FDA regulatory requirements as follows
- Most of the complex medical device instruments require premarket notification [510(k) or even a PMA (premarket approval)
- 510(k) and PMA Guidance Documents include requirements for reprocessing instructions for the user:
-Detailed cleaning instructions, including disassembly.
-Detailed disinfection & sterilization instructions with specific sterilization parameters.
-Expected end of life & how this can be determined by user.
-Roles and Responsibilities
-21CFR 820.30 Design Controls
-21 CFR 820.70 Production & Process Controls
-21CFR 820.75 Process Validation
EU Regulatory Requirements
-European Medical Device Directive, MDD 93/42/EEC.
-Annex I, Essential Requirements
para 7,8, & 13.6 (h)
-7.3 Design & Development
-22.214.171.124.1 Cleanliness of Product
Instructions for USE need to be developed as follows
- Start with determining intended use.
- Consider intended use during design.
- Obtain FDA guidance documents.
- Obtain & review consensus standards.
- Develop validation protocol.
Determine Intended USE
The Center for Disease Control & Prevention (CDC) recommends disinfection or sterilization based on three end use categories (CDC, 1985):
Devices in direct contact with blood or areas of the body not usually in contact with contaminants. Examples include biopsy forceps, endo cavity probes, and implants. Sterilization is required for these devices.
These devices are non-invasive and normally contact intact mucous membranes. Examples include endotracheal tubes, specula. High level disinfection is a minimum process requirement for these device.
Devices not in contact with patient, or only with intact skin, such as blood pressure cuffs, hospital beds, crutches, etc. High, intermediate, and/or low level disinfection is recommended
Intended USE during design
1 -Cleaning ports -Ease of use.
2- Minimize hard to reach areas.
-Dead ends, rough surfaces, luer locks
-Crevices, hinges, areas between insulation and device
3-Compatibility with cleaning agents & sterilants.
-Chemical disinfectants & sterilants
4-Ease of disassembly & reassembly.
-The easier to do so, the more likely a thorough job.
-Disassembly/reassembly instructions are often lost/misplaced
Obtain FDA guidance documents
Labeling for reprocessing reusable medical devices.
- FDA - Guidance document for washers and washer-disinfectors intended for reprocessing reusable medical devices. June 2, 1998
- FDA - Labeling reusable medical devices for reprocessing in health care facilities: FDA reviewer guidance. April 1996.
- FDA - Questions and answers for the FDA reviewer guidance: Labeling reusable medical devices for reprocessing in health care facilities. September 1996.
- 510(k) guidance for specific devices
Obtain and Review consesus standards
1>ANSI/AAMI ST81:2004 - Sterilization of medical devices-Information to be provided by manufacturers for reprocessing of resterilizable medical devices.
2>AAMI TIR-12:2003 Designing, testing, and labeling reusable medical devices for healthcare facilities: a guide for medical device manufacturers.
3>AAMI TIR-30:2003 – A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices.
4>AAMI ST:2004 – Information provided by manufacturers for the processing of resterilizable medical devices
5>ISO/TS 15883-5:2005 – Washer-disinfectors – Part 5: Test soils and methods for demonstrating cleaning efficacy of washer-disinfectors.
Develop validation protocol
1>Cleaning is the most important activity.
-Often inadequate, hard to confirm cleaning efficacy.
-Definition of cleaning is the removal of visible contaminants. The manufacturer must design the test to demonstrate that a soiled device can be rendered free from contamination to the degree that the device is free of soil. The accepted endpoints depend on the degree of disinfection recommended. FDA has guidance documents on validating sterilization processes8.
-Cleaning must be validated as well as sterilization.
2>Organic material works as a shield to Ethylene Oxide, steam, other sterilants.
-Blood & tissue
-Fluids introduced during medical procedures
Salient Features of cleaning validation
-Reusable devices must be designed to function safely & effectively following multiple cleaning/disinfection/sterilization cycles.
-Most devices composed of cleaning and sterilant tolerant materials will withstand more than 100 cycles
- Testing should be designed to address not only cleaning & sterilization efficacy, but also bio-compatibility & functional performance.
- Not just the sterilization cycles, but the simulated soils added, disassembly must also occur after cycles
-The cleaning process must remove blood, protein, fat, carbohydrates, endotoxins, microorganisms from all joints, lumens, crevices.
-Test soils have been developed to test the efficacy of cleaning as well as testing methods in AAMI TIR 303 .
-No single test soil is appropriate for all medical devices.
-Depends on contact points, mucosa, intact skin, blood pathways, etc.
-For example, intravascular devices should be tested with whole blood and serum.
-Simulated blood or body fluids may be formulated using a mixture of calf serum, dry milk powder, and a 1:1 rabbit blood/saline mixture (Miles, 1991).
-One method proposed by AAMI is to add Geoacillus stereothermopilis spores @ about 104 to 105 organisms.
-The soiled device is then cleaned according the given directions and the remaining spores are recovered & enumerated.
-The recovery technique must be validated prior to determining the efficacy of cleaning.
-Cleaning efficacy can then be determined by subtracting the spores recovered from the device after cleaning from the spores recovered from a control sample (soiled w/o cleaning).
-Ensure the cleaning procedure can be duplicated in the health care facilities.
-A good benchmark bioburden reduction level should show at least a three log reduction. This was demonstrated as possible for flexible endoscopes (Alfa, et. Al, 1999)
- Markers such as protein & carbohydrates can be used to evaluate the cleaning effectiveness.
-Blood cells contain hemoglobin which can be tested from extracts of the device. (Alfa, et. Al, 1999)
-Endotoxins (gram negative bacterial cell wall molecule) are found in tap water & can cause systemic pyrogenic reactions.
-Endotoxin levels extracted from a device can be analyzed by various methods. (ANSI/AAMI ST 72)
-The phenol-sulfuric acid assay can be used to measure both mono and poly saccharides.
-The bicinchonic acid (BCA) protein assay is a highly sensitive reagent for the photometric determination of protein.