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To do a good job of quality management system verification under the medical device registrant system，Improve the quality of medical device registration quality management system verification，根据《十大电子游艺平台首选》（国务院令第739号）及《十大电子游艺平台首选》（市场监管总局令第47号）、《十大电子游艺平台首选》（市场监管总局令第48号）、《十大电子游艺网站》（市场监管总局令第53号）等要求，The State Drug Administration has revised the Guidelines for the Verification of the Quality Management System for Medical Device Registration (see Annex).，Hereby published，Effective from the date of promulgation。The Notice of the State Drug Administration on Issuing the Verification Guidelines for the Quality Management System of Medical Device Registration (No. 19, 2020) shall be repealed at the same time。
Hereby inform。
Attachment: Verification Guide for medical device Registration Quality management system
附件
Medical device registration quality management system verification guide
I. Purpose and basis
To strengthen the medical device registration quality management system verification management，Ensure the quality of inspection work，根据《十大电子游艺平台首选》《十大电子游艺平台首选》《十大电子游艺平台首选》《十大电子游艺网站》《十大电子游艺平台首选》《十大电子游艺网站》《Medical device registration self-test management provisions》Etc., develop this guide。
2. Scope of application
This guide applies to the on-site verification of the registered quality management system of Class II and Class III medical devices carried out by the medical device regulatory authorities。
3. Basic requirements
3.1(Quality Management System)The registration applicant (referred to as the applicant) shall comply with the requirements of the Medical Device Manufacturing Quality Management Practice and the appendix，Based on scientific knowledge, experience and risk management principles，Establish a quality management system that is compatible with the product realization process，Including commissioned production (if any), clinical evaluation (including clinical trials) and other links，To ensure its effective operation during the whole life cycle management of medical devices，Ensure design, development, production and other process data true, accurate, complete and traceable，And consistent with the registration information。
3.2(Registration verification requirements)The registration quality management system verification shall be organized in combination with the registration and application data, focusing on the design and development, procurement, production management, quality control and other contents related to product development and production。Product authenticity verification shall be comprehensive and objective。
3.3(Self-inspection and verification requirements)Submit againstThe self-inspection report shall be in accordance with the"Medical device registration self-test management provisionsIn combination with the submitted product technical requirements, the applicant's quality management system and ability are verified item by item。
3.4(Commissioned activity inspection, extended inspection requirements)For applicants who entrust other enterprises with design, development, product production and other activities, the scope of verification shall cover entrusted research and development and entrusted production activities。When necessary, extended inspection shall be carried out on other units that provide products or services for the research and development or production of medical devices。
4. Focus on the content of verification
4.1Principles of quality management system
4.1.1(Quality Management System)applicant应当结合产品特点，建立涵盖Design and development、生产、Quality control和放行审核等与产品实现过程相适应的质量管理体系，且应当包括Commissioned production（如有）、临床评价（含临床试验）等。
4.1.2(Risk Management)The applicant shall establish a risk management system to assess the quality risks of the product realization process based on scientific knowledge and experience to ensure product quality。
4.1.3（自检）Where the applicant carries out self-inspection, the self-inspection work shall be incorporated into the product quality management system and meet the requirements。
4.2Organization and personnel
4.2.1(Organization)The applicant shall establish a management organization suitable for the research and development and production of medical devices, clarify the responsibilities of each department, and ensure that the design and development and technology conversion are reasonable and traceable。
4.2.2（人员）The applicant shall be equipped with an appropriate number and corresponding R & D, production and quality control personnel, personnel should have the professional knowledge and work skills suitable for the application of registered products。
4.2.3(Key personnel)Management representative, production person in charge, quality person in charge, technical person in charge, product release audit person and other key personnel should be familiar withRegistered productThe key quality control, key production operation requirements。
4.2.4(self-testing personnel)Where the applicant submits the self-inspection report, the quality inspection department shall be equipped with a sufficient number of full-time inspection personnel。The educational background and technical ability of the inspectors shall match the product inspection work。Inspectors, examiners, approving personnel, etc. shall be authorized by the applicant in accordance with regulations。
4.3Plant, facilities and equipment
4.3.1(Plant facilities)applicantIt shall be equipped with plants and facilities suitable for the production of registered products。Product design and development should be carried out in suitable plants and facilities。The factories and facilities for the production of inspection products (referred to as registered inspection products) and clinical trial products that apply for registration shall meet the quality control requirements of the products。
4.3.2(Production equipment)applicantIt shall be equipped with production equipment and technological equipment suitable for the production of the declared and registered products。The production equipment and process equipment of registered inspection products and clinical trial products shall meet the requirements of product quality and production scale。
4.3.3(Inspection equipment)applicantEnvironmental facilities and instruments that meet the requirements of product inspection methods shall be equipped。For laboratories that carry out special professional inspections, the environmental facilities shall meet the specific professional requirements。
4.3.4(Registered laboratory and clinical trial product production)Plant facilities and equipment used for the development and production of registered inspection products and clinical trial products and related usage records shall be maintained。If force majeure cannot be retained, shall be retained to prove the product research and development, production, verification and other product realization process activities true, complete and traceable evidence。
4.4File management
4.4.1(System document)The applicant shall establish quality management system documents suitable for the application of registered products, including quality manuals, procedure documents, technical documents and data records。Technical documents shall include product technical requirements and related standards, production process rules, operation instructions, inspection and test operation rules and other relevant documents。Data recording shall ensure traceability of activities such as product design and development, material procurement, production, quality control and product release。
4.4.2(R&D original record)The original materials of design and development shall be included in the file management。In addition to the direct output test data, auxiliary records in the design and development process should be kept, such as records of main materials, instrument and equipment use records, weighing records, preparation records, etc。To carry out clinical trials, records of test instruments (reagents) in the process of clinical trials shall be kept, records of storage and transportation, records of recovery and disposal, etc。
4.4.3(Verification data)The applicant shall retain the research data and records verified after product design and development or technology transfer, and shall ensure that the data is true, accurate, complete and traceable。
4.4.4(Clinical trial document Management)The applicant shall establish a clinical trial basic document management system according to the "Medical devices./The In Vitro Diagnostic Reagents Clinical Trial Basic Documentation Catalogue requires the management of clinical trial documentation and ensuring its authenticity, completeness and traceability。
4.5Design and development
4.5.1(Design and development document)医疗器械设计和开发文档应当源于Design and development策划、输入、输出、评审、验证、确认、转换、变更的相关文件，包含Design and development过程中建立的记录，应当确保历次Design and development最终输出过程及其相关活动可追溯。
4.5.2(Design and development input)设计和开发输入一般应当包括法律法规、国家标准、行业标准、国内外指南文件、标准品或者参考物质信息（体外诊断试剂产品适用）、用户需求、产品适用范围、前代或者同类产品的技术指标、产品风险等。
4.5.3(Design and development output)The design and development output shall meet the input requirements, as well as meet the needs of users and product design requirements, and shall pay attention to the scope of product application, functionality, safety, effectiveness, and quality control。
4.5.3.1(Passive medical devices)无The raw material components of the source medical device shall meet the relevant standards and requirements, and the biocompatibility evaluation shall be completed for the part of the product that comes into contact with the human body。When reusable sterile products are repeatedly sterilized, the performance of the finished product should be evaluated and the study of tolerance to repeated sterilization should be completed。
4.5.3.2(Active medical devices)Active medical devices shall complete relevant studies according to the requirements of the standard, such as electric shock hazard protection, mechanical hazard protection, radiation hazard protection, overtemperature hazard protection, electromagnetic compatibility, biocompatibility, etc。
4.5.3.3(Animal origin includes allogeneic medical devices)动Source medical devices shall完成Animal species (strains must be identified if the risk is related to the strain), geographical origin (for species whose geographical origin cannot be determined)，Provide identification and traceability requirements during the life of the source animal), age (where applicable in relation to risk，For example, the susceptibility of animals to naturally occurring transmissible spongiform encephalopathy), the types of sample sites and tissues, the health status of animals and tissues, and the applicability of virus inactivation methods。
4.5.3.4(in vitro diagnostic reagents)体外诊断试剂研究过程中涉及的主要原材料、中间体、重要辅料等应当明确来源并符合要求，研究过程中使用的设备、仪器和试剂应当满足研究要求。
4.5.4(Verification confirmation)Based on the results of the risk assessment, the applicant shall determine the scope and extent of the work to be verified or validated and ensure that key elements of the operation are effectively controlled。
4.5.5(Design conversion)The applicant shall maintain all records of product design conversion activities，To demonstrate that the design and development outputs have been adequately validated and applicable to routine production before becoming final product specifications，And ensure that the production process in the use of determined raw materials and equipment conditions，Continuously and steadily produce products that meet the intended use and product technical requirements。如：无菌提供产品的灭菌工艺及相关设备设施验证与确认、有源医疗器械基本安全和基本性能的实现确认评估、体外诊断试剂生产过程、工艺参数以及批量放大验证等。
4.5.6(Packaging, expiration date, reuse)applicant应当对产品包装、有效期或者重复使用次数等开展研究并留存相关记录，如：产品的包装设计及验证、稳定性研究数据、产品说明书和最小销售单元标签的设计记录等。
4.5.7(Verification record)Detailed original data records of design and development verification activities should be kept, including verification schemes, verification reports, verification records (such as test data, sample handling records, etc.), and auxiliary records。
4.5.8(Clinical Confirmation Management)设计和开发确认过程中，对Registered product需要用临床试验的方式进行确认的，applicant应当按照临床试验方案及合同履行相应职责，并保存相关文件和记录。
4.5.9(Requirements for clinical trial products)For products to be tested in clinical trials, before the start of clinical trials, the applicant shall ensure that the product design has been finalized and the product inspection has been completed, and its safety and functionality are suitable for clinical trials。Records of relevant evaluation and validation processes should be maintained。
4.5.10(Clinical Trial Product Management)The applicant shall maintain the distribution, storage and recovery of clinical trial products/Return record。
4.5.11（Design and development变更）设计和开发更改包括产品变更、引用文件更新（如法规、强制性标准）、设计转换的变更（如设备、原材料供应商、工艺、环境等）、来自外部的变更要求（检验、动物实验、临床试验、技术审评更改意见）、强制性医疗器械标准变化引发的变更等，It shall be subject to risk assessment, verification or confirmation，Ensure changes are controlled。
4.5.12(Commissioned R & D management)Where there is commissioned research and development, the applicant shall have quality management measures for relevant activities。
4.5.12.1(Agent capability Assessment)The applicant shall specify the scope and extent of product research and development activities entrusted。The R&D capability and continuous technical support capability of the entrusted R&D institution shall be required and evaluated accordingly。
4.5.12.2The applicant shall sign a commissioned research and development agreement with the commissioned research and development institution, which clearly stipulates the responsibilities of each party, research and development content and related technical matters。The applicant shall be responsible for the process and results of the commissioned research and development, and shall have measures to ensure the reliability of the commissioned research and development process data。The entrusted R & D institution shall comply with the requirements of the agreement and ensure that the R & D process is standardized and the data is true, accurate, complete and traceable。
4.5.12.3(Commissioned research and development technical documents)The applicant shall ensure that the entrusted R&D institution transfers the design and development output documents in accordance with the agreement requirements and meets the design and development input requirements。
4.6采购
4.6.1(Procurement system)The applicant shall establish procurement control procedures to ensure that the procured goods comply with the specified requirements。
4.6.2(Source of raw materials)注册检验产品及临床试验产品所需的原材料，包括与产品直接接触的包材、软件等应当具有合法来源证明，如供货协议、订单、发票、入库单、送货单、批准证明性文件复印件等。
4.6.3(Major Material purchase)The purchase time or supply time of the main raw materials shall correspond to the production time of the product, and the quantity purchased shall meet the production demand of the product, and there shall be an inspection report or qualification certificate。
4.6.4(Purchase record)The procurement records of major raw materials shall conform to the requirements of product design and the provisions of the procurement agreement, and the records shall be true, accurate, complete and traceable。
4.6.5(In vitro diagnostic reagent purchase record)The procurement of raw materials for in vitro diagnostic reagents shall have procurement contracts or procurement records。质控品、校准品、企业参考品的采购应满足追溯要求，如涉及人体来源的样本，应当有相应原料的检验方法、检验过程、检验数据、检验记录，以及表明生物安全性的证明材料等。
4.6.6(In vitro diagnostic reagents key material requirements)体外诊断试剂设计定型后，关键原材料本身如抗原（来源、氨基酸序列、构象等）、抗体（来源、细胞株等）、引物探针序列等不应发生变化。
4.7生产
4.7.1(Development and production requirements)The applicant shall organize the production activities of registered inspection products and clinical trial products in accordance with the requirements of the Medical Device Production Quality Management Practice。
4.7.2(Production process documents)The applicant shall prepare production process regulations, operation instructions and other documents, and specify key processes and special processes。On animal-derived medical devices, inactivate and remove viruses and/Or infectious agent processes and methods for reducing the immunogenicity of animal-derived materials/Or process shall be confirmed。
4.7.3(Production and recording requirements)It shall organize the production of registered inspection products and clinical trial products in accordance with the production process regulations, and truthfully fill in the production records。Production records shall be true, accurate, complete and traceable。
4.7.4(In vitro diagnostic reagent production requirements)体外诊断试剂的生产应当确保不同工作液的配制浓度、生产工艺过程、Quality control过程等符合设计输出的要求，尤其是生物活性材料的浓度、活性应当确保稳定，并符合相关标准。The material balance of raw materials shall meet the requirements。
4.8Quality control
4.8.1（Basic requirement）The applicant shall establish quality control procedures, specify product inspection departments, personnel, operation and other requirements, and specify the use of inspection instruments and equipment, calibration and other requirements, as well as product release procedures。
4.8.2（自检）applicant开展自检的，应当按照有关检验工作和申报产品自检的要求，将与自检工作相关的质量管理要求纳入企业质量管理体系文件（包括质量手册、程序、作业指导书等），并确保其有效实施和受控。
4.8.3(Inspection equipment)applicantFiles, operating procedures and measurements of inspection equipment and environmental facilities shall be established and kept/Calibration certification, service and maintenance records。
4.8.4(inspection procedure)Based on the principles of science and risk management, the incoming inspection procedures for raw materials, semi-finished products and finished products shall be formulated and the basis shall be clearly formulated。
4.8.5(Inspection record)应当保存注册检验、临床试验等相关产品的检验报告和记录，包括：进货检验、过程检验和成品检验等原始记录、检验报告或者证书以及检验方法确认或者验证记录等。Where there is commissioned inspection of some projects, there should be relevant project inspection reports and commissioned inspection agreements。
4.8.6(Release procedure)Product release procedures shall be established and implemented to clarify product release conditions and requirements for review and approval。
4.8.7(Tracing of in vitro diagnostic reagents)The traceability process of in vitro diagnostic reagents should be reasonable, and the process and method of assigning each batch of products should be consistent。
4.8.8（留样）The applicant shall retain a certain number of registered inspection products and clinical trial products in combination with the characteristics of the products。The quantity and specifications of products produced or samples retained shall meet the needs of product inspection and clinical evaluation (including clinical trials)。The destination of the samples shall be traceable。
4.9Commissioned production
4.9.1(General requirements)Where there is entrustment in the process of producing products, the applicant shall specify the departments and personnel responsible for guiding and supervising the quality management system of the entrusted production enterprise。In principleA management representative shall be appointed to be responsible for the quality control of commissioned production。
4.9.2（人员）applicant应当配备专职的质量管理人员，人员应当熟悉产品The key quality control, key production operation requirements，能够对applicant和Entrusted to a production enterprise质量管理体系进行评估、审核和监督。Entrusted to a production enterpriseKey personnel such as the production person in charge, the quality person in charge, and the production release auditor shall be familiar with the key quality control and key production operation requirements of the entrusted products。
4.9.3(Trust agreement)applicantAn entrustment agreement shall be signed with the agent，Clarify the rights, obligations and responsibilities of both parties，协议至少应当包括Entrusted to a production enterprise生产条件、技术文件的转移、物料采购控制、生产工艺和过程控制、成品检验、产品放行控制、文件与记录控制、变更控制、质量管理体系审核等，Ensure that the entrusted production enterprises organize production in accordance with laws and regulations, medical device production quality management norms, mandatory standards, and product technical requirements。
4.9.4(on-site audit)Commissioned production前，The applicant shall conduct on-site evaluation and review of the quality management system of the entrusted production enterprise，Audit content should at least include the organization and personnel, plant and facilities, equipment, production management, quality control capabilities，Ensure that the entrusted production enterprise has a quality management system suitable for the entrusted production products。
4.9.5(Design conversion)The applicant shall jointly plan and complete the design conversion activities with the entrusted production enterprise to ensureProduct technical requirements, production processes, raw material requirements, instructions and labels and other product technical documents can be effectively transferred to the entrusted production enterprises。
4.9.6(Technical document conversion and process verification)受托生产企业应当结合本企业的生产条件和质量管理体系，将applicant的产品技术文件转化为本企业的技术文件，确保产品技术要求的关键技术参数、操作方法与applicant移交的保持一致。Trial production and process validation should be carried out, and trial production should include all transferred production processes and quality control processes。
4.9.7(Technology transformation risk control)applicant应当结合原生产工艺文件，对受托生产企业执行的生产工艺文件进行比对评估，确保因生产条件等质量管理体系变化带来的风险已得到充分识别和控制。The applicant shall participate in the verification and confirmation work related to the entrusted products carried out by the entrusted production enterprise, and review the relevant process documents and reports。
4.9.8（Registered inspection products and clinical trial product production）Where the applicant carries out the production of registered inspection products and clinical trial products in the commissioned production enterprise, it shall ensure that the commissioned production enterprise has plants, facilities and equipment suitable for the production of the products。The applicant shall ensure the completion of process verification or validation and other related work。
4.9.9(Material Purchase)The applicant shall clarify the procurement method, procurement approach, quality standards and inspection requirements of the commissioned product materials, and implement procurement in accordance with the requirements of the medical device commissioned production quality agreement。When necessary, the applicant and the entrusted production enterprise together to screen, audit, sign quality agreements, regular review of material suppliers。
4.9.10(Production process Management)applicant应当会同受托生产企业对产品工艺流程、工艺参数、外协加工过程（如：辐照灭菌、环氧乙烷灭菌、阳极氧化、喷涂工艺等）、物料流转、批号和标识管理、生产记录追溯性等生产过程明确监控方式和标准，Specify who authorizes monitoring，And keep monitoring records。
4.9.11(Document Management)applicant和受托生产企业共同持有的文件至少应当包括：委托协议，受托生产企业执行的产品技术要求、原材料要求、生产工艺和检验规程、产品说明书和标签以及产品放行程序等。
4.9.12(Product release)applicantProduct release review and approval procedures should be established and ensure that both partiesRelease registered inspection products, clinical trial products and marketed products in accordance with their respective responsibilities。The commissioned production enterprise shall formulate production release audit procedures, shall ensure that the commissioned production products meet the applicant's acceptance standards and keep release records。All records relating to the production of products shall be true, accurate, complete and traceable。
4.9.13(Regular audit)applicantThe entrusted production management situation and related records of the entrusted production enterprise shall be reviewed regularly, and the audit records shall be kept。The entrusted production enterprise shall keep all production records related to entrusted production, and may provide them to the applicant for reference at any time。If the entrusted production enterprise has the same product in production, it should have a significantly different number, batch number and process identification management method from the entrusted production product to avoid confusion。
4.9.14(Communication mechanism) The applicant shall establish an effective communication mechanism with the entrusted production enterprise, and shall promptly notify the entrusted production enterprise of any design changes and procurement changes and supervise the implementation。For changes to the quality management system of the entrusted production enterprise that may affect the quality of the product, the applicant shall have measures to ensure that the entrusted production enterprise can inform the applicant in a timely manner and carry out a joint assessment。
4.9.15(Applicant's responsibility)applicant应当对Design and development、生产、储运和不良事件监测情况进行全流程追溯、监控，保持质量管理体系的持续改进，并落实对Entrusted to a production enterprise监督。
4.10Product authenticity
4.10.1(Registered inspection products)Registration of inspection products, including inspection product batch number (No/Serial number, etc.) and specifications, inspection time, inspection quantity, inspection basis, inspection conclusion, key raw materials and/Or components and other information, calibration substances and/Or quality control substances, inspection product photos (including photos of independent software release version information), labels and other information, should be consistent with the production record and traceable。
4.10.2(Clinical trial products)Clinical trial products, including clinical trial product lot numbers (No/Serial number, etc.) and specifications shall be consistent with production records and traceable。
4.10.3(Development and production traceability requirements)The production batch and production batch number or product number, specifications and models/包装规格、每批数量、注册检验产品和临床试验产品批号及数量、留样产品批号及数量、现存产品生产批号或者产品编号及数量、主要原材料批号及数量等应当可追溯。
4.10.5(Production and inspection records)Production records, process inspection original records, finished product inspection original records, etc. shall meet the requirements of design output files。
4.10.6（留样）If it is necessary to retain samples, the samples shall be retained, and the product ledger and the observation record of the samples shall be kept。
5. Judgment principle of on-site verification results
5.1There are a number of verification items in this guide73Item, where annotated“*”Key item32Item, general item41Item (see attached table)。The on-site inspection team shall make the items one by one against all the verification items“符合”、“inconformity”或者“inapplicability”Decision result of。Judge as“inconformity”In the verification of items, inspectors shall record in detail the specific problems existing。
5.2Principles for judging the results of on-site verification
The conclusion of on-site verification is divided into“Pass the check”、“Failed verification”、“Pass the verification after rectification”、“Failed to pass the verification after rectification”4case。
5.2.1If on-site verification does not find that the applicant does not meet the project, the recommended conclusion is“Pass the check”。
5.2.2If on-site verification finds one of the following circumstances, the recommended conclusion is“Failed verification”。（1On-site verification finds that the applicant has authenticity problems;(2The on-site verification did not find the authenticity problem, but found that the applicant had key items3Items (including) above or general items10The above items (including) do not meet the requirements。
5.2.3On-site verification did not find any authenticity problems, and it was found that the applicant had key items3Items (not included) below and general items10If the following items (not included) do not meet the requirements, the recommended conclusion is“Review after rectification”。The verification conclusion is“Review after rectification”The applicant shall be registered after the completion of the verification6Complete the rectification within a month and submit a one-time rectification report to the original verification department. If necessary, the verification department can carry out on-site review。If all the project rectification meets the requirements, the recommended conclusion is“Pass the verification after rectification”。
5.2.4For the failure to submit the rectification report within the prescribed time limit or the review still does not meet the project, the recommended conclusion is“Failed to pass the verification after rectification”。
附表
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Chapter name
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章节
序号
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内容
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Decision result
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符合
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不
符合
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不
适用
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Principles of quality management system
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*4.1.1
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(Quality Management System)applicant应当结合产品特点，建立涵盖Design and development、生产、Quality control和放行审核等与产品实现过程相适应的质量管理体系，且应当包括Commissioned production（如有）、临床评价（含临床试验）等。
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4.1.2
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(Risk management) The applicant shall establish a risk management system to assess the quality risks of the product realization process based on scientific knowledge and experience to ensure product quality。
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*4.1.3
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(Self-inspection) Where the applicant carries out self-inspection, the self-inspection work shall be incorporated into the product quality management system and meet the requirements。
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Organization and personnel
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4.2.1
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(Organization) The applicant shall establish a management organization suitable for the research and development and production of medical devices, clarify the responsibilities of each department, and ensure that the design and development and technology conversion are reasonable and traceable。
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4.2.2
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(Personnel) The applicant shall be equipped with an appropriate number and corresponding R & D, production and quality control personnel, personnel should have the professional knowledge and work skills suitable for the application of registered products。
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Organization and personnel
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*4.2.3
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(Key personnel)Management representative, production person in charge, quality person in charge, technical person in charge, product release audit person and other key personnel should be familiar withRegistered productThe key quality control, key production operation requirements。
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*4.2.4
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(self-inspection personnel) Where the applicant submits the self-inspection report, the quality inspection department shall be equipped with a sufficient number of full-time inspection personnel。The educational background and technical ability of the inspectors shall match the product inspection work。Inspectors, examiners, approving personnel, etc. shall be authorized by the applicant in accordance with regulations。
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Plant, facilities and equipment
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*4.3.1
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(Plant facilities) The applicant shall be equipped with plants and facilities suitable for the production of the registered products。Product design and development should be carried out in suitable plants and facilities。The factories and facilities for the production of inspection products (referred to as registered inspection products) and clinical trial products that apply for registration shall meet the quality control requirements of the products。
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*4.3.2
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(Production equipment) The applicant shall be equipped with production equipment and technological equipment suitable for the production of the registered products。The production equipment and process equipment of registered inspection products and clinical trial products shall meet the requirements of product quality and production scale。
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*4.3.3
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(Inspection equipment) The applicant shall be equipped with environmental facilities and instruments that meet the requirements of product inspection methods。For laboratories that carry out special professional inspections, the environmental facilities shall meet the specific professional requirements。
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*4.3.4
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(Production of registered inspection and clinical trial products) The plant facilities and equipment used for research and development and production of registered inspection products and clinical trial products and related use records shall be kept。If force majeure cannot be retained, shall be retained to prove the product research and development, production, verification and other product realization process activities true, complete and traceable evidence。
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File management
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*4.4.1
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(System documents) The applicant shall establish quality management system documents suitable for the application of registered products, including quality manuals, procedure documents, technical documents and data records。Technical documents shall include product technical requirements and related standards, production process rules, operation instructions, inspection and test operation rules and other relevant documents。Data recording shall ensure traceability of activities such as product design and development, material procurement, production, quality control and product release。
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4.4.2
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(R & D original records) The original design and development data shall be included in the file management。In addition to the direct output test data, auxiliary records in the design and development process should be kept, such as records of main materials, instrument and equipment use records, weighing records, preparation records, etc。To carry out clinical trials, records of test instruments (reagents) in the process of clinical trials shall be kept, records of storage and transportation, records of recovery and disposal, etc。
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File management
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4.4.3
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(Verification data) The applicant shall retain the research data and records of product design and development or technology transfer verification, and shall ensure that the data is true, accurate, complete and traceable。
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4.4.4
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(Clinical trial document management) The applicant shall establish a clinical trial basic document management system according to the "Medical Devices./The In Vitro Diagnostic Reagents Clinical Trial Basic Documentation Catalogue requires the management of clinical trial documentation and ensuring its authenticity, completeness and traceability。
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Design and development
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*4.5.1
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(Design and development document)医疗器械设计和开发文档应当源于Design and development策划、输入、输出、评审、验证、确认、转换、变更的相关文件，包含Design and development过程中建立的记录，应当确保历次Design and development最终输出过程及其相关活动可追溯。
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4.5.2
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(Design and development input)设计和开发输入一般应当包括法律法规、国家标准、行业标准、国内外指南文件、标准品或者参考物质信息（体外诊断试剂产品适用）、用户需求、产品适用范围、前代或者同类产品的技术指标、产品风险等。
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*4.5.3
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(Design and development output)The design and development output shall meet the input requirements, as well as meet the needs of users and product design requirements, and shall pay attention to the scope of product application, functionality, safety, effectiveness, and quality control。
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4.5.3.1
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(Passive medical devices) The raw material components of passive medical devices shall meet the relevant standards and requirements, and the biocompatibility evaluation of the product and the human body contact part shall be completed。When reusable sterile products are repeatedly sterilized, the performance of the finished product should be evaluated and the study of tolerance to repeated sterilization should be completed。
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4.5.3.2
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(Active medical devices)Active medical devices shall complete relevant studies according to the requirements of the standard, such as electric shock hazard protection, mechanical hazard protection, radiation hazard protection, overtemperature hazard protection, electromagnetic compatibility, biocompatibility, etc。
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Design and development
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4.5.3.3
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(Animal origin includes allogeneic medical devices)动Source medical devices shall完成Animal species (strains must be identified if the risk is related to the strain), geographical origin (for species whose geographical origin cannot be determined)，Provide identification and traceability requirements during the life of the source animal), age (where applicable in relation to risk，For example, the susceptibility of animals to naturally occurring transmissible spongiform encephalopathy), the types of sample sites and tissues, the health status of animals and tissues, and the applicability of virus inactivation methods。
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4.5.3.4
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(in vitro diagnostic reagents)体外诊断试剂研究过程中涉及的主要原材料、中间体、重要辅料等应当明确来源并符合要求，研究过程中使用的设备、仪器和试剂应当满足研究要求。
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4.5.4
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(Validation) The applicant shall, based on the results of the risk assessment, determine the scope and extent of the work to be validated or validated and ensure that key elements of the operation can be effectively controlled。
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4.5.5
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(Design Conversion) The Applicant shall maintain all records of product design conversion activities，To demonstrate that the design and development outputs have been adequately validated and applicable to routine production before becoming final product specifications，And ensure that the production process in the use of determined raw materials and equipment conditions，Continuously and steadily produce products that meet the intended use and product technical requirements。如：无菌提供产品的灭菌工艺及相关设备设施验证与确认、有源医疗器械基本安全和基本性能的实现确认评估、体外诊断试剂生产过程、工艺参数以及批量放大验证等。
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4.5.6
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(Packaging, expiration date, reuse)applicant应当对产品包装、有效期或者重复使用次数等开展研究并留存相关记录，如：产品的包装设计及验证、稳定性研究数据、产品说明书和最小销售单元标签的设计记录等。
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4.5.7
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(Verification record)Detailed original data records of design and development verification activities should be kept, including verification schemes, verification reports, verification records (such as test data, sample handling records, etc.), and auxiliary records。
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Design and development
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4.5.8
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(Clinical Confirmation Management)设计和开发确认过程中，对Registered product需要用临床试验的方式进行确认的，applicant应当按照临床试验方案及合同履行相应职责，并保存相关文件和记录。
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4.5.9
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(Requirements for clinical trial products)For products to be tested in clinical trials, before the start of clinical trials, the applicant shall ensure that the product design has been finalized and the product inspection has been completed, and its safety and functionality are suitable for clinical trials。Records of relevant evaluation and validation processes should be maintained。
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4.5.10
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(Clinical Trial Product Management) The applicant shall maintain the distribution, storage, transportation, and recovery of clinical trial products/Return record。
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4.5.11
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（Design and development变更）设计和开发更改包括产品变更、引用文件更新（如法规、强制性标准）、设计转换的变更（如设备、原材料供应商、工艺、环境等）、来自外部的变更要求（检验、动物实验、临床试验、技术审评更改意见）、强制性医疗器械标准变化引发的变更等，It shall be subject to risk assessment, verification or confirmation，Ensure changes are controlled。
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4.5.12
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(Commissioned research and development management) Where there is commissioned research and development, the applicant shall have quality management measures for related activities。
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4.5.12.1
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The applicant shall clarify the scope and extent of product research and development activities entrusted。The R&D capability and continuous technical support capability of the entrusted R&D institution shall be required and evaluated accordingly。
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Design and development
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4.5.12.2
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The applicant shall sign a commissioned research and development agreement with the commissioned research and development institution, which clearly stipulates the responsibilities of each party, research and development content and related technical matters。The applicant shall be responsible for the process and results of the commissioned research and development, and shall have measures to ensure the reliability of the commissioned research and development process data。The entrusted R & D institution shall comply with the requirements of the agreement and ensure that the R & D process is standardized and the data is true, accurate, complete and traceable。
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4.5.12.3
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(Commissioned R & D Technical Documents) The applicant shall ensure that the entrusted R & D institution transfers the design and development output documents in accordance with the agreement requirements and meets the design and development input requirements。
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采购
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*4.6.1
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(Procurement system) The applicant shall establish procurement control procedures to ensure that the purchased goods comply with the specified requirements。
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4.6.2
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(Source of raw materials)注册检验产品及临床试验产品所需的原材料，包括与产品直接接触的包材、软件等应当具有合法来源证明，如供货协议、订单、发票、入库单、送货单、批准证明性文件复印件等。
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*4.6.3
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(Major Material purchase)The purchase time or supply time of the main raw materials shall correspond to the production time of the product, and the quantity purchased shall meet the production demand of the product, and there shall be an inspection report or qualification certificate。
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*4.6.4
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(Procurement records) The procurement records of major raw materials shall comply with the requirements of product design and the provisions of the procurement agreement, and the records shall be true, accurate, complete and traceable。
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采购
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4.6.5
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(In vitro diagnostic reagent procurement records) The procurement of raw materials for in vitro diagnostic reagents shall have procurement contracts or procurement records。质控品、校准品、企业参考品的采购应满足追溯要求，如涉及人体来源的样本，应当有相应原料的检验方法、检验过程、检验数据、检验记录，以及表明生物安全性的证明材料等。
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*4.6.6
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(In vitro diagnostic reagents key material requirements)体外诊断试剂设计定型后，关键原材料本身如抗原（来源、氨基酸序列、构象等）、抗体（来源、细胞株等）、引物探针序列等不应发生变化。
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生产
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*4.7.1
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(Development and production requirements) The applicant shall organize the production activities of registered inspection products and clinical trial products in accordance with the requirements of the Medical Device Production Quality Management Practice。
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*4.7.2
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(Production process documents) The applicant shall prepare production process regulations, operation instructions and other documents, and specify key processes and special processes。On animal-derived medical devices, inactivate and remove viruses and/Or infectious agent processes and methods for reducing the immunogenicity of animal-derived materials/Or process shall be confirmed。
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*4.7.3
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(Production and record requirements) shall organize the production of registered inspection products and clinical trial products in accordance with the production process regulations, and truthfully fill in the production records。Production records shall be true, accurate, complete and traceable。
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4.7.4
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(In vitro diagnostic reagent production requirements)体外诊断试剂的生产应当确保不同工作液的配制浓度、生产工艺过程、Quality control过程等符合设计输出的要求，尤其是生物活性材料的浓度、活性应当确保稳定，并符合相关标准。The material balance of raw materials shall meet the requirements。
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Quality control
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4.8.1
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（Basic requirement）The applicant shall establish quality control procedures, specify product inspection departments, personnel, operation and other requirements, and specify the use of inspection instruments and equipment, calibration and other requirements, as well as product release procedures。
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*4.8.2
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（自检）applicant开展自检的，应当按照有关检验工作和申报产品自检的要求，将与自检工作相关的质量管理要求纳入企业质量管理体系文件（包括质量手册、程序、作业指导书等），并确保其有效实施和受控。
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4.8.3
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(Inspection equipment) The applicant shall establish and keep the files, operating procedures and measurement of inspection equipment and environmental facilities/Calibration certification, service and maintenance records。
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4.8.4
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(Inspection procedures) shall be based on the principles of science and risk management, formulate raw material incoming inspection procedures, semi-finished products and finished products inspection procedures, and clearly formulate the basis。
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*4.8.5
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(Inspection record)应当保存注册检验、临床试验等相关产品的检验报告和记录，包括：进货检验、过程检验和成品检验等原始记录、检验报告或者证书以及检验方法确认或者验证记录等。Where there is commissioned inspection of some projects, there should be relevant project inspection reports and commissioned inspection agreements。
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*4.8.6
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(Release procedures) Product release procedures shall be established and implemented to clarify product release conditions and requirements for review and approval。
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Quality control
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4.8.7
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(In vitro diagnostic reagent traceability) In vitro diagnostic reagent traceability process should be reasonable, each batch of product assignment process and assignment method should be consistent。
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4.8.8
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(Sample retention) The applicant shall retain a certain number of registered inspection products and clinical trial products in combination with product characteristics。The quantity and specifications of products produced or samples retained shall meet the needs of product inspection and clinical evaluation (including clinical trials)。The destination of the samples shall be traceable。
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Commissioned production
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4.9.1
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(General requirements) In the production of products in the process of entrustment, the applicant shall be responsible for the guidance and supervision of the entrusted production enterprise quality management system of the department and personnel。In principle, a management representative should be appointed to be responsible for the quality control of commissioned production。
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*4.9.2
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（人员）请人应当配备专职的质量管理人员，人员应当熟悉产品The key quality control, key production operation requirements，能够对applicant和Entrusted to a production enterprise质量管理体系进行评估、审核和监督。The key personnel of the entrusted production enterprise, such as the production person in charge, the quality person in charge, and the production release auditor, shall be familiar with the key quality control and key production operation requirements of the entrusted product。
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*4.9.3
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The applicant shall sign an entrustment agreement with the agent，Clarify the rights, obligations and responsibilities of both parties，协议至少应当包括Entrusted to a production enterprise生产条件、技术文件的转移、物料采购控制、生产工艺和过程控制、成品检验、产品放行控制、文件与记录控制、变更控制、质量管理体系审核等，Ensure that the entrusted production enterprises organize production in accordance with laws and regulations, medical device production quality management norms, mandatory standards, and product technical requirements。
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Commissioned production
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4.9.4
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(on-site audit) before commissioning production，The applicant shall conduct on-site evaluation and review of the quality management system of the entrusted production enterprise，Audit content should at least include the organization and personnel, plant and facilities, equipment, production management, quality control capabilities，Ensure that the entrusted production enterprise has a quality management system suitable for the entrusted production products。
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*4.9.5
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(Design conversion)The applicant shall jointly plan and complete the design conversion activities with the entrusted production enterprise to ensureProduct technical requirements, production processes, raw material requirements, instructions and labels and other product technical documents can be effectively transferred to the entrusted production enterprises。
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4.9.6
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(Technical document conversion and process verification)受托生产企业应当结合本企业的生产条件和质量管理体系，将applicant的产品技术文件转化为本企业的技术文件，确保产品技术要求的关键技术参数、操作方法与applicant移交的保持一致。Trial production and process validation should be carried out, and trial production should include all transferred production processes and quality control processes。
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4.9.7
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(Technology transformation risk control)applicant应当结合原生产工艺文件，对受托生产企业执行的生产工艺文件进行比对评估，确保因生产条件等质量管理体系变化带来的风险已得到充分识别和控制。The applicant shall participate in the verification and confirmation work related to the entrusted products carried out by the entrusted production enterprise, and review the relevant process documents and reports。
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*4.9.8
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（Registered inspection products and clinical trial product production）applicant在受托生产企业开展Registered inspection products and clinical trial product production的，应当确保受托生产企业有与产品生产相适应的厂房、设施和设备。The applicant shall ensure the completion of process verification or validation and other related work。
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4.9.9
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(Material Purchase)The applicant shall clarify the procurement method, procurement approach, quality standards and inspection requirements of the commissioned product materials, and implement procurement in accordance with the requirements of the medical device commissioned production quality agreement。When necessary, the applicant and the entrusted production enterprise together to screen, audit, sign quality agreements, regular review of material suppliers。
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Commissioned production
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4.9.10
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(Production process Management)applicant应当会同受托生产企业对产品工艺流程、工艺参数、外协加工过程（如：辐照灭菌、环氧乙烷灭菌、阳极氧化、喷涂工艺等）、物料流转、批号和标识管理、生产记录追溯性等生产过程明确监控方式和标准，Specify who authorizes monitoring，And keep monitoring records。
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4.9.11
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(Document Management)applicant和受托生产企业共同持有的文件至少应当包括：委托协议，受托生产企业执行的产品技术要求、原材料要求、生产工艺和检验规程、产品说明书和标签以及产品放行程序等。
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*4.9.12
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(Product Release) The applicant shall establish product release review and approval procedures and ensure that both parties release registered inspection products, clinical trial products and marketed products in accordance with their respective responsibilities。The commissioned production enterprise shall formulate production release audit procedures, shall ensure that the commissioned production products meet the applicant's acceptance standards and keep release records。All records relating to the production of products shall be true, accurate, complete and traceable。
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4.9.13
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(Regular review) The applicant shall regularly review the entrusted production management of the entrusted production enterprise and relevant records, and keep audit records。The entrusted production enterprise shall keep all production records related to entrusted production, and may provide them to the applicant for reference at any time。If the entrusted production enterprise has the same product in production, it should have a significantly different number, batch number and process identification management method from the entrusted production product to avoid confusion。
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4.9.14
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(Communication mechanism) The applicant shall establish an effective communication mechanism with the entrusted production enterprise, and shall promptly notify the entrusted production enterprise of any design changes and procurement changes and supervise the implementation。For changes to the quality management system of the entrusted production enterprise that may affect the quality of the product, the applicant shall have measures to ensure that the entrusted production enterprise can inform the applicant in a timely manner and carry out a joint assessment。
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4.9.15
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(Applicant's responsibility)applicant应当对Design and development、生产、储运和不良事件监测情况进行全流程追溯、监控，保持质量管理体系的持续改进，并落实对Entrusted to a production enterprise监督。
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Product authenticity
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*4.10.1
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(Registered inspection products) Registered inspection products, including the inspection product batch number (No/Serial number, etc.) and specifications, inspection time, inspection quantity, inspection basis, inspection conclusion, key raw materials and/Or components and other information, calibration substances and/Or quality control substances, inspection product photos (including photos of independent software release version information), labels and other information, should be consistent with the production record and traceable。
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*4.10.2
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(Clinical Trial products) Clinical trial products, including clinical trial product lot numbers (No/Serial number, etc.) and specifications shall be consistent with production records and traceable。
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*4.10.3
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(Development and production traceability requirements) Production of product batches and production batch numbers or product numbers, specifications and models/包装规格、每批数量、注册检验产品和临床试验产品批号及数量、留样产品批号及数量、现存产品生产批号或者产品编号及数量、主要原材料批号及数量等应当可追溯。
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*4.10.4
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(Purchase record)应当保留用于产品生产的原材料采购记录，至少包括：原材料品名、型号规格、批号、材质（牌号）、供应商（生产商）、质量标准及进货验收、采购凭证、出入库记录及台账等。The relevant information of the procurement record shall be consistent with the corresponding contents of the production record and the registered inspection report。
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*4.10.5
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(Production and inspection records) Production records, process inspection original records, finished product inspection original records, etc. shall meet the requirements of the design output file。
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*4.10.6
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(Sample retention) If it is necessary to retain samples, the product shall be retained, and the product ledger and the observation record of the sample shall be kept。
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