YY 0033-2000 Sterile medical device production management specification
Some standard content:
Record number: 0854-2001
Pharmaceutical Industry Standard of the People's Republic of China
YY 0033-2000
Good manufacture practice for sterile medical devices2000-08-18 Issued
State Drug Administration Issued
2000-09-15 Implementation
YY0033-2000
This standard is the first revised version of YY/T0033-1990 "Good manufacture practice for sterile medical devices". The purpose of this revision is to implement the "Medical Device Supervision and Management Regulations". At the same time, in order to strengthen the supervision and management of sterile medical devices and ensure the safety and effectiveness of sterile medical devices, the standard is changed from a recommended standard to a mandatory standard. The main differences between this standard and YY/T0033--1990 are as follows: a) "Organization and personnel" is changed to "quality system", requiring enterprises producing sterile medical devices to establish and implement an effective quality management system and form a complete quality management system document; b) "Production environment and layout" is changed to "Production environment, facilities and layout", adding requirements for water and electricity lines, workbenches, compressed air, etc. in the clean room (area); it also adds purification requirements for personnel and materials entering the clean room (area) and process layout requirements; c) "Equipment and tooling" adds requirements for process water preparation, storage and transportation equipment; d) "Raw materials and purchased parts" is changed to "Purchasing and material management", proposing that suppliers should be evaluated; e) "Technical documents" is changed to "documents", in addition to the requirements for technical documents, it also requires enterprises to prepare "quality manuals" and "procedure documents", and puts forward requirements for document control; f) "Quality inspection and supervision" is changed to "quality management"; g) "Production process management" adds "product identification and traceability", "control of non-conforming products", "corrective and preventive measures" and other contents. The content of the packaging mark was supplemented; h) "Product sales and user service" added that enterprises should establish a sterile medical device adverse event reporting system, accident reporting system and product recovery system.
i) The content of Appendix B\Control area, clean area indoor environment requirements and scope of application\ was greatly modified, divided into Appendix B\Guidelines for setting the cleanliness level of sterile medical device production environment" and Appendix C\Requirements and monitoring of clean air (area) environment for photobacterial medical devices"; i) Added Appendix D\Procedures for personnel entering and exiting clean rooms (areas)" and Appendix E\Verification and confirmation" and other prompt appendices. Chapters 5, 6, 7 and 11 of this standard are mandatory, and the other chapters are recommended. From the date of implementation, this standard will replace YY/T0033-1990. Appendix A, Appendix B and Appendix C of this standard are all standard appendices. Appendix D, Appendix E and Appendix F of this standard are all prompt appendices. This standard is proposed by the State Food and Drug Administration. This standard is under the jurisdiction of the National Technical Committee for Standardization of Medical Infusion Devices. 1 The main drafting unit of this standard is the Jinan Medical Device Quality Supervision and Inspection Center of the State Food and Drug Administration. The participating drafting units of this standard are: Medical Device Department of the State Food and Drug Administration, China Medical Device Quality Certification Center, Tianjin Hanahao Medical Materials Co., Ltd., and Shanghai Municipal Drug Administration Drug Testing Institute. The main drafters of this standard are: Wang Yanwei, Xia Changsheng, Shi Yanping, Chen Zhi, Cao Shiguang, Chen Li, Wu Zhenmin, and Ji Wei. 1 Scope
Pharmaceutical Industry Standards of the People's Republic of China
Manufacture and Management Specifications for Sterile Medical Devices
Good manufacture practice for sterile medical devices This standard specifies the basic requirements for the production and quality management of sterile medical devices and their components. The production of primary packaging materials for sterile medical devices shall also comply with the provisions of this standard. 2 Reference standards
YY,0033—2000
Replaces YY/T0033—1990
The provisions contained in the following standards constitute the provisions of this standard through reference in this standard. When this standard is published, the versions shown are valid. All standards will be revised. All parties using this standard should explore the possibility of using the latest versions of the following standards. GB/T6583--1994 Terminology of quality management and quality assurance GB/T16292-1996 Test method for suspended particles in clean rooms (areas) of pharmaceutical industry GB/T16293-1996 Test method for floating bacteria in clean rooms (areas) of pharmaceutical industry GB/T16294-1996 Test method for settling bacteria in clean rooms (areas) of pharmaceutical industry YY/T0313-1998 Packaging, marking, transportation and storage of medical polymer products JGJ71-1990 Specification for construction and acceptance of clean rooms 3 Definitions
This standard uses the definitions of GB/T6583 and YY/T0313 and the following definitions. 3.1 Lot
The determined quantity of a product with the same properties and quality produced when the production conditions are relatively stable. 3.2 Lot number
A group of numbers or letters and numbers used to identify a "batch". Based on this, the production history of the batch of products can be traced and reviewed. 3.3 Production lot
refers to the number of products with the same properties and quality that are continuously produced under the same process conditions within a period of time. Note: For some continuously produced products, it is sometimes difficult to divide the production batch. For management needs, the products produced on each working day or shift are often regarded as production batches.
3.4 Sterilization lot
The number of products with the same sterility assurance level that are sterilized in the same sterilization cabinet under the same process conditions. 3.5 Sterilization
A confirmed process used to make the product free of any form of viable microorganisms. 3.6 Sterile
The absence of viable microorganisms on medical devices.
3.7 Primary package
Packaging that is in direct contact with sterile medical devices. 3.8 Sterile medical device sterilemedicaldevice Approved by the State Food and Drug Administration on August 18, 2000 and implemented on September 15, 2000
Refers to any medical device marked "sterile". YY0033-2000
3.9 Cleanroom (area) cleanroom (area) A room (area) that needs to control the dust particles and microorganisms. Its building structure, equipment and its functions have the function of reducing the intervention, generation and retention of pollution sources in the room (area). 3.10 Cleanliness cleanliness
The allowed statistical number of suspended particles greater than or equal to a certain particle size in a unit volume of air in a clean environment. 3.11 Air purification airpurification
The act of removing pollutants in the air to make the air clean. 3.12 Personnel purification room personnelpurificationroom Auxiliary room where personnel purify according to a certain procedure before entering the clean room (area). 3.13 Material purification room Material purification room Auxiliary room where materials are purified according to a certain procedure before entering the clean room (area). 3.14 Material material
Refers to raw materials, auxiliary materials, packaging materials, purchased (co-purchased) spare parts, etc. 4 Quality system
Sterile medical device manufacturers should establish and implement an effective quality management system and form a complete set of quality management system documents. And conduct management reviews and internal audits regularly.
Note 1: GB/T19001 and YY/T0287 or GB/T19G02 and YY/T0288 stipulate the requirements of the quality management system. 4.1 Quality policy
The quality policy should be promulgated by the most senior management of the enterprise in the form of documents, and should ensure the establishment of quality objectives and the understanding and implementation of the quality policy at relevant functions and levels.
4.2 Organizational Structure
4.2.1 The enterprise shall establish an organizational structure that is compatible with the quality management system and product production requirements, define its functions and relationships (including responsibilities and authority) and form documents to promote effective quality management. 4.2.2 The top management of the enterprise shall designate one or more management representatives from the management personnel and define their responsibilities and authority. 4.3 Personnel
4.3.1 The enterprise shall be equipped with management personnel and technical personnel of all levels and types who have professional knowledge, production experience, organizational ability and are familiar with the relevant national medical device supervision and management regulations that are compatible with the production of sterile medical devices, and are responsible for organizing production and quality management. 4.3.2 The top management of the enterprise must pay close attention to product quality, be familiar with product production technology, have organizational skills, have certain scientific and cultural knowledge, be able to organize production according to the requirements of this standard, and be fully responsible for the implementation of this standard and product quality. 4.3.3 The leader in charge of sterile medical device production technology and quality management in the enterprise should have a college degree or above in this major or related majors or equivalent, have practical experience in medical device production and quality management, and be responsible for the implementation of this standard and product quality. 4.3.4 The person in charge of the production management and quality management department of the enterprise should have professional knowledge and management experience suitable for their job, and have the ability to make correct judgments and handle practical problems in the production and quality management of sterile medical devices. The person in charge of the sterile medical device production management department and the quality department shall not hold the positions of each other. 4.3.5 Operators and quality inspectors engaged in key positions and special processes should have a high school degree or above, have received professional technical training, and have basic theoretical knowledge and practical skills. Full-time inspectors should also undergo appropriate technical training and hold certificates before taking up their posts. 4.3.6 General production operators should have a cultural level suitable for their jobs and take up their posts after professional technical training. 4.3.7 Enterprises should train and assess all types of personnel in product production technology, clean environment control, medical and health knowledge, and product handling, storage, protection, etc. in accordance with the requirements of this standard, and continuously improve their business capabilities and quality awareness. And keep records of additional training. 4.3.8 The supply and sales departments should be equipped with personnel with professional knowledge and competent for the supply, marketing and management of sterile medical devices. 2
5 Production environment, facilities and layout
5.1 Factory site and factory area
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Sterile medical device manufacturers must have a clean production environment. The ground, road surface and transportation in the factory area should not cause pollution to the production of sterile medical devices.
5.7.1 The factory site should be selected in an area with good sanitary conditions, fresh air, low dust and bacteria concentration in the atmosphere, no harmful gases, and a good natural environment. 5.1.2 The factory site should be far away from railways, docks, airports, traffic arteries, factories, storage warehouses, yards and other areas with serious air pollution, water pollution, vibration or noise interference that emit a lot of dust and harmful gases. The distance between the clean workshop and the municipal traffic artery should not be less than 50m. 5.1.3 The main roads in the factory area should be wide and smooth, and should be built with materials that are not easy to generate dust. 5.1.4 The layout of the factory area should be reasonable. The administrative area, living area and auxiliary area shall not have adverse effects on the production area. Animal houses and sterilization workshops should be located in secluded and safe locations, and should have corresponding safety, ventilation and sewage (toxic) facilities. Their design and construction should comply with relevant national regulations. 5.1.5 The area around the production plant should be free of four (no stagnant water, no weeds, no garbage, no mosquito and fly weed habitat). It is better to have no exposed land. 5.2 Production plant
The production plant is divided into general production area and clean area according to production process and product quality requirements. The factory building should be reasonably laid out according to the production process and the required air cleanliness level. 5.2.1 General production area
The general production area should be reasonably designed, with good lighting and ventilation to meet production needs. 5.2.2 Clean area
5.2.2.1 In addition to meeting 5.2.1, an air conditioning and purification system corresponding to the cleanliness level should be configured. Appendix A gives the air cleanliness level of the clean room (area) of sterile medical devices, and Appendix B gives the setting guide for the cleanliness level of the production environment of sterile medical devices
5.2.2.2 When designing, building and decorating clean workshops, it should be easy to clean. The inner surface of the clean room (area) should be flat, smooth, without cracks, with tight interfaces, no particles falling off, and able to withstand cleaning and disinfection. The junction between the wall and the ground should be made into an arc or other measures should be adopted to reduce dust accumulation and facilitate cleaning. There should also be facilities such as dust prevention, pollution prevention, and prevention of insects and other animals and foreign objects from mixing in. 5.2.2.3 The external windows of personnel purification rooms and clean rooms (areas) should be double-layer windows with good sealing performance. The ceiling of the clean room (area) and the pipes, air vents and walls or roof terraces entering the clean room (area) should be sealed. 5.2.2.4 The doors of the clean room (area) should be well sealed and open in the direction of high cleanliness. 5.2.2.5 The clean room (area) should be equipped with a safety door, which should be opened in the direction of safe evacuation. It should be well sealed at ordinary times. It should be easy to open in an emergency, and the safety passage should be barrier-free.
5.2.2.6 The clean room (area) should be reasonably laid out according to the process flow, and the flow of people and logistics should be separated and fixed in direction. 5.2.2.7 The water, electricity and other transmission lines in the clean room (area) should be concealed. The pipe openings of electrical pipelines, various electrical equipment installed on the wall and the joints of the wall should be reliably sealed.
5.2.2.8 Clean rooms (areas) should use lighting fixtures with simple exterior shapes, not easy to accumulate dust, and easy to wipe. Lighting fixtures should be installed on the surface rather than hanging. When ceiling installation is adopted, reliable sealing measures should be adopted at the joints between the lamps and the ceiling cabinets. 5.2.2.9 The operating table should be smooth, flat, without gaps, without shedding dust particles and fibers, without dust accumulation, easy to clean and disinfect, and wooden or painted countertops should not be used.
5.2.2.10 Compressed air and other gases used in clean rooms (areas) should be purified. In particular, the cleanliness of gases that are in direct contact with the product surface should be verified and routinely controlled to adapt to the products produced. 5.2.2.11 The pools and floors in the clean room (area) shall not contaminate sterile medical devices. 5.3 Personnel purification
5.3.1 Personnel purification rooms should include shoe changing rooms, outer clothes storage rooms, dishwashing rooms, clean work clothes wearing rooms, airlock rooms or air shower rooms, etc. 5.3.2 Personnel entering the sterile medical device production clean room (area) or sterile operation clean room (area) should be purified. Appendix I) gives the general procedures for entering and leaving the clean room (area).
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5.3.3 At the shoe changing area for entering the personnel purification area, pay attention to avoid cross-contamination of the two types of shoes. There should be a clear boundary between the shoes for going out and the shoes to be changed that is not easy to cross at will. Slippers should not be worn in the clean room (area). 5.3.4 The flow of personnel should strictly follow the direction from the low cleanliness area to the high cleanliness area. 5.3.5 The faucet in the dishwashing room should be set at one for every 10 people in the maximum shift, and the faucet should not be opened and closed manually. 5.3.6 The entrance and exit doors of the airlock room should be prevented from being opened at the same time. When a single-person air shower room is set up, one should be set up for every 30 people in the maximum shift. When there are more than 5 staff members in the clean room (area), a one-way bypass door should be set up on one side of the air shower room. 5.3-7 The average area per person for clean room (area) staff should be no less than 4m2. 5.4 Material purification
5.4.1 Materials entering the clean production area should have cleaning measures, such as outer packaging room, dust removal room, etc. 5.4.2 An airlock room or double-layer transfer window should be set up between the material purification room and the clean room (area) for the transfer of materials and other items. 5.4.3 The outer packaging of materials for transportation and storage and packaging materials that are easy to shed dust and fibers shall not enter the clean room (area). Primary packaging materials that directly contact the product should be effectively prevented from contamination during transportation, storage and transfer, and at least two layers of sealed packaging should be used. 5.5 Process layout
5.5.1 The clean room should be arranged in the direction of the product formation process, the process flow should be tight and reasonable, and the material transfer route should be as short as possible to facilitate operation and process control. The flow of people and logistics should be strictly separated and cross-flow is prohibited. 5.5.2 Only necessary process equipment and facilities can be set up in the clean room (area). There should be space suitable for the production scale to store the intermediate products or products produced in the clean room (area), and as close as possible to the production area associated with it to reduce mixing and contamination during transportation. Inspection areas, qualified areas and unqualified areas should be arranged in the storage area with obvious signs. 5.5.3 Clean rooms (areas) with high air cleanliness should be arranged in areas where the least people pass or arrive. Clean rooms (areas) of different cleanliness levels should be arranged from high to low from inside to outside. There should be anti-pollution measures such as airlocks or double-layer transfer windows when clean rooms (areas) of different levels are connected to each other.
5.5.4 When conveying materials between areas with different air cleanliness, in order to prevent cross contamination, the conveyor belt should not pass through the partition wall, and it is advisable to convey in sections on both sides of the partition wall.
For the material transfer between areas with different air cleanliness in the production area of non-sterile products, it must be conveyed in sections, unless the transfer device adopts continuous disinfection.
5.5.5 For instruments cleaned in the clean room (area), the air cleanliness level of the clean room should be consistent with the product requirements. Equipment and instruments in Class 100 and Class 10000 clean rooms (areas) should be cleaned outside the area, and the air cleanliness of the cleaning room should not be lower than Class 100000. 5.5.6 Cleaning tools should be washed, dried and sanitary ware stored in an independent, sanitary and well-ventilated sanitary ware room. Sanitary ware should not be stored in the clean room (area).
6 Equipment and tooling
6.1. The design and selection of equipment should meet production requirements, with reasonable layout and convenient operation, repair and maintenance. 6.2. The equipment and tooling selected in the clean room (area) should have dust and pollution prevention measures, simple structure, low noise and no dust during operation. The surface of equipment, tooling and pipeline should be smooth and flat, without any granular material falling off, easy to clean and eliminate sagging or sterilize, and can reduce pollution. 6.3. The surface of equipment, tooling and pipeline in direct contact with materials or products should be non-toxic, corrosion-resistant, without dead corners, easy to clean and eliminate or sterilize, and not chemically react or adhere with materials or products. 6.4. The lubricant, coolant, cleaning agent used in the equipment and the release agent used for the spare parts that are not cleaned after being molded in the clean area shall not cause pollution to the product.
6.5. An independent mold room (or area) should be set up for the maintenance and storage of molds to prevent the mold from contaminating the clean room (area). 6.6. A sufficient number of workstations and tools should be equipped, and they should have good sealing and be easy to clean and sterilize. The workstations and tools in the clean room (area) and the general production area should be strictly separated and clearly marked, and they must not be used crosswise. 6.7 There should be equipment for preparing process water, and the water preparation capacity should meet the production requirements. Process water should be tested regularly according to standards. The storage tanks and delivery pipelines of process water should be made of stainless steel or other non-stallable materials, and should be cleaned and disinfected regularly. YY0033—2000
6.8 The scope of application and accuracy of instruments, meters, measuring tools, scales, etc. used for production and inspection should meet the requirements of production and quality inspection, and should have obvious status identification and be verified or calibrated according to the prescribed cycle. 6.9 Equipment and tooling should be maintained, serviced and verified regularly. When equipment is updated, it should be verified and can only be used when it is determined that there is no impact on product quality. See Appendix E.
6.10 There should be regulations for the management of production and inspection equipment (including spare parts), tooling and workstation tools, and equipment files should be established to keep records of equipment use, maintenance, repair and improvement. 7 Procurement and Material Management
7.1·The enterprise should have regulations to control the procurement process, prepare procurement documents such as procurement plans, contracts, technical agreements, etc., clearly state the quality requirements of the purchased materials to ensure that they meet the standard requirements, and keep copies of the procurement documents. 7.2 The supplier should be evaluated, and its production environment (especially when there is a purification requirement), quality assurance, whether it has certificates and licenses that meet national regulations, reputation, etc. should be investigated and analyzed. Before placing a large number of orders, a small amount should be tried first, and it can only be used for production after passing the inspection. The supplier should be relatively stable. The supplier's quality records should be established and preserved. 7.3 After the purchased materials enter the factory, they should be placed in an area with obvious "to be inspected" signs. Only after they are inspected and qualified by the quality inspection department can they go through the warehouse procedures. 7.4 Materials should be stored in a warehouse with temperature and relative humidity that meet their respective requirements, no corrosive gases, good ventilation, and fire protection measures. Products to be inspected, qualified products, and unqualified products should be strictly separated, with status identification, which can effectively prevent mixing. Various types of materials should be classified and stored in batches, and the cargo location cards should be filled in.
7.5 The issuance of materials should be recorded and signed by the person who issues and receives the materials. The issuance of materials should follow the principle of first-in-first-out. 7.6 Labels, certificates of conformity, instruction manuals, and small packages should be kept by a dedicated person, and their issuance, use, and destruction should be recorded. 7.7 Special isolation measures should be taken for flammable and explosive materials. 8 Documents
8.1 Quality system documents
8.1.1 The enterprise should prepare a description of its quality management Quality manual of the system. 8.1.2 The enterprise shall prepare the procedure documents, management documents and regulations required by this standard, and implement them effectively. Note 1: GB/T19001 and YY/T0287 or GB/T19002 and YY/T0288 stipulate the requirements for quality management system documents. 8.2 Technical documents
The enterprise shall have technical documents to guide the production and use of products. The technical documents shall be unified, complete and correct. 8.3 Document control
8.3.1 The enterprise shall prepare a document control procedure, and all documents related to quality (including quality manuals, procedure documents, specifications, drawings, standards, process documents or work instructions, etc.) shall be controlled. It should be approved before release; the documents used should be valid versions; they should be modified as required; at least one copy of the obsolete controlled document should be kept, and its shelf life should ensure that it is sterile. The production specifications of the medical device can be obtained during the life of the medical device.
8.3.2 Written procedures should be formulated for the control of documents serving as quality records, stipulating the identification, storage, retrieval, protection, retention period and disposal of quality records. The retention period of quality records should be no less than the life of the medical device, but at least no less than two years. 9 Quality Management
9.1 The enterprise should establish a quality management department under the direct leadership of the top management, and the person in charge of the quality management department should meet the requirements of Article 4.3.4. 9.2 The quality management department should be equipped with a certain number of quality management and inspection personnel, and have physical, chemical, biological laboratories and testing instruments and equipment that are suitable for the production scale, variety and inspection requirements of sterile medical devices. 9.3 Responsibilities and powers of the quality management department: a) Responsible for the quality management and inspection of the entire production process of sterile medical devices. According to b) Have the right to approve or deny the use of all materials and intermediate products and the delivery of products; c) Decide whether packaging materials, labels, and instructions for use are allowed; d) Evaluate whether the storage conditions of materials, intermediate products, and products are applicable; e) Keep samples of products for observation and regular inspection to evaluate the quality stability of products and provide a basis for determining the shelf life of products; f) Review the procedures for handling non-conforming products and the procedures for corrective and preventive measures; Decide on the handling methods for returned, recalled and non-conforming products; g) Be responsible for the management of equipment, instruments, reagents and measuring instruments for inspection and testing; h) Be responsible for the monitoring and recording of clean rooms (areas) and process water. 9.4 The quality management department shall conduct incoming inspection or verification, process inspection, and final product inspection in accordance with regulations. And issue inspection records and reports: The records and/or reports shall be signed by the person responsible for executing the inspection and authorizing the release of products. 9.5 The quality management department shall conduct sampling in accordance with regulations, and the sampling shall be representative. 9.6 The quality management department shall evaluate the supplier together with the relevant departments. 10 Production process management
10.1 The enterprise shall control the entire production process of the product. 10.2 Before the product is officially put into production, the production process shall be fully verified to determine the feasibility of the process. 10.3 Quality control points shall be set for special processes and key processes, and control point management documents and operation instruction documents (such as process cards or operation instructions, etc.) shall be formulated to carry out continuous monitoring and control, and all control parameters shall be recorded. 10.4 According to the different requirements of the product for the cleanliness of the production environment, various operation processes are limited to designated production areas. Personnel and items entering the clean room (area) must be purified according to the purification procedures for personnel and materials required by the corresponding product. The transfer and use of workstations in different cleanliness areas should prevent cross contamination. 10.5 There should be measures to prevent contamination for intermediate products in the production process stored in the clean room (area). There are also product names and inspection status labels, and unqualified intermediate products should be stored and recorded separately to prevent mixing. 10.6 For spare parts that need to be cleaned, the final cleaning should be carried out in a clean air (area) of the corresponding level with process water of corresponding requirements. The cleaning water and cleaning process should be confirmed and routinely controlled to adapt to the products produced. 10.7 Product identification and traceability
10.7.1 Manufacturers of sterile medical devices should stipulate that appropriate methods should be used to identify products throughout the production process. Each batch or each product should have a clear, firm and unique identification during the formation process and keep records to ensure traceability. 10.7.2 The enterprise should formulate control documents for batch number (production batch number and sterilization batch number) management. Each batch or each product should have quality records reflecting product identification and input materials, production process (including clean room (area) environmental monitoring, key processes and special processes such as sterilization parameters, etc.), use of relevant equipment, production date, signatures of operators and reviewers, and inspection results. 10.8 Packaging, marking, labeling and instructions for use 10.8.1 Sterile medical devices must be sealed. The packaging materials should be selected and designed according to the product performance and sterilization method, and should meet the storage requirements.
Note: ISO/DIS11607 stipulates the basic requirements for evaluating the packaging performance of sterile medical devices. 10.8.2 The largest unit of sterile packaging for sterile medical devices should be a single package. The word "sterile" and/or symbol should be marked on the single package, and the words "do not use if the package is damaged" should be written. 10.8.3 The markings on the packaging should correctly guide the transportation, storage, unpacking and use of the product, and should be obvious, clear and firm, and should not fall off or become blurred due to the sterilization, transportation and storage processes used. 10.8.4 The markings on the packaging must meet the requirements of the corresponding product standards. 10.9 Sterilization
10.9.1 Sterile medical devices that need to be sterilized should be sterilized using a confirmed sterilization method to ensure the reliability of the sterilization effect. Note: For the confirmation and routine control requirements of appropriate sterilization methods and medical device sterilization processes, see ISO11131, ISO11135, and ISO11137. 10.9.2 Products before and after sterilization should be strictly separated, labeled, and strictly distinguished from qualified products. 6
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10.9.3 Operators should perform sterilization operations in strict accordance with document regulations and have complete records of the sterilization process and parameters. 10.10 Control of non-conforming products
10.10.1 The enterprise should formulate a procedure document for the control of non-conforming products to prevent the unintended use or delivery of non-conforming products. 10.10.2 Non-conforming products should be labeled, registered, evaluated, isolated and disposed of. 10.10.3 Nonconforming products can only be accepted as concessions if they meet regulatory requirements. If rework is required, the adverse effects of rework on the product should be confirmed. After rework, re-inspection should be carried out in accordance with regulations and records should be kept. 10.11 Corrective and preventive measures
10.11.1 The enterprise should formulate and implement procedural documents for corrective and preventive measures. 10.11.2 The enterprise should effectively handle customer complaints and nonconformity reports: investigate the causes of nonconformities related to product production processes and quality management systems: take corrective measures and verify them. 10.11.3 The enterprise should use various sources of information to discover and analyze potential factors of nonconformity, take preventive measures and implement controls. 10.11.4 If the enterprise does not take corrective and preventive measures in response to customer complaints, the reasons should be recorded. 11 Hygiene management
The enterprise should formulate hygiene management documents that are compatible with product quality requirements and production processes, and implement them conscientiously and keep records. 11.1 Clean room (area) hygiene
11.1.1 Clean rooms (areas) should be cleaned, washed and disinfected regularly according to the document regulations, and the disinfectants or disinfection methods used should not cause pollution to equipment, tooling, materials and products. The types of disinfectants should be changed regularly. 11.1.2 Clean rooms (areas) should be monitored and recorded regularly in accordance with the requirements of Appendix C. 11.2 Personal hygiene
11.2.1 The enterprise should formulate a hygiene code for operators, which should include regular haircuts, bathing, nail clipping, no makeup, no jewelry, and no personal items brought into the clean room (area), etc., and there should be special personnel to check. 11.2.2 The enterprise should establish employee health files, and operators who directly contact materials and products should have a physical examination at least once a year. Personnel with infectious and contagious diseases shall not engage in work that directly contacts products. 11.2.3 Personnel entering the clean room (area) must be purified according to the personnel purification procedures required by the corresponding products. And wear clean work clothes, work hats, masks, and work shoes. Operators who directly contact the product should disinfect their hands again at regular intervals. 11.3 Process Hygiene
11.3.1 Equipment and pipelines should be cleaned regularly and kept clean, without running, covering, dripping, or leaking. 11.3.2 Parts of equipment and work clothes that are in direct contact with the product, as well as work surfaces and workstations and tools should be cleaned and disinfected regularly to keep them clean. The workstations and tools in the clean room (area) should be cleaned and disinfected with purified water in the clean room (area). 11.3.3 Clean work clothes should be made of materials with smooth texture, no static electricity, and no fiber and granular substances. Their work clothes and sperm should be able to effectively cover underwear and hair. Clean work clothes used at different cleanliness levels should be regularly concentrated in the clean environment of the corresponding level for cleaning, drying, and finishing.
11.3.4 Clean rooms (areas) are limited to production operations in the area and entry by approved personnel. 12 Product Sales and User Service
12.1 The enterprise shall establish user files, frequently contact users, actively solicit user opinions, and provide services to users in a timely manner. 12.2 Each batch of products shall have sales records, and once unqualified products are found, they can be immediately recovered. The records shall be retained for at least one year after the expiration date. 12.3 User complaints can be handled in a timely manner, and information on the sales service process should be fed back to the relevant functional departments in a timely manner, and measures shall be taken and recorded.
12.4 The enterprise shall establish a medical device adverse event reporting system and designate a special agency or personnel to be responsible for asset management. Adverse events shall be reported to the local drug supervision and administration department in a timely manner.
12.5 Establish a product accident reporting system and a product tracking system. When major quality problems occur in medical devices, they shall be reported to the local drug supervision and administration department in a timely manner. If unqualified products are found to have been shipped out due to sample observation or national sampling, they shall be immediately recovered and handled according to the unqualified product control procedure.
Cleanliness level
Class 100
Class 10000
Class 100000
Class 300000
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Appendix A
(Appendix to the standard)
Air cleanliness level table for clean rooms (areas) for sterile medical devices Table A1
Maximum allowable number of dust particles, pieces/m
≥0.5μm|| tt||350000
3500000
10500000
Appendix B
(Appendix to the standard)
Maximum allowable number of microorganisms
Floating bacteria, pieces/m
Settling bacteria, pieces/shift
Guidelines for setting cleanliness levels in the production environment of sterile medical devices 5
B1 Sterile medical devices should adopt production technology that minimizes contamination. When considering the cleanliness level of the production environment, it should be combined with production technology. When production technology cannot ensure that the surface of the medical device is not contaminated or cannot effectively eliminate contamination, the cleanliness of the production environment should be improved as much as possible under the premise of conditions permitting. B2 When there are multiple processes in the clean room (area), different air cleanliness levels should be adopted according to the different requirements of each process. Under the condition of meeting the production process requirements, the airflow organization of the clean room (area) can be a combination of local work area air purification and whole room air purification, such as a local Class 100 clean area under 10,000. B3 For sterile medical devices that are implanted in the body, directly or indirectly in contact with circulating blood and bone cavity, or accessories shipped in single packaging, the production areas such as processing, final cleaning, assembly, primary packaging and sealing of parts (non-cleaned parts) should not be lower than Class 100,000 cleanliness level. Sterile medical devices implanted in blood vessels and sterile medical devices that can realize the entire process of production, assembly and packaging in a local environment should be produced in a clean room (area) of not less than Class 10,000 (preferably Class 100). B4 The processing, final fine cleaning, assembly, primary packaging and sealing of sterile medical devices or parts (non-cleaned parts) shipped in single packaging other than those specified in B3 should be carried out in a clean room (area) of not less than Class 300,000. B5 For the primary packaging of products that are in direct contact with the surface of the product and are used without cleaning, the cleanliness level of the production plant should be the same as that of the product production plant (in the same area as much as possible). If the primary packaging does not come into direct contact with the surface of the product, it is preferred to produce it in a clean room (area) of not less than 300000. B6 For sterile medical devices (including materials) implanted in the body that are processed using aseptic operation technology, they should be produced in a local Class 100 clean room (area) under Class 10000.
B7 The air cleanliness level of the cleaning, drying and final cleaning and disinfection areas of clean work clothes and special workstations and equipment can be one level lower than the production area. The sorting and storage of sterile work clothes after sterilization should be in a Class 10000 clean room (area). 8
Monitoring items
Temperature, ℃
Relative humidity, %
Wind speed, m/s
Ventilation frequency, times/h
Static pressure difference, Pa
Dust count
≥0.5 μm
>5 μm
Number of floating bacteria, pieces/m
Number of settling bacteria, pieces/dish
YY0033—2000
Appendix C
(Appendix to the standard)
Environmental requirements and monitoring table for clean rooms (areas) for sterile medical devices C1
Class 100
Horizontal laminar flow
Vertical laminar flow
Class 10000
10 0000 level
(without special requirements)18~28
300000 level
between clean rooms (areas) of different levels and between clean rooms (areas) and non-clean rooms (areas)≥5
between clean rooms (areas) and outdoor air≥10
≤3500
350000
≤2000
≤3500000
≤2 0000
≤10500000
Monitoring method
IGL71-1990
GB/T16292—1996
GB/T16293--1996
GB/T16294—1996
Blue test Lai
1 time/shift
1 time/shift
1 time/month||t t||1 time/month
1 time/month
1 time/quarter
1 time/quarter
1 time/week
Description:
The number of dust, floating bacteria or settling bacteria, ventilation times (100-level laminar wind speed), static pressure difference, temperature, and relative humidity detected in the sterile medical device clean room (area) under static conditions must comply with the regulations, and the above parameters should be dynamically tested according to the monitoring frequency. Appendix D
(Suggested Appendix)
General procedures for personnel entering and exiting clean production areas The general procedures for personnel entering and exiting clean production areas and sterile operation clean production areas are shown in Figures DI and D2. Enter
Hand disinfection
Gas or blow
South air shower
Air room
Single side door
Procedure for personnel entering and exiting the clean production areaWash hands
Wear meat-free
Turn over outer clothes
Hand disinfection
Fufo production area
Gas acid blow
Procedure for personnel entering and exiting the aseptic operation clean production areaNo clean
YY0033-2000
Appendix E
(Suggested appendix)
Verification and confirmation
E1 Before sterile medical devices are put into production, the clean workshop, main facilities, equipment, tooling and processes should be verified or confirmed. E2 When the main factors affecting the product, such as process, tooling, quality control method, main raw materials and auxiliary materials, and main production equipment, change, and after a certain production cycle, re-verification or confirmation should be carried out. E3, according to the verification or confirmation object, the verification or confirmation project should be proposed, the verification or confirmation plan should be formulated, and the implementation should be organized. E4 After the verification or confirmation work is completed, the document should be formed. The verification or confirmation document should include the verification or confirmation plan, verification or confirmation report, evaluation and suggestions, approver, etc. bzxZ.net
E5 The documents formed during the verification or confirmation process should be archived. E6 The verification or confirmation items in the production of sterile medical devices include (but not limited to): a) air purification system;
b) main production equipment;
c) key production process, tooling and its changes; d) changes in main raw materials and auxiliary materials:
e) process water system and final cleaning process (if any); f) process compressed air or other gases (if any); g) sterilization equipment and process (if any). Appendix F
(Suggested Appendix)
Bibliography
［1] GB/T19001—1991
[2] GB/T19002-1994
[3] YY/T0287—1996
Quality Assurance Model for Design, Development, Production, Installation and Service Quality System
Quality System
Quality Address System
[4] YY/T0288—1996
Quality System
Quality Assurance Model for Production, Installation and Service of Medical Devices GB/T1 9001—Special requirements for the application of ISO9001 Medical devices according to GB/T19002—Special requirements for the application of ISO9002 [5] 1 ISO11134:1994 Sterilization of medical care products—Requirements for validation and routine control Industrial wet heat sterilization [6 ISO11135:1994 Medical devices—Validation and routine control of ethylene oxide sterilization [7 ISO11137:1995 Sterilization of medical care products—Requirements for validation and routine control—Radiation sterilization [8 ISO/DIS11607:1999 Final sterilization of medical devices 101999 Medical equipment finally eliminated 101999 Medical equipment finally eliminated 10
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