State Food and drug administration issues on-site verification plan for medical devices (key points)

On October 22, according to the information on the official website of the State Food and drug administration, in order to further strengthen the verification of the medical device registration quality management system and improve the level of the medical device registration management, the State Food and Drug Administration organized the drafting of the guidelines for the on-site verification of the medical device registration quality management system (Draft for comments) (see the annex), which is now open to the public for comments In order to standardize the on-site verification of the medical device registration quality management system, strengthen the connection between the review and verification, and ensure the quality of the on-site verification of the medical device registration, this guide is formulated in accordance with the administrative measures for the registration of medical devices, the administrative measures for the registration of in vitro diagnostic reagents, the quality management specifications for the production of medical devices and their appendices （1） This guide should be used on the premise of following the "medical device production quality management specification" and its supporting documents （2） It is necessary to focus on the "design and development", "procurement", "production management", "quality control" and other contents related to product development and production, as well as the authenticity verification requirements, in combination with the registration application materials （3） The applicant for medical device registration (hereinafter referred to as the applicant) shall establish and maintain an effective quality management system suitable for the product realization process, be responsible for the whole life cycle management of medical device, ensure the authenticity, reliability, integrity and traceability of data in the design, development, production and other processes, and be consistent with the registration application data （4） The conclusion of the verification shall be determined in accordance with the requirements of the procedures for verification of the registration quality management system for class III medical devices in China (Provisional) （1） Organization and personnel Medical device design and development personnel shall be equipped to meet the product requirements Personnel shall have appropriate education background, professional knowledge and working skills for the developed products （2） Plant, facilities and equipment 1 Product R & D shall be carried out in appropriate plants and facilities, and the plants and facilities used for registration inspection and clinical trial sample production shall meet the quality control requirements of R & D and production products 2 It shall be equipped with places, equipment and instruments suitable for the research project, including production and testing equipment for trial production of samples used for registration and application for inspection and clinical trials, and the equipment capacity shall meet the requirements for trial production of samples 3 The production address applying for on-site verification of the registered quality management system shall retain the factory building and facilities for trial production of samples for registration inspection and clinical trial, and meet the requirements of trial production quantity, model and specification （3） Document management 2 The original design and development data shall be included in the document management The applicant shall keep the research data verified after the product development or technology transfer to ensure the authenticity, integrity and traceability of the data; in addition to the test data directly output, the applicant shall also keep the auxiliary records during the development process, such as the main material acquisition records, instrument and equipment use records, weighing records, preparation records, etc., to increase the traceability of the development process （4） Design and development The design and development documents of medical devices shall be derived from the relevant documents of design and development review, verification, confirmation and design conversion activities, including the design and development procedures, development plans and established records, and shall ensure the traceability of the final output process and related activities of previous design and development 1 The basis of design and development input shall include laws and regulations, national standards, industry standards, domestic and foreign guide documents, national reference products, international reference products, standard products or technical indicators of similar products, and the input shall include clear scope of application, clinical significance and application value 2 The design and development output shall meet the needs of users and product design, and shall pay attention to the scope of application, functionality, safety, effectiveness and quality controllability of products; Passive medical devices should focus on the requirements of raw material components, physical and chemical properties and biocompatibility of raw materials or medical grade requirements, as well as the performance requirements that raw materials should meet when non disposable sterile products are re sterilized and the research results that can withstand re sterilization In addition, the determination process, determination basis and experimental data of production process and reaction system, such as solution preparation, antibody coating process and experimental process, shall be reviewed For medical devices of animal origin, attention shall be paid to the species (if the risk is related to the strain, the strain shall be specified), geographical source (for species that cannot be determined, the identification and traceability requirements for the survival period of the source animal shall be provided), age (applicable when the risk is related, such as the susceptibility of animals to naturally occurring transmissible spongiform encephalopathy), sampling location and group Requirements for the type of fabric, animal and tissue health 3 The records of design conversion activities shall indicate that the design and development output is verified before it becomes the final product specification, and the verification records shall be kept to ensure that the design and development output is suitable for production In the process of design conversion, we should pay more attention to the process research and determine the test data and time of the process Passive medical devices should focus on the processing performance, technological process, residue control, chemical reaction controllability of main raw materials Attention should be paid to the performance of raw materials, technological process, product performance, quality control methods of products and raw materials, quantity value transfer methods, etc 4 When verifying the design and development, the detailed original data records of the verification activities shall be kept, including the test scheme, sample processing at each step, use records of the instruments and equipment used, test reports, etc Validation and validation records of key processes of production process (such as sterilization process) shall focus on validation records of product validity period or repeated use times, design records of product specification and minimum sales unit label, product packaging design and packaging integrity validation records, etc In vitro diagnostic reagents should focus on the detailed experimental data of multiple batches of products, and the experimental results should meet the requirements of output technical indicators The specific process, results and sample composition of testing and identification shall be able to evaluate various technical indicators of products, and keep detailed and complete verification data records 5 Design and development changes include product changes, normative reference document updates, design conversion changes (such as equipment, raw material suppliers, process, environment, etc.), external change requirements (registration inspection, animal experiment, clinical experiment, technical review change opinions), changes caused by changes in mandatory medical device standards, etc., and the applicant's change should be focused on Risk assessment, verification or confirmation has been carried out If the inspection organization puts forward rectification requirements for the inspected samples in the type inspection, the rectification scheme shall be implemented in the design and development process, the rectification measures shall be identified and recorded in the design change process and design transformation process, and the records related to the rectification measures shall be available in the design main document and production main document （5） Procurement The purchase time or supply time of raw and auxiliary materials shall correspond to the sample trial production time, and the purchase quantity shall meet the sample trial production demand, and there shall be an inspection report 2 If the purchase of the same item comes from different suppliers, the audit data of different suppliers shall be provided If the purchased item needs to be processed before processing, it shall be explained in the data 3 The procurement control records of key parts and components, and raw materials of parts expected to contact with human body shall meet the product design requirements and be traceable 4 For the procurement of raw materials of in vitro diagnostic reagent quality control products, calibration products and enterprise reference products, if samples from human body are involved, the identification method, identification process, identification data and identification record of corresponding raw materials shall be focused, and the detection record of biosafety shall be focused The purchase of other raw materials shall have a purchase contract or purchase record, and attention shall be paid to the material balance of raw materials 5 According to the appendix of product technical requirements and the main raw material suppliers in the main raw material requirements, check whether the supplier is the manufacturer of raw materials If the supplier in the technical requirements is not the manufacturer of raw materials, check the manufacturer of raw materials according to the ex factory inspection report of raw materials, and focus on checking whether the manufacturer of raw materials changes in the production process of multiple batches of products Change, such as whether the change has been registered （6） Production 1 Methods and / or processes for inactivating and removing viruses and / or infectious factors and reducing immunogenicity of animal derived materials shall be checked for animal derived medical devices 2 Batch (set) records of samples used for registration inspection, animal experimental research and clinical experimental research shall be traceable The batch number (number / serial number, etc.) and specification and model, inspection time, inspection basis, inspection conclusion, key raw materials and / or components, calibration materials and / or quality control materials, etc of the samples to be inspected, together with the photos, labels and other information of the samples to be inspected, shall be consistent with and traceable to the production batch record 3 The batch number (number / serial number, etc.) and specification and model of the clinical trial sample shall be consistent with the production batch record and traceable 4 In vitro diagnostic reagents shall check the production records of multiple batches of products, including whether the configuration concentration of different working solutions, production process, process quality control are consistent and meet the requirements of design output, especially the concentration and activity of bioactive materials shall be consistent Samples for performance evaluation and clinical trials should be produced under the actual production system （7） Quality control 1 the inspection records (including the inspection records, inspection reports or certificates of the incoming inspection, process inspection and finished product inspection) of the samples used in the registration inspection, animal experimental research and clinical research shall be kept and shall be traceable 2 The traceability process of in vitro diagnostic reagents should be reasonable and should not be traced to product Calibrators of other products The assignment process and experimental data of each batch of products shall be consistent 3 The inspection items of the incoming inspection of raw materials shall meet the requirements for raw materials in the product technical requirements If they are not completely consistent, the reasons shall be explained The important items in the COA shall be verified again, and the important indexes not included in the COA shall also be verified 4 The inspection items and rules of semi-finished products and finished products shall be reviewed The setting of inspection items shall be scientific and reasonable and provide basis If the setting of factory inspection items is inconsistent with the technical requirements, the reasons shall be explained 5 It shall be able to provide trial production samples or reserved samples The trial production quantity, specification and model of samples shall meet the needs of self-test, registration test and clinical test (clinical evaluation) The direction of samples shall be traceable （1） Verification of the authenticity of product registration inspection samples: batch number (No / serial number, etc.) and specification and model, inspection time, inspection basis, inspection conclusion, information of key raw materials and / or components, information of calibration materials and / or quality control materials, etc., with photos of inspection samples, photos and labels containing version information of independent software, etc., shall be recorded with the production batch Records are consistent and traceable If rectification is involved in the inspection process, the rectification content shall be reflected in the quality system documents （2） Verification of the authenticity of clinical trial samples: the batch number (number / serial number, etc.) and specification and model of clinical trial samples shall be consistent with the production batch record and traceable （3） The production address of registered test samples and clinical test samples shall be the same as that of the production address of the application registration system verification, such as products