Biocompatibility Testing for Surface Medical Devices: An Overview
All medical device companies must subject their products to a volley of FDA-approved tests to establish the safety of their devices. A particular series of these tests measure the biocompatibility of a product where a device/material cannot measure outside of acceptable tolerance ranges in the following "big three" categories: cytotoxicity, sensitivity, and irritation; other tests may be necessary. Furthermore, the types of tests each device must be subjected to vary according to the amount of contact the product has with a patient:
- Case "A" - limited (<= 24 hours),
- Case "B" - prolonged (> 24 hours to <= 30 days), and
- Case "C" - permanent (> 30 days).
Each test is distinct and should be well-understood by anyone dealing with medical devices in any capacity.
The ISO 10993-1 standard lists "surface devices" as a subcategory of products that are in direct contact with the body. This subcategory is further subdivided into three groups: devices that interact with intact skin (latex gloves, stethoscopes, transdermal patches, etc), devices that interact with mucous membranes (such as nasal sprays, intravaginal rings, and contact lenses), and devices that interact with breached or compromised surfaces (including elastic bandages, syringes, surgical instruments, and more). Each group is subject to different testing contingencies. Devices that interact with intact skin usually only require the "big three" assessments whereas the other two groups may, depending on the length of contact, require more extensive testing. Refer to the ISO 10993-1 biocompatibility testing matrix for further information.
The Big Three:
Cytotoxicity tests, along with sensitivity and irritation assessments, count as one of the three measures which are usually mandatory for any medical device to be approved for the market. Cytotoxicity studies examine the cytotoxic ramifications of potential leachables from a device. Type "A", "B", and "C" surface devices must undergo cytotoxicity test. In this assessment, devices/materials are extracted in mammalian cell culture medium (MEM) for 24-25 hours after which the extracts are placed in contact with a single layer of mouse fibroblasts. Afterward, the cells are incubated for 48-72 hours and then, on a scale of 0 - 4, rated for cytopathic effect. A rating greater than two qualifies as a failure.
Sensitization biocompatibility tests measure the effect a device has on inducing a sensitizing or allergenic impact on a patient. For medical devices, an extract of a device is taken and is, in the case of surface devices, applied topically to an animal's skin. The animal is then monitored for signs of skin sensitization 24-48 hours after removal of test extracts.
Irritation assessments indicate the degree to which a device/material induces an irritability reaction. Animal subjects are injected intracutaneously with device extracts and evaluated 24, 48, and 72 hours after administration for signs of irritation such as redness and inflammation.
Devices/materials that interact with either mucous membranes or compromised surfaces usually must be subjected to further toxicological testing. A device's precise testing requirements vary depending on the length of patient contact and other factors that must be determined by trained toxicologists.
Acute Systemic Toxicity
Acute systemic toxicity tests measure the immediate potential toxicological and systematic (remote) effects of any device that makes contact with the interior of the body.
Subacute and Subchronic Toxicity
Subacute and subchronic toxicity measurements are used to determine the toxicological effects of repeated, intermittent exposure to a device or material on a patient.
Genotoxicity assessments test for the presence of mutagens in a material. This is usually accomplished via an Ames test which delineates point mutations in a subject's DNA.
Measures the long-term toxicological effects of material in the body.
Measures the potential carcinogenic effect of material exposure over the lifetime of a test animal.
Medical device and material manufacturers must, from the earliest phases of product development, consider the biocompatibility of their products. Their materials must meet cytotoxicity, sensitization, irritation, and other toxicological standards. To ignore these factors is to risk product disapproval.