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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，According to the Regulations on the Supervision and Administration of Medical Devices (Decree No. 739 of The State Council) and the Measures for the Administration of Registration and Filing of Medical Devices (Decree No. 47 of the General Administration of Market Supervision), the Measures for the Administration of Registration and filing of in vitro diagnostic reagents (Decree No. 48 of the General Administration of Market Supervision), the Measures for the Supervision and Administration of Medical Device Production (Decree No. 53 of the General Administration of Market Supervision) and other requirements，国家药品监督管理局组织修订了《十大电子游艺平台首选》（见附件），Hereby published，Effective from the date of promulgation。国家药品监督管理局《十大电子游艺网站》（2020年第19号）同时废止。
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，According to the Regulations on the Supervision and Administration of Medical Devices, the Measures for the Registration and filing of Medical Devices, the Measures for the registration and filing of in vitro diagnostic reagents, the Measures for the supervision and Administration of Medical Device Production, the Standards for the quality Management of Medical Device Production, the Standards for the quality management of Medical device Clinical Trials, and the regulations for the management of medical device Registration and self-examination》Etc., develop this guide。
2. Scope of application
本指南适用于医疗器械监管部门对第二类、第三类医疗器械开展的注册质量管理体系现场核查。
3. Basic requirements
3.1(Quality Management System)注册applicant（简称applicant）应当按照《十大电子游艺网站》及附录的要求，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)应当结合注册申报资料组织开展注册质量管理体系核查，重点关注与产品研制、生产有关的Design and development、采购、生产管理、Quality control等内容。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 provisions》，结合提交的产品技术要求，对applicant的质量管理体系和能力逐项进行核实。
3.4(Commissioned activity inspection, extended inspection requirements)对存在Design and development、产品生产等活动委托其他企业的applicant，核查范围应当涵盖受托研发、受托生产活动。必要时，应当对为医疗器械研发、生产活动提供产品或者服务的其他单位开展延伸检查。
4. Focus on the content of verification
4.1Principles of quality management system
4.1.1(Quality Management System)The applicant shall, in combination with the characteristics of the product, establish a quality management system covering design and development, production, quality control and release audit that is compatible with the product realization process, and shall include commissioned production (if any), clinical evaluation (including clinical trials), etc。
4.1.2(Risk Management)applicant应当建立风险管理制度，根据科学知识及经验对产品实现过程的质量风险进行评估，以保证产品质量。
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)applicant应当建立与医疗器械研发、生产相适应的管理机构，明确各部门职责，确保Design and development和技术转换合理并可追溯。
4.2.2（人员）applicant应当配备适当数量并具有相应的研发、生产和Quality control人员，人员应当具有与Registered product相适应的专业知识和工作技能。
4.2.3(Key personnel)管理者代表、生产负责人、质量负责人、技术负责人、产品放行审核人等关键人员应当熟悉Registered 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。申请注册的检验用产品（简称注册检验产品）和临床试验产品生产的厂房与设施，应当满足产品的Quality control要求。
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。Registered inspection products and clinical trial product production设备和工艺装备，应当满足产品质量和生产规模要求。
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)应当保留用于注册检验产品和临床试验产品研发、生产的厂房设施与设备以及相关使用记录。如遇不可抗力无法保留的，应当留存可以证明产品研发、生产及验证等产品实现过程活动真实、完整和可追溯的证据资料。
4.4File management
4.4.1(System document)applicant应当建立与Registered product相适应的质量管理体系文件，包括质量手册、程序文件、技术文件和数据记录等。技术文件应当包括产品技术要求及相关标准、生产工艺规程、作业指导书、检验和试验操作规程等相关文件。数据记录应当确保产品Design and development、物料采购、生产、Quality control以及产品放行等活动可追溯。
4.4.2(R&D original record)The original materials of design and development shall be included in the file management。除直接输出的试验数据外，还应当保留Design and development过程中的辅助记录，如主要物料领用记录、仪器设备使用记录、称量记录、配制记录等。开展临床试验的，应当保留临床试验过程有关的试验器械（试剂）出库记录、储运记录、回收处置记录等。
4.4.3(Verification data)applicant应当保留产品Design and development或技术转让后验证的研究资料和记录，并应当确保数据的真实、准确、完整和可追溯。
4.4.4(Clinical trial document Management)The applicant shall establish a clinical trial basic document management system according to the "Medical devices./体外诊断试剂临床试验基本文件目录》要求管理临床试验有关文件并确保其真实、完整和可追溯。
4.5Design and development
4.5.1(Design and development document)Medical device design and development documents should be derived from design and development planning, input, output, review, verification, confirmation, conversion, change related documents, including records established in the design and development process, should ensure that the final output process of previous design and development and related activities can be traced。
4.5.2(Design and development input)Design and development input should generally include laws and regulations, national standards, industry standards, domestic and foreign guide documents, standard products or reference material information (in vitro diagnostic reagent products), user needs, product scope of application, technical indicators of previous or similar products, product risks, etc。
4.5.3(Design and development output)设计和开发输出应当满足输入要求，以及符合用户需求和产品设计需求，应当关注产品适用范围、功能性、安全性、有效性、质量可控性。
4.5.3.1(Passive medical devices)无源医疗器械原材料组分应当符合相关标准要求，产品与人体接触部分应当完成生物相容性评价。可重复使用的无菌产品在进行重复灭菌时，应当对成品性能进行评估并完成可耐受重复灭菌研究。
4.5.3.2(Active medical devices)有源医疗器械应当根据标准要求完成相关研究，如电击危险防护、机械危险防护、辐射危险防护、超温危险防护、电磁兼容性、生物相容性等。
4.5.3.3(Animal origin includes allogeneic medical devices)动Source medical devices shall完成动物种属（若风险与品系有关还需明确品系）、地理来源（对无法确定地理来源的种属，Provide identification and traceability requirements during the life of the source animal), age (where applicable in relation to risk，例如动物对自然发生的传播性海绵状脑病的易感性）、取材部位和组织的类型、动物及取材组织健康状况、病毒灭活方法适用性验证等研究。
4.5.3.4(in vitro diagnostic reagents)The main raw materials, intermediates and important excipients involved in the research process of in vitro diagnostic reagents should be clearly source and meet the requirements, and the equipment, instruments and reagents used in the research process should meet the research requirements。
4.5.4(Verification confirmation)applicant应当基于风险评估结果来确定需要进行验证或者确认的工作范围和程度，并确保有关操作的关键要素能够得到有效控制。
4.5.5(Design conversion)The applicant shall maintain all records of product design conversion activities，以表明设计和开发输出成为最终产品规范前已得到充分验证且适用于常规生产，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。Such as: sterilization process of aseptic products and related equipment and facilities verification and confirmation, the realization of basic safety and basic performance of active medical devices confirmation evaluation, in vitro diagnostic reagents production process, process parameters and batch scale-up verification。
4.5.6(Packaging, expiration date, reuse)The applicant shall conduct research on product packaging, expiration date or number of re-uses and keep relevant records, such as: product packaging design and verification, stability study data, product specifications and minimum sales unit label design records。
4.5.7(Verification record)应当保存设计和开发验证活动的详细原始数据记录资料，包括验证方案、验证报告、验证记录（如测试数据、样品处理记录等）、辅助记录等。
4.5.8(Clinical Confirmation Management)In the process of design and development confirmation, if it is necessary to confirm the registered product by clinical trial, the applicant shall perform the corresponding duties in accordance with the clinical trial plan and contract, and keep the relevant documents and records。
4.5.9(Requirements for clinical trial products)开展临床试验的产品，在临床试验开始前，applicant应当确保产品设计已定型且完成产品检验，其安全性、功能性适于开展临床试验。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 changes) Design and development changes include product changes, citation document updates (such as regulations, mandatory standards), design conversion changes (such as equipment, raw material suppliers, processes, environment, etc.), external change requirements (inspection, animal experiments, clinical trials, technical review changes), changes caused by mandatory medical device standards，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。应当对受托研发机构的研发能力与持续技术支持能力提出相应要求并进行评估。
4.5.12.2（委托研发协议）applicant应当与受托研发机构签订委托研发协议，明确规定各方责任、研发内容及相关的技术事项。applicant应当对委托研发的过程和结果负责，应当有措施确保委托研发过程数据的可靠性。受托研发机构应当遵守协议要求，保证研发过程规范、数据真实、准确、完整和可追溯。
4.5.12.3(Commissioned research and development technical documents)applicant应当确保受托研发机构按照协议要求移交Design and development输出文档并满足Design and development输入要求。
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)The raw materials required for registered inspection products and clinical trial products, including packaging materials and software in direct contact with the products, should have legal source proof, such as supply agreement, order, invoice, warehouse receipt, delivery note, copy of approval documents, etc。
4.6.3(Major Material purchase)主要原材料购入时间或者供货时间应当与产品生产时间相对应，购入量应当满足产品生产需求，且应当有检验报告或者合格证明。
4.6.4(Purchase record)主要原材料的采购记录应当符合产品设计需求和采购协议的规定，记录应真实、准确、完整和可追溯。
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。The procurement of quality control products, calibration products and enterprise reference products should meet the traceability requirements, such as samples from human sources, there should be the inspection method, inspection process, inspection data, inspection records of the corresponding raw materials, as well as proof materials indicating biosafety。
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)applicant应当按照《十大电子游艺网站》要求，组织注册检验产品和临床试验产品的生产活动。
4.7.2(Production process documents)applicant应当编制生产工艺规程、作业指导书等文件，并明确关键工序和特殊过程。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)应当按照生产工艺规程组织Registered inspection products and clinical trial product production，并如实填写生产记录。Production records shall be true, accurate, complete and traceable。
4.7.4(In vitro diagnostic reagent production requirements)The production of in vitro diagnostic reagents should ensure that the preparation concentration, production process and quality control process of different working fluids meet the requirements of the design output, especially the concentration and activity of bioactive materials should ensure stability and meet the relevant standards。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）Where the applicant carries out self-inspection, it shall incorporate the quality management requirements related to self-inspection into the enterprise quality management system documents (including quality manuals, procedures, operation instructions, etc.) in accordance with the requirements of relevant inspection work and self-inspection of declared products, and ensure its effective implementation and control。
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)应当基于科学和风险管理原则，制定原材料进货检验规程、半成品与成品检验规程等并明确制定依据。
4.8.5(Inspection record)Inspection reports and records of registered inspection, clinical trials and other related products shall be kept, including original records such as incoming inspection, process inspection and finished product inspection, inspection reports or certificates, and inspection method confirmation or verification records。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)体外诊断试剂溯源过程应当合理，每批产品赋值过程与赋值方法应当具有一致性。
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。生产产品或者留样产品数量和规格型号应当能满足产品检验和临床评价（含临床试验）的需要。The destination of the samples shall be traceable。
4.9Commissioned production
4.9.1(General requirements)在生产产品过程中存在委托情形的，applicant应当明确负责指导、监督受托生产企业质量管理体系的部门和人员。In principleA management representative shall be appointed to be responsible for the quality control of commissioned production。
4.9.2（人员）The applicant shall be equipped with full-time quality management personnel, who shall be familiar with the key quality control of the product and the key production operation requirements, and be able to evaluate, review and supervise the quality management system of the applicant and the entrusted production enterprise。Entrusted to a production enterprise生产负责人、质量负责人、生产放行审核人等关键人员应当熟悉受托生产产品The key quality control, key production operation requirements。
4.9.3(Trust agreement)applicantAn entrustment agreement shall be signed with the agent，Clarify the rights, obligations and responsibilities of both parties，The agreement shall at least include the production conditions of the entrusted manufacturer, the transfer of technical documents, material purchase control, production process and process control, finished product inspection, product release control, document and record control, change control, quality management system audit, etc，确保受托生产企业按照法律法规、医疗器械生产质量管理规范、强制性标准、产品技术要求组织生产。
4.9.4(on-site audit)Before commissioning production, the applicant shall carry out on-site evaluation and audit of the quality management system of the entrusted production enterprise, and the audit content shall at least include the organization and personnel, plant and facilities, equipment, production management, quality control capabilities, etc., to 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 ensure产品技术要求、生产工艺、原材料要求及说明书和标签等产品技术文件能有效转移到受托生产企业。
4.9.6(Technical document conversion and process verification)The entrusted production enterprise shall, in combination with its own production conditions and quality management system, convert the applicant's product technical documents into its technical documents to ensure that the key technical parameters and operation methods of the product technical requirements are consistent with those handed over by the applicant。应当进行试生产及工艺验证工作，试生产应当包括全部转移的生产过程及Quality control过程。
4.9.7(Technology transformation risk control)The applicant shall, in combination with the original production process documents, compare and evaluate the production process documents executed by the entrusted production enterprise to ensure that the risks caused by changes in the quality management system such as production conditions have been fully identified and controlled。applicant应当参与受托生产企业开展的与受托生产产品相关的验证与确认工作，并对相关的过程文件及报告进行审核。
4.9.8（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Plant, facilities and equipment。The applicant shall ensure the completion of process verification or validation and other related work。
4.9.9(Material Purchase)applicant应当明确Commissioned production产品物料的采购方式、采购途径、质量标准、检验要求，并按照医疗器械Commissioned production质量协议要求实施采购。必要时，applicant与受托生产企业一起对物料供应商进行筛选、审核、签订质量协议、定期复评。
4.9.10(Production process Management)The applicant shall, together with the entrusted production enterprise, clarify the monitoring methods and standards for product process flow, process parameters, outsourced processing (such as irradiation sterilization, ethylene oxide sterilization, anodizing, spraying process, etc.), material flow, batch number and marking management, production record traceability and other production processes，Specify who authorizes monitoring，And keep monitoring records。
4.9.11(Document Management)The documents jointly held by the applicant and the entrusted manufacturer shall at least include the entrustment agreement, product technical requirements, raw material requirements, production processes and inspection procedures, product specifications and labels, and product release procedures implemented by the entrusted manufacturer。
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。受托生产企业应当制定生产放行审核程序，应当保证受托生产产品符合applicant的验收标准并保留放行记录。All records relating to the production of products shall be true, accurate, complete and traceable。
4.9.13(Regular audit)applicant应当定期对Entrusted to a production enterprise受托生产管理情况和相关记录进行审核，并保留审核记录。受托生产企业应当保留受托生产相关的全部生产记录，并可随时提供给applicant备查。如果受托生产企业有相同产品在生产，应当与受托生产产品有显著区别的编号、批号及过程标识管理方式，避免混淆。
4.9.14（沟通机制）applicant应当与受托生产企业建立有效的沟通机制，任何设计变更、采购变更等均应当及时通知受托生产企业并监督执行。对受托生产企业质量管理体系发生的可能影响产品质量的变更，applicant应当有措施确保受托生产企业能及时告知applicant并开展联合评估。
4.9.15(Applicant's responsibility)The applicant shall trace and monitor the whole process of design and development, production, storage and transportation and adverse event monitoring, maintain the continuous improvement of the quality management system, and implement the supervision of the entrusted production enterprise。
4.10Product authenticity
4.10.1(Registered inspection products)Registration of inspection products, including inspection product batch number (No/序列号等）及规格型号、检验时间、检验数量、检验依据、检验结论、关键原料和/Or components and other information, calibration substances and/或质控物质、检验产品照片（含独立软件发布版本信息的照片）、标签等信息，应当与生产记录相符并可追溯。
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/Package specifications, quantity of each batch, batch number and quantity of registered inspection products and clinical trial products, batch number and quantity of retained sample products, batch number or product number and quantity of existing product production, batch number and quantity of main raw materials, etc., shall be traceable。
4.10.5(Production and inspection records)生产记录、过程检验原始记录、成品检验原始记录等应当符合设计输出文件要求。
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 verification6个月内完成整改并向原核查部门一次性提交整改报告，必要时核查部门可开展现场复查。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) The applicant shall, in combination with the characteristics of the product, establish a quality management system covering design and development, production, quality control and release audit that is compatible with the product realization process, and shall include commissioned production (if any), clinical evaluation (including clinical trials), etc。
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4.1.2
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(Risk Management)applicant应当建立风险管理制度，根据科学知识及经验对产品实现过程的质量风险进行评估，以保证产品质量。
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*4.1.3
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（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。
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Organization and personnel
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4.2.1
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(Organization)applicant应当建立与医疗器械研发、生产相适应的管理机构，明确各部门职责，确保Design and development和技术转换合理并可追溯。
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4.2.2
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（人员）applicant应当配备适当数量并具有相应的研发、生产和Quality control人员，人员应当具有与Registered product相适应的专业知识和工作技能。
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Organization and personnel
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*4.2.3
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(Key personnel) Key personnel such as the management representative, the production person in charge, the quality person in charge, the technical person in charge, and the product release auditor shall be familiar with the key quality control and key production operation requirements of the registered product。
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*4.2.4
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(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。
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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。申请注册的检验用产品（简称注册检验产品）和临床试验产品生产的厂房与设施，应当满足产品的Quality control要求。
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*4.3.2
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(Production equipment)applicantIt shall be equipped with production equipment and technological equipment suitable for the production of the declared and registered products。Registered inspection products and clinical trial product production设备和工艺装备，应当满足产品质量和生产规模要求。
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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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(Registered laboratory and clinical trial product production)应当保留用于注册检验产品和临床试验产品研发、生产的厂房设施与设备以及相关使用记录。如遇不可抗力无法保留的，应当留存可以证明产品研发、生产及验证等产品实现过程活动真实、完整和可追溯的证据资料。
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File management
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*4.4.1
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(System document)applicant应当建立与Registered product相适应的质量管理体系文件，包括质量手册、程序文件、技术文件和数据记录等。技术文件应当包括产品技术要求及相关标准、生产工艺规程、作业指导书、检验和试验操作规程等相关文件。数据记录应当确保产品Design and development、物料采购、生产、Quality control以及产品放行等活动可追溯。
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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。除直接输出的试验数据外，还应当保留Design and development过程中的辅助记录，如主要物料领用记录、仪器设备使用记录、称量记录、配制记录等。开展临床试验的，应当保留临床试验过程有关的试验器械（试剂）出库记录、储运记录、回收处置记录等。
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File management
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4.4.3
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(Verification data)applicant应当保留产品Design and development或技术转让后验证的研究资料和记录，并应当确保数据的真实、准确、完整和可追溯。
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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./体外诊断试剂临床试验基本文件目录》要求管理临床试验有关文件并确保其真实、完整和可追溯。
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Design and development
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*4.5.1
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(Design and development documents) Medical device design and development documents should be derived from design and development planning, input, output, review, verification, confirmation, conversion, change related documents, including records established in the design and development process, should ensure that the final output process of previous design and development and related activities can be traced。
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4.5.2
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(Design and development input) Design and development input should generally include laws and regulations, national standards, industry standards, domestic and foreign guide documents, standard products or reference material information (in vitro diagnostic reagent products), user needs, product scope of application, technical indicators of previous or similar products, product risks, etc。
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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)无源医疗器械原材料组分应当符合相关标准要求，产品与人体接触部分应当完成生物相容性评价。可重复使用的无菌产品在进行重复灭菌时，应当对成品性能进行评估并完成可耐受重复灭菌研究。
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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) Animal origin medical devices should be completed animal species (if the risk is related to the strain, the strain needs to be defined), 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，例如动物对自然发生的传播性海绵状脑病的易感性）、取材部位和组织的类型、动物及取材组织健康状况、病毒灭活方法适用性验证等研究。
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4.5.3.4
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(In vitro diagnostic reagents) The main raw materials, intermediates, and important excipients involved in the research process of in vitro diagnostic reagents should be clearly derived and meet the requirements, and the equipment, instruments and reagents used in the research process should meet the research requirements。
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4.5.4
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(Verification confirmation)applicant应当基于风险评估结果来确定需要进行验证或者确认的工作范围和程度，并确保有关操作的关键要素能够得到有效控制。
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4.5.5
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(Design Conversion) The Applicant shall maintain all records of product design conversion activities，以表明设计和开发输出成为最终产品规范前已得到充分验证且适用于常规生产，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。Such as: sterilization process of aseptic products and related equipment and facilities verification and confirmation, the realization of basic safety and basic performance of active medical devices confirmation evaluation, in vitro diagnostic reagents production process, process parameters and batch scale-up verification。
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4.5.6
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(Packaging, expiration date, reuse) The applicant shall conduct research on product packaging, expiration date or reuse times and keep relevant records, such as: product packaging design and verification, stability study data, product specifications and minimum sales unit label design records。
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4.5.7
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(Verification records) Detailed original data records of design and development verification activities shall 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) In the process of design and development confirmation, if the declared registered product needs to be confirmed by clinical trial, the applicant shall perform the corresponding duties in accordance with the clinical trial plan and contract, and keep the relevant documents and records。
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4.5.9
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(Requirements for clinical trial products) Before the clinical trial begins, 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 changes) Design and development changes include product changes, citation document updates (such as regulations, mandatory standards), design conversion changes (such as equipment, raw material suppliers, processes, environment, etc.), external change requirements (inspection, animal experiments, clinical trials, technical review changes), changes caused by mandatory medical device standards，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 R & D management)Where there is commissioned research and development, the applicant shall have quality management measures for relevant 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。应当对受托研发机构的研发能力与持续技术支持能力提出相应要求并进行评估。
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Design and development
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4.5.12.2
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（委托研发协议）applicant应当与受托研发机构签订委托研发协议，明确规定各方责任、研发内容及相关的技术事项。applicant应当对委托研发的过程和结果负责，应当有措施确保委托研发过程数据的可靠性。受托研发机构应当遵守协议要求，保证研发过程规范、数据真实、准确、完整和可追溯。
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4.5.12.3
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(Commissioned research and development technical documents)applicant应当确保受托研发机构按照协议要求移交Design and development输出文档并满足Design and development输入要求。
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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) The raw materials required for registered inspection products and clinical trial products, including packaging materials and software in direct contact with the products, should have legal source proof, such as supply agreement, order, invoice, warehouse receipt, delivery note, copy of approval documents, etc。
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*4.6.3
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The purchase time or supply time of the main raw materials shall correspond to the production time of the product, and the purchased quantity 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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(Purchase record)主要原材料的采购记录应当符合产品设计需求和采购协议的规定，记录应真实、准确、完整和可追溯。
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采购
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4.6.5
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(In vitro diagnostic reagent purchase record)The procurement of raw materials for in vitro diagnostic reagents shall have procurement contracts or procurement records。The procurement of quality control products, calibration products and enterprise reference products should meet the traceability requirements, such as samples from human sources, there should be the inspection method, inspection process, inspection data, inspection records of the corresponding raw materials, as well as proof materials indicating biosafety。
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*4.6.6
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(Requirements for key materials of in vitro diagnostic reagents) After in vitro diagnostic reagents are designed and finalized, the key raw materials themselves, such as antigens (source, amino acid sequence, conformation, etc.), antibodies (source, cell line, etc.), primer probe sequence, etc., should not change。
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生产
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*4.7.1
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(Development and production requirements)applicant应当按照《十大电子游艺网站》要求，组织注册检验产品和临床试验产品的生产活动。
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*4.7.2
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(Production process documents)applicant应当编制生产工艺规程、作业指导书等文件，并明确关键工序和特殊过程。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 recording requirements)应当按照生产工艺规程组织Registered inspection products and clinical trial product production，并如实填写生产记录。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) The production of in vitro diagnostic reagents should ensure that the preparation concentration of different working fluids, production process, quality control process, etc. meet the requirements of the design output, especially the concentration and activity of bioactive materials should ensure stability, and meet the relevant standards。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 requirements) 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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(Self-inspection) Where the applicant carries out self-inspection, it shall incorporate the quality management requirements related to self-inspection into the enterprise quality management system documents (including quality manuals, procedures, work instructions, etc.) in accordance with the requirements of relevant inspection work and self-inspection of declared products, and ensure its effective implementation and control。
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4.8.3
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(Inspection equipment)applicantFiles, operating procedures and measurements of inspection equipment and environmental facilities shall be established and kept/Calibration certification, service and maintenance records。
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4.8.4
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(inspection procedure)应当基于科学和风险管理原则，制定原材料进货检验规程、半成品与成品检验规程等并明确制定依据。
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*4.8.5
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(Inspection records) Inspection reports and records of registered inspection, clinical trials and other related products shall be kept, including original records such as incoming inspection, process inspection and finished product inspection, inspection reports or certificates, and inspection method confirmation or verification records。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 procedure)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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(Tracing of in vitro diagnostic reagents)体外诊断试剂溯源过程应当合理，每批产品赋值过程与赋值方法应当具有一致性。
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4.8.8
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（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。生产产品或者留样产品数量和规格型号应当能满足产品检验和临床评价（含临床试验）的需要。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)在生产产品过程中存在委托情形的，applicant应当明确负责指导、监督受托生产企业质量管理体系的部门和人员。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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(Personnel) The applicant shall be equipped with full-time quality management personnel, who shall be familiar with the key quality control of the product and the key production operation requirements, and be able to evaluate, review and supervise the quality management system of the applicant and the entrusted production enterprise。Entrusted to a production enterprise生产负责人、质量负责人、生产放行审核人等关键人员应当熟悉受托生产产品The key quality control, key production operation requirements。
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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，The agreement shall at least include the production conditions of the entrusted manufacturer, the transfer of technical documents, material purchase control, production process and process control, finished product inspection, product release control, document and record control, change control, quality management system audit, etc，确保受托生产企业按照法律法规、医疗器械生产质量管理规范、强制性标准、产品技术要求组织生产。
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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 carry out on-site evaluation and audit of the quality management system of the entrusted production enterprise, and the audit content shall at least include the organization and personnel, plant and facilities, equipment, production management, quality control capabilities, etc., to 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 commissioned production enterprise to ensure that product technical requirements, production processes, raw material requirements and product technical documents such as instructions and labels can be effectively transferred to the commissioned production enterprise。
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4.9.6
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(Technical document conversion and process verification) The entrusted production enterprise shall, in combination with its production conditions and quality management system, convert the applicant's product technical documents into its technical documents to ensure that the key technical parameters and operating methods of the product technical requirements are consistent with those handed over by the applicant。应当进行试生产及工艺验证工作，试生产应当包括全部转移的生产过程及Quality control过程。
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4.9.7
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(Technology transformation risk control) The applicant shall, in combination with the original production process documents, compare and evaluate the production process documents executed by the entrusted production enterprise to ensure that the risks caused by changes in the quality management system such as production conditions have been fully identified and controlled。applicant应当参与受托生产企业开展的与受托生产产品相关的验证与确认工作，并对相关的过程文件及报告进行审核。
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*4.9.8
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(Production of registered inspection products and clinical trial products) 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 factories, facilities and facilities suitable for product production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 procurement) The applicant shall clarify the procurement method, procurement approach, quality standards, inspection requirements of the commissioned product materials, and implement procurement in accordance with the requirements of the medical device commissioned production quality agreement。必要时，applicant与受托生产企业一起对物料供应商进行筛选、审核、签订质量协议、定期复评。
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Commissioned production
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4.9.10
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(Production process management) The applicant shall, together with the entrusted production enterprise, clarify the monitoring methods and standards for product process flow, process parameters, external processing processes (such as irradiation sterilization, ethylene oxide sterilization, anodizing, spraying process, etc.), material flow, batch number and marking management, production record traceability and other production processes，Specify who authorizes monitoring，And keep monitoring records。
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4.9.11
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(Document management) The documents jointly held by the applicant and the entrusted production enterprise shall at least include: the entrustment agreement, the product technical requirements, raw material requirements, production processes and inspection procedures, product specifications and labels, and product release procedures。
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*4.9.12
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(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。受托生产企业应当制定生产放行审核程序，应当保证受托生产产品符合applicant的验收标准并保留放行记录。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 audit)applicant应当定期对Entrusted to a production enterprise受托生产管理情况和相关记录进行审核，并保留审核记录。受托生产企业应当保留受托生产相关的全部生产记录，并可随时提供给applicant备查。如果受托生产企业有相同产品在生产，应当与受托生产产品有显著区别的编号、批号及过程标识管理方式，避免混淆。
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4.9.14
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（沟通机制）applicant应当与受托生产企业建立有效的沟通机制，任何设计变更、采购变更等均应当及时通知受托生产企业并监督执行。对受托生产企业质量管理体系发生的可能影响产品质量的变更，applicant应当有措施确保受托生产企业能及时告知applicant并开展联合评估。
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4.9.15
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(Responsibility of the applicant) The applicant shall trace and monitor the whole process of design and development, production, storage and transportation and adverse event monitoring, maintain continuous improvement of the quality management system, and implement the supervision of the entrusted production enterprise。
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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/序列号等）及规格型号、检验时间、检验数量、检验依据、检验结论、关键原料和/Or components and other information, calibration substances and/或质控物质、检验产品照片（含独立软件发布版本信息的照片）、标签等信息，应当与生产记录相符并可追溯。
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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/Package specifications, quantity of each batch, batch number and quantity of registered inspection products and clinical trial products, batch number and quantity of retained sample products, batch number or product number and quantity of existing product production, batch number and quantity of main raw materials, etc., shall be traceable。
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*4.10.4
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(Procurement records) The procurement records of raw materials used for product production shall be kept, including at least: raw material name, model specification, batch number, material (brand number), supplier (manufacturer), quality standard and purchase acceptance, purchase voucher, import and export records and ledger, etc。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)生产记录、过程检验原始记录、成品检验原始记录等应当符合设计输出文件要求。
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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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