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Can you randomly choose analytes to use as end-points for the cleaning validation of a reusable device?

The FDA guidance on reprocessing medical devices in health care settings: validation methods and labeling states, that when performing cleaning validations, the artificial test soil that is chosen should allow for at least two clinically relevant soil components to be quantified during validation testing[1]. AAMI TIR30[2] provides guidance on what soil analytes can be used to determine cleaning efficacy and lists the following possibilities:

  • Protein
  • Carbohydrate
  • Hemoglobin
  • Endotoxin
  • Lipid
  • Bioburden
  • Total Organic Carbon (TOC)
  • Others: Sodium Ion, Adenosine Triphosphate (ATP)

Whereas different options exist for evaluating the cleanliness of a reprocessed device during a cleaning validation, this does not mean that all options are considered equal. For example, FDA does not recommend the use of microbial log reduction testing to determine the effectiveness of a cleaning method, as there is lack of adequate scientific evidence regarding whether removal of microbes directly correlates to the removal of clinical organic soil from the devices1.

Although certain analytes are not recommended, others are strongly preferred. Protein is the analyte most commonly used for evaluating cleaning efficacy2. It is one of the biggest contributors to soil found on medical devices and several assays exist to quantitatively measure protein content. In practice, evaluating protein will almost always be required by regulatory agencies (whether US FDA or EU) and consequently, it will usually automatically be the first analyte to investigate. Other typical components of organic soil include lipids, carbohydrates, and hemoglobin—if the devices are soiled with blood. Therefore, the analytes that are mostly used in addition to protein are hemoglobin when the devices come in contact with blood or TOC when the majority of the soil is not blood based. Given that TOC analysis quantifiably measures all organic carbon, which encompasses liquids and carbohydrates, it is preferred over lipid or carbohydrate testing.

What about Endotoxins?

Although endotoxin is a major concern for medical devices used in sterile body sites, it is not expected to be present in large amounts during normal reprocessing of such devices2. It is therefore rarely tested as an analyte, but may be evaluated for devices that come in contact with the brain, eye, or cerebral spine fluid. In these cases, endotoxins are usually evaluated alongside other analytes such as protein and TOC or protein and hemoglobin as a third analyte.

Analytes as an accurate reflection of the (test) soil

The most important consideration to keep in mind is that the analytes used should be an accurate reflection of the soil the devices will contact during clinical use and should also be present in a considerable amount in the test soil. It does not make sense to test for an analyte that does not accurately reflect the soil the device will be exposed to during clinical use. Similarly, the analytes that are tested must be present in sufficient amounts in the test soil so they may be accurately measured in the validation. For example, at Nelson Labs we will only test hemoglobin when at least 50% of the soil is blood based given that our quantitative assay will otherwise not be able to detect the hemoglobin in sufficient amounts. Other percentages of blood may be added to the test soil (e.g., 10%) depending on the clinical relevance, TOC will be measured in these cases which will cover hemoglobin as well.

In conclusion

The test analytes selected should accurately reflect the soil that is present on the device in a clinical setting and should also be present in sufficient amounts in the artificial test soil to accurately measure. For the vast majority of devices, protein will be the first analyte that is selected. Based on whether or not the device comes in contact with blood in a clinical setting (and depending on the quantity of blood), the second analyte will usually be hemoglobin or TOC.

[1] Food and Drug Administration, 2015 “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling”

[2] AAMI TIR30:2011 A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices

Alpa Patel

Alpa Patel

B.S., RM (NRCM)
Principal Scientist

Alpa Patel is a certified microbiologist and has been part of the medical device industry for 18 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...

Lise Vanderkelen

Lise Vanderkelen

PhD
Pharmaceuticals and Microbiology Expert

Lise Vanderkelen received her Ph.D. from the Faculty of Bioscience Engineering at the University of Leuven (Belgium) in 2012. She started at Nelson Labs Europe in 2013 as Study Director Extractables & Leachables, focusing on parenteral applications, and in 2014, she became responsible for the chemical characterization testing of medical devices (ISO 10993-18). In 2016,...