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State Food and Drug Administration: Guidelines for the verification of medical device registration quality management system

 Last Update: 2022-10-21
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In order to do a good job in the verification of the registration quality management system under the medical device registrant system and improve the quality of the verification of the medical device registration quality management system, in accordance with the Regulations on the Supervision and Administration of Medical Devices (Order No.
739 of the State Council), the Administrative Measures for the Registration and Filing of Medical Devices (Order No.
47 of the State Administration of Market Regulation), the Administrative Measures for the Registration and Filing of in Vitro Diagnostic Reagents (Order No.
48 of the State Administration of Market Regulation), and the Measures for the Supervision and Administration of Medical Device Production (Order No.
53 of the State Administration of Market Regulation), The State Medical Products Administration has organized and revised the Guidelines for the Verification of Quality Management System for Medical Device Registration (see annex), which is hereby issued and implemented
from the date of promulgation.
The Notice of the State Medical Products Administration on Issuing Guidelines for the Verification of Quality Management System for Medical Device Registration (No.
19 of 2020) was abolished
at the same time.

Notice is hereby given
.

Annex: Guidelines for the verification of medical device registration quality management system

NMPA

September 29, 2022

Guidelines for the verification of quality management system for medical device registration

1.
Purpose and basis

In order to strengthen the verification and management of the medical device registration quality management system and ensure the quality of the verification work, this guide
is formulated in accordance with the Regulations on the Supervision and Administration of Medical Devices, the Administrative Measures for the Registration and Filing of Medical Devices, the Administrative Measures for the Registration and Filing of in Vitro Diagnostic Reagents, the Measures for the Supervision and Administration of Medical Device Production, the Good Manufacturing Practice for Medical Devices, the Good Manufacturing Practice for Medical Devices, the Good Management Practice for Clinical Trials of Medical Devices, and the Regulations on the Administration of Self-Inspection of Medical Device Registration.

2.
Scope of application

This guideline is applicable to the on-site verification
of the registration quality management system carried out by the medical device regulatory authorities for Class II and Class III medical devices.

3.
Basic requirements

3.
1 (Quality Management System) The registration applicant (hereinafter referred to as the applicant) shall, in accordance with the requirements of the Good Manufacturing Practice for Medical Devices and its appendices, establish a quality management system suitable for the product realization process based on scientific knowledge, experience and risk management principles, including commissioned production (if any), clinical evaluation (including clinical trials), etc.
, to ensure its effective operation in the whole life cycle management process of medical devices, and ensure the truthfulness, accuracy, completeness and traceability of process data such as design and development and production.
And consistent with
the registration application materials.

3.
2 (Registration Verification Requirements) The verification of the registration quality management system shall be organized in combination with the registration application materials, focusing on 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) For the submission of self-inspection reports, the applicant's quality management system and capabilities shall be verified
item by item in accordance with the Administrative Provisions on Medical Device Registration and Self-inspection, combined with the submitted product technical requirements.

3.
4 (Requirements for Entrusted Activity Inspection and Extended Inspection) For applicants who entrust other enterprises with design and development, product production and other activities, the scope of verification shall cover entrusted research and development and entrusted production activities
.
When necessary, extended inspections
shall be carried out for other products or services provided for medical device research and development and production activities.

4.
Key verification content

4.
1 Quality Management System Principles

4.
1.
1 (Quality Management System) The applicant shall establish a quality management system that covers design and development, production, quality control and release review and other products in combination with the characteristics of the product, and shall include commissioned production (if any), clinical evaluation (including clinical trials), etc
.

4.
1.
2 (Risk Management) The applicant shall establish a risk management system to evaluate the quality risks of the product realization process based on scientific knowledge and experience to ensure product quality
.

4.
1.
3 (Self-inspection) If the applicant carries out self-inspection, the self-inspection work shall be included in the product quality management system and meet the requirements
.

4.
2 Institutions and Personnel

4.
2.
1 (Organizational Structure) 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 development and technology transfer are reasonable and traceable
.

4.
2.
2 (Personnel) The applicant shall be equipped with an appropriate number of R&D, production and quality control personnel, and the personnel shall have professional knowledge and work skills
suitable for the declared registered products.

4.
2.
3 (Key Personnel) Key personnel such as management representatives, production leaders, quality leaders, technical leaders, product release auditors and other key personnel shall be familiar with the key quality control and key production operation requirements
of the declared registered products.

4.
2.
4 (Self-inspection personnel) Where the applicant submits a 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 inspectors shall match
the product inspection work.
Inspectors, auditors, approving personnel, etc.
shall be authorized
by the applicant in accordance with provisions.

4.
3 Plant, facilities and equipment

4.
3.
1 (Plant Facilities) The applicant shall be equipped with plants and facilities
suitable for the production of the declared registered products.
Product design and development shall be carried out
in suitable plants and facilities.
Plants and facilities for the production of inspection products (hereinafter referred to as registered inspection products) and clinical trial products applying for registration shall meet the quality control requirements of
the products.

4.
3.
2 (Production equipment) The applicant shall be equipped with production equipment and process equipment
suitable for the production of the products declared for registration.
The production equipment and process equipment for registered inspection products and clinical trial products shall meet the requirements of
product quality and production scale.

4.
3.
3 (Inspection Equipment) The applicant shall be equipped with environmental facilities and instruments that
meet the requirements of product inspection methods.
Laboratories carrying out special professional inspections shall have environmental facilities and conditions that meet specific professional requirements
.

4.
3.
4 (Registration Inspection and Production of Clinical Trial Products) Plant facilities and equipment used for the research and development and production of registered inspection products and clinical trial products and related use records
shall be kept.
In case of force majeure that cannot be retained, evidence that
can prove the truthfulness, completeness and traceability of product realization process activities such as product development, production and verification shall be retained.

4.
4 File Management

4.
4.
1 (System Documents) The applicant shall establish quality management system documents suitable for the declared registered products, including quality manuals, procedure documents, technical documents and data records
.
Technical documents shall include product technical requirements and related standards, production process procedures, work instructions, inspection and test operating procedures and other relevant documents
.
Data records 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 records) The original design and development materials shall be included in the document management
.
In addition to the directly output test data, auxiliary records in the design and development process should also be kept, such as main material collection records, instrument and equipment use records, weighing records, preparation records, etc.

When conducting clinical trials, the records of the outbound storage, storage and transportation, and recycling and disposal records of
the experimental instruments (reagents) related to the clinical trial process shall be retained.

4.
4.
3 (Verification Materials) The applicant shall retain research materials and records for verification after product design and development or technology transfer, and shall ensure the truthfulness, accuracy, completeness and traceability
of the data.

4.
4.
4 (Management of clinical trial documents) The applicant shall establish a management system for basic clinical trial documents, manage relevant documents of clinical trials in accordance with the requirements of the Catalogue of Basic Documents for Clinical Trials of Medical Devices/In Vitro Diagnostic Reagents and ensure their authenticity, completeness and traceability
.

4.
5 Design and Development

4.
5.
1 (Design and Development Documents) Medical device design and development documents shall originate from relevant documents for design and development planning, input, output, review, verification, confirmation, conversion, and change, including records established during the design and development process, and shall ensure the traceability
of the final output process of previous design and development and its related activities.

4.
5.
2 (Design and development input) Design and development input shall generally include laws and regulations, national standards, industry standards, domestic and foreign guidance documents, standard or reference material information (applicable to in vitro diagnostic reagent products), user needs, product scope of application, technical indicators of previous generation or similar products, product risks, etc
.

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, and shall pay attention to the scope of application, functionality, safety, effectiveness, and quality controllability
of the product.

4.
5.
3.
1 (Passive medical devices) The raw material components of passive medical devices shall meet the requirements of relevant standards, and the biocompatibility evaluation
shall be completed for the contact part of the product and the human body.
Reusable sterile products should be subjected to repeated sterilization by evaluating the performance of the finished product and completing a tolerable repeat sterilization study
.

4.
5.
3.
2 (Active Medical Devices) Active medical devices shall complete relevant research 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 sources include allogeneic medical devices) Medical devices of animal origin shall complete studies on animal species (if the risk is related to the strain, the strain needs to be specified), geographical source (for species whose geographical origin cannot be determined, provide identification and traceability requirements for the survival of the source animal), age (applicable when related to risk, such as the susceptibility of animals to naturally occurring transmitted spongiform encephalopathy), type of site and tissue, health status of animals and tissues, and verification of the applicability of virus inactivation methods
。

4.
5.
3.
4 (In vitro diagnostic reagents) The main raw materials, intermediates, important excipients, etc.
involved in the research process of in vitro diagnostic reagents shall be clearly sourced and meet the requirements, and the equipment, instruments and reagents used in the research process shall meet the research requirements
.

4.
5.
4 (Verification and confirmation) The applicant shall determine the scope and extent of work that needs to be verified or confirmed based on the results of the risk assessment, and ensure that the key elements of the relevant operation can be effectively controlled
.

4.
5.
5 (Design Conversion) The Applicant shall keep all records of product design conversion activities to show that the design and development outputs have been fully validated and suitable for routine production before becoming the final product specification, and to ensure that the production process continues to produce products
that meet the intended use and product technical requirements under the conditions of using the determined raw materials and equipment.
Such as: sterile product sterilization process and related equipment and facilities verification and confirmation, active medical device basic safety and basic performance realization confirmation evaluation, in vitro diagnostic reagent 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 reuses and keep relevant records, such as: product packaging design and verification, stability study data, product manual and minimum sales unit label design records, etc
.

4.
5.
7 (Verification Records) Detailed original data records of design and development verification activities shall be kept, including verification plans, verification reports, verification records (such as test data, sample processing records, etc.
), auxiliary records, etc.

4.
5.
8 (Clinical Confirmation Management) In the process of design and development confirmation, if the declared registered product needs to be confirmed by means of clinical trials, the applicant shall perform corresponding duties in accordance with the clinical trial protocol and contract, and keep relevant documents and records
.

4.
5.
9 (Requirements for Clinical Trial Products) For products undergoing 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 conducting clinical trials
.
Records of the relevant assessment and validation processes should be kept
.

4.
5.
10 (Management of Clinical Trial Products) The applicant shall keep records
of the distribution, storage and transportation, recycling/return of clinical trial products.

4.
5.
11 (Design and development changes) Design and development changes include product changes, citation document updates (such as regulations, mandatory standards), changes in design conversion (such as equipment, raw material suppliers, processes, environment, etc.
), changes from external sources (inspection, animal experiments, clinical trials, technical review changes), changes caused by changes in mandatory medical device standards, etc.
, shall be subject to risk assessment, verification or confirmation to ensure that changes are controlled
.

4.
5.
12 (Entrusted R&D Management) Where there is entrusted R&D, the applicant shall have quality management measures for
relevant activities.

4.
5.
12.
1 (Trustee Capacity Assessment) The applicant shall clarify the scope and extent of
entrustment of product research and development activities.
The R&D capacity and continuous technical support capacity of the entrusted R&D institution shall be put forward and evaluated
.

4.
5.
12.
2 (Entrusted R&D Agreement) The applicant shall sign a commissioned R&D agreement with the entrusted R&D institution, clearly stipulating the responsibilities of each party, the R&D 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 data in the entrusted research and development process.
The entrusted R&D institution shall comply with the requirements of the agreement to ensure the standardization, accuracy, completeness and traceability
of the R&D process and data.

4.
5.
12.
3 (Commissioned R&D technical documents) The applicant shall ensure that the entrusted R&D institution hands over the design and development output documents and meets the design and development input requirements
in accordance with the requirements of the agreement.

4.
6 Purchasing

4.
6.
1 (Procurement System) The applicant shall establish procurement control procedures to ensure that the purchased items meet the specified requirements
.

4.
6.
2 (Source of raw materials) The raw materials required for registration and inspection products and clinical trial products, including packaging materials and software that are in direct contact with the products, shall have proof of legal origin, such as supply agreements, orders, invoices, warehouse receipts, delivery notes, copies of approval supporting documents, etc
.

4.
6.
3 (Procurement of Main Materials) The purchase time or supply time of the main raw materials shall correspond to the production time of the product, and the purchase quantity shall meet the production needs of the product, and there shall be an inspection report or certificate of
conformity.

4.
6.
4 (Purchase Records) The purchase records of major raw materials shall comply with the product design requirements and the provisions of the purchase agreement, and the records shall be true, accurate, complete and traceable
.

4.
6.
5 (In vitro diagnostic reagent purchase record) The purchase of raw materials for in vitro diagnostic reagents shall be subject to a purchase contract or purchase record
.
The procurement of quality control products, calibrators, and enterprise reference products should meet the traceability requirements, such as samples involving human origin, there shall be corresponding raw material testing methods, inspection processes, inspection data, inspection records, and certification materials indicating biological safety
.

4.
6.
6 (Requirements for key materials of in vitro diagnostic reagents) After the design and shaping of in vitro diagnostic reagents, 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
.

4.
7 Production

4.
7.
1 (R&D 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 Good Manufacturing Practice for Medical Devices.

4.
7.
2 (Production process documents) The applicant shall prepare production process regulations, work instructions and other documents, and clarify key processes and special processes
.
For medical devices of animal origin, processes for inactivating and removing viruses and/or infectious agents and methods and/or processes for reducing the immunogenicity of materials of animal origin shall be confirmed
.

4.
7.
3 (Production and Record Requirements) The production of registered inspection products and clinical trial products shall be organized in accordance with the production process regulations, and the production records
shall be filled in truthfully.
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 shall ensure that the preparation concentration, production process, quality control process, etc.
of different working fluids meet the requirements of design output, especially the concentration and activity of bioactive materials should be stable and meet relevant standards
.
The material balance of raw materials should meet the requirements
.

4.
8 Quality Control

4.
8.
1 (Basic Requirements) The applicant shall establish quality control procedures, stipulate the requirements of the product inspection department, personnel, operation, etc.
, and stipulate the requirements for the use and calibration of inspection instruments and equipment, as well as the procedures for product release
.

4.
8.
2 (Self-inspection) If the applicant carries out self-inspection, it shall, in accordance with the requirements of the relevant inspection work and the self-inspection of the declared products, incorporate the quality management requirements related to the self-inspection work into the enterprise's quality management system documents (including quality manuals, procedures, work instructions, etc.
), and ensure their effective implementation and control
.

4.
8.
3 (Inspection Equipment) The applicant shall establish and keep the files, operating procedures, measurement/calibration certificates, use and maintenance records
of the inspection equipment and environmental facilities.

4.
8.
4 (Inspection Procedures) Based on scientific and risk management principles, raw material purchase inspection procedures, semi-finished products and finished product inspection procedures shall be formulated and the basis for
formulation shall be clarified.

4.
8.
5 (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 are some projects entrusted for inspection, there shall be relevant project inspection reports and entrusted inspection agreements
.

4.
8.
6 (Release Procedures) Product release procedures shall be established and implemented, and product release conditions and review and approval requirements
shall be clarified.

4.
8.
7 (In vitro diagnostic reagent traceability) The traceability process of in vitro diagnostic reagents shall be reasonable, and the value assignment process and the assignment method of each batch of products shall be consistent
.

4.
8.
8 (Sample retention) The applicant shall retain a certain number of registered inspection products and clinical trial products
in combination with the characteristics of the product.
The quantity and specifications of the production products or retained sample products shall meet the needs of
product inspection and clinical evaluation (including clinical trials).
The destination of the retained sample product should be traceable
.

4.
9 Commissioned production

4.
9.
1 (General Requirements) If there is a situation of 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 principle, a management representative shall be appointed to be responsible for the quality management
of commissioned production.

4.
9.
2 (Personnel) The applicant shall be equipped with full-time quality management personnel, who shall be familiar with the key quality control and key production operation requirements of the product, and be able to evaluate, audit and supervise
the quality management system of the applicant and the entrusted production enterprise.
Key personnel such as the person in charge of production, the person in charge of quality, and the production release auditor of the entrusted production enterprise shall be familiar with the key quality control and key production operation requirements
of the entrusted production products.

4.
9.
3 (Entrustment Agreement) The applicant shall sign an entrustment agreement with the entrusted party to clarify the rights, obligations and responsibilities of both parties, and the agreement shall at least include the production conditions of the entrusted production enterprise, the transfer of technical documents, material procurement control, production process and process control, finished product inspection, product release control, document and record control, change control, quality management system audit, etc.
, to ensure that the entrusted production enterprise complies with laws and regulations, medical device production quality management practices, mandatory standards, Product technology requires the organization of production
.

4.
9.
4 (On-site audit) Before entrusting production, the applicant shall carry out on-site assessment and audit of the quality management system of the entrusted production enterprise, and the audit content shall at least include institutions 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 that the product technical requirements, production process, raw material requirements, instructions and labels and other product technical documents can be effectively transferred to the entrusted production enterprise
.

4.
9.
6 (Technical Document Transformation and Process Verification) The entrusted production enterprise shall combine the production conditions and quality management system of the enterprise to convert the applicant's product technical documents into the technical documents of the enterprise, and ensure that the key technical parameters and operating methods of the product technical requirements are consistent
with those handed over by the applicant.
Trial production and process verification shall be carried out, and trial production shall include all transferred production processes and quality control processes
.

4.
9.
7 (Technology Transformation Risk Control) The applicant shall compare and evaluate the production process documents executed by the entrusted production enterprise in combination with the original production process documents to ensure that the risks caused by changes in the quality management system such as production conditions have been fully identified and controlled
.
The applicant shall participate in the verification and confirmation work related to the entrusted production products carried out by the entrusted production enterprise, and review
the relevant process documents and reports.

4.
9.
8 (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 entrusted production enterprise, it shall ensure that the entrusted production enterprise has plants, facilities and equipment
suitable for the production of the products.
The applicant shall ensure that the relevant work
such as process verification or confirmation is completed.

4.
9.
9 (Material Procurement) The applicant shall clarify the procurement methods, procurement channels, quality standards and inspection requirements of the materials entrusted for the production of products, and implement the procurement in accordance with the requirements of the quality agreement for the
commissioned production of medical devices.
If necessary, the applicant and the entrusted production enterprise will screen, audit, sign quality agreements, and regularly re-evaluate
the material suppliers.

4.
9.
10 (Production Process Management) The applicant shall, together with the entrusted production enterprise, clarify the monitoring methods and standards for the production process such as product process, process parameters, outsourcing processing process (such as: irradiation sterilization, ethylene oxide sterilization, anodizing, spraying process, etc.
), material flow, batch number and identification management, production record traceability, etc.
, designate authorized monitoring personnel, and keep monitoring records
.

4.
9.
11 (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 process and inspection procedures implemented by the entrusted production enterprise, product manuals and labels, and product release procedures
.

4.
9.
12 (Product Release) The applicant shall establish a product release review and approval procedure, and ensure that both parties release registered inspection products, clinical trial products and marketed products
in accordance with their respective responsibilities.
The entrusted production enterprise shall formulate production release review procedures, and shall ensure that the entrusted production products meet the acceptance standards of the applicant and keep release records
.
All records relating to the production of products shall be true, accurate, complete and traceable
.

4.
9.
13 (Periodic Audit) The applicant shall regularly review the entrusted production management and relevant records of the entrusted production enterprise, and keep the audit records
.
The entrusted production enterprise shall keep all production records related to the entrusted production and may provide them to the applicant for reference
at any time.
If the entrusted manufacturer has the same product in production, it shall have a significantly different number, batch number and process identification management method from the entrusted product to avoid confusion
.

4.
9.
14 (Communication Mechanism) The applicant shall establish an effective communication mechanism with the entrusted production enterprise, and any design changes, procurement changes, etc.
shall be notified to the entrusted production enterprise in a timely manner and supervise their implementation
.
For changes in the quality management system of the entrusted production enterprise that may affect product quality, 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) 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.

4.
10 Product Authenticity

4.
10.
1 (Registered Inspection Products) Registered inspection products, including the batch number (number/serial number, etc.
) and specification model of the inspection product, inspection time, inspection quantity, inspection basis, inspection conclusion, key raw materials and/or components and other information, calibration substances and/or quality control substances, photos of inspection products (including photos of independent software release version information), labels and other information, shall be consistent with the production records and traceable
.

4.
10.
2 (Clinical trial products) Clinical trial products, including clinical trial product batch numbers (numbers/serial numbers, etc.
) and specifications and models, shall be consistent with production records and traceable
.

4.
10.
3 (R&D and Production Traceability Requirements) The batch of products produced and the production batch number or product number, specification model/packaging specification, the quantity of each batch, the batch number and quantity of registered inspection products and clinical trial products, the batch number and quantity of retained sample products, the production batch number or product number and quantity of existing products, the batch number and quantity of major raw materials, etc.
shall be traceable
.

4.
10.
4 (Procurement records) Raw material procurement records used for product production shall be kept, including, at least: raw material names, model specifications, batch numbers, materials (grades), suppliers (manufacturers), quality standards and incoming acceptance, procurement vouchers, warehousing records and ledgers
.
The relevant information of the procurement record shall be consistent
with the corresponding content of the production record and the registration inspection report.

4.
10.
5 (Production and inspection records) Production records, original records of process inspection, original records of finished product inspection, etc.
shall meet the requirements of
design output documents.

4.
10.
6 (Retained samples) If it is necessary to retain samples, the sample products shall be retained, and the product ledger and sample observation records
shall be retained.

5.
Principles for determining on-site verification results

5.
1 There are a total of 73 verification items in this guideline, including 32 key items marked with "*" and 41 general items (see attached table).

The on-site inspection team shall make a judgment that the item is "compliant", "non-compliant" or "not applicable" one by one
against all the verification items.
For verification items judged to be "non-conforming", inspectors shall record in detail the specific problems
that exist.

5.
2 Principles for determining on-site verification results

The on-site verification conclusions are divided into four situations
: "passed verification", "failed verification", "passed verification after rectification", and "failed verification after rectification".

5.
2.
1 If the on-site inspection does not find that the applicant does not conform to the project, the recommended conclusion is "passed the verification"
.

5.
2.
2 If the on-site inspection finds any of the following circumstances, the recommended conclusion is "failed verification"
.
(1) On-site verification finds that the applicant has authenticity problems; (2) The on-site inspection does not find any authenticity problems, but it is found that the applicant has more than 3 key items (including) or more than 10 general items (inclusive) that do not meet the requirements
.

5.
2.
3 If no authenticity problem is found during the on-site inspection, and it is found that the applicant has less than 3 key items (excluded) and less than 10 general items (excluded) that do not meet the requirements, the recommended conclusion is "review after rectification"
.
The applicant whose verification conclusion is "review after rectification" shall complete the rectification within 6 months after the end of the registration verification and submit a one-time rectification report to the original verification department, and the verification department may carry out on-site review when necessary
.
If all projects are rectified and meet the requirements, the recommended conclusion is "pass the verification after rectification"
.

5.
2.
4 If the rectification report is not submitted within the specified time limit or there are still non-compliant items in the review, the recommended conclusion is "failure to pass the verification after rectification"
.

schedule

Chapter name	chapter serial number	content	The verdict
Chapter name	chapter serial number	content	accord with	No accord with	No apply
Quality Management System Principles	*4. 1. 1	(Quality management system) The applicant shall establish a quality management system that covers design and development, production, quality control and release review and other products that is compatible with the product realization process in combination with the characteristics of the product, and shall include commissioned production (if any), clinical evaluation (including clinical trials), etc .
	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	(Self-inspection) Where the applicant carries out self-inspection, the self-inspection work shall be included in the product quality management system and meet the requirements .
Institutions & Personnel	4. 2. 1	(Organizational structure) The applicant shall establish a management institution suitable for the research and development and production of medical devices, clarify the responsibilities of each department, and ensure that the design development and technology transfer are reasonable and traceable .
Institutions & Personnel	4. 2. 2	(Personnel) The applicant shall be equipped with an appropriate number and have corresponding R & D, production and quality control personnel, and the personnel shall have professional knowledge and work skills suitable for the declared registered products.
Institutions & Personnel	*4. 2. 3	(Key personnel) management representatives, production leaders, quality leaders, technical leaders, product release auditors and other key personnel shall be familiar with the key quality control and key production operation requirements of the declared registered products.
Institutions & Personnel	*4. 2. 4	(Self-inspection personnel) Where the applicant submits a self-inspection report, the quality inspection department shall allocate a sufficient number of full-time inspectors . The educational background and technical ability of inspectors shall match the product inspection work. Inspectors, auditors, approving personnel, etc. shall be authorized by the applicant in accordance with provisions.
Plant, facilities and equipment	*4. 3. 1	(Plant facilities) The applicant shall be equipped with plants and facilities suitable for the production of the products declared for registration. Product design and development shall be carried out in suitable plants and facilities. Plants and facilities for the production of inspection products (hereinafter referred to as registered inspection products) and clinical trial products applying for registration shall meet the quality control requirements of the products.
	*4. 3. 2	(Production equipment) The applicant shall be equipped with production equipment and process equipment suitable for the production of the declared registered products. The production equipment and process equipment for registered inspection products and clinical trial products shall meet the requirements of product quality and production scale.
	*4. 3. 3	(Inspection equipment) The applicant shall be equipped with environmental facilities and instruments and equipment that meet the requirements of product inspection methods. Laboratories carrying out special professional inspections shall have environmental facilities and conditions that meet specific professional requirements .
	*4. 3. 4	(Registration inspection and production of clinical trial products) shall retain plant facilities and equipment used for the research and development and production of registered inspection products and clinical trial products, as well as relevant use records . In case of force majeure that cannot be retained, evidence that can prove the truthfulness, completeness and traceability of product realization process activities such as product development, production and verification shall be retained.
File management	*4. 4. 1	(System documents) The applicant shall establish quality management system documents suitable for the declared registered products, including quality manuals, procedure documents, technical documents and data records . Technical documents shall include product technical requirements and related standards, production process procedures, work instructions, inspection and test operating procedures and other relevant documents . Data records shall ensure traceability of activities such as product design and development, material procurement, production, quality control, and product release.
File management	4. 4. 2	(R&D original records) The original materials for design and development shall be included in document management . In addition to the directly output test data, auxiliary records in the design and development process should also be kept, such as main material collection records, instrument and equipment use records, weighing records, preparation records, etc. When conducting clinical trials, the records of the outbound storage, storage and transportation, and recycling and disposal records of the experimental instruments (reagents) related to the clinical trial process shall be retained.
File management	4. 4. 3	(Verification data) The applicant shall retain research materials and records of product design and development or post-technology transfer verification, and shall ensure the truthfulness, accuracy, completeness and traceability of the data.
File management	4. 4. 4	(Management of clinical trial documents) The applicant shall establish a management system for basic clinical trial documents, manage the relevant documents of clinical trials in accordance with the requirements of the "Catalogue of Basic Documents for Clinical Trials of Medical Devices/In Vitro Diagnostic Reagents" and ensure their truthfulness, completeness and traceability .
Design development	*4. 5. 1	(Design and development documents) Medical device design and development documents shall originate from relevant documents for design and development planning, input, output, review, verification, confirmation, conversion, and change, including records established in the design and development process, and shall ensure the traceability of the final output process of previous design and development and its related activities.
	4. 5. 2	(Design and development input) Design and development input shall generally include laws and regulations, national standards, industry standards, domestic and foreign guidance documents, reference materials or reference material information (applicable to in vitro diagnostic reagent products), user needs, product scope of application, technical indicators of previous generation or similar products, product risks, etc .
	*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, and shall pay attention to the scope of application, functionality, safety, effectiveness, and quality controllability of the product.
	4. 5. 3. 1	(Passive medical devices) The raw material components of passive medical devices shall meet the requirements of relevant standards, and the biocompatibility evaluation shall be completed for the contact part of the product and the human body. Reusable sterile products should be subjected to repeated sterilization by evaluating the performance of the finished product and completing a tolerable repeat sterilization study .
	4. 5. 3. 2	(Active medical devices) Active medical devices shall complete relevant research 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 .
Design development	4. 5. 3. 3	(Animal sources include allogeneic medical devices) Medical devices of animal origin shall complete studies on animal species (if the risk is related to the strain, the strain needs to be specified), geographical source (for species whose geographical origin cannot be determined, provide identification and traceability requirements for the survival of the source animal), age (applicable when related to risk, such as the susceptibility of animals to naturally occurring transmitted spongiform encephalopathy), the type of site and tissue taken from the material, the health status of the animal and the tissue taken from the material, and the verification of the applicability of the virus inactivation method 。
	4. 5. 3. 4	(In vitro diagnostic reagents) The main raw materials, intermediates, important excipients, etc. involved in the research process of in vitro diagnostic reagents shall be clear from the source and meet the requirements, and the equipment, instruments and reagents used in the research process shall meet the research requirements .
	4. 5. 4	(Verification and confirmation) The applicant shall determine the scope and extent of work that needs to be verified or confirmed based on the results of the risk assessment, and ensure that the key elements of the relevant operation can be effectively controlled .
	4. 5. 5	(Design Transformation) The applicant shall keep all records of product design conversion activities to show that the design and development output has been fully verified and suitable for routine production before becoming the final product specification, and to ensure that the production process continues to stably produce products that meet the intended use and product technical requirements under the condition of using the determined raw materials and equipment. Such as: sterile product sterilization process and related equipment and facilities verification and confirmation, active medical device basic safety and basic performance realization confirmation evaluation, in vitro diagnostic reagent 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 reuses and keep relevant records, such as: product packaging design and verification, stability study data, product manual and minimum sales unit label design records, etc.
	4. 5. 7	(Verification records) shall keep detailed original data records of design and development verification activities, including verification plans, verification reports, verification records (such as test data, sample processing records, etc. ), auxiliary records, etc.
Design development	4. 5. 8	(Clinical Confirmation Management) In the process of design and development confirmation, if the declared registered product needs to be confirmed by means of clinical trials, the applicant shall perform corresponding duties in accordance with the clinical trial protocol and contract, and keep relevant documents and records .
	4. 5. 9	(Clinical trial product requirements) 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 conducting clinical trials . Records of the relevant assessment and validation processes should be kept .
	4. 5. 10	(Clinical trial product management) The applicant shall keep records of the distribution, storage and transportation, recycling/return of clinical trial products.
	4. 5. 11	(Design and development changes) Design and development changes include product changes, reference document updates (such as regulations, mandatory standards), changes in design transformation (such as equipment, raw material suppliers, processes, environment, etc. ), change requirements from the outside (inspection, animal experiments, clinical trials, technical review changes), changes caused by changes in mandatory medical device standards, etc. , shall be subject to risk assessment, verification or confirmation to ensure that changes are controlled .
	4. 5. 12	(Entrusted R&D management) Where there is a situation of commissioned R&D, the applicant shall have quality management measures for relevant activities.
	4. 5. 12. 1	(Trustee Capacity Assessment) The applicant shall clarify the scope and extent of the entrustment of product research and development activities. The R&D capacity and continuous technical support capacity of the entrusted R&D institution shall be put forward and evaluated .
Design development	4. 5. 12. 2	(Entrusted R&D Agreement) The applicant shall sign a commissioned R&D agreement with the entrusted R&D institution, clearly stipulating the responsibilities of each party, the content of R&D 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 data in the entrusted research and development process. The entrusted R&D institution shall comply with the requirements of the agreement to ensure the standardization, accuracy, completeness and traceability of the R&D process and data.
Design development	4. 5. 12. 3	(Entrusted R&D technical documents) The applicant shall ensure that the entrusted R&D institution hands over the design and development output documents and meets the design and development input requirements in accordance with the requirements of the agreement.
procurement	*4. 6. 1	(Procurement system) The applicant shall establish procurement control procedures to ensure that the purchased items meet the specified requirements .
	4. 6. 2	(Source of raw materials) The raw materials required for registration and inspection products and clinical trial products, including packaging materials and software that are in direct contact with the product, shall have proof of legal source, such as supply agreements, orders, invoices, warehouse receipts, delivery notes, copies of approval certification documents, etc.
	*4. 6. 3	(Procurement of main materials) The purchase time or supply time of the main raw materials shall correspond to the production time of the product, the purchase quantity shall meet the production needs of the product, and there shall be an inspection report or certificate of conformity.
	*4. 6. 4	(Procurement records) The purchase records of major raw materials shall comply with the product design requirements and the provisions of the purchase agreement, and the records shall be true, accurate, complete and traceable .
procurement	4. 6. 5	(In vitro diagnostic reagent purchase records) The purchase of raw materials for in vitro diagnostic reagents shall be subject to a purchase contract or purchase record . The procurement of quality control products, calibrators, and enterprise reference products should meet the traceability requirements, such as samples involving human origin, there shall be corresponding raw material testing methods, inspection processes, inspection data, inspection records, and certification materials indicating biological safety .
procurement	*4. 6. 6	(Requirements for key materials for in vitro diagnostic reagents) After the design and shaping of in vitro diagnostic reagents, 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 .
produce	*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 "Good Manufacturing Practice for Medical Devices".
	*4. 7. 2	(Production process documents) The applicant shall prepare production process regulations, work instructions and other documents, and clarify the key processes and special processes . For medical devices of animal origin, processes for inactivating and removing viruses and/or infectious agents and methods and/or processes for reducing the immunogenicity of materials of animal origin shall be confirmed .
	*4. 7. 3	(Production and record requirements) shall organize the production of registered inspection products and clinical trial products in accordance with the production process regulations, and fill in the production records truthfully. 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 shall ensure that the preparation concentration, production process, quality control process, etc. of different working solutions meet the requirements of design output, especially the concentration and activity of bioactive materials should ensure stability and meet relevant standards . The material balance of raw materials should meet the requirements .
quality control	4. 8. 1	(Basic requirements) The applicant shall establish quality control procedures, stipulate the requirements of product inspection departments, personnel, operations, etc. , and stipulate the requirements for the use and calibration of inspection instruments and equipment, as well as the procedures for product release .
	*4. 8. 2	(Self-inspection) If the applicant carries out self-inspection, it shall, in accordance with the requirements of relevant inspection work and self-inspection of declared products, incorporate the quality management requirements related to self-inspection work into the enterprise's quality management system documents (including quality manuals, procedures, work instructions, etc. ), and ensure their effective implementation and control .
	4. 8. 3	(Inspection equipment) The applicant shall establish and keep the files, operating procedures, measurement/calibration certificates, use and maintenance records of the inspection equipment and environmental facilities.
	4. 8. 4	(Inspection procedures) shall be based on scientific and risk management principles, formulate raw material purchase inspection procedures, semi-finished products and finished product inspection procedures, etc. , and clearly formulate the basis .
	*4. 8. 5	(Inspection records) shall keep inspection reports and records of registered inspection, clinical trials and other related products, including: original records such as purchase inspection, process inspection and finished product inspection, inspection reports or certificates, and inspection method confirmation or verification records . Where there are some projects entrusted for inspection, there shall be relevant project inspection reports and entrusted inspection agreements .
	*4. 8. 6	(Release procedures) shall establish and implement product release procedures, clarifying product release conditions and review and approval requirements .
quality control	4. 8. 7	(In vitro diagnostic reagent traceability) The traceability process of in vitro diagnostic reagents shall be reasonable, and the value assignment process and the assignment method of each batch of products shall be consistent .
quality control	4. 8. 8	(Sample retention) The applicant shall retain a certain number of registered inspection products and clinical trial products in combination with the characteristics of the product. The quantity and specifications of the production products or retained sample products shall meet the needs of product inspection and clinical evaluation (including clinical trials). The destination of the retained sample product should be traceable .
Contract production	4. 9. 1	(General requirements) If there is a situation of 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 principle, a management representative shall be appointed to be responsible for the quality management of commissioned production.
	*4. 9. 2	(Personnel) The applicant shall be equipped with full-time quality management personnel, and the personnel shall be familiar with the key quality control and key production operation requirements of the product, and be able to evaluate, review and supervise the quality management system of the applicant and the entrusted production enterprise. Key personnel such as the person in charge of production, the person in charge of quality, and the production release auditor of the entrusted production enterprise shall be familiar with the key quality control and key production operation requirements of the entrusted production products.
	*4. 9. 3	(Entrustment agreement) The applicant shall sign an entrustment agreement with the entrusted party to clarify the rights, obligations and responsibilities of both parties, and the agreement shall at least include the production conditions of the entrusted production enterprise, the transfer of technical documents, material procurement control, production process and process control, finished product inspection, product release control, document and record control, change control, quality management system audit, etc. , to ensure that the entrusted production enterprise organizes production in accordance with laws and regulations, medical device production quality management practices, mandatory standards, and product technical requirements 。
Contract production	4. 9. 4	(On-site audit) Before commissioning production, the applicant shall conduct an on-site assessment and audit of the quality management system of the entrusted production enterprise, and the audit content shall at least include institutions 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 that the product technical requirements, production process, raw material requirements, instructions and labels and other product technical documents can be effectively transferred to the entrusted production enterprise .
	4. 9. 6	(Technical document transformation and process verification) The entrusted production enterprise shall combine the production conditions and quality management system of the enterprise to convert the applicant's product technical documents into the technical documents of the enterprise, and ensure that the key technical parameters and operating methods of the product technical requirements are consistent with those handed over by the applicant. Trial production and process verification shall be carried out, and trial production shall include all transferred production processes and quality control processes .
	4. 9. 7	(Technology transformation risk control) The applicant shall compare and evaluate the production process documents implemented by the entrusted production enterprise in combination with the original production process documents to ensure that the risks caused by changes in the quality management system such as production conditions have been fully identified and controlled . The applicant shall participate in the verification and confirmation work related to the entrusted production 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 entrusted production enterprise, it shall ensure that the entrusted production enterprise has plants, facilities and equipment suitable for product production. The applicant shall ensure that the relevant work such as process verification or confirmation is completed.
	4. 9. 9	(Material procurement) The applicant shall clarify the procurement method, procurement channel, quality standards and inspection requirements of the materials entrusted for the production of products, and implement the procurement in accordance with the requirements of the quality agreement for commissioned production of medical devices. If necessary, the applicant and the entrusted production enterprise will screen, audit, sign quality agreements, and regularly re-evaluate the material suppliers.
Contract production	4. 9. 10	(Production process management) The applicant shall, together with the entrusted production enterprise, clarify the monitoring methods and standards for the production process such as product process, process parameters, outsourcing processing process (such as: irradiation sterilization, ethylene oxide sterilization, anodizing, spraying process, etc. ), material circulation, batch number and identification management, production record traceability, etc. , designate authorized monitoring personnel, and keep monitoring records .
	4. 9. 11	(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 manuals and labels implemented by the entrusted production enterprise, and product release procedures .
	*4. 9. 12	(Product release) The applicant shall establish a product release review and approval procedure, and ensure that both parties release registered inspection products, clinical trial products and marketed products in accordance with their respective responsibilities. The entrusted production enterprise shall formulate production release review procedures, and shall ensure that the entrusted production products meet the acceptance standards of the applicant and keep release records . All records relating to the production of products shall be true, accurate, complete and traceable .
	4. 9. 13	(Periodic audit) The applicant shall regularly review the entrusted production management and related records of the entrusted production enterprise, and keep the audit records . The entrusted production enterprise shall keep all production records related to the entrusted production and may provide them to the applicant for reference at any time. If the entrusted manufacturer has the same product in production, it shall have a significantly different number, batch number and process identification management method from the entrusted product to avoid confusion .
	4. 9. 14	(Communication mechanism) The applicant shall establish an effective communication mechanism with the entrusted production enterprise, and any design changes, procurement changes, etc. shall be notified to the entrusted production enterprise in a timely manner and supervise the implementation . For changes in the quality management system of the entrusted production enterprise that may affect product quality, 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) 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.
Product authenticity	*4. 10. 1	(Registered inspection products) Registered inspection products, including the batch number (number/serial number, etc. ) and specification model of the inspection product, inspection time, inspection quantity, inspection basis, inspection conclusion, key raw materials and/or components and other information, calibration substances and/or quality control substances, photos of inspection products (including photos of independent software release version information), labels and other information, shall be consistent with production records and traceable .
	*4. 10. 2	(Clinical trial products) Clinical trial products, including clinical trial product batch numbers (numbers/serial numbers, etc. ) and specifications and models, shall be consistent with production records and traceable .
	*4. 10. 3	(R&D and production traceability requirements) The production batch and production batch number or product number, specification model/packaging specification, quantity per batch, registration inspection product and clinical trial product batch number and quantity, retained sample product batch number and quantity, existing product production batch number or product number and quantity, main raw material batch number and quantity, etc. shall be traceable .
	*4. 10. 4	(Procurement records) shall keep raw material procurement records for product production, including, at least: raw material names, model specifications, batch numbers, materials (grades), suppliers (manufacturers), quality standards and incoming acceptance, procurement vouchers, warehousing records and ledgers . The relevant information of the procurement record shall be consistent with the corresponding content of the production record and the registration inspection report.
	*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 documents.
	*4. 10. 6	(Retained samples) If it is necessary to retain samples, the sample products shall be retained, and the product ledger and sample observation records shall be retained.

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