoscope type and manufacturer instructions.

These factors create challenges in providing ready-to-use endoscopes promptly.

Endoscope manufacturers provide guidelines in their IFUs to address bioburden, typically recommending high level disinfection, liquid chemical sterilization, or terminal sterilization.

The general process includes leak testing, pre-cleaning, cleaning, disinfection, rinsing, and drying steps that maybe performed manually or with automatic endoscope reprocessor (AERs). Differences exist between high-level disinfection, liquid chemical sterilization, and terminal sterilization, primarily in the sterility assurance level (SAL) each alternative delivers.

This article will focus on liquid chemical sterilization and terminal sterilization.

LIQUID CHEMICAL STERILIZATION

Liquid chemical sterilization^[1] has been a valuable process in device reprocessing, helping prevent infections spread when medical devices are potential vectors. Typically, liquid chemical sterilization follows thorough cleaning by immersing devices in agents, such as hydrogen peroxide, glutaraldehyde, or peracetic acid under controlled conditions (e.g. specific concentration, temperature, and time).

Although this process can achieve a sterility assurance level (SAL) of 10^-6, it presents several limitations, particularly with complex devices such as flexible endoscopes. Key challenges include ensuring adequate contact time across lumens, potential bioburden affecting sterilant concentration, the absence of sterile barriers, and the inability to verify the SAL using chemical and biological indicators. The primary drawback of this method is the lack of a sterile barrier, which allows environmental exposure before the device´s next use. Additionally, water retention in channels^[2-3] may foster biofilms formation, especially if water quality is suboptimal.

High quality water, is critical for effectively removing residuals and minimizing recontamination risks once the liquid chemical sterilization process concludes. Advanced AERs incorporate single or double reprocessing basins, connecting multiple channels to the endoscope and forcing chemical agents through the device pass-through systems to separate contaminated reception areas from clean storage, featuring high-efficiency air (HEPA) filters that prevent contamination and facilitate moisture removal. However, these systems still lack a sterile barrier, leaving devices susceptible to contamination between reprocessing and prior patient use.

TERMINAL STERILIZATION

Terminal sterilization provides a sterility assurance level (SAL) of 10⁻⁶, ensuring that devices remain sterile until the point of use. In this process, medical devices such as flexible endoscopes are protected in sterile barriers that allow sterilant diffusion to surfaces, crevices and channels, with is removed in the final sterilization phase. This method enhances patient safety by delivering a sterile device at the point of use, thus via pumps to ensure thorough exposure at specific temperatures and times. Some AERs also offer contamination prevention in regular storage.

Due to the nature of flexible endoscopes, conventional steam sterilization is not feasible, as it requires high temperatures. Low-temperature sterilization technologies such as ethylene oxide (EO)^[4], vaporized hydrogen peroxide (VHP)^[5],  and low temperature steam formaldehyde (LTSF)^[6-7], are preferred. Each method offers specific advantages and limitations (Table 1).

Table 1. Summary of endoscope reprocessing technologies

ETHYLENE OXIDE (EO)

EO has shown efficacy and compatibility with flexible endoscopes by effectively diffusing into channels and achieving sterilization^[4]. However, environmental concerns, stringent occupational safety regulations, and long aeration times (up to 12 hours) have limited its use.

VAPORIZED HYDROGEN PEROXIDE (VHP) AND HYDROGEN PEROXIDE PLASMA (HPP)

VHP and HPP are technologies that have proven effective^[5], especially for shorter endoscopic devices, with cycle time under one hour. However, VHP and HPP diffusion faces challenges in longer channels (i > 100 cm), which restricts its suitability for some endoscopes Recently, ASP addressed this by announcing the compatibility of its HPP-based Sterrad system with one specific Pentax duodenoscope specially designed for VH2O2 and only sold in the US.

LOW TEMPERATURE STEAM AND FORMALDEHYDE (LTSF)

Combining the benefits of EO and VHP and HPP, LTSF can achieve adequate diffusion in long channels (e.g., duodenoscopes, enteroscopes), offers a manageable solution and has no restrictions on channel numbers or endoscope length, making it a feasible alternative to liquid chemical sterilization.  These options have different inactivation pathways and characteristics, including cycle time and abatement requirements (Table 2).

The LTSF process operates at temperatures between 50°C and 80°C (122°F – 176°F), typically around 60°C (140°F), using a mixture of steam and 2% formaldehyde. A typical LTSF cycle takes approximately 90 minutes to achieve terminal sterilization for flexible endoscopes over 300 cm. The process includes conditioning, exposure and drying phases.

During conditioning, several negative pulses remove air from the vessel and devices lumens, enabling effective exposure to steam-formaldehyde. In the exposure phase, formaldehyde cross-links proteins and saturated coagulates proteins, inactivating microorganisms by altering their structure and function.

Once sterilization is complete, a two-stage process removes formaldehyde residuals. First sterile steam flushes out residues, followed by a vacuum pulse to remove both steam and desorbed formaldehyde. A final deep vacuum stage vaporizes any remaining condensate, ensuring the load is dry, sterile, and free of residuals.

Table 2. Summary of endoscopes, characteristics and reprocessing technology

Source: Modified from Lorenzo et al. NSW SRACA Conference 18th- 20th March Opal Cove, Coffs Harbour.

VHP*: In September 2024 it was announced compatibility of one specific Pentax Duodenoscope only sold in the US with ASP Sterrad VHP system.

GLOBAL STANDARDS AND TRENDS IN FLEXIBLE ENDOSCOPE REPROCESSING

The reprocessing of flexible endoscopes has garnered increased attention due to the risk of multidrug-resistant microorganism (MDRO) outbreaks associated with these devices^[9]. Numerous studies have highlighted the importance of reassessing flexible endoscope practices, advocating for improved reprocessing protocols, greater resource allocation for endoscopy departments (including skilled personnel) and updates to the Spaulding Classification^{[10-11-12-13 -14-15-16]}.

Specifically, recommendations for reprocessing include enhanced inspection protocols, improved cleanliness monitoring, microbiological surveillance of endoscopes and the transition from high-level disinfection and liquid chemical sterilization to terminal sterilization.

United States:

The predominant reprocessing practice for long flexible endoscopes involves using AERs, which rely on liquid chemical sterilization. While AERs streamline reprocessing by combining sterilization, decontamination, exposure to chemical agents, rinsing, and drying in a single process, they lack the sterility assurance of terminal sterilization.

Adverse events related to endoscope-linked infections continue to occur. One hypothesis is that a lack of sterile suction cylinders connected to scopes^[17], and inadequate decontamination contribute to conditions that favour biofilm formation^[18]. The FDA acknowledges^[19] that sterilization with liquid chemical sterilants does not convey the same sterility assurance as sterilization using low temperature thermal or gas/vapor/plasma sterilization methods’.

The Association for the Advancement of Medical Instrumentation (AAMI), launched the ANSI/AAMI ST91 in 2015^[20], offering a comprehensive framework to enhance patient safety in the reprocessing of flexible endoscopes. This standard includes detailed guidelines for high level disinfection, liquid chemical sterilization and terminal sterilization. This standard was updated in 2021 and is currently partially recognized by the FDA.

Australia:

The Australian Standard AS5369 mandates that when critical reprocessable medical devices are incompatible with moist heat sterilization, they should undergo validated low temperature sterilization processes between uses^[21]. The standard lists several low temperature sterilization methods, including peracetic acid, hydrogen peroxide, and low temperature steam formaldehyde (LTSF).

Europe:

In Europe, the debate between liquid chemical sterilization and terminal sterilization for endoscopes has been effectively resolved in favour of the latter. The European Society of Gastroenterology and Endoscopy Nurses and Associated (ESGENA)^[22] recommends against liquid chemical sterilization for endoscope reprocessing, due to the lack of a sterile barrier. ESGENA also stresses the importance of water quality during the final rinse stage, as water quality can affect the SAL of the process. Some manufacturers, including Olympus and Pentax, have integrated these recommendations into their IFUs.

Although outbreaks and adverse events still affect many patients worldwide, feasible alternatives are available for healthcare providers, including LTSF and newer vaporized hydrogen peroxide applications. These technologies offer sufficient product compatibility, diffusion in complex geometries and long channels, reduced cycle time and enhanced patient safety.

CURRENT TECHNOLOGIES

In medical device reprocessing, there appears to be a separation between the nature of the device and the way to assess the risk of using such a device. For most medical procedures involving tissue manipulation, ranging from a suture kit to a hip replacement container, there is no question that reusable devices are sterilized before use.

However, due to multiple reasons, including device evolution, reprocessing time, and industry recommended practices, flexible endoscope reprocessing has deviated from this standard. Although several types of flexible endoscopes are considered semi-critical, during certain procedures they may damage patient tissue, exposing sterile tissue, blood, or lymph nodes. When this occurs, the risk to patients increases, as the device is no longer semi-critical but instead becomes a critical device for which terminal sterilization is required.

In terms of risk management principles (avoid, identify, analyze, evaluate, and address), the “avoid risk” portion is often overlooked when there is a chance contact with sterile tissue through incidental damage. This is particularly relevant for patients with weakened health, who may be more susceptible to infections that could lead to additional treatment or other adverse events.

Globally, healthcare facilities generally provide sterile devices for all surgical procedures, yet not consistently for endoscopic procedure but for limited endoscopic procedures. This inconsistency raises questions about patient safety during endoscopic procedure. Given the risks associated with endoscopic procedures, potential tissue damage, and known lapses in current reprocessing technologies, exploring alternatives to terminally sterilize endoscopes appears to be the appropriate path to enhance patient safety.

To prevent hospital-acquired infections where flexible endoscopes are the vector, the gold standard is terminal sterilization. However, terminal sterilization requires longer processing time compared to regular liquid chemical sterilization. Thus, if flexible endoscopes are terminally sterilized, fewer devices may be available for procedures unless additional endoscopes are purchased.

While terminal sterilization meets the need for increased patient safety, it may not be feasible from a workflow or throughput perspective unless more endoscopes are added to the system. Although this approach presents challenges to the economic and operational efficiency of healthcare facilities, the evaluation should consider both the cost of additional endoscopes and the enhanced patient safety, which is translated into fewer adverse events. In the pay-for-performance healthcare system, this may even result in higher reimbursement rates from the health insurance providers.

Clinicians and reprocessing professionals are part of a complex decision-making process that affects reprocessing strategies. Quality of care can be improved by reducing risks to patients, which reduces the overall burden on the healthcare system.

Endoscopic procedures will continue to increase due to the benefits of minimally invasive diagnostics, the rising prevalence of chronic diseases, the need to address multiple disorders related to chronic illnesses^[23] and obesity^[24], and the expansion of early detection programs. Endoscopic procedures represent some of the most advanced diagnostic and therapeutic techniques available to clinicians today, yet their safety could be substantially enhanced by shifting from liquid chemical sterilization to terminal sterilization. Current technologies such as LTSF, are already in use, offering facilities increased patient safety and reduced adverse events.

References 

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² Tian H, Sun J, Guo S, Zhu X, Feng H, Zhuang Y, Wang X. The Effectiveness of Drying on Residual Droplets, Microorganisms, and Biofilms in Gastrointestinal Endoscope Reprocessing: A Systematic Review. Gastroenterol Res Pract. 2021 Apr 8;2021:6615357. doi: 10.1155/2021/6615357. PMID: 33927758; PMCID: PMC8049816.

³ Fluid retention in endoscopes: A real-world study on drying effectiveness

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¹¹ Focused Review Series: Endoscopic Disinfection in the Era of MERS. Clinical Endoscopy 2015; 48(5): 351-355. Published online: 30 September 2015 DOI: https://doi.org/10.5946/ce.2015.48.5.351

¹² Shellnutt, Cathleen MSN, APRN, AGCNS-BC, CGRN. Advances in Endoscope Reprocessing Technology and Its Impact on Pathogen Transmission. Gastroenterology Nursing 39(6):p 457-465, November/December 2016. | DOI: 10.1097/SGA.0000000000000267

¹³ Multisociety guideline on reprocessing flexible GI endoscopes: 2016 update. Petersen, Bret T. et al. Gastrointestinal Endoscopy, Volume 85, Issue 2, 282 – 294.e1

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¹⁹ FDA: Liquid Chemical Sterilization. https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/liquid-chemical-sterilization. Accessed on July 18th, 2024.

²⁰ ANSI/AAMI ST91:2021. Flexible And Semi-Rigid Endoscope Processing in Health Care Facilities.

²¹ Australian Standard AS 5369:2023: Reprocessing of reusable medical devices and other devices in health and non-health related facilities

²² ESGENA position statement. Reprocessing of flexible endoscopes and endoscopic accessories used in gastrointestinal endoscopy: Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology Nurses and Associates (ESGENA) – Update 2018. 20.11.2018.

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