Guidance for Medical Device Production Quality Management  in China, ([2014] No. 64)

Our Comment

Good Manufacturing Practice for Medical Devices = Guidance for Medical Device Production Quality Management

Order of the State Council No. 650 invalid, see No. 739

CFDA is former NMPA

Chapter I General Provisions

Article 1 With a view to ensuring the safety and effectiveness of medical devices and standardizing the management on quality of medical devices manufacturing, the Good Manufacturing Practice for Medical Devices (“GMP”) is hereby formulated in accordance with Regulations for the Supervision and Administration of Medical Devices (Order of the State Council No. 650) and the Measures for Supervision and Administration of Medical Devices Manufacturing (CFDA Order No. 7).

Article 2 Medical device manufacturers (hereinafter referred to as “manufacturers”) shall comply with the requirements set out in the GMP when designing and developing, manufacturing and selling medical devices, as well as providing after-sales services.

Article 3 Manufacturers shall establish and improve the quality management system adapted to the medical devices manufactured in combination with product features according to the requirements in the GMP and ensure its effective operation.

Article 4 Manufacturers shall conduct risk management through the whole process of design and development, manufacture, sales and after-sales service and take the measures adapted to product risks.

Chapter II Institution and Personnel

Article 5 Manufacturers shall establish the regulatory agency adapted to medical device manufacture with the organizational chart which clarifying the responsibilities and authorities of all divisions as well as quality function & responsibilities. Neither the head of manufacture management department nor the head of quality management department shall hold a concurrent post with each other.

Article 6 The principal of manufacturers is the main responsible person of the quality of medical devices and shall fulfill the following responsibilities:

(1)   Organize the formulation of quality policy and quality objectives of manufacturers;

(2)   Ensure the human resources, infrastructures and working environment required for the effective operation of quality management system, etc.;

(3)   Organize the management review and carry out periodical evaluation on the operation of quality management system, and continuously improve it;

(4)   Organize the manufacture in accordance with laws and regulations.

Article 7 The person in charge of the manufacturer shall appoint a management representative. Such management representative shall be responsible for establishing, implementing and maintaining the quality management system, report the working conditions and improvement needs of the quality management system, and enhance the employees’ awareness of complying with the regulations, rules and customer requirements.

Article 8 The head of technical, manufacture and quality management department shall be familiar with laws and regulations related to medical devices, have practical experiences on quality management and be able to make correct judgment and handling for the practical problems in manufacture management and quality management.

Article 9 Manufacturers shall be equipped with the professional and technical personnel, management and operating personnel adapted to the products manufactured and have corresponding quality testing institutions or full-time testing personnel.

Article 10 The personnel engaged in the work affecting the product quality shall receive the training adapted to their job requirements and have relevant theoretical knowledge and practical operation skills.

Article 11 Manufacturers shall manage the health of the personnel engaged in the work affecting the product quality and establish health records.

Chapter III Buildings and Facilities

Article 12 Buildings and facilities shall conform to manufacturing requirements. The overall layout of manufacture, administration and the auxiliary areas shall be rational without interference with each other.

Article 13 Buildings and facilities shall be rationally designed, deployed and applied according to the features, technological process and corresponding air cleanness class of the products manufactured. The manufacturing environment shall be clean and tidy and comply with the need of product quality and requirements in relevant technical standards. Where products have special requirements, it shall be ensure that the external environment of the buildings has no effect on products, and carry out verification if necessary.

Article 14 It shall ensure the quality of the products manufactured and stored and properties of relevant equipment not directly or indirectly influenced in the buildings, which shall be equipped with appropriate illumination, temperature, humidity and ventilating control conditions.

Article 15 For the design and installation of buildings and facilities, necessary measures shall be taken in accordance with the product features so as to effectively prevent the insects or other animals from entering. The maintenance and repair of buildings and facilities shall not affect the product quality.

Article 16 There shall be sufficient space in the production area, matching with the manufacturing scale and type of the products to be manufactured there.

Article 17 The warehousing area shall meet the storage conditions and requirements necessary for the raw materials, packaging materials, intermediate products and finished products, within which they shall be stored in different segments as per their following status, namely, products to be inspected, conforming, nonconforming, returned or recalled, so as to facilitate the inspection and monitoring.

Article 18 Manufacturers shall be equipped with inspection place and facilities adapted to the manufacturing scale, varieties and inspection requirements of products.

Chapter IV Equipment

Article 19 Manufacturers shall be equipped with manufacturing equipment and technological equipment matched with the products manufactured and manufacturing scale, and ensure their effective operation.

Article 20 Manufacturing equipment shall conform to intended use in terms of design, model selection, installation, repair and maintenance to facilitate the operation, cleaning and maintenance. Manufacturing equipment shall have obvious status identification to prevent non-intended use.

Manufacturers shall establish the operating procedures for the use, cleaning, maintenance and repair of manufacturing equipment and maintain corresponding operating records.

Article 21 Manufacturers shall be equipped with related inspection instruments and equipment according to the product inspection requirements. There shall be clear operating procedures for main inspection instruments and equipment.

Article 22 Manufacturers shall establish usage records of inspection instruments and equipment, including the usage, calibration, maintenance and repair, etc.

Article 23 Manufacturers shall be equipped with appropriate measuring instruments, of which the measuring range and precision shall meet operating requirements, the expiry date of calibration indicated, and the corresponding records maintained.

Chapter V Document Management

Article 24 The manufacturer shall establish and perfect the quality management system documents, including the quality policies and quality objectives, the quality manual, the procedure files, the technical documents and records, and other documents. 

Quality manual shall include the requirements for quality management system.

Procedure files shall be formulated according to all working procedures to be established in product manufacturing and quality management, and shall contain all procedures specified in the GMP.

Technical documents shall include relevant documents such as product technical requirements and relevant standards, manufacturing process procedures, operation instruction, operating procedures for inspection and testing, and operating procedures for installation and service, etc.

Article 25 Manufacturers shall establish the document control procedure, systematically design, develop, review, approve and issue the documents of quality management system, which shall at least conform to the following requirements:

(1)   The draft, revision, review, approval, replacement or withdrawal, duplication, storage and destruction of documents shall be managed according to control procedures with corresponding records of document distribution, replacement or withdrawal, duplication and destruction;

(2)   The update or revision of documents shall be reviewed and approved according to regulations. The modification and revision status of the documents shall be able to be identified;

(3)   The documents to be distributed and used shall be the appropriate documents, and those withdrawn or abolished shall be indicated to prevent misuse.

Article 26 Manufacturers shall validate the retention period of obsolete technical documents and other necessary quality management system documents so as to meet the need for product maintenance and traceability of product quality responsibilities.

Article 27 Manufacturers shall establish the record control procedure, including the identification, storage, searching, storage life and disposal requirements, etc. of the records, which shall meet the following requirements:

(1)   The records shall ensure the traceability of the activities such as product manufacturing and quality control;

(2)   The records shall be clear, complete and easy to be identified and prevented from damage and loss;

(3)   The records shall not be arbitrarily altered or destroyed. It shall endorse one’s name and date for altering the records with original information that shall still be clear, and the reason for the alteration shall be illustrated when necessary;

(4)   The storage life of records shall at least be equivalent to the shelf life of medical devices specified by manufacturers, but shall not be less than two years upon releasing date of products or in compliance with relevant laws and regulations, and shall be traceable.

Chapter VI Design and Development

Article 28 The manufacturer shall establish the design control procedures and formulate corresponding documents, and the medical device design and development process may be planned and controlled.

Article 29 When planning the medical device design and development, the manufacturer shall validate the design and development stages, as well as the review, verification, validation and design conversion in each stage, and identify and validate the design and development activities attributable to each department and the interfaces so as to define their respective duties and functions.

Article 30 The design and development input shall include the performance and safety requirements, regulatory requirements, risk control measures and other requirements set out in the intended use. The design and development input shall be reviewed and obtain approval, and relevant records shall be maintained.

Article 31 The design and development output shall meet the input requirements, including the information and technical requirements necessary for the product procuring, manufacturing and service. The design and development output shall be approved, and relevant records shall be maintained.

Article 32 In the process of design and development, the manufacturer shall perform the manufacturing conversion activities relating to design and development, so as to ensure the design and development output to be verified prior to final product specifications and ensure that the design and development output applicable to the manufacturing.

Article 33 The manufacturer shall schedule review in suitable design and development stage and maintain the records related to the review results and any necessary measures.

Article 34 The manufacturer shall verify the design and development to ensure that the output meets the input requirements and maintain the records related to the verification results and any necessary measures.

Article 35 The manufacturer shall validate the design and development to ensure that the products meet the required technical requirements or the  intended use and maintain the records related to the validation results and any necessary measures.

Article 36 The manufacturer shall validate whether clinical evaluation or performance evaluation may be applied. Any clinical trial shall be conducted in accordance with the regulations for medical device clinical trials. 

Article 37 The manufacturer shall identify any changes to the design and development and maintain relevant records. When necessary, the manufacturer shall review, verify and validate such changes, and may not implement them until the same is approved.

In the event that any change to the selected materials, parts or product functions may affect the safety and effectiveness of any medical device, the manufacturer shall evaluate the risks which may arise from such change, and if necessary, take measures to reduce the risks to an acceptable degree, meanwhile, pursuant to the requirements set out in relevant regulations.

Article 38 In the whole process, including the product design and development, the manufacturer shall establish the risk control requirements and formulate corresponding documents, and maintain relevant records.

Chapter VII Procurement

Article 39 Manufacturers shall establish procurement control procedure to ensure that the procured articles conform to the requirements specified, which shall at least meet the relevant provisions in laws and regulations and relevant requirements in national mandatory standards.

Article 40 Manufacturers shall validate the way and degree of control on procured articles according to the procured articles’ effect on products.

Article 41 Manufacturers shall establish supplier review system and carry out review and evaluation on the suppliers in which carrying out on-spot review when necessary.

Article 42 Manufacturers shall conclude and sign Quality Agreement with the suppliers of main raw materials clarifying the quality responsibilities of both sides.

Article 43 In case of procurement, manufacturers shall clarify procurement information and clearly describe procurement requirements, including the category of procured articles, acceptance criteria, models and specifications, procedures and drawings. Procurement records shall be established, including Procurement Contract, list of raw materials, supporting documents of supplier’s qualification, quality standards, testing report and acceptance criteria. Procurement records shall meet the requirements for traceability.

Article 44 The manufacturer shall inspect or verify any articles procured thereby so as to ensure that they meet the manufacturing requirements.

Chapter VIII Manufacture Management

Article 45 Manufacturers shall carry out manufacture according to established quality management system to ensure that the products conform to mandatory standards as well as product technical requirements registered or filed.

Article 46 Manufacturers shall compile manufacturing process procedures and operation instructions to clarify critical process and special process.

Article 47 Where raw materials, work-in-progress require to be cleaned during the manufacturing process, cleaning method and requirements shall be clarified, and cleaning effect shall be verified.

Article 48 Manufacturers shall carry out environment monitoring according to manufacturing process features and maintain the records.

Article 49 Manufacturers shall verify the special manufacturing process and maintain the records, including validation plan, validation method, operators, result evaluation and re-validation, etc.

Where computer software used in the manufacturing process has effect on the product quality, the verification or validation shall be carried out.

Article 50 There shall be manufacturing record for each batch (set) of products which can meet the requirements for traceability.

Manufacturing records shall include the product name, model and specification, batch number of raw materials, manufacturing batch number or product ID, manufacturing date, quantity, main equipment, technological parameters and operators.

Article 51 Manufacturers shall establish product identification control procedure and identify the products with appropriate method to facilitate identification and prevent mixing and misuse.

Article 52 Manufacturers shall indicate the inspection status of products during manufacturing process to prevent the nonconforming, work-in-progress from flowing to next procedure.

Article 53 Manufacturers shall establish a procedure for the traceability of products and specify its scope, degree and necessary records.

Article 54 The product instruction for use and labels shall conform to relevant laws and regulations as well as standards.

Article 55 Manufacturers shall establish product protection procedure and specify the protection requirements for products and their components, including requirements for pollution protection, electrostatic protection, dust protection, corrosion prevention and transportation protection, etc. The protection shall include identification, transportation, packaging, storage and protection, etc.

Chapter IX Quality Control

Article 56 Manufacturers shall establish quality control procedure specifying requirements for product inspection department, personnel and operation, and requirements for the use and calibration of inspection instruments and equipment as well as product release procedure.

Article 57 The management and use of inspection instruments and equipment shall conform to the following requirements:

(1)   Carry out calibration or verification of inspection instruments and equipment periodically and identify them;

(2)   Specify the protection requirements for the inspection instruments and equipment during their transportation, maintenance and storage to prevent the inaccuracy of inspection results;

(3)   Where inspection instruments and equipment failing to meet the requirements, evaluate the previous inspection results and maintain verification records;

(4)   Validate the computer software used for inspections.

Article 58 Manufacturers shall develop inspection procedures of products according to mandatory standards as well as product technical requirements registered or filed, and issue corresponding inspection report or certificate.

The incoming inspection, process inspection and finished product inspection projects requiring routine control shall not be entrusted for inspection in principle. Where the projects have comparatively high requirements for inspection conditions and equipment needing entrusted inspection, a qualified institution may be entrusted to carry out inspections so as to prove that products conform to mandatory standards as well as product technical requirements registered or filed.

Article 59 Each batch (set) of products shall be accompanied with such inspection records that can be traceable. Such incoming records shall include any inspection records, testing reports or certificates arising out of incoming quality control, process inspection and finished product inspection.

Article 60 Manufacturers shall specify product release procedure, conditions and requirements for release approval. Certificate of Conformance shall be attached for the products released.

Article 61 Manufacturers shall formulate administrative provisions for sample retention according to product and process features, retain the samples according to relevant provisions and maintain the observation records of retention samples.

Chapter X Sales and After-sales Service

Article 62 Manufacturers shall establish product sales records meeting the requirements for traceability which shall at least include: the name, specification, model and quantity of medical devices; batch number, expiry date, distribution date, the name, address and contact of procuring units, etc.

Article 63 The manufacturer, which sells or retains a medical device distributing enterprise to sell any products manufactured by it, shall comply with the relevant medical devices regulations and rules. Upon their awareness of any distributing activities by such medical device distributing enterprise in violation of any laws or regulations, the manufacturer shall promptly report to the local food and drug regulatory authority.

Article 64 Manufacturers shall be equipped with after-sales service ability adapted to the products manufactured, and establish and improve after-sales service system. They shall specify the requirements for after-sales service and establish after-sales service record, and meet the requirements for traceability.

Article 65 Where the medical devices need to be installed by manufacturers, manufacturers shall validate the installation requirements and acceptance criteria for installation and verification and establish installation and acceptance record.

Where the medical devices are installed and repaired by consumption units or other enterprises, manufacturers shall provide installation requirements and criteria and components and parts, data and password, etc., and provide guidance.

Article 66 Manufacturers shall establish the customer feedback handling procedure, and carry out follow-up analysis on customer feedback information.

Chapter XI Control of Nonconforming Products

Article 67 The manufacturer shall establish control procedures of non-conforming products and define the responsibilities and authorities of the departments and personnel controlling nonconforming products. 

Article 68 The manufacturer shall mark, record, isolate and review any non-conforming products and take corresponding disposal measures against them based on the review results.

Article 69 Where manufacturers discover products nonconforming after sale, they shall promptly take corresponding measures, such as recall or destruction, etc.

Article 70 Where nonconforming products may be reworked, manufacturers shall develop control document of rework including the contents of operation instruction, re-inspection and re-verification, etc. Where nonconforming products cannot be reworked, manufacturers shall establish relevant disposal systems.

Chapter XII Adverse Events Monitoring, Analysis and Improvement

Article 71 Manufacturers shall assign relevant department to receive, investigate, evaluate and handle customer complaints and maintain relevant records.

Article 72 Manufacturers shall establish the medical device adverse event monitoring system in accordance with relevant laws and regulations, carry out monitoring and re-evaluation of adverse events and maintain the relevant records.

Article 73 Manufacturers shall establish the data analysis procedure, collect and analyze the data related to the product quality, adverse event, customer feedback and operation of quality management system, verify the safety and effectiveness of products, and maintain relevant records.

Article 74 The manufacturer shall establish corrective action and procedures to validate the cause of any problem and take efficient measures to prevent the reoccurrence of such problem.

The manufacturer shall establish preventive measures and procedures to validate the cause of any potential problem and take efficient measures to prevent such problem from happening.

Article 75 For the medical devices with potential safety hazards, manufacturers shall take measures such as recall, etc. in accordance with relevant laws and regulations, and report to relevant authorities in accordance with relevant provisions.

Article 76 Manufacturers shall establish the notification procedure of product information and promptly inform consumption unit, enterprises or consumers concerned of supplementary information such as product change and usage, etc.

Article 77 The manufacturer shall establish internal review procedures for the quality management system and specify the requirements for reviewing rules, scope, frequency, participants, method, records, as well as evaluation on the effectiveness of corrective and preventive action so as to ensure that the quality management system meets the requirements in the GMP.

Article 78 The manufacturer shall perform regular management review, through which the quality management system may be evaluated and reviewed, to ensure its continuous suitability, sufficiency and effectiveness.

Chapter XIII Supplementary Provisions

Article 79 Where medical devices registration applicant or filing applicant conducting product development, they shall also comply with the relevant requirements in the GMP.

Article 80 CFDA shall formulate detailed provisions for different categories of medical devices according to their respective manufacturing requirements.

Article 81 The manufacturer may identify those inapplicable provisions in the GMP according to the characteristics of the medical devices manufactured thereby and explain the reasons. 

Article 82 The following terms in the GMP are defined as:

Verification: the affirmation that the requirements specified have been satisfied through providing objective evidence.

Validation: the affirmation that specific intended use or application requirements have been satisfied through providing objective evidence.

Critical process: refers to the process that plays decisive role in product quality.

Special process: refers to the process the quality of which is hard to be correctly evaluated through experiments and tests.

Article 83 The GMP shall be explained by CFDA.

Article 84 The GMP shall come into force as of March 1, 2015, and the Good Manufacturing Practice for Medical Devices (Interim) (GSYJX [2009] No. 833) published by the former CFDA on December 16, 2009 shall be abolished simultaneously.