Developing the Instructions for Use (IFU) for any medical device can be challenging, but reusable devices have a unique challenge that requires focused attention to ensure patient safety: the reprocessing method. Without properly designing and detailing the reprocessing procedure, future patients may be at risk — regardless of device classification or initial estimations.
Teams that wait to critique the efficacy of their reprocessing instructions until the final stages of a project may face setbacks if the needed reprocessing validations do not proceed as intended and retesting or instruction redaction is necessary. Manufacturers should consider designing the reprocessing methods with patient safety, end-user comprehension, and process validations in mind. Planning ahead can help manufacturers avoid potential delays, additional costs, or lost revenue.
Developing or Refining the Reprocessing Instructions
It is a manufacturer’s responsibility to ensure that the reprocessing instructions for reusable devices are clear, comprehensive, and effective. There are many points in a product’s life cycle when validation or revalidation may be necessary, such as product launch, design changes, production transfers, or remediation. When approaching validation testing, a cross-functional team generally unites together to review all design inputs and develop, or possibly edit, the IFU. Aligning different perspectives and considering engineering, regulatory, and clinical needs can be cumbersome. Even when a team reaches a compromise, gaps in the reprocessing instructions can remain until it is put to the test.
When drafting reprocessing instructions for a new IFU, the development team should factor in various aspects of the device, including:
The device’s geometry.
The material makeup.
Device durability expectations.
Cleaning methods anticipated (manual, automated, or both).
When device design is more intricate, consider these device-specific challenges in the reprocessing instructions. Manufacturers should be aware that certain device complexities such as unique surfaces, porous materials, mated surfaces, narrow channels, and occluded lumens may increase patient safety risk. These design attributes may warrant additional attention in the development of comprehensive reprocessing instructions.
Project teams may also review or revalidate an existing set of reprocessing instructions for projects such as design change or remediation effort. They will need to consider whether the techniques described can yield passing validation results that meet the current standards, guidance, or latest scientific trends. New design features or historical testing results may not meet the current expectations for validation testing. Adding supplemental instructions may be necessary to address unique design features, or potentially executing a comprehensive rewrite of the reprocessing instructions. This can help to better articulate the directions and ensure a robust design that will result in an effective method — even if not followed exactly.
When validating the reprocessing instructions, the testing laboratory will construct an experimental design that evaluates a worst-case scenario for cleaning instructions, disinfection, and sterilization. They will intentionally expose the device to worst-case variables that are specific to each validation. The worst-case approach is a function of U.S. Food & Drug Administration (FDA) and AAMI literature guidance, which exposes areas where reprocessing directions may fall short. Manufacturers entering these evaluations can minimize room for error by reviewing even the smallest details in their reprocessing procedures. For example, if the instructions call for a brush to be used in the cleaning of the device, manufacturers should be prepared to specify the important attributes about the brush such as shape, size, and material.
Factoring in Guidance Principles to Meet Regulatory Expectations
Testing laboratories tailor the worst-case approach to consider each product and its unique properties. The guidance documents provide principles to consider when validating reprocessing instructions in order to meet a worst-case study design. However, they don’t specifically lay out a direct testing plan for each device type or validation. Companies should be familiar with the applicable guidance documents and the testing variables per validation and then anticipate the expectations of the agencies they will be providing the validation data to.
Validation Principles. AAMI, ISO, and the U.S. FDA provide direction for the various types of reprocessing validations required for reusable devices: cleaning, disinfection, and sterilization. In reviewing these documents, an initial and foundational approach is for the manufacturer to assign a master product or products to represent a product family. Identifying a master product allows manufacturers to streamline validation by testing one product to minimize the entire family’s testing. With proper justification, grouping devices based on materials, indications for use, product design, reprocessing congruencies, and other factors can help save time and reduce costs.
Applying the worst-case approach to applicable variables in each type of validation reveals the robustness of the reprocessing instructions. In steam sterilization, this is accomplished by using a specific challenge organism and reduced exposure times. However, when it comes to cleaning validations, worst-case applies to artificial soils, their application, reduced cleaning parameters, and more. A visual inspection accompanied with chemistry testing for specific analyte residuals determine whether the cleaning methods achieve the acceptance criteria.
Applying Soils. Manufacturers must act as informative partners and work with qualified laboratories to instruct them about the device and help them understand clinical use. The selected soils for testing should represent organic components, inorganics, and viscosity of the clinical use scenario. A clear understanding of a device's clinical setting is critical to this fundamental step. This information then guides the selection and application of a representative artificial soil in order to accurately create simulated use conditions.
The worst-case experimental design must closely reflect the clinical use scenario, so the validation procedures apply the soils correctly to the proper locations in relevant quantities. Without attention to detail, a test bias can occur and skew results, for better or worse. In some cases, device inoculation is not challenging enough to simulate a worst-case representation. Alternatively, some devices could become over inoculated and create an impossible challenge. Leveraging an experienced partner’s expertise can help find the correct balance and save time by avoiding costly retests.
Compromised Cleaning. After determining an inoculation method that will produce a worst-case simulated clinical device, another parameter to adjust is the cleaning process variables. Since cleaning methods are unique to manufacturers and device type, there is no one straight answer on what cleaning parameters to adjust for the validation or by how much.
To demonstrate a worst-case cleaning method, simulate the least rigorous cleaning application that could happen in the clinical setting, such as decreased washing or rinsing times, decreased temperatures, or detergent concentrations. As teams design or edit the cleaning instructions, keep in mind that even when adjusting multiple variables to challenge the cleaning process, the device must still meet the cleaning end-point acceptance criteria.
Measuring Residual Analytes. Testing laboratories must identify the relevant analytes that comprise the artificial soils, which will be the basis for what they will measure to prove adequate cleaning of a device. In the past, log reductions of bacteria were an acceptable primary cleaning endpoint, but regulatory advancements have shifted to more organically relevant analytes. These analytes can include proteins, hemoglobin, carbohydrates, and total organic carbon (TOC).
In some cases, supplementing the two analyte measurements with bioburden reduction may be beneficial; however, the bioburden reduction data can no longer be a primary cleaning measurement. Finding the correct balance between the artificial soil, its application, and the cleaning procedures is an intricate process. When laboratories go too far — or not far enough — with even just one variable, they may compromise the testing, cause delays in the validation process, and prompt questions during a regulatory review.
EU MDR and U.S. FDA. The EU Medical Device Regulation (MDR) is challenging the industry to push the boundaries of evaluating device safety, leading to more comprehensive validation expectations than those that were previously accepted for reusable devices. This advancement of regulation means that manufacturers aiming for product approval under the new terms, especially legacy products with possibly dated submission packages, may need to revalidate and ensure that their technical files meet the latest scientific trends. These trends follow the latest published guidance and standards from ISO, AAMI, and U.S. FDA.
Manufacturers must present a successful cleaning validation accomplished by testing for at least two clinically relevant analytes that comprise the artificial soil along with the visual inspection. By using scientifically justified sample sizes, manufacturers can show repeatability and reproducibility of the process.
Embracing the Best-Case Scenario
Developing or refining reprocessing instructions can be a big undertaking, but those who recognize the potential difficulties that may be ahead and work with competent partners when validation is on the horizon are less likely to have unanticipated testing outcomes. Many testing partners are willing to engage in the development phase and leverage feasibility testing to stay ahead of risks. It is essential to keep timelines on track by identifying opportunities to strengthen the reprocessing instruction before final reprocessing validation.
Creating a safe, effective medical device is an increasingly extensive process. Proactively staying up to date with guidance, validation principles, and regulatory environment requires a keen eye across the entire design verification and validation process.
Companies can maintain productivity in their projects through awareness of testing risks, partnerships with testing experts and compliance with the latest scientific, industry and regulatory expectations. For further details on how to keep up with other new development procedures, read the article “New Regulations, New Timelines: How Chemistry Changed in Response to ISO 10993-18:2020,” in the January 2021 issue of MDB.3
- FDA. (March 2015). “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling, Guidance for Industry and Food and Drug Administration Staff.” Guidance document.
- AAMI, (August 10, 2011). “A Compendium of Processes, Materials, Test Methods, and Acceptance Criteria for Cleaning Reusable Medical Devices, Association of the Advancement of Medical Instrumentation.”
- S. Schaible, “New Regulations, New Timelines: How Chemistry Changed in Response to ISO 10993-18:2020,” Medical Design Briefs, 2021: 09–10, Vol. 11, No. 1, January 2021.
This article was written by Dan Fowler, Principal Scientist at WuXi AppTec Medical Device Testing, St. Paul, MN. For more information, visit here .