Validation of cleaning and sterilization of

reusable medical devices

MG-FSI72-119

Last revision: June 2012 Aurélien BIGNON

5, Chemin du Catupolan - 69120 Vaulx en Velin - France - Tel. 33 (0)4 72 81 22 62 - Fax : 33 (0)4 72 81 22 72

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MEDICAL LAB Established in 1989, MedicalGroup presently has five subsidiary companies specialising in the biomedical field: MedicalCoating, MedicalPackaging, MedicalBiomat, MedicalManufacturing and MedicalLab. All of these organisations are EN ISO 13485 certified. MedicalLab is a lab specialized in tests on medical devices: microbiological tests, composition and structure analysis of implant materials and coatings, static and dynamic mechanical tests on implants and coatings, cleaning, packaging and sterilization validation…

VALIDATED CLEANING AND STERILIZATION INSTRUCTIONS FOR REUASABLE MEDICAL DEVICES Reusable medical devices come in various shape and size. The design of these instruments, which are more and more complex, aims at helping the surgeons in their task, but cleaning and sterilization of these device should also be taken into account. Manufacturers of reusable medical devices shall provide validated cleaning and sterilization instructions with their product to ensure that their product can be properly cleaned and sterilized in health care facilities. Cleaning a device is the critical first step in reprocessing any device after it has been used on a patient. Failure to remove foreign material (e.g., soil, lubricants, microorganisms, organic and inorganic materials) from both the outside and the inside of the device can interfere with the effectiveness of subsequent disinfection and/or sterilization. Contamination of a variety of reusable devices and instruments (e.g., surgical instruments, ophthalmic instruments, laryngeal mask airways, endoscopes) are causes of concern for patient safety from cross-contamination between patients. Cleaning is normally accomplished by manual wiping, brushing, or flushing or by using mechanical aids (e.g., ultrasonic cleaners, washer–decontaminators, washer–sterilizers) in conjunction with water and detergents to remove foreign material.

There are few tests that can be used to verify cleaning. To verify cleaning of a given device, one must have a test soil and a quantitative test method for detecting residual soil after cleaning. In addition, manufacturers must consider:

a) that exposure to chemicals, such as cleaning agents, could alter the material used in the device;

b) whether the materials of construction will absorb or adsorb chemical agents, which could then gradually leach from the material over time;

c) how cleaning processes could affect the function of the device; and d) that cleaning processes and tools must be able to contact all areas of the device that

could become contaminated.

In general, reprocessing reusable medical devices involves three steps: 1. First, reprocessing begins at the point of use, which includes initial cleaning and

measures to prevent drying of soil and contaminants in and on the device. 2. Second, the device is thoroughly cleaned in the dedicated cleaning area. 3. Third, depending on the intended use of the device, the device will be disinfected or

sterilized, and routed back into use.

STANDARDS AND REGULATIONS Recently, the U.S. Food and Drug Administration (FDA) began requiring additional information on 510(k) concerning validation of cleaning and sterilisation of reusable medical device. A draft guidance was published on this subject in May 2011. It states that: “Manufacturers of reusable medical devices should provide adequate labeling that includes instructions for reprocessing and reusing devices safely. The labeling should provide sufficient instructions on how to prepare the device for the next patient use. The user should be able to follow these instructions because they should refer to materials and equipment available to device users. The manufacturer should maintain in the Device Master Record and/or design history file as appropriate, documentation of tests that were performed to demonstrate that the instructions are complete and understandable and can reasonably be executed by the user. The users should ensure that they have the facilities, equipment, and easy access to manufacturer-specified sterilization/disinfection agents to execute the instructions, and that the instructions are followed for every patient use of the device.” In Europe, 93/42/EEC directive states that: “Where appropriate, the instructions for use must contain the following particulars: […] if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, packaging and, where appropriate, the method of sterilization of the device to be resterilized, and any restriction on the number of reuses” Below is a list of applicable documents for validation of cleaning and sterilization of reusable devices: FDA Draft Guidance: Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling (March 2, 2011) AAMI TIR30 (2003): A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices AAMI TIR12 (2010): Designing, testing, and labelling reusable medical devices for reprocessing in health care facilities: A guide for medical device manufacturers

VALIDATION OF THE CLEANING PROCESS FDA admits that “although many FDA-recognized consensus standards related to medical device sterilization are currently available, no standards and no dedicated guidance is currently available related to medical device cleaning.” FDA instructions for this validation are:

- To use soils that are clinically relevant to the type of device. - To use the worst case (least rigorous) implementation of the cleaning process, - To use medical devices that represent worst case (most contaminated) test devices.

Predetermined cleaning test endpoints shall be specified. Validation protocols should be designed to establish that the most inaccessible locations on the devices can be adequately cleaned during routine processing. For all testing, a statistically significant number of replicate samples shall be chosen. This last recommendation of FDA, is not always easy to follow when validation is done on complex and expensive reusable medical devices. 1. PRODUCT FAMILIES

Before starting validation, product families shall be carefully established taking into account:

- The device shape and size - The materials constituting the device - The soils in contact with the device - The cleaning cycle(s) to be validated - The sterilization cycle(s) to be validated

2. ARTIFICIAL SOIL - INNOCULATION The manufacturer should select an artificial test soil composed of a formulation that includes or accurately represents all materials that the device would likely be subjected to during an actual clinical use, and would create the greatest (worst case) challenge to the cleaning process. FDA does not recommend the use of spore log reduction testing as a method to determine the effectiveness of the cleaning methodology. It is unclear whether or not the removal of bacterial spores directly correlates to the removal of clinical organic soil from the devices. Such testing only indicates how well a process reduces spore count, and provides no information on any other component of organic soil. AAMI TIR 12 provides different type of possible soils. Eg: Hucker’s soil: Peanut butter 10g, butter10g, milk 15ml, printer’s ink 20 drops, blood 1g, flour 10g, lard 10g, saline 3ml, egg 10g. This soil presents the advantage to represent all the different kind of product to clean (protein, blood, etc…) Soil inoculations should mimic worst case clinical use conditions.

- FDA recommends using the artificial soil to inoculate the device in all locations likely to contact patient materials, including all locations that are difficult to clean.

- Simulated use conditions for the validation studies should be device specific. Simulated use conditions should account for real world use conditions, to mimic worst case clinical use, for example, the worst case duration of clinical exposure.

- All functional procedures (articulations, flexures, manipulations) for which the device is intended to soil the device shall be conducted to represent worst case conditions. If the device is likely to be repeatedly subjected to "pushing" soil into a hard to reach area during use, validation soiling should include repeated soiling to adequately reproduce the "worst case" use situation.

- If after use of the device, drying of soil might occur and cleaning might not be performed immediately after use, the validation methods should allow soils to dry for a length of time that simulates worst case (longest duration).

3. CLEANING PROCESS The cleaning validation protocols should specify the shortest times, lowest temperatures, weakest dilutions, etc., for each step of the cleaning instructions. Examples of worst-case scenarios:

• If the cleaning instructions recommend a 10 to 20 minute pre-soak, the validation protocols should specify 10 minutes or less.

• If the cleaning instructions advise the user to manually clean at 45ºC ± 5ºC, the validation protocols should specify cleaning at 40ºC or less.

• If a device consists of several components to be disassembled for adequate cleaning, examine what will result if the device is not disassembled or is incompletely disassembled.

• Enzymatic Detergents: In general, “worst case” implies shortest times, lowest temperatures, etc. A noteworthy exception to validation at lowest temperature would be the enzymatic detergents, which typically have “optimally effective” temperature ranges. Validation protocols should adequately address the temperature range specified in the cleaning instructions for enzymatic detergents.

• Medical Washers/Disinfectors: If your process validation uses automated medical washers/washer disinfectors or ultrasonic cleaners, your worst-case should include the worst extremes of the intended cycle parameters.

4. TESTING AFTER CLEANING – ACCEPTANCE CRITERIA FDA recommends that you use a quantitative test method capable of measuring meaningful levels of clinically relevant soil to meet a related, predetermined cleaning endpoint. Many potential test methods exist for the evaluation of organic soil contamination, and the effectiveness of cleaning processes. AAMI TIR 30 provides a summary of what is available in the literature. Examples of possible tests are: Hydrocarbon oil index as per ISO 9377-2: Water quality — Determination of hydrocarbon oil index — Part 2: Method using solvent extraction and gas chromatography Bioburden as per ISO 11737-1: Sterilization of medical devices -- Microbiological methods -- Part 1: Determination of a population of microorganisms on products Protein rate as per ISO 15883-1: Washer-disinfectors -- Part 1: General requirements, terms and definitions and tests Endotoxine LAL test as per European Pharmacopoeia §2.6.14 Devices should be subjected to a validated method of extraction for testing. Exhaustive extraction is a commonly used method, and extraction using a known quantity of inoculum is also common (but has some procedural limitations). Extractions and calculations should address all hard to

clean internal surfaces (such as lumens), and worst case soiled surfaces (such as mated surfaces that have been soiled repeatedly or under pressure). Acceptance criteria shall be defined. Examples of acceptance criteria are:

• HCT rate < 1.8µg/cm² (AAMI TIR 30) • Reduction of at least a 3log10 in recoverable bacteria (total aerobic bacterial count)

(AAMI TIR 30) • Protein rate ≤ 3 µg/device (ISO 15883-1) • Endotoxin ≤ 2.2 EU/cm² (AAMI TIR 30) • No visible soil after cleaning • …

VALIDATION OF THE STERILIZATION PROCESS Sterilization shall be validated according to available standards. The most used sterilization method in healthcare facilities is moist heat. In this case, validation shall be conducted as per: ISO 17665-1: Sterilization of health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices The goal of this validation is to ensure that the sterilization process can inactivate the standard number of 106 thermo-resistant micro-organisms Geobacillus stearothermophilus on a group of 3 sterilized devices (inoculation in the critical location of the device). Then the group is exposed to the sterilization agent during a specified period and sterility tests are performed on the devices. This treatment is repeated three times in order to validate the sterilization reproducibility. After this validation, the official duration of the sterilization process will be doubled in order to ensure the sterilization process.

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DESIGN: QUESTIONS TO ASK

What are the guidelines and recognized standards in the countries targeted for product sales?

Will my reusable medical device be easy to clean?

What are my product families?

How many samples will be needed for the validation?

What type of soil will be in contact with the device?

What part of the device will be in contact with the soil in real life clinical use?

What are the worst case conditions for clinical use?

What are the worst case conditions for cleaning?

What type of cleaning agent will be available in healthcare facilities?

What type of sterilization will be available in healthcare facilities?

Will the materials of the device resist to repeated cleaning and sterilization?

What is my recommended cleaning procedure?

What is my recommended sterilization procedure?

REASONS FOR CHOOSING MEDICAL LAB

Acknowledged expertise in medical device testing, and French, European, Chinese and US standards and regulations

A full service partner offering training, assistance in establishing validation protocols and testing services

An efficient ISO 13485:2003 quality control system

ISO 17025 accredited lab (by COFRAC, www.cofrac.fr)

A multilingual sales team (English, German, Italian, Spanish, Arabic, Chinese…)

Our experts can assist you with your regulatory processes, and help you determine validation protocols

Our collaborative interaction with the MEDICAL GROUP helps you limit your suppliers, save time in having your batches released and reduce your transport costs

Fast communication of results (by e-mail or on our website)

CONTACTS

Aurélien BIGNON MedicalLab General Manager a.bignon@medicalgroup.fr

Alice MARTINHO Manager of

test department a.martinho@medicalgroup.fr

Régine GRIES Quality Control Director r.gries@medicalgroup.fr

OUR SALES TEAM

Alain BRUNEL Sales Manager

a.brunel@medicalgroup.fr

Rachid ZEROUALI Export Sales Manager

r.zerouali@medicalgroup.fr

Richard PUZENAT Sales Manager (France)

r.puzenat@medicalgroup.fr

MedicalGroup World Wide

5, Chemin du Catupolan - 69120 Vaulx en Velin - France - Tel. 33 (0)4 72 81 22 62 - Fax : 33 (0)4 72 81 22 72