Medical Device Testing
Biomaterials and polymers are increasingly combined with drugs and biologics. Regenerative products may have medical device–based scaffolding and may be treated as biologics, reflecting the cell and tissue components. Therefore, biomaterials, medical device components, and 3-D printed materials need to be fully characterized for biocompatibility. Biological reactivity tests (see USP <87> and ISO 10993-5 guidances) are designed to determine the biocompatibility of mammalian cell cultures following contact with elastomeric plastics and other polymeric materials with direct or indirect patient contact or of specific extracts prepared from the materials under test.
For medical devices, all biocompatibility and efficacy testing occurs prior to any clinical testing. Being aware of and applying the proper testing standards to development and testing of the device can facilitate entry into the desired national or global market place. Medical devices are characterized using cell culture assay to assess the biocompatibility of a material or extract through the use of mammalian cells. These techniques provide an excellent way to screen materials prior to expensive animal testing.
Per the USP <87> monograph, there are three cytotoxicity tests commonly used for medical devices. The direct contact test is designed for materials in a variety of shapes. The procedure allows for simultaneous extraction and testing of leachable chemicals from the specimen with a serum-supplemented medium. The procedure is not appropriate for very low- or high-density materials that could cause mechanical damage to the cells. Reactivity of the test sample is indicated by changes in morphology, membrane degeneration and lysis of cells around the test material.
The agar diffusion test is designed for elastomeric closures in a variety of shapes. The agar layer acts as a cushion to protect the cells from mechanical damage while allowing the diffusion of leachable chemicals from the polymeric specimens.
The MEM Elution test is designed for the evaluation of extracts of polymeric materials. The procedure allows for extraction of the specimens at physiological or non-physiological temperature. This test may use different extraction media and extraction conditions to test devices according to actual use conditions or to exaggerate those conditions. After preparation, the extracts are transferred onto a layer of cells (typically mouse fibroblast L-929 cells). Following incubation, the cells are examined microscopically for morphology and lysis of the cells.
Recent regulations (ANSI/AAMI/ISO 10993-5:2009) on biocompatibility for devices state that the three qualitative cytotoxicity tests are appropriate for screening purposes, but that quantitative evaluation is recommended. There are several quantitative cell viability assays available such as colorimetric MTT assay, FL staining for live/dead cells, or luciferase based cell viability testing. Our laboratory has cell imaging capabilities that include multi-color Fluorescence (using the Thermo Evos cell imaging platform) or plate based quantitative spectrophotometric analysis using UV/Vis, FL, and luminescence detection (using Molecular Devices platforms). Cell cytotoxicity assays are just one way we can characterize your medical device, or biopharmaceutical product.