As devices become more complex, biocompatibility and material evaluations must necessarily become more complex and thorough as well. Allergic and immunogenic reactions are a serious safety concern not only for pharmaceuticals, but because of increasing device complexity, they are also an emerging concern for devices. In the past, evaluation of devices looked only at allergic potential (not at immunogenicity), and was done by looking for sensitization to the device itself. This testing - for a delayed-type of hypersensitivity in guinea pigs - is still required for all devices.
Complex and Novel Materials Require More In-Depth Testing
However, it has become more common to see devices comprised of engineered biomaterials (such as stents coated in collagen or using other biologically-derived scaffolds.) Drug/device combination products pose novel immunogenicity safety concerns – for example, nano-particles often combine natural or synthetic polymers with drugs. Nano medicines such as liposomes, carbon nanotubes, dendrimers, and polymer conjugated proteins have physical, chemical, and biological properties that may attract the attention of the immune system.
These complex devices, and those containing novel materials (e.g., plastics, polymers, metals, ceramics, biological materials) or devices that are lacking adequate testing for immunotoxicity, should also be tested for additional immune responses.
It becomes important to evaluate immunogenicity because the results of an immunological response can be so serious. Immunological effects include inflammatory responses, immunosuppression, immunostimulation, or autoimmune responses.
Performing Immunogenicity Testing of Devices
Testing for immunogenicity may involve animal implantation studies followed by analysis of serum for changes in total circulating IgG, and/or antigen specific responses by ELISA. Hemocompatibility testing should include measurement of complement activation. This can be performed in vivo or in vitro. Device material or extracts are incubated with specially handled human serum and then activated complement cascade proteins are measured by ELISA. Alternatively, serum from animals implanted with the device can be tested for complement activation. These bioanalytical tests provide information to manufacturers and regulators about the safety and biocompatibility of the product.
It is important to identify early whether your device may need an immunogenicity evaluation, and to begin collecting this data along with your biocompatibility data to support your 510(k) or PMA submission. Pacific BioLabs has an experienced staff and is here to help in determining what may be needed for your device.
Additional information can also be found at the FDA website, including a flow chart to determine whether immunotoxicity testing is necessary: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080495.htm