Biocompatibility testing is a critical part of the regulatory approval process for medical devices as even the best-designed products could produce unintended complications if the materials used, cause a biological reaction in the patient. An integral part of biological risk assessment, biocompatibility testing assesses the compatibility of medical devices with the biological system. It studies the interaction between the device and the various types of living tissues and cells that are exposed to the device when it comes into contact with patients.
Almost all medical devices that come in contact with human tissue require biocompatibility testing.
Endpoints of Biocompatibility
Depending on the nature and duration of exposure of the device on the host tissue, the biological endpoints of the device are evaluated. These endpoints can include cytotoxicity, irritation, sensitization, systemic toxicity, pyrogenicity, hemocompatibility, implantation, genotoxicity, carcinogenicity, and reproductive toxicity.
Importance of Biocompatibility testing
The human body’s immune system is complex, so materials can produce a toxic response in the short term, long term, or when combined with other materials. For that reason, biocompatibility testing is critical for all classes of medical devices that come in contact with the human body to ensure that the device fulfils its intended use without any biological risks to the user. Biocompatibility testing is a critical part of the regulatory approval process for medical devices as even the best-designed products could produce unintended complications if the materials used, cause a biological reaction in the patient.
Identifying the required Biocompatibility tests
FDA recognizes the standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process,” which provides information on evaluating the biological response to medical devices, such as considering the physical and chemical characteristics of device materials and the nature, degree, frequency, and duration of device exposure to the body.
FDA clears only the finished medical device and not the individual materials used for the manufacturing of the device, so the risk assessment should evaluate the materials used in the device, and also the processing of the materials, the manufacturing methods (including the sterilization process), and any residuals from manufacturing aids used during the process.
The risk assessment should also consider the proposed clinical use of the device, including the anatomical location, duration of exposure, and intended use population. Once it is determined that the device needs biocompatibility tests. identification of the required biocompatibility tests can be done by first finding the biological endpoints of the device that needs evaluation. The biological endpoints can be found with the help of the FDA modifies matrix based on the nature and duration of contact of the medical device with the human tissue. Different biological endpoints may require evaluation for a particular medical device, including additional or fewer endpoints than indicated in the matrix.
Biocompatibility tests are required in the case of all medical devices that come in contact with human tissue. However, a device or device component that has no direct or indirect contact with the body (for example, stand-alone software or database), does not require biocompatibility testing. The most important parameters to consider while going for biocompatibility testing are the chemical and physical nature of its component materials. the types of patient tissue that will be exposed to the device and the duration of that exposure.
Biocompatibility tests can be performed both in vitro and in vivo (in animals). Biocompatibility tests done on animals helps in determining if the device is compatible or safe to use in an animal’s body, this is completely different from the performance tests of the medical device conducted on animals. In the case of performance testing-animal, the goal is to test if the device is functioning as it is supposed to and is fulfilling the intended use.
The nature of the biocompatibility information needed is determined by the intended use and the materials used in the manufacture of the new or modified device. Some devices are made of materials that have been well characterized both chemically and physically and have a long history of safe use. Therefore, it may not be necessary to conduct testing for all endpoints outlined in ISO 10993-,1 provided that materials and manufacturing information demonstrate that there are no new biocompatibility concerns.
If the materials, manufacturing processes, and intended use are not identical to those in the legally marketed device(s), or if manufacturing information is not available for a comparator device, additional biocompatibility information should be provided. Any biocompatibility information, including any testing, should be well organized, complete, and included in a separate, identified biocompatibility section.
The 510k submission for devices that undergo biocompatibility tests must contain a list of patient-contacting device components and associated materials of construction, including identification of color additives if present along with Test protocol (including identification and description of device), methods, pass/fail criteria, and results provided for each completed test.
Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process” https://www.fda.gov/media/85865/download
Special Considerations for 510(k)s https://www.fda.gov/medical-devices/premarket-notification-510k/special-considerations-510ks#bio