Medical Device Testing: Start With a Strategy and Plan
Most medical device manufacturers must first receive approval from the U.S. Food and Drug Administration (FDA) before they can market a medical device. Device manufacturers must demonstrate that their device is safe and effective for the intended application. The tests that must be performed vary with the device, application of the device, and components of the device, such as coatings, as well as the length of time that the device may be used in a patient. To prevent delays in the FDA review process, manufacturers must ensure that they complete the necessary tests and avoid wasting time on tests that are not required or do not add to the assurance of safety of the product.
A provider of full, life-cycle testing services for medical devices, such as Nelson Laboratories of Salt Lake City, UT, can help formulate this plan to determine which tests a specific type of device may need. Many medical devices are unique and could require individualized or niche testing to get to market. The tests listed in this article are some of the most widely used.
Biocompatibility
Biocompatibility analyses consist of several defined tests including: sensitization, cytotoxicity, hemocompatibility, irritation, and systemic toxicity. These preclinical biocompatibility tests provide a degree of confidence about how a device will react when used in the human body.
Sensitization: The sensitization test evaluates whether or not the device, or a device extract, will elicit an immune system reaction from repeated exposures. The test uses guinea pigs, the animal model that most closely mirrors the reaction of humans to an immunizing substance. The test is performed by repeatedly exposing the animals to device or device extracts followed by a rest period to allow antibody production, and then a challenge to determine the presence of antibodies.
Examples of materials that can cause allergic reactions from second or subsequent exposures include detergents, solvents, adhesives, and biodegradable polymers. Initial exposure produces no response, but after the body has been exposed to an allergen, it makes an antibody that can cause dangerous, even life-threatening reactions from subsequent exposures.
Cytotoxicity: Cytotoxicity is arguably the most sensitive of the biocompatibility tests. It is a basic in vitro test that uses mammalian cells in culture to respond to any cytotoxic material present in the device or that can be extracted from the device. Cytotoxicity tests may include elution tests, which employ device extracts, or may be performed directly on cells with the agar overlay procedure. The cytotoxicity test is used as a finished device test as well as a device component screen, and is often used for monitoring each incoming lot of raw material.
Irritation: Irritation tests are performed on rabbits. Extracts of the device are injected into the skin and monitored for irritation reactions, typically redness, swelling, or both. This test allows manufacturers to determine if any toxic materials are leaching off their devices at levels that can be detected in a live mammalian system.
Hemocompatibility: If a device is designed for direct or indirect contact with circulating blood, it needs to be tested for blood compatibility. Hemolysis tests are performed by exposing the device or device extract to mammalian (typically human or rabbit) red blood cells. Blood cells and test samples are incubated together for sufficient time to allow any hemolysis to occur. The cell containing liquid is then analyzed for the presence of hemoglobin that cannot be removed by centrifugation. If the cells were unaffected by the device or extract, centrifuging the cells from the mixture will result in little or no hemoglobin in the supernatant fluid. This is a passing result. If hemolysis occurs, manufacturers must determine if the level of hemolysis is significant. This often requires comparison of the device under test to a predicate (already on the market) product with the same claims or usage.
Based on device design and application, additional blood compatibility tests may be required; including coagulation/thrombogenicity, complement activation, implantation, systemic toxicity, cytogenetic tests such as Ames, mouse lymphoma, or chromosomal aberration tests. Devices used in specific areas of the body often need tests designed to simulate the intended use. These would include eye irritation or mucosal irritation tests.
Chemistry
Chemistry tests are usually basic and are designed to determine if the polymeric or other device component received is the one that the FDA was told would be in the device. Chemistry tests are also valuable to characterize new materials to determine the level of extractables or residual manufacturing materials present.
USP Physicochemical series: This series of tests is used to characterize leachable substances. These tests include heavy metals, non-volatile residues, residues on ignition and materials that may change the pH in the body (buffering capacity). These tests are described in the compendia and have defined acceptance criteria. Their intent is to reduce risk when employed in new applications.
Identification tests: Identification tests include Fourier Transform Infrared (FTIR) and differential scanning calorimetry (DSC). FTIR is used to confirm the identity of a polymeric material and DSC characterizes the thermal events that may be significant such as the glass transition point (Tg).
