Guideline For Evaluation Of Raw Material Changes For Passive Medical Devices (Draft)
2021-06-22
Feedback form (download) Guideline for Evaluation of Raw Material Changes for Passive Medical Devices After approval of medical device products for marketing, the registrant is required to change the manufacturing, raw material, production method, testing method and quality control frequently to improve product quality. The establishment of an effective change control procedure y the licensee is the key to ensuring continuous improvement of the production management system to achieve high quality products and is also an important link in the quality management system of medical devices. According to quality management system requirements, the licensee should complete a comprehensive evaluation of the possible impact on the change on the final medical device product and implement effective change control to mitigate the risk to an appropriate level. In general, change control programs include initiation, analysis, review verification, confirmation, approval and change implementation; and the analysis, verification and confirmation of the different changes are an essential part of industrial work and review. Similarly, such work and review are the foci of technical review. As raw materials are essential for medical products to achieve their function, and are essential to ensure safety and effectiveness, the change control related to raw materials for medical device products is especially important amongst all types of change controls. This guidance intends to provide a systematic, instructive guide to the risk analysis of raw material changes in passive medical device products, to guide the licensee on how to bring product research and development, registration and quality control into compliance. Additionally, the guidance seeks to guide regulatory authorities in the registration review of change control requests stemming from changes in device raw materials. This guide provides a general evaluation for raw material changes in passive medical device products and is summarized along with relevant examples. The certificate holder should provide additional content as to the registration application based on the characteristics of products in question. The relevance of the application content will depend on the characteristics of the specific product, if the content is irrelevant, explanations on why and scientific evidence must be provided to supplement the application. The audience of the guidance is the licensee and reviewers and does not cover administrative matters related to registration and approval and are not enforced as regulation. Additional methods to fulfill the requirements of relevant regulations can also be used but must be supplemented with detailed research support and testing documents. This guide should be used in accordance with the relevant regulations. This guide is developed under current regulations, standards and research knowledge available. With continuous improvements of laws and standards, development of science and technology, the content of the guidance may be adjusted.
Scope This guidance only covers requirements for changes in raw materials of passive medical device products and does not apply to other changes and is not applicable to active medical device and diagnostic reagents. Other changes in production leading to changes in biocompatibility and physical property of the final product can also be referred to in this guide, such as changes in the sandblasting process of metal orthopedic materials, and in the surface etching process of dental implants. This guidance does not define the registration format due to changes in raw materials nor registration approval, companies should refer to “Medical Device Registration Management Measures”, “Guidelines for the division of medical device registration units”, additional regulations and guidance requirements and changes in the company product to make an appropriate judgement. Due to the different product risks and scope, this Guidance cannot provide all possible examples of raw material changes but provides the process for evaluating changes in raw materials. The Guidance seeks to help the licensee with relevant analysis and testing methods through analysis of different types of change controls. The licensee can refer to the evaluation flowchart for relevant changes and can base the evaluation also on specific product characteristics. 2.Basic Rules The licensee should strictly follow industrial development and change controls requirements when making medical device raw material changes. Change control should follow the risk management requirements of the quality management system, especially risk analysis, risk evaluation, risk control and re-evaluation. With regard to risk control, there must be an effective risk control plan and analysis of the effectiveness of the risk control plan (including validation/verification). After implementing risk control, additional risks should be evaluated through the guidelines of the risk management plan. If remaining risks are not applicable to the risk management plan, additional steps are required to ensure risk control measures and risk benefit analysis are carried out. Change controls also must consider the basic requirements of the basic safety and effectiveness list of medical devices. The list has three aspects of basic requirements, method adopted and objective evidence, and companies should refer to the list and consider if the change will affect basic requirements. When appropriate, companies should implement specific methods to prove that there is no new risk associated with the change. Benchwork, comparative evaluation of appropriate use of animal models or clinical evaluation are all appropriate ways of evaluating and verifying the effectiveness of the risk control measures. Licensees can maximize the use of preclinical research (such as benchwork etc) to test the effectiveness of risk control measures associated with identified risks, only when lab testing is insufficient, should there be consideration of animal testing for further testing, and when necessary, there must be clinical trials for evaluating the risk control measure. With regard to animal testing and clinical testing, one can refer to relevant Guidances.
Path for Change Evaluation To clarify, medical devices come in a variety and all have different raw materials even if it they are changes on the same type of raw material, the use of the raw material in different devices differ. Also, material changes cause differing risks to the product in question and require different forms of evaluation on the products. Therefore, to, go through a common path to evaluate all the risks associated with all forms of material changes is unrealistic, but it is possible to use similar formats to simplify. This guidance provides description of common forms of evaluating risk control. The basis of the evaluation is the requirements of risk control management, firstly based on the the medical device characteristics and intended use, and also according to the basic safety and effectiveness list of medical devices, and additionally, to evaluate each type of risk, such as biological compatibility hazard, sterility (if applicable), biosafety hazard, change in validity and others are all possible risks. Different forms of risks need to be evaluated and tested in different forms, such as through lab testing or research on documents, when necessary, there should be animal testing or even clinical testing to obtain evaluation. If the evaluated risk does not get approved, there must be procedures to decrease or control the risk, or to decline the change. To clarify, there must be a requirement to continue evaluating the risk of the hazard or damage after the change control, to continue in the evaluation and controls, to ensure product safety and effectiveness. Generally speaking, the various hazards that are caused by a risk associated with a change in raw material include biocompatibility, biosafety, sterilization or disinfection effect. At the same time, different products will have different specific requirements and possible risks, and this document will not provide an explanation of all types of products, but all should be replaced with lab research. Specific evaluations can refer to applicable industry standards, guiding principles and product design and development documents. Other non-biological evaluations, animal experimentation is to be included in the laboratory research section, such as the expiration date and packaging material, sterilization and disinfection effect, biosafety etc. Firstly, we can refer to Appendix 1 regarding the change of raw materials for the regulatory strategy for evaluation, licensee should determine whether the raw material has been changed. Of particular importance is that the medical device production company has the responsibility to obtain the specific content of the change in raw material. However, if it becomes difficult to obtain the raw material component information, it is possible to look at associated standards and literature, or chemical analysis to obtain further evidence, procedure for chemical analyses, methods and requirements and to refer to GG/T 16886 standards and associated guidelines. With regard to chemical analysis, not only is it necessary to determine if the main raw material has been changed, but should also through appropriate filtering studies to evaluate if the material has been changed.
