Pyrogen and Sterility Testing for Medical Device Quality Control

August 14, 2026

Pyrogen and sterility tests are two crucial microbiology tests for the quality control (QC) of medical devices. For some devices, these tests can be performed simply. A device can be tested for pyrogens by being immersed in Lysate Reagent Water (LRW) or saline solution. The eluate would then be tested to ensure the device contains < 20 EU/mL of endotoxins for devices that contact the bloodstream, and < 2.15 EU/mL per device that contacts cerebrospinal fluid.¹ Since endotoxins are the most potent and resilient pyrogen, many pyrogen testing requirements are fulfilled by the Bacterial Endotoxin Test (BET). In a similar manner, the device can be directly inoculated into a growth media, and the resulting 14-day incubation with no growth would confirm sterility.² However, the extraction and testing needs of many medical devices require a more comprehensive testing strategy.

Pyrogen Testing for Medical Devices: Challenges and Solutions

For pyrogen testing, several factors can result in the need for a more accommodating endotoxin extraction, including surface characteristics and size. If the surface is not hydrophilic, a water-solution will not be effective. Since BET samples need to be aqueous, a specialized extraction solution that can adhere to the device walls and also test suitably with the BET may need to be used. An example being the Endotoxin Extraction Solution from FUJIFILM Biosciences. This solution contains human serum albumin (HSA), which can effectively remove endotoxins from several surfaces that cannot be soaked by water. Once the extraction is established, the testing can continue as normal.

Some medical devices may be too large or irregularly shaped. As guidance requires the medical device to be submerged, this can become a problem for two reasons. First, a large medical device with a set endotoxin limit may require so much extract that the resulting endotoxin limit for the eluate would be too low for a conventional endotoxin test. Second, the device might not fit a conventional container, making a clean, effective extraction difficult.

Disassembling or washing medical devices is a mitigating strategy. Guidance allows cutting or disassembling irregular devices to allow them to fit into the extraction vessel. However, careful prevention from environmental or contact contamination is imperative. Depyrogenated tools are required, and appropriate handling and environmental controls of endotoxin should also be used during this process.

Rinsing can also be used to perform the endotoxin extraction. Constant agitation is needed for continuous rinsing and extraction of the entire device. An object that cannot be immersed due to size will need to be appropriately rinsed. Rinsing is also a strategy to reduce the amount of extract needed. The reduced volume will allow a higher endotoxin limit and more flexible testing options.

There are several test methods for the client to select based on the customer’s needs. These methods can accommodate needs such as required test sensitivity, time, number of samples needed, and cost per test. FUJIFILM Biosciences provides endotoxin test reagents and instruments for the lowest sensitivities of all test methods, as well as sustainable and related reagents and accessories to ensure the suitability of any sample of the desired test method.

Sterility Testing for Medical Devices: Challenges and Solutions

For sterility testing, the size of the product is also an issue that may need to be overcome. Unlike endotoxin testing, performing an extraction and then sampling the eluate is not a suitable method. The entire media sample used to immerse a medical device needs to be tested for sterility. However, there are other strategies that can be used.

First, although the entire extract would need to be tested, guidance allows for a sample item portion (SIP) to be tested instead of an entire medical device. An appropriate SIP size can be calculated based on the medical device’s dimensions. The portion used should be representative of the potential bioburden of the device, and the suitability of this method will need to be evaluated.³

Second, an extraction method, similar to the method for endotoxin testing, can be used for microorganism extraction. The device needs to be immersed in an appropriate liquid that will collect microorganisms. This liquid then needs to be filtered and then inoculated in growth media and tested for sterility. If this method is used, the recovery efficiency should be established to confirm the test is effectively mitigating associated risks associated.⁴

An additional issue that is unique to traditional sterility testing is the need for a several day incubation period. This extended time can be a limitation for medical devices, such as allografts and custom implants, that have a short time from manufacture to administration.⁵

Regulations allow for rapid methods to be used in these situations. One rapid technology is RiboNAT Rapid Sterility Test, which uses the nucleic acid test method. This method can detect < 10 CFU/mL within a single day by isolating rRNA after both anerobic and aerobic incubation while also detecting both fungal and bacterial RNA sequences using real-time, reverse transcription PCR. This method can be used to test the eluate from a medical device immediately without the need for a long incubation time, allowing same-day results.

Conclusion

There are several ways to conduct QC testing for medical devices depending on the goals and workflow of the lab. To learn more about how FUJIFILM Biosciences can enhance your testing strategy, visit the Pyrogen and Sterility Testing landing page.

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