How to perform medical device sterility testing by EU and FDA requirements

Laura Ahola, Testing Expert at Measurlabs explains how to perform medical device sterility testing by EU and FDA requirements.

Ensuring that medical devices labelled as sterile are truly free of viable microorganisms is paramount for patient safety, and both the European Union and the United States have rigorous legislation in place to achieve this goal. In the EU, the main regulatory framework governing sterility requirements is the new Medical Device Regulation (MDR), while in the US, the Food and Drug Administration (FDA) requires information on sterility as part of the 510(k) Premarket Notification process.

Both frameworks adhere to the same international standards – primarily ISO 11737 – as the basis for performing sterility testing. The process is challenging and consists of multiple steps, including evaluating the bioburden of the device before sterilisation, establishing and validating the required sterilisation dose, and finally assessing the sterility of devices

subjected to sterilisation. Having experienced personnel plan the testing procedure and perform the tests is crucial for obtaining high-quality results.

How is sterility defined and how are medical devices sterilised?

To be considered sterile, medical devices should have a sterility assurance level (SAL) of 10−6 or less, corresponding to a probability of one in one million for a viable microorganism to survive on the device during the sterilisation process. In the US, this requirement is outlined in the FDA’s guidance document on 510(k) submissions for sterile devices, while in Europe it is specified in the EN 556 standard series on the requirements for designating medical devices as sterile.

Medical devices are sterilised by exposing them to either a chemical sterilising agent, such as ethylene oxide or hydrogen peroxide, or a physical treatment, such as heating or radiation. The effectiveness of the sterilising treatment should be assessed at multiple points throughout the process by determining the presence or absence of viable microorganisms on the device.

Sterility testing by ISO 11737

ISO 11737 standards – Part 1 for assessing the bioburden of devices before sterilisation and Part 2 for assessing sterility after devices have been exposed to a sterilising treatment – are classified as harmonised standards for medical devices in the EU and as FDA-recognised consensus standards in the US. Effectively, these designations mean that devices that meet the sterility requirements outlined in ISO 11737 standards are presumed to comply with regulatory requirements on sterility. Additionally, ISO 11737 – Part 3 assesses the presence of endotoxins, which can resist sterilisation and thus must be considered independently if gram-negative bacteria may be present on the device before sterilisation.

Bioburden testing is a necessary preliminary step for sterility testing, as it provides information on the type and number of microorganisms present on the device in a non-sterile state that need to be eliminated through sterilisation. A sterilisation method is chosen by accounting for the characteristics of the device and the microbes that should be eliminated during the process. The sterilisation method must be validated for the device through testing and the minimum sterilisation dose should be verified to ensure effective sterilisation of the device.

Sterility testing is performed next, starting with the selection of a representative sample. Generally, a minimum of three replicate samples are needed to ensure the reliability of the results. An appropriate testing method, chosen from the three outlined in ISO 11737-2, is then selected, again accounting for the characteristics of the device:

1. Direct immersion of the tested product in a culture medium.

2. An elution of microorganisms from the product.

3. Filtration of liquid products to capture the microbes in a filter, which will then be tested.

The direct immersion method is the preferred method and should be chosen if there is no rationale for selecting another method. If the direct immersion method cannot be used, the elution or filtration methods are appropriate. The elution method is used when a solid device cannot be immersed, for example, when it floats due to high

porosity. The filtration method, on the other hand, is applicable for liquid medical devices

ISO 11737 requirements for nonsterile products

An important note is that not all medical devices are required to be sterile. The microbiological safety, however, must be assessed for non-sterile products as well. In this case, safety limits for viable microorganisms are determined based on the intended use of the device, and bioburden testing is used to evaluate the cleanliness of the device against the stated limits. All kinds of devices should be evaluated for their microbiological safety according to the manufacturer’s risk assessment and non-sterile products are no exception.

Microbiological safety and sterility testing are an important part of the risk assessment of medical devices and should be included in the market submission for both FDA and MDR. While the ISO 11737 standard provides a framework for ensuring microbiological safety, assistance from testing experts is recommended if having doubts about the suitable testing method to minimise the risk of having to redo any tests.

“Microbiological safety and sterilty testing are an important part of the risk assessment of medical devices and should be included in the market.