Leachable substances of medical devices refer to the general term for substances released by medical devices or materials during clinical use. Leachable substances generally include sterilization residues, process residues, degradation products, monomers and additives in materials (including stabilizers, antioxidants, plasticizers, colorants, etc.). In the process of medical device products coming into contact with the human body and functioning, the leachable substances also cause safety hazards to the human body in the short or long term. Therefore, it needs to be assessed for safety. On the other hand, the safety research of leachable substances is also an important part of the biological evaluation of medical devices, and the results of safety research can also be used to support product or material equivalence determination, stability research, etc.
Guidelines for the technical review of the verification and confirmation of the method for determining the known leachable substances of medical devices
How to evaluate the safety of leachable substances?
First, sufficient information collection should be carried out to obtain information on leachable substances. The collected content generally includes the structure and material composition of the device, information from raw material suppliers, the physical and chemical properties of the materials to be studied/devices and related to leachable substances Document information, equipment production process information, existing historical database information, clinical application information, etc.
It is worth noting that the source of leachable substances may not only be the additives, monomers, and processing aids themselves provided in the device raw materials and process information, in some cases, the hydrolysis, degradation or reaction products of the above-mentioned chemical substances produced during the production, storage and use of devices and their raw materials should also be considered in the risk assessment of leachable substances.
With the improvement of China’s medical device review system, NMPA pays more and more attention to the research data of medical device products, such as the safety evaluation of leachable substances, and has successively issued the "Establishment of Evaluation Methods for Unknown Leachable Substances and Technical Review of Characterization" "Guiding Principles", "Technical Review Guidelines for the Establishment of Allowable Limits of Known Leachable Substances", "Guidelines for the Application of Toxicological Concern Thresholds in Medical Device Risk Management" and other related review guidelines and guidance documents.
CIRS has rich experience in medical device registration, registration testing, clinical trials, and also professional toxicologists and laboratories. CIRS can assist companies in formulating safety evaluation plans for leachable substances and completing safety evaluations.