The Importance of Cleaning Validation

For sterilized medical devices, ensuring sterility requires that residual contaminants must not pose a risk to the human body, necessitating the establishment of reliable sterilization assurance. To achieve this, decomposition and removal of residue through cleaning is of paramount importance. Through cleaning validation, the intended cleaning effectiveness of an established cleaning process must be verified in advance, thereby ensuring reliable cleaning implementation in actual clinical settings.

In particular, “reprocessed single-use devices” (Reuse Single-Use Device: R-SUD) are devices that are disassembled and cleaned to appropriately remove contamination incurred during medical use, then reassembled and redistributed as SUDs possessing equivalent quality, effectiveness, and safety to the original medical device. In the reprocessing of SUDs, appropriate cleaning, disinfection, and sterilization methods tailored to the target R-SUD are required, and validation of the cleaning process is mandated by regulatory requirements.

The cleaning of medical device products aims to remove residue, contaminants, and microorganisms. Medical devices requiring cleaning fall into two categories: those cleaned by healthcare facilities prior to sterilization or use, and those supplied non-sterile and requiring cleaning prior to sterilization or use. In either case, prior verification of the effectiveness of the cleaning process is essential.

In 2015, the FDA issued warning letters to three Japanese endoscope manufacturers. Multiple cases of hospital-acquired infections caused by highly resistant bacteria were mediated by endoscopes in the United States. This incident raised international awareness regarding the importance of medical device cleaning processes. Because duodenoscopes have movable components at their tip, resulting in complex configurations, bacteria are believed to have originated from residual body tissue that was overlooked during the cleaning procedures performed by healthcare workers. While manufacturers bear responsibility for providing appropriate cleaning manuals, variation exists in the types of cleaning equipment and the competency levels of healthcare facility staff, making it difficult to eliminate infection risk entirely. In the warning letter, the FDA stated that it was aware of infections occurring “even when manuals were followed precisely,” emphasizing the importance not only of providing procedural documentation but also of ongoing education and monitoring.

The requirements for information that medical device manufacturers must provide to healthcare facilities regarding cleaning and related processes are consolidated in ISO 17664-1:2021, “Processing of healthcare products—Information to be provided by medical device manufacturers for the processing of medical devices.” This standard specifies the content and format of processing information (including cleaning, disinfection, and sterilization) that manufacturers must provide to healthcare facilities. Instructions for use must include precautions and other information related to cleaning, disinfection, sterilization, and related processes.

When healthcare facilities implement cleaning methods such as automated cleaning or manual cleaning, cleaning validation must be performed to ensure that specified levels of cleanliness are achieved. Manual cleaning carries risks of exposure to blood and body fluids, as well as potential cuts to healthcare workers; therefore, automated cleaning is preferred. It is also more effective for infection prevention.

The entities responsible for cleaning implementation are classified into three categories: medical device manufacturers, reprocessing medical device manufacturers, and healthcare facilities. The responsibilities and requirements of each differ, and each must perform appropriate validation activities.

Cleaning Validation by Medical Device Manufacturers

Medical device manufacturers must perform cleaning validation as necessary during the manufacturing process. However, ISO 13485:2016 does not contain direct requirements for cleaning validation. In the practical guidance for ISO 13485:2016, the cleaning process is classified as “a process for which the necessity of validation should be determined on an individual basis.” In other words, the necessity of cleaning validation must be determined based on the type of medical device, manufacturing process, and final sterilization method.

ASTM F3127-16, “Standard Guide For Validating Cleaning Processes Used During The Manufacture Of Medical Devices,” is the only comprehensive guideline in this area and is positioned as an FDA Recognized Consensus Standard. This guideline specifies in detail the methods for validating cleaning processes implemented by manufacturers. However, ASTM F3127-16 does not address reusable medical devices that are cleaned in healthcare facilities. Cleaning in healthcare settings is conducted according to different guidelines.

On the other hand, cleaning prior to sterilization is necessary to ensure sterilization and to reduce sterilization time. Inadequate cleaning compromises the effectiveness of the sterilization process; therefore, manufacturers should establish an integrated process validation strategy that combines cleaning and sterilization.

Cleaning Validation by Reprocessing Medical Device Manufacturers

In the case of “reprocessed single-use devices” (R-SUD), contamination with blood and body fluids is present, making cleaning validation more critical than for original medical devices. Following the 2021 revision of the Quality Management System Regulation (QMS Regulation), Section 5-2, “Manufacturing Control and Quality Management for Reprocessed Single-Use Medical Devices” (Articles 81-2 through 81-2-4), was added. The QMS Regulation legally requires validation of the cleaning process involved in the reprocessing of “reprocessed single-use medical devices” (R-SUD).

The principal guidelines related to cleaning validation for “reprocessed single-use medical devices” (R-SUD) include the following: The June 17, 2019 administrative notice from the Ministry of Health, Labour and Welfare, Medical Devices Review and Approval Division, titled “Cleaning Guidelines and Q&A for Operators of Reprocessed Single-Use Medical Devices,” serves as the standard guideline for Japanese reprocessing operators. Additionally, the FDA/AAMI joint publication “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling” (final revision: June 9, 2017) is widely referenced as the standard for implementation in North America. Furthermore, the ANSI/AAMI ST79:2017 series includes the latest technical requirements for reprocessing processes in general.

Cleaning Validation by Healthcare Facilities

Healthcare facilities implement cleaning through manual cleaning, immersion cleaning, ultrasonic cleaning, and washer-disinfectors. Cleaning and disinfection typically render microorganisms non-viable, though sterilization is not always achieved. Currently, many healthcare facilities implement high-level disinfection rather than sterilization, and this situation is currently accepted as interim practice.

However, equipment deterioration over time can result in gaps and cracks that prevent complete cleaning. Therefore, healthcare facilities must periodically inspect equipment condition and perform repairs or replacement when necessary.

Japanese language versions of guidelines established by organizations such as the German Society for Sterilization (DGSV) are available and are referenced as implementation standards for healthcare facilities. The “Validation Guidelines for Manual Cleaning and Manual Disinfection of Medical Devices” aims to standardize manual processes, while the “Guidelines for Validation and Daily Monitoring of Automated Cleaning and Hot Water Disinfection Processes for Medical Devices” specifies operational requirements for automated systems.

In healthcare settings, the performance of Performance Qualification (PQ) in sterilization validation and cleaning validation is legally required. PQ is the final stage of equipment and process suitability assessment, confirming that equipment and processes meet specified requirements in the actual operational environment. Ongoing validation maintenance activities are equally important; healthcare facilities have an obligation to implement continuous monitoring and process management.

The implementation of cleaning validation is a fundamental requirement for ensuring the safety and effectiveness of medical devices. When manufacturers, reprocessing operators, and healthcare facilities appropriately fulfill their respective responsibilities, infection risk to patients can be minimized and the quality of medical care enhanced.