Alpa Patel, Principal Scientist at Nelson Labs10.03.22
The Association for the Advancement of Medical Instrumentation (AAMI) recently released the first cleaning validation standard for medical device manufactures, ANSI/AAMI ST98:2022 Cleaning validation of healthcare products—Requirements for development and validation of a cleaning process for medical devices.
This new standard that replaces AAMI TIR30 provides guidance and recommendations for manufacturers on how to design a validation plan to address their processing instructions, which must be specified in their instructions for use (IFU). If a medical device manufacturer is developing and validating a cleaning process for medical devices, then ST98 is required.
Although the standard provides a lot of details regarding validation strategies, there are some things that have been left to interpretation. If these things are not carefully considered, they can impact the outcome of the validation. Some of the significant changes in ST98 are discussed below.
A big change that will be noticed right away is that the sample size for test articles is not specified but has been left to the manufacturer to determine based on the device’s complexity and criticality and the reproducibility of the data. TIR30 previously recommended a sample size of 3 test samples, with 1 positive control and 1 negative control. ST98, however, has allowed the manufacturer to choose the appropriate sample size for their device. Sample sizes of 3, 6, and 9 have been provided as examples. However, justification of sample size will be required for any number selected.
This sounds clear enough, however, if we look at the example provided in ST98 and shown below, we find that the approach to satisfy this requirement will need additional investigations and discussions.
Example:
The data generated in this example has too high of a variability to demonstrate accuracy and precision during the cleaning validation with the selected sample size. The sample size would, therefore, need to increase.
However, two more have been added to the list: total organic carbon (TOC) and Adenosine Triphosphate (ATP). The acceptance criteria for TOC has been set at ≤ 12µg/cm2 and for ATP it has been set at ≤ 22 femtomole/cm2. One thing to consider is that the use of ATP would be most applicable for R&D studies and not for cleaning validations. Furthermore, ST98 specifies that at least two quantitative analytes are required to assess the efficacy of a cleaning process for critical and semi-critical devices. One benefit from ST98 that will give manufacturers a sigh of relief is that non-critical devices are no longer subjected to endpoint testing; visual inspection alone is sufficient. This is a significant change from what was previously expected by regulatory agencies.
Alpa Patel is a certified microbiologist and has been part of the medical device industry for 17 years specializing in cleaning/disinfection and sterilization of reusable medical devices, endoscopes and validation of tissue disinfection or sterilization processes. Her current role as a principal scientist at Nelson, involves overseeing test method validations for reprocessing, writing standard test protocols (STP) and standard operating procedures (SOP) for reprocessing and other internal and globally related documents, providing technical consulting for the Reprocessing sections at Nelson Laboratories in Salt Lake City and globally. Alpa presents at Nelson Laboratories’ seminars, tradeshows, FDA, AAMI, and client facilities across the U.S and International sites.
This new standard that replaces AAMI TIR30 provides guidance and recommendations for manufacturers on how to design a validation plan to address their processing instructions, which must be specified in their instructions for use (IFU). If a medical device manufacturer is developing and validating a cleaning process for medical devices, then ST98 is required.
Although the standard provides a lot of details regarding validation strategies, there are some things that have been left to interpretation. If these things are not carefully considered, they can impact the outcome of the validation. Some of the significant changes in ST98 are discussed below.
Simulated-Use Cycling
Simulated use cycles will be required prior to performing a cleaning validation. This preparatory step challenges the everyday use of a medical device in a healthcare facility, where simulated soiling, cleaning, and sterilization are cycled several times to challenge the cleaning process and ultimate sterility of the device. Although the number of simulated-use cycles that has been recommended prior to ST98 is 6, the language in the standard has now left the interpretation to the manufacturers to determine the suitable number of cycles based on the criticality and specific use of the device.Additional Controls for Test Method
The standard also includes additional test method controls that were not previously specified in TIR30. These controls include a positive sample control and a negative device control. The controls were added to ensure that the validity of test results relates to the analytical test methods utilized for the validation. ST98 also increased the sample size for the positive device control for semi-critical and critical devices from 1 to 3 test samples and added the requirement of performing an extraction efficiency for each one of the samples in the hopes of achieving a >70% extraction efficiency. Although it is not clearly specified how these efficiencies should be applied to the test results, a recommendation has been provided, where averages or lowest recovery efficiency could be used based on the variation of the extraction efficiencies recovered.A big change that will be noticed right away is that the sample size for test articles is not specified but has been left to the manufacturer to determine based on the device’s complexity and criticality and the reproducibility of the data. TIR30 previously recommended a sample size of 3 test samples, with 1 positive control and 1 negative control. ST98, however, has allowed the manufacturer to choose the appropriate sample size for their device. Sample sizes of 3, 6, and 9 have been provided as examples. However, justification of sample size will be required for any number selected.
Interpretation of Test Results
Another notable change affecting cleaning validations will be how the test results should be interpreted. ST98 proposes that a standard deviation be calculated for the test sample results for each analyte tested. ST98 also requests that the standard deviation calculated from the test sample set be applied to the highest result for the test replicate for each analyte tested. If the results fall out of the acceptance criteria specified for that analyte, additional testing, using a higher sample count, will be required.This sounds clear enough, however, if we look at the example provided in ST98 and shown below, we find that the approach to satisfy this requirement will need additional investigations and discussions.
Example:
- The initial sample size for a device is selected as 6 data points, based on device complexity.
- The following data points are generated: 0.9 µg/cm2, 1.1 µg/cm2, 4.5 µg/cm2, 0.9 µg/cm2, 2.3 µg/cm2 and 5.6 µg/cm2 for protein residuals.
- Protein has an acceptance criterion of 6.4 µg/cm2.
- All data points fall below the acceptance criteria.
- The standard deviation calculated from the data points are then added to the highest value (2.0 + 5.6 µg/cm2 = 7.6 µg/cm2) does exceed the acceptance criteria.
The data generated in this example has too high of a variability to demonstrate accuracy and precision during the cleaning validation with the selected sample size. The sample size would, therefore, need to increase.
Additional Acceptance Criteria
One thing that was not affected during the drafting of ST98 was the acceptance criteria for cleaning validations. All the acceptance criteria outlined in TIR30 are still valid for ST98.However, two more have been added to the list: total organic carbon (TOC) and Adenosine Triphosphate (ATP). The acceptance criteria for TOC has been set at ≤ 12µg/cm2 and for ATP it has been set at ≤ 22 femtomole/cm2. One thing to consider is that the use of ATP would be most applicable for R&D studies and not for cleaning validations. Furthermore, ST98 specifies that at least two quantitative analytes are required to assess the efficacy of a cleaning process for critical and semi-critical devices. One benefit from ST98 that will give manufacturers a sigh of relief is that non-critical devices are no longer subjected to endpoint testing; visual inspection alone is sufficient. This is a significant change from what was previously expected by regulatory agencies.
Alpa Patel is a certified microbiologist and has been part of the medical device industry for 17 years specializing in cleaning/disinfection and sterilization of reusable medical devices, endoscopes and validation of tissue disinfection or sterilization processes. Her current role as a principal scientist at Nelson, involves overseeing test method validations for reprocessing, writing standard test protocols (STP) and standard operating procedures (SOP) for reprocessing and other internal and globally related documents, providing technical consulting for the Reprocessing sections at Nelson Laboratories in Salt Lake City and globally. Alpa presents at Nelson Laboratories’ seminars, tradeshows, FDA, AAMI, and client facilities across the U.S and International sites.