Elina Tenhunen

A biological evaluation plan (BEP) is a critical part of assessing the safety of a medical device. It involves a detailed examination of various aspects such as the device's design & structure, its material composition, manufacturing process & potential contaminants, the intended use, existing test results, and clinical history. The BEP ensures that the device undergoes sufficient biocompatibility testing, with parameters selected from the ISO 10993-1 standard. As a manufacturer, you will need to have a BEP during the regulatory approval process to demonstrate the safety of your medical device. The BEP should be developed during the initial design phase of the medical device. At this stage, manufacturers can identify potential biological risks associated with the device's intended use, materials, and components. A new BEP or updates to the existing one may also be needed if changes are made to the device's design or material composition at a later point. At Measurlabs, we can provide a BEP for a range of medical devices while also guiding manufacturers throughout the process. Do not hesitate to contact us if you are developing a new device, seeking regulatory approval, making changes to an existing product, conducting post-market surveillance, or performing preclinical testing.  We are also happy to create an offer for biocompatibility testing according to the BEP, as well as a biological evaluation report (BER) to summarize the results of the biological evaluation.

The term bioburden describes the presence of microorganisms on a product, raw material, or surface. Bioburden testing plays a crucial role in the quality control of medical devices, pharmaceutical products, and their components. This analysis follows the ISO 11737-1 standard to detect populations of viable microorganisms on a product before sterilization, indicating the microbiological cleanliness of the product. ISO 11737-1 is recognized in the EU as a harmonized medical device standard and by the FDA as a consensus standard. This makes it the recommended way to evaluate bioburden under the EU MDR and the FDA 510(k) premarket submission process. This example testing package includes the following: Testing of 3 identical specimens, Detecting the presence of aerobic bacteria and fungi (yeasts and molds), Validating the bioburden determination technique, Results expressed as total CFU/test product (CFU=colony forming units). We can also offer custom bioburden test packages, especially for customers with large annual sample volumes. Please ask our experts for a quotation and estimated turnaround time.

MEM elution is a qualitative study to determine the cytotoxic properties of medical devices. It is often performed together with a quantitative test, such as the MTT or XTT assay. In the test, mammalian fibroblast cells are grown in a serum-supplemented minimum essential medium (MEM). Once the cells have been cultured, medical device extracts are introduced. After incubation, the overall health of the cells is visually observed under a light microscope and assigned a grade between 0 and 4, based on the extent of cellular damage. Grade 3 (moderate reactivity) or greater is considered a cytotoxic effect.

The MTT assay is a quantitative study to determine the potential biological reactivity of a mammalian cell culture in response to a medical device extract. It is one of the in vitro methods outlined in standard ISO 10993-5 for evaluating the cytotoxicity of medical devices. For the assay, the test item is extracted in cell culture medium, and the cells are grown in tissue culture plates and exposed to the test item extract. The plates are incubated, after which cell viability is assessed by measuring the conversion of the yellow MTT by the mitochondrial reductase enzymes into blue-violet insoluble formazan.  As only viable cells convert MTT into formazan, the number of viable cells correlates with the color intensity of the resulting cell culture, which is determined by photometric measurements. The medical device is considered non-cytotoxic if 70% or more of the cells are viable when compared to a control sample.