Recent Changes to Reprocessing Validations

for Reusable Medical Devices

GRIFFIN CAMMACK, B.S – EXPERT TECHNICAL CONSULTANT
Reusable Devices
• Reusable medical device: Device intended
for repeated use on different patients,
with appropriate decontamination and
other processing between uses.
– These devices can be invasive, non-
invasive or non-patient contacting

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 Spaulding Classification
Device
Patient Contact Example
Classification

No patient contact or
Non-Critical
intact skin contact

Mucous membranes
Semi-Critical
or non-intact skin

Sterile areas of the

body including blood Critical
contact

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 Process Overview – Reusable Devices

Point of use treatment – Initial treatment to remove

NOT TESTED AS PART OF
Point-of-Use
and/or prevent drying
VALIATIONS – only if its Processing of soil and contamination
mandatory step in the
process
Thorough
Cleaning

Low-, Intermediate-,
Sterilization Disinfection or High-Level

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Overview – Reprocessing Validations
• Updates to Cleaning Validations

• Updates to Disinfection Validations

• Updates to Sterilization Validations

• Lifecycle Validations

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Updates to Cleaning Validations

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 Cleaning Validation Steps

Soiling, Cleaning,
Disinfection/Sterilization

Soiling Cleaning Testing of

Simulated Samples through Extraction Analytes
Use Cycles with Manual or of the (protein,
(6X) Simulated Automated Samples hemoglobin,
Use Test Soil Methods TOC)

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Updates to Cleaning Validations
• Cleaning validations have seen a lot of updates over the last few years with updated and new standards.

• Final Guidance for Industry and FDA Staff: Reprocessing Medical Devices in Health Care Settings: Validation
Methods and Labeling
o Initially published in 2015 and revised in 2017.

• American Association of Medical Instrumentation (AAMI)

o ST98 – This is a new standard that was developed from and replaced AAMI TIR30. ST98 was published in August
2022.

• American Society for Testing and Materials (ASTM)

o F3208 – Updated in 2020
o F3321 – Published in 2019
o F3293 – Published in 2018
o F3438 – Published in 2021

• International Organization of Standardization (ISO)

o 17664-1 and 17664-2 – ISO 17664 was split into two documents (part 1 and part 2). Part 1 covers the requirements
for critical and semi-critical devices. Part 2 covers the requirements for non-critical devices. Updated in 2021.
o 15883-5 – Updated in 2021.

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 AAMI ST98 Updates and Changes Overview
HIGHLIGHTS OF MAJOR CHANGES:

CHANGE AAMI TIR30 - Guidance AMMI ST98 - REQUIREMENTS

Recommendation of 6 simulated use
Simulated use cycles clearly identified Did not have simulated use cycles
cycles
Controls needed for the testing are
Controls needed for the testing were
Controls are defined clearly defined, based on 2015 FDA
not clearly defined
Guidance

Positive control 1 (4 extractions) 3 (4 extractions each)

Extraction Efficiency criterion Not specified >70%

Sample size 3 ? (3, 6, 9)

Results reported without any Standard deviation will be applied to

Interpretation of Final Results
statistical impact the test results

Non-critical devices 2 analyte markers (protein, TOC) No analyte testing

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AAMI ST98 – Simulated use Cycles
• Multiple, sequential simulated use and processing
cycles to simulate soil accumulation shall be performed. Contamination
o Sequential (soiling, drying, cleaning and disinfection
/sterilization (FULL CYCLE))

Manual
• Shall consider all worst-case use of the medical devices Sterilizer
(full range of motion/actuation, cauterizing, heating) Cleaning

6x
• Number of cycles NOT DETERMINED

• Non-critical devices – not needed for cleaning validation

o as we are only assessing soils through visually not impact full Automated
Disinfection
enough Washer
o Risk for HAI is low

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AAMI ST98 – Added Controls from the FDA document to standard
• Controls align with FDA guidance document on labelling and validation methods for
reusable devices, 2015 (2017)
Validation
Control Definition
Type
Negative Device
Test Method Device that is not soiled but cleaned
Control
Device that is soiled but not cleaned. This shall be used to
Positive Device Control Test Method demonstrate that an appropriate amount of test soil was
applied to the devices

This sample control is quantifying low levels of soil (e.g.

Negative Sample
Assay protein) that can be present in the extract fluid. “Extraction”
Control
is conducted with NO DEVICE. This sample is used a BLANK.

Extract that is spiked with a known amount of test soil that is

Positive sample control Assay
close the LOQ of the assay.

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 Sample Size and Controls

Positive Device Positive sample Negative Negative

Test article Cytotoxicity
control control Device control sample control

Sample size
3 samples per
1 sample undefined per 1 sample 1 sample 1-3 devices
ST98*
ST98

Extraction fluid
Testing lowest
extracted in same
Soiled concentration of Soiled Processed processed
container as test
test soil
articles

Unprocessed Processed BLANK

*1 sample for visual inspection only validations

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AAMI ST98 – Positive Device Control – Test Method
• For critical and semi-critical devices, a minimum of 3 positive controls
shall be used
• In some instances, a smaller size can be used however will have to be
scientifically justified

• Extraction efficiency (EE) shall be determined for cleaning validations

• Generally, should be greater than 70% (A.6.5), ISO 15883-5 (4.2.4)
• Should be performed until 10% of the first extraction (A.6.5.2)
• EE Value shall be used to calculate a correction factor to applied to the
test samples

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AAMI ST98 – Sample Size Selection
• Sample size should be determined based on:
• Medical device complexity
• Data reproducibility
• Criticality

• The sample size is deemed sufficient if:

• Minimum number of data points are generated per analyte
• All data points fall below the acceptance criteria
• Allowable variation of results from sample to sample – the standard deviation of the
sample set added to the highest data point does not exceed the acceptance criterion If
these conditions are not met, the number of sample should be increased.

• Previous discussions have alluded to 6 – 9 devices for critical devices.

• Robotic devices
• Flexible or rigid endoscopes
• Surgical instruments

• 3 devices for non-critical (surface contact & non-patient contacting devices)

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AAMI ST98 – Data Reproducibility Example

Standard Deviation Higher than acceptance criteria –

Fail test repeat with < sample size

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 Acceptance Criteria Update
AAMI ST98 ISO 15883-5 2021
Clinically Relevant
Recommended Level Clinically Relevant
Analyte Alert Level Action Level
Analyte
Protein ≤ 6.4 μg/cm2
Protein ≥ 3 μg/cm2 ≥ 6.4 μg/cm2
Hemoglobin ≤ 2.2 μg/cm2
Hemoglobin ≥ 1.0μg/cm2 ≥ 2.2 μg/cm2
Total Organic Carbon
≤ 12 µg/cm2
(TOC) Carbohydrate ≥ 0.9 μg/cm2 ≥ 1.8 μg/cm2
Carbohydrate ≤ 1.8 μg/cm2 Endotoxin ≥ 2.2 EU/device ≥ 20 EU/device
Adenosine ≥ 10 fmoles of ≥ 22 fmoles of
≤ 22 femtomoles/cm2 ATP
Triphosphate (ATP) ATP/cm2 ATP/cm2
TOC ≥ 6 μg/cm2 ≥ 12 μg/cm2

• Critical and Semi-critical – Visual inspection and 2 quantitative analytes

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Non-Critical Devices
AAMI ST98:2022; Section 8 - Endpoints

ISO 15883-5:2021; Section 4.4, Cleaning efficacy test criteria

“Non-invasive medical devices shall require visual examination only.”

ISO 17664-2:2021; Section 6.2, Processing instructions

“NOTE 2 The requirements for cleaning and disinfection are stated as separate clauses in
this document. However, when the steps are concurrent, the requirements of both stages
can be considered as one. In such cases removal of soil, a reduction in microorganisms and
inactivation of viable microorganisms can be achieved as a result of the combination of
applying the disinfecting agent and a physical action..”

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Updates to Disinfection Validations

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Disinfection Validation steps

Contaminating Disinfecting
Testing for
Samples with through Manual Extraction of the
Microbial
Microorganism or Automated Samples
Reduction
(Bacteria) Methods

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 Spaulding Classification for Chemical Disinfection
Patient Device Disinfection
Examples
Contact Classification Level
v
No patient Low-level or
contact or intact Non-Critical Intermediate-
skin contact Level Disinfection

Mucous
High-Level
membranes or Semi-Critical
Disinfection
non-intact skin

Sterile areas of
the body
Critical Sterilization
including blood
contact

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Updates to Disinfection Validations
• American Association of Medical Instrumentation (AAMI)
o TIR12 – This document was updated in 2020.

• International Organization of Standardization (ISO)

o 17664-1 and 17664-2 – ISO 17664 was split into two documents (part 1 and part 2). Part 1 covers
the requirements for critical and semi-critical devices. Part 2 covers the requirements for non-
critical devices. Updated in 2021.
o 15883-5 – Updated in 2021.

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Disinfection Levels and Acceptance Criteria

Critical Devices = Semi-Critical Devices = Non-Critical Devices =

Sterilization – SAL 10-6 High-Level Disinfection Intermediate-/Low-Level
• Mycobacterium – 6-Log Disinfection
reduction • Mycobacterium – 3-Log
reduction
• Four Vegetative Organisms –
6-log reduction separately*

*New requirement in AAMI TIR12:2020.

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AAMI TIR12 – Update to Inoculum Preparation
• The updated AAMI TIR12 instructs to evaluate the four vegetative organisms separately and not in a
mixed suspension.
o Mixed suspensions can engage in competitive inhibition.

Staphylococcus aureus
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa

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 Non-Critical Devices in AAMI TIR12
Minimum
Patient Contact Expected Contamination Disinfection
Level
Intact skin of patient
Intermediate-
or Blood or other potentially infectious materials
level disinfection
Health care personnel
Low-level
None Blood or other potentially infectious materials
disinfection
Intact skin of patient
or
Health care personnel Not blood or other potentially infectious
*visibly clean
or materials
None

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TIR12:2020 – Annex F
• Gives some guidance regarding distinguishing between Intermediate level
disinfection (ILD) and low-level disinfection (LLD).
• ILD
o It is appropriate for use on certain patient care items that contact intact skin and on
environmental or medical equipment surfaces (e.g., adjustment knobs, handles, buttons, or
levers on X-ray equipment, instrument trays and carts, and dental units) which are generally
not intended to come into direct contact with the patient.
o In addition, these environmental and medical equipment surfaces can be touched repeatedly
by health care personnel during procedures involving parenteral or mucous membrane
contact
• LLD
o It is appropriate for use on non-critical devices and equipment surfaces which ordinarily do
not contact patients during routine use and are not expected to be contaminated with blood
or Other Potentially Infectious Materials (OPIMs)

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Sample Size and Controls

Positive
Test article Neutralization Cytotoxicity
control

Undefined
1 sample per AAMI 1 sample 1-3 samples
TIR12

Inoculated Inoculated Processed processed

unprocessed Processed

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Sample Size
• AAMI TIR12:2010 previously gave a recommended sample size of three test replicates (test articles)
and one concurrent positive control.

• AAMI TIR12:2020 removed this sample size recommendation.

o Current industry standard is still three test articles and one positive control.
➢ However, certain more complex devices may require a different sample size (i.e., endoscopes)
o A similar considerations listed in AAMI ST98 can be used for the sample size justification.

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Updates to Sterilization Validations

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Steam Sterilization Validation Steps

Sterility Assurance
Level (SAL) Dry Time
Temperature Profiling
Validation with Validation with full
full cycle parameters
half or full cycle cycle parameters
parameters

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Recent and Upcoming Changes
• AAMI TIR12:2020 - Minimum drying times for steam sterilization were removed from Table B.1 in
Annex B.

• The next revision of ISO 17665 (Sterilization of health care products — Moist heat — Requirements for
the development, validation and routine control of a sterilization process for medical devices) is going
to Final Draft International Standard (FDIS) stage, which is the final stage before it is published.

• ISO 22441 (Sterilization of health care products — Low temperature vaporized hydrogen peroxide —
Requirements for the development, validation and routine control of a sterilization process for medical
devices) has been published and has been recognized by US FDA as a consensus standard.

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Lifecycle Validations

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Is End-of-Life Testing Needed?

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End-of-Life Cycles
• What is the appropriate number of cycles?

Patient use

Cycles?
Disinfection
Cleaning
/sterilization

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End-of-Life Testing

ISO 17664:2017

• MDM must determine if reprocessing leads to a degree of degradation that will limit the useful
life
• MDM must determine the number of reprocessing cycles or other indication of the end of it’s
life

FDA Guidance Document: 2017

• Labeling should inform how many times the device can be reused based on testing
• Provide a mechanism or method to ascertain whether the device has exceeded its use life and
if the device is functioning properly
• Include appropriate disposal

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MDR
• CHAPTER III: Requirements regarding the information supplied with the Device
o Information in the IFU

o Information that allow the user to be informed of any warnings, precautions, measures
to be taken and limitations to use regarding device.

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End-of-Life Testing
• ISO 10993-1:2018 Section 4.7 and 4.8:
o 4.7 The biological safety of a medical device shall be evaluated by the manufacturer over the whole
life-cycle of a medical device.
o 4.8 For re-usable medical devices, biological safety shall be evaluated for the maximum number of
validated processing cycles by the manufacturer.

• MDR 2017, ANNEX I, Chapter I, General Safety and Performance Requirements

(GSPR) #6:
o “The characteristics and performance of a device shall not be adversely affected to such a degree
that the health or safety of the patient or the user and, where applicable, of other persons are
compromised during the lifetime of the device, as indicated by the manufacturer, when the device
is subjected to the stresses which can occur during normal conditions of use and has been properly
maintained in accordance with the manufacturer's instructions.”

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 Standards for Reprocessing
• AAMI • ASTM • ISO
• AAMI ST98 (cleaning validation) • ASTM F3208 (test soils) • ISO 17664 (cleaning/disinfection)
• AAMI TIR12 (cleaning, disinfection, • ASTM F3293 (application of test • ISO 17665 (sterilization)
sterilization) soils)
• ASTM F3438 (Analytes test • ISO 15883 (washer/disinfector)
• AAMI ST58 (HLD &Chemical sterilization) method)
• TIR68 (ILD,LLD) • ASTM F3321 (Extraction test
• AAMI TIR34 -ST108 (water for soils for cleaning)
reprocessing)
• AAMI ST84 (Flexible Endoscope)
• AAMI TIR99 (TEE, dilators)
• AAMI ST79 (Steam sterilization)

2015 FDA Guidance document on validation methods and labelling (R2017)

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Griffin Cammack, B.S.

Expert Technical Consultant
Nelson Laboratories, LLC
801-290-7535
[email protected]

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