ISO 10993-9:2019 Biological evaluation of medical devices – Part 9: Framework for identification and quantification of potential degradation products

ISO 10993-9:2019 Biological evaluation of medical devices – Part 9: Framework for identification and quantification of potential degradation products. The approved study plan for multi-component devices shall take into account each individual component/material and shall consider synergistic effects on the degradation of the different components as well as the possibility of secondary reactions between/among the degradation products. NOTE Degradation can in most cases be modelled by in vitro tests. During degradation pH needs to be controlled to a clinically relevant range, especially if pH can affect degradation product composition. The user needs to be aware that both the degradation rate and amount of generated by-products can be affected if pH is different from that expected for the service environment. 4.4 Characterization of degradation products from medical devices The degradation products produced in the study can be particulate or soluble compounds or ions. Appropriate analytical methods to characterize these products shall be used and reported in the study report. These methods shall be adequately qualified for their intended purpose. If particles are generated, they shall be characterized with regard to size, shape, surface area and other relevant characteristics. Because the physical and chemical properties of particulate materials can change at the nanoscale (approximately 1 nm to 100 nm), this can affect their toxicological properties. For those medical devices composed of or containing nanoscale materials, the user is referred to ISO/TR 10993-22 for a thorough consideration of the impact on the risk assessment of nanoscale products. If biological evaluation of the degradation products is required, then care shall be taken in the design of the degradation study in order to ensure that it does not interfere with the biological assay. Considerations for the degradation study are provided in Annex B. The protocol shall include a) identification and characterization of device and/or material and intended use, b) identification and characterization of possible mechanism of degradation, c) identification and characterization of known, probable and potential degradation products, and d) test methodologies. The extent and rate of release of degradation products depends on variables such as manufacturing processes that alter surface composition and structures; migration to the surface from within the material; solubility in, and chemical composition of, the physiological milieu; etc. 5 Study report The study report shall include the following information, where relevant: a) description of material(s) or device (see 2), including intended use and nature of body contact; b) description of proposed...