中国新版GMP 2010英文版

Good Manufacturing Practice for Pharmaceutical Products (Revised in 2010) (Decree No.79 of the Ministry of Health) The Good Manufacturing Practice for Pharmaceutical Products (Revised in 2010) was reviewed and adopted at the Executive Meeting of the Ministry of Health on Oct. 19, 2010, and it is hereby promulgated and shall go into effect as of March 1, 2011. Minister Chen Zhu Jan.17, 2011 Chapter 1 General Provisions Article 1 This Practice is enacted in accordance with the Drug Administration Law of the People's Republic of China and the Regulations for The Implementation of the Drug Administration Law of the People's Republic of China for the purpose of regulating the management of drug manufacturing quality. Article 2 The manufacturers shall establish drug quality management system, which shall cover all the factors affecting drug quality including all organized and planned activities to ensure that drug quality is in compliance with requirements of intended use. Article 3 This Practice as a part of quality management system is the basic requirements for drug manufacturing management and qualitycontrol aiming at minimizing the risk of contamination, cross-contamination, mix-up and errors during production in order to ensure that the production is consistent and stable, and drug in compliance with requirements of intended use and registration. Article 4 The manufacturers shall strictly implement this Practice, adhere to be honest and true to one’s promise and prohibit any false and cheating actions. Chapter 2 Quality Management Section 1 Principle Article 5 The manufacturers shall establish quality objectives which meet requirements of drug quality management, and must systematically carry out all the requirements in drug registration related to the safety, efficacy and quality controllability throughout all processes of the drug production, control, release, storage and delivery to ensure all drugs manufactured in compliance with requirements of intended use and its registration. Article 6 Senior management personnel of a manufacturer should ensure to attain preset quality objectives. Staff members at different levels, suppliers and distributors should jointly participate in and bear respective duties. Article 7 The manufacturers should provide adequate personnel, premises, facilities and equipment which are in compliance with set requirements, and necessary conditions to attain quality objectives. Section 2 Quality Assurance Article 8 Quality assurance is a part of quality management system. A manufacturer must establish a quality assurance system and a complete documentation system to assure that the system is effectively operational. Article 9 The quality assurance system should ensure the followings: 1. A drug design and R & D embody the requirements of this Practice; 2. Production management and quality control activities are in compliance with this Practice; 3. Managerial responsibilities are clearly defined; 4. Raw materials and excipients, and packaging materials purchased and used are correct; 5. Intermediate products are effectively controlled; 6. Implementation of qualification and validation; 7. Production, examination, testing and check are strictly in accordance with procedures; 8. Release of every batch of products is subject to the qualified-person in drug quality management: 9. Appropriate measures for assuring drug quality should be taken in the process of storage, delivery and follow-up operations; and 10. Regularly check and assess effectiveness and suitability of the quality assurance system in accordance with self-inspection operating procedures. Article 10 Basic requirements of drug manufacturing quality management: 1. To formulate production process, and systematically review and demonstrate that it can be used for sustained and stably manufacturing products in compliance with requirements; 2. Production process and its major alternation need validating; and 3. Resources provided at least including: 1) Persons with appropriate qualifications and having been trained; 2) Adequate premises and space; 3) Appropriate equipment and maintenance assurance; 4) Correct raw materials and excipients, packaging materials and labels; 5) Approved production process procedures and operating procedures; and 6) Appropriate storage and transportation conditions. 4. Accurate and easy-understanding language should be used to formulate operating procedures; 5. Operators have been trained and are able to operate correctly in accordance with operating procedures; 6. An entire production process should be recorded; all deviations should be investigated and recorded; 7. Batch records and delivery and transportation records can be used for tracing a complete history of a batch production, and be well kept for looking up; 8. To reduce quality risks during drug delivery; 9. To establish a drug recall system to ensure that any batch of products delivered can be recalled; and 10. To investigate causes led to drug quality complains and defects, and take measures to prevent occurrence of similar defects once again Section 3 Quality Control Article11 Quality control consists of relevant organizational structures, documentation system, sampling, testing etc. to ensure that materials or products have necessary testing before they are released, and ensure that they are in compliance with requirements. Article12 Basic requirements of quality control: 1. Should provide appropriate facilities, equipment, instruments and trained persons, effectively and reliably accomplish all relevant activities of quality control; 2. Should possess approved operating procedures for sampling, checking, testing and stability study of raw materials and excipients, packaging materials, intermediate products, bulk products and finished products, and monitor environment if necessary, to ensure that they are in compliance with requirements of this Practice; 3. Sampling of raw materials and excipients, packaging materials, intermediate products, bulk products and finished products are performed by authorized persons in accordance with specified methods; 4. Testing methods should be validated or qualified; 5. Sampling, checking, testing should be recorded, and deviations should be investigated and recorded; 6. Materials, intermediate products, bulk products and finished products must be checked and tested in accordance with quality standards and be recorded; and 7. Should have enough sample retentions of materials and finished products in final package for necessary checking and testing; package of sample retentions for finished products should be the same as the final package except the product whose final packaging container is too big. Section 4 Quality Risk Management Article 13 Quality risk management is a systematic process for the assessment, control, communication and check of quality risks throughout the product life cycle by applying proactive or retrospective pattern. Article 14 Quality risk assessment should be based on scientific knowledge and experience as to assure product quality. Article 15 The methods, measures, patterns taken and documents formed in the process of quality risk management should correspond to the levels of existing risks. Chapter 3: Organization and Personnel Section 1 Principle Article 16 A manufacturer should establish a management organization which is suitable to its drug production, and have an organizational chart. A manufacturer should establish an independent quality management department responsible for quality assurance (QA) and quality control (QC). The quality management department can set up the QA and QC section separately. Article 17 The quality management department should participate in all quality related activities and affairs, and be responsible for reviewing all documents related to this Practice. Persons in the quality management department are not allowed to delegate their duties to persons of other departments. Article 18 A manufacturer should staff enough management and operation persons with appropriate qualifications (including schooling records, training and practical experience), and clearly define responsibilities of each department and position. Position’s responsibility cannot be omitted and overlapped responsibility should be clarified. The responsibilities undertaken by each person should not be too many. All persons should clearly aware of and understand their responsibilities and be familiar with requirements related to their responsibilities, and receive necessary trainings, including before-work training and continuing training. Article 19 Responsibility may not be delegated to others in general. It may be delegated to designated persons with equivalent qualification if really needed. Section 2 Key Personnel Article 20 Key personnel should be full-time employees, at least including the head of the manufacturer, the head of manufacturing management, the head of quality management and the qualified person(s). The head of quality management and the head of manufacturing management cannot hold two posts one another. The head of quality management and the qualified person (s) can be the same person. An operating procedure should be established to ensure that the qualified person(s) can perform his or her duties independently and be interfere-free from the head of the manufacturer and others. . Article 21 Head of Manufacturer The head of manufacturer is the main responsible person for drug quality and comprehensively responsible for routine management of a manufacturer. In order to ensure the achievement of quality objectives and the drug produced in compliance with this Practice, the head of manufacturer has responsibility of providing the necessary resources, reasonable plans, organization and coordination to ensure that the quality management department performs its duties independently. Article 22 Head of Manufacturing Management 1. Qualification: The responsible person of the manufacturing management must, at a minimum, have an educational qualification of an undergraduate course in pharmacy or related sciences (or with a technical title at middle grade or a qualification of licensed pharmacist) and also at least three-years practical experience in management of drug production and quality, of which minimal one year practical experience in management of drug production, and have received professional training in relevant products manufactured. 2. Main Responsibilities: 1) To ensure products manufactured and stored according to approved operating procedures in order to obtain the quality required; 2) To ensure strict implementation of the various procedures related to production operation; 3) To ensure that the batch production records and batch packaging records are checked and signed by an authorized person, and submitted to the quality management department; 4) To ensure the maintenance of premises and equipment to keep them in good working conditions; 5) To ensure that the various necessary validations are done; and 6) To ensure that the required before-work training and continuing training of personnel related to production are carried out, and training content is adjusted according to real needs. Article 23 Head of Quality Management 1. Qualification: The responsible person of the quality management must, at a minimum, have an educational qualification of an undergraduate course in pharmacy or related sciences (or with technical title at middle grade or qualification of licensed pharmacist) and also at least five-years practical experience in management of drug production and quality, of which minimal one year practical experience in management of drug production, and have received professional training in relevant products manufactured. 2. Main Responsibilities: 1) To ensure that raw materials and excipients, packaging materials, intermediate products, bulk products and finished products comply with approved requirements in registration and relevant quality standards; 2) To ensure that batch records are checked before releasing products; 3) To ensure that all necessary testing complete; 4) To approve quality standards, sampling methods, testing methods and other operating procedures of quality management; 5) To approve all the changes related to the quality; 6) To ensure that all severe deviations and testing results out of limits of have been investigated and handled timely; 7) To approve and supervise contracted testing; 8) To monitor the maintenance of premises and equipment, and keep them in good working conditions; 9) To ensure that the necessary qualifications or validations are done, and a qualification or validation protocol and report reviewed and approved; 10) To ensure accomplishment of self-inspection; 11) To assess and approve the suppliers of materials; 12) To ensure that all complaints about product quality have been investigated and handled timely and correctly; 13) To ensure that the plan for sustained stability study of product accomplishes, and stability study data are provided; 14) To ensure that the product quality review accomplishes; and 15) To ensure that required before-work training and continuing training of the personnel in QC and QA are carried out, and the training content is adjusted according to real needs. Article 24 The head of manufacturing management and the head of quality management generally have some common responsibilities as follows: 1. To review and approve product production process, operating procedures etc. of documents; 2. To monitor the hygiene of premises; 3. To ensure that the key equipment and instruments have been qualified; 4. To ensure that validation of production process accomplishes; 5. To ensure that required before-work training and continuing training of the relevant personnel in the manufacturer are carried out, and the training content is adjusted according to real needs; 6. To approve and supervise contracted manufacturing; 7. To define and monitor storage conditions for materials and products; 8. To keep records; 9. To supervise the implementing situation of this Practice; and 10. To monitor and control factors that may affect product quality. Article 25 Qualified Person 1. Qualification: The Qualified person must, at a minimum, has an educational qualification of an undergraduate course in pharmacy or related sciences (or with a technical title at middle grade or a qualification of licensed pharmacist), and also at least five-years practical experience in management of drug production and quality, and experiences in process control of drug production and quality testing. The qualified person should have necessary professional theory knowledge and been trained in product release and before he or she can carry out duties independently. 2. Main Responsibilities: 1) To participate in establishment of quality system of the manufacturer, internalinspection, external quality auditing, validation, adverse drug reaction report, product recall etc. of quality management activities; 2) To undertake responsibility of product release to ensure that the production and testing of products having been released comply with relevant regulations, requirements of drug registration and quality standards; and 3) The qualified person must produce check record for product release before it releases in accordance with Item 2 above-mentioned, and bring the record into batch records. Section 3 Training Article 26 The manufacturer should designate a department or special persons in charge of the management of training. The training program or plan should be reviewed and approved by the head of production management or the head of the quality management. The training results should be kept. Article 27 All the personnel who have duties in drug production and quality should be trained and the training content should correspond to position needs. Besides the theory and practice training of this Practice, the training of relevant regulations, relevant responsibility and skill of position should be also provided, and training effectiveness assessed regularly. Article 28 Personnel working in areas where is of high-risk (e.g. in production areas where is of high-active, high-toxic, high-infectious or handling highly-sensitizing materials) should receive a special training. Section 4 Personnel Hygiene Article 29 All persons should receive the training of hygiene requirements. The manufacturer should establish hygiene operating procedures in order to minimize the risk of man-caused contamination to drug manufacturing. Article 30 Detailed hygiene operating procedures should include content relating to health, hygiene practices and personnel clothing. Persons of production areas and quality control areas should correctly understand relevant personnel hygiene operating procedures. The manufacturer should take measures for ensuring the implementation of personnel hygiene operating procedures. Article 31 The manufacturer should carry out management of personnel health and establish health records. The production personnel who directly contact with drug product should take physical examination before working in those areas and from then on receive a physical examination at least once a year. Article 32 The manufacturer should take appropriate measures to avoid the persons to engage in the manufacturing that directly contacts with drug product, who have open lesions on the exposed surface of the body, suffered of an infectious disease or have other diseases that may contaminate drug product. Article 33 Visitors or untrained personnel should be prohibited from accessing to production and quality control areas. Under special circumstances that they need to enter the areas, they should be given guidance in personal hygiene and way-to-wear protective garment in advance. Article 34 Any person entering the production areas should change clothing according to prescriptions. The selection of materials and style of the protective garment and the way-to-wear it should be appropriate to the operations to be carried out and the requirements of air cleanliness level. Article 35 The person who enters clean production areas is not allowed to use cosmetics or wear ornaments. Article 36 Eating, drinking, smoking, or the storage of food, beverage, cigarettes, personal medication, etc. of non-production used articles should be prohibited in production and storage areas. Article 37 Operators should avoid using bare hands to directly contact drug, packaging materials directly contacted with drug, and the surface of equipment. Chapter 4 Premises and Facilities Section 1 Principle Article38 Location selections, design, layout, construction, reconstruction and maintenance of premises must comply with requirements of drug manufacturing to be carried out, and they should permit to maximally avoid contamination, cross-contamination, mix-up and errors, and facilitate effective cleaning, operation and maintenance. Article 39 Location selections should be determined on the basis of considering protective measures of premises and production. The premises should be situated in an environment where the risks of causing contamination of materials or products can be maximally reduced. Article 40 A manufacturer should possess clean production environment