Good Manufacturing Practice for Pharmaceutical Products (Revised in 2010) (full text)
Release time: 2011-02-17 Source:
stake online sports bettingOrder No. 79 of the Ministry of Health of the People’s Republic of China
"Good Manufacturing Practice for Drugs (Revised in 2010)" was reviewed and adopted by the Ministry of Health at the executive meeting on October 19, 2010，Now published，Effective from March 1, 2011。
Department Long Chen Zhu
January 17, 2011
Chapter 1 Total then
Article 1 To standardize drug production quality management，According to the "Drug Administration Law of the People's Republic of China"、"Regulations on the Implementation of the Drug Administration Law of the People's Republic of China"，Develop this specification。
Article 2 Enterprises should establish a drug quality management system。The system should cover all factors affecting drug quality，Includes the organization that ensures the quality of pharmaceutical products is consistent with their intended use、All planned activities。
Article 3 This specification is part of the quality management system，Is the basic requirement for pharmaceutical production management and quality control，Aimed to minimize contamination during pharmaceutical production、Cross contamination and confusion、Risks such as errors，Ensure the continuous and stable production of drugs that meet the intended use and registration requirements。
Article 4 Enterprises should strictly implement these regulations，Insist on honesty and trustworthiness，No falsehoods、Deception。
Chapter 2 Quality Management
Section 1 Original then
Article 5 Enterprises should establish quality objectives that comply with drug quality management requirements，Safety related to drug registration、All requirements for effectiveness and quality control，Systematically implemented into pharmaceutical production、Control and Product Release、Storage、In the process of shipment，Ensure that the drugs produced comply with the intended use and registration requirements。
Article 6: Enterprise senior managers shall ensure the achievement of established quality objectives，Different levels of personnel and suppliers、Dealers should participate together and assume their respective responsibilities。
Article 7 Enterprises should be equipped with sufficient、Personnel who meet the requirements、Factory、Facilities and Equipment，Provide necessary conditions to achieve quality goals。
Section 2 Quality Assurance
Article 8 Quality assurance is part of the quality management system。Enterprises must establish a quality assurance system，Establish a complete file system at the same time，To ensure the effective operation of the system。
Article 9 The quality assurance system should ensure:
(1) The design and development of pharmaceuticals reflect the requirements of this specification；
(2) Production management and quality control activities comply with the requirements of this specification；
(3) Clear management responsibilities;
(4) The raw materials, auxiliary materials and packaging materials purchased and used are correct；
(5) Intermediate products are effectively controlled;
(6) Implementation of confirmation and verification;
(7) Production in strict accordance with regulations、Check、Inspection and Review；
(8) Each batch of products can be released only after approval by the quality authorized person；
(9) In storage、Appropriate measures to ensure drug quality during shipment and subsequent operations；
(10) Follow the self-inspection operating procedures，Regular inspection and evaluation of the effectiveness and suitability of the quality assurance system。
Article 10 Basic requirements for pharmaceutical production quality management:
(1) Formulate production process，Systematically review and prove that it can sustainably and stably produce products that meet the requirements；
(2) The production process and its major changes have been verified；
(3) Equip the required resources, including at least:
1.Appropriately qualified and trained personnel；
2. Sufficient factory building and space;
3. Applicable equipment and maintenance support;
4. Correct raw materials, packaging materials and labels;
5. Approved process procedures and operating procedures;
6. Appropriate storage and transportation conditions.
(4) It should be used accurately、Develop operating procedures in easy-to-understand language；
(5) Operators have been trained，Able to operate correctly according to operating procedures；
(6) The entire production process should be recorded，Deviations have been investigated and recorded；
(7) Batch records and shipping records should be able to trace the complete history of the batch of products，And keep it properly、Easy to read；
(8) Reduce quality risks during drug shipment;
(9) Establishing a drug recall system，Ensure that any batch of products shipped for sale can be recalled；
(10) Investigate the causes of drug complaints and quality defects，And take measures，Prevent similar quality defects from happening again。
Section 3 Quality Control
Article 11 Quality control includes corresponding organizational structures、File system and sampling、Inspection, etc.，Ensure that materials or products complete necessary inspections before release，Confirm that its quality meets the requirements。
Article 12 Basic requirements for quality control:
(1) Appropriate facilities should be equipped、Equipment、Instruments and trained personnel，valid、Reliably complete all quality control related activities；
(2) There should be approved operating procedures，Used for raw and auxiliary materials、Packaging materials、Intermediate products、Sampling of products to be packaged and finished products、Check、Inspection and product stability inspection，Carry out environmental monitoring when necessary，To ensure compliance with the requirements of this specification；
(3) The raw and excipient materials shall be inspected by authorized personnel in accordance with the prescribed methods、Packaging materials、Intermediate products、Sampling of products to be packaged and finished products；
(4) The inspection method should be verified or confirmed;
(5) Sampling、Check、Inspection should be recorded，Deviations should be investigated and documented；
(6) Materials、Intermediate products、Products to be packaged and finished products must be inspected and inspected according to quality standards，With record；
(7) There should be sufficient samples of materials and final packaged finished products，To prepare for necessary inspection or inspection；Except for finished products whose final packaging container is too large，The sample packaging of the finished product should be the same as the final packaging。
Section 4 Quality Risk Management
Article 13 Quality risk management is a forward-looking or retrospective approach throughout the product life cycle，Assess quality risks、Control、Communication、Audit system process。
Article 14 Quality risks should be assessed based on scientific knowledge and experience，To ensure product quality。
Article 15 Methods adopted in the quality risk management process、Measures、The form and documentation should be appropriate to the level of risk present。
Chapter 3 Organization and personnel
Section 1 Original then
Article 16 Enterprises should establish management institutions suitable for drug production，With organizational chart。
Enterprises should establish an independent quality management department，Perform quality assurance and quality control responsibilities。The quality management department can set up a quality assurance department and a quality control department respectively。
Article 17 The quality management department shall participate in all quality-related activities，Responsible for reviewing all documents related to this specification。Quality management department personnel shall not delegate responsibilities to personnel from other departments。
Article 18 Enterprises shall have sufficient personnel with appropriate qualifications (including academic qualifications、Training and practical experience) management and operations personnel，The responsibilities of each department and each position should be clearly defined。Position responsibilities must not be omitted，Intersecting responsibilities should be clearly defined。Everyone should not have too many responsibilities。
All personnel should clearly understand their responsibilities，Be familiar with the requirements associated with their responsibilities，And receive the necessary training，Including pre-job training and continuing training。
Article 19 Responsibilities shall not normally be delegated to others。Really need to entrust，The responsibilities may be delegated to appropriately qualified designated persons。
Section 2 Key Personnel
Article 20 Key personnel shall be full-time personnel of the enterprise，At least the person in charge of the company should be included、Production Management Manager、Quality management person in charge and quality authorized person。
The person in charge of quality management and the person in charge of production management shall not hold concurrent posts for each other。The person in charge of quality management and the quality authorized person can serve concurrently。Operating procedures should be formulated to ensure that the quality authorized person performs his duties independently，Free from interference from company leaders and other personnel。
Article 21 Corporate person in charge
The person in charge of the enterprise is the main person responsible for drug quality，Fully responsible for the daily management of the enterprise。To ensure that enterprises achieve quality goals and produce drugs in accordance with the requirements of this specification，The person in charge of the enterprise should be responsible for providing necessary resources，Reasonable plan、Organization and Coordination，Ensure the quality management department independently performs its duties。
Article 22 Production Management Manager
(1) Qualifications:
The person in charge of production management should have at least a bachelor's degree in pharmacy or related majors (or intermediate professional and technical titles or practicing pharmacist qualifications)，Have at least three years of practical experience in pharmaceutical production and quality management，At least one year of pharmaceutical production management experience，Received professional knowledge training related to the products produced。
(2) Main responsibilities:
1.Ensure that drugs are produced in accordance with approved process procedures、Storage，To ensure drug quality；
2.Ensure strict implementation of various operating procedures related to production operations；
3.Ensure that batch production records and batch packaging records are reviewed by designated personnel and sent to the quality management department；
4.Ensure the maintenance of plant and equipment，To keep it in good operating condition；
5. Ensure that all necessary verification work is completed;
6.Ensure that production-related personnel undergo necessary pre-job training and continuing training，And adjust the training content according to actual needs。
Article 23 Quality Management Manager
(1) Qualifications:
The person in charge of quality management should have at least a bachelor's degree in pharmacy or related majors (or intermediate professional and technical titles or practicing pharmacist qualifications)，Have at least five years of practical experience in pharmaceutical production and quality management，At least one year of pharmaceutical quality management experience，Received professional knowledge training related to the products produced。
(2) Main responsibilities:
1.Ensure raw materials、Packaging materials、Intermediate products、Products to be packaged and finished products comply with registered and approved requirements and quality standards；
2.Ensure review of batch records is completed before product release；
3. Ensure all necessary inspections are completed;
4.Approved quality standards、Sampling method、Inspection methods and other quality management operating procedures；
5. Review and approve all quality-related changes;
6.Ensure that all major deviations and out-of-spec inspection results have been investigated and dealt with promptly；
7. Approve and supervise the commissioned inspection;
8.Supervise the maintenance of plant and equipment，To keep it in good operating condition；
9.Ensure that any necessary confirmation or verification work is completed，Review and approve validation or validation protocols and reports；
10. Make sure the self-test is completed;
11. Evaluate and approve material suppliers;
12.Ensure all complaints related to product quality are investigated，And get it in time、Correct handling；
13.Ensure the completion of the product’s ongoing stability investigation plan，Provide data for stability investigation；
14. Ensure the completion of product quality review analysis;
15.Ensure that quality control and quality assurance personnel have received necessary pre-job training and continuing training，And adjust the training content according to actual needs。
Article 24 The person in charge of production management and the person in charge of quality management usually have the following common responsibilities:
(1) Review and approve product process procedures、Operating procedures and other documents；
(2) Supervise the health status of the factory area;
(3) Ensure that key equipment has been confirmed;
(4) Ensure the completion of production process verification;
(5) Ensure that all relevant personnel of the enterprise have received necessary pre-job training and continuing training，And adjust the training content according to actual needs；
(6) Approving and supervising commissioned production;
(7) Determine and monitor the storage conditions of materials and products；
(8) Keeping records;
(9) Supervise the implementation of this specification;
(10) Monitor factors affecting product quality.
Article 25 Quality Authorized Person
(1) Qualifications:
The quality authorized person should have at least a bachelor's degree in pharmacy or related majors (or intermediate professional technical title or practicing pharmacist qualification)，Have at least five years of practical experience in pharmaceutical production and quality management，Engaged in pharmaceutical production process control and quality inspection。
The quality authorized person should have the necessary professional theoretical knowledge，and have undergone training related to product release，Only in order to independently perform its duties。
(2) Main responsibilities:
1.Participate in the establishment of enterprise quality system、Internal self-test、External quality audit、Verification and Adverse Drug Reaction Report、Product recall and other quality management activities；
2.Be responsible for product release，Ensure production of each batch of released product、All inspections comply with relevant regulations、Drug registration requirements and quality standards；
3.Before product release，The quality authorized person must issue product release audit records in accordance with the requirements of item 2 above，And included in batch records。
Section 3 PE Training
Article 26 The enterprise should designate a department or dedicated person to be responsible for training management，There should be a training plan or plan that has been reviewed or approved by the person in charge of production management or the person in charge of quality management，Training records should be kept。
Article 27 and Pharmaceutical Production、All personnel involved in quality should be trained，The content of training should be adapted to the requirements of the position。In addition to training on the theory and practice of this specification，There should also be relevant regulations、Responsibilities of corresponding positions、Skills training，And regularly evaluate the actual effect of training。
Article 28 High-risk operation area (e.g.: high activity、Highly toxic、Infectious、Staff in areas where highly allergenic materials are produced) should receive specialized training。
Section 4 Personnel hygiene
Article 29 All personnel shall receive training on health requirements，Enterprises should establish personnel hygiene operating procedures，Minimize the risk of personnel contamination in pharmaceutical production。
Article 30: Personnel hygiene operating procedures shall include information related to health、Content related to hygiene habits and personnel clothing。Personnel in the production area and quality control area should correctly understand the relevant personnel hygiene operating procedures。Enterprises should take measures to ensure the implementation of personnel hygiene operating procedures。
Article 31 Enterprises shall manage personnel health，And create a health file。Production personnel who are in direct contact with drugs should undergo a health examination before taking up work，In the future, have a health check-up at least once a year。
Article 32 Enterprises should take appropriate measures，Avoid wounds on the body、Personnel suffering from infectious diseases or other diseases that may contaminate drugs are engaged in the production of direct contact with drugs。
Article 33 Visitors and untrained personnel are not allowed to enter the production area and quality control area，Those who really need to enter under special circumstances，Personal hygiene should be done in advance、Guidance on changing clothes and other matters。
Article 34 Anyone entering the production area must change clothes in accordance with regulations。Selection of work clothes、The style and wearing method should be suitable for the work being performed and the air cleanliness level requirements。
Article 35 Personnel entering the clean production area are not allowed to wear makeup or accessories。
Article 36 Production Area、Smoking and eating should be prohibited in storage areas，No storage of food、Drinks、Non-production items such as cigarettes and personal medicines。
Article 37 Operators should avoid direct contact with drugs with bare hands、Packaging materials and equipment surfaces in direct contact with pharmaceuticals。
Chapter 4 Plant and facilities
Section 1 Original then
Article 38 Site selection of factories、Design、Layout、Build、Renovation and maintenance must comply with pharmaceutical production requirements，Contamination should be avoided to the greatest extent、Cross contamination、Confusion and Error，Easy to clean、Operation and Maintenance。
Article 39 Site selection shall be comprehensively considered based on the factory building and production protection measures，The environment of the factory should be able to minimize the risk of contamination of materials or products。
Article 40 Enterprises should have a clean production environment；Floor of factory area、Roads and transportation should not cause pollution to the production of pharmaceuticals；Production、Administration、The overall layout of living and auxiliary areas should be reasonable，Do not hinder each other；People in the factory area and factory buildings、Logistics direction should be reasonable。
Article 41 The factory building should be properly maintained，And ensure that maintenance activities do not affect the quality of the medicine。The factory building should be cleaned or disinfected as necessary in accordance with detailed written operating procedures。
Article 42 Factory buildings should have appropriate lighting、Temperature、Humidity and ventilation，Ensure that the quality of products produced and stored and the performance of related equipment are not directly or indirectly affected。
Article 43 Factory Building、Facility should be designed and installed to effectively prevent the entry of insects or other animals。Necessary measures should be taken，Avoid the use of rodenticide、Pesticide、Fumigant and other equipment、Material、Product causes pollution。
Article 44 Appropriate measures should be taken，Prevent entry of unauthorized persons。Production、Storage and quality control areas should not serve as direct passages for non-area personnel。
Article 45 Factory buildings should be preserved、Utilities、As-built drawings after fixed pipe construction or modification。
Section 2 Production Area
Article 46 To reduce the risk of contamination and cross-contamination，Factory、Production facilities and equipment should be based on the characteristics of the drugs produced、Process flow and corresponding cleanliness level requirements are reasonably designed、Layout and usage，And meet the following requirements:
(1) The characteristics of the drug should be comprehensively considered、Factors such as craftsmanship and intended use，Determine the factory、The feasibility of sharing production facilities and equipment for multiple products，With corresponding evaluation report；
(2) Production of drugs with special properties，Such as highly allergenic drugs (such as penicillins) or biological products (such as BCG or other drugs prepared with live microorganisms)，Must use dedicated and independent factory building、Production Facilities and Equipment。The operating area where penicillin drugs produce large amounts of dust should maintain a relatively negative pressure，The exhaust gas discharged to the outdoors should be purified and meet the requirements，The exhaust vent should be far away from the air inlets of other air purification systems；
(3) Production of β-lactam structural drugs、Sex hormonal contraceptives must use dedicated facilities (such as independent air purification systems) and equipment，And strictly separated from other pharmaceutical production areas；
(4) Production of certain hormones、Cytotoxicity、Highly active chemicals should use dedicated facilities (such as independent air purification systems) and equipment；Special circumstances，If special protective measures are taken and necessary verification is carried out，The above pharmaceutical preparations can share the same production facilities and equipment through staged production；
(5) is used for the above (2)、(3)、Air purification system of item (4)，The exhaust air should be purified；
(6) Pharmaceutical production plants shall not be used to produce non-medicinal products that may adversely affect the quality of pharmaceuticals。
Article 47 The production area and storage area should have sufficient space，Ensure equipment is stored in an orderly manner、Material、Intermediate products、Products to be packaged and finished products，Avoid confusion between different products or materials、Cross contamination，Avoid omissions or errors in production or quality control operations。
Article 48 It should be based on the type of drug、Configure air-conditioning purification system for production operation requirements and external environmental conditions，Ventilate production areas effectively，With temperature、Humidity control and air purification filtration，Ensure that the production environment of drugs meets the requirements。
Between clean area and non-clean area、The pressure difference between clean areas of different levels should not be less than 10 Pascals。When necessary，Appropriate pressure gradients should also be maintained between different functional areas (operating rooms) of the same cleanliness level。
Oral liquid and solid dosage forms、Oral administration (including rectal administration)、Exposed process areas for the production of non-sterile preparations such as epidermal topical drugs and exposed process areas for final processing of packaging materials that directly contact the drugs，Should be set up in accordance with the requirements for Class D clean areas in the appendix of "Sterile Drugs"，Enterprises can take appropriate microbiological monitoring measures in this area according to the standards and characteristics of the products。
Article 49 Internal surface (wall) of clean area、Ground、Ceiling) should be flat and smooth、No cracks、Strict interface、No particles falling off，Avoid dust accumulation，Easy for effective cleaning，Disinfection should be carried out when necessary。
Article 50 Various Pipelines、Lighting facilities、The design and installation of air vents and other public facilities should avoid areas that are difficult to clean，It should be maintained outside the production area whenever possible。
Article 51 Drainage facilities should be of appropriate size，And install a device to prevent backflow。Open ditch drainage should be avoided as much as possible；When inevitable，Open ditches should be shallow，To facilitate cleaning and disinfection。
Article 52 The weighing of raw materials and excipients of preparations should usually be carried out in a specially designed weighing room。
Article 53 Dust-producing operation room (such as sampling of dry materials or products、Weighing、Mixed、Packaging and other operation rooms) should maintain a relative negative pressure or take special measures，Prevent the spread of dust、Avoid cross-contamination and facilitate cleaning。
Article 54 Factory buildings or areas used for pharmaceutical packaging shall be reasonably designed and laid out，To avoid confusion or cross-contamination。As if there are several packaging lines in the same area，There should be isolation measures。
Article 55 The production area should have appropriate lighting，The lighting in the visual operation area should meet the operation requirements。
Article 56 An intermediate control area can be set up in the production area，However, intermediate control operations must not bring quality risks to drugs。
Section 3 Storage area
Article 57 The storage area should have sufficient space，Ensure orderly storage pending verification、Qualified、Unqualified、Returned or recalled raw materials、Packaging materials、Intermediate products、Various materials and products such as products to be packaged and finished products。
Article 58 The design and construction of storage areas should ensure good storage conditions，With ventilation and lighting facilities。The storage area should be able to meet the storage conditions of materials or products (such as temperature and humidity、Protection from light) and safe storage requirements，And conduct inspection and monitoring。
Article 59 Highly active materials or products and printed packaging materials should be stored in a safe area。
Article 60 Acceptance、Release and shipping areas should be able to protect materials、The product is protected from outside weather (such as rain、The influence of snow。The layout and facilities of the receiving area should be able to ensure that the outer packaging of incoming materials can be cleaned as necessary before entering the storage area。
Article 61 If a separate isolation area is used to store materials to be inspected，The area to be inspected should have eye-catching signs，Access is limited to approved personnel。
Unqualified、Returned or recalled materials or products should be stored in isolation。
If other methods are used instead of physical isolation，Then the method stake betting appStake Sports Bettingshould have the same security。
Article 62 There should usually be a separate sampling area for materials。The air cleanliness level in the sampling area should be consistent with the production requirements。If sampling in other areas or using other methods，Should prevent contamination or cross-contamination。
Section 4 Quality Control Area
Article 63 Quality control laboratories should generally be separated from production。Biology Check、Microbiology and radioisotope laboratories should also be separated from each other。
Article 64 The design of the laboratory shall ensure that it is suitable for the intended purpose，and avoid confusion and cross-contamination，There should be adequate area for sample handling、Storage of retained samples and stability test samples and preservation of records。
Article 65 When necessary，A special instrument room should be set up，Protect sensitive instruments from static electricity、Vibration、Interference from moisture or other external factors。
Article 66 Laboratories that handle special items such as biological samples or radioactive samples shall comply with relevant national requirements。
Article 67 The experimental animal room should be strictly separated from other areas，its design、Construction should comply with relevant national regulations，It also has independent air treatment facilities and special passages for animals。
Section 5 auxiliary area
Article 68 The setting of the rest room should not interfere with the production area、Adverse effects on storage areas and quality control areas。
Article 69 Changing rooms and washrooms should be convenient for people to enter and exit，And adapt to the number of users。The bathroom must not be directly connected to the production area and storage area。
Article 70 The maintenance room should be as far away from the production area as possible。Maintenance spare parts and tools stored in clean area，Should be placed in a special room or tool cabinet。
Chapter 5 set Prepared
Section 1 Original then
Article 71 Design of equipment、Selection、Install、Modification and maintenance must be consistent with intended use，Pollution should be reduced as much as possible、Cross contamination、Risk of confusion and error，Easy to operate、Cleaning、Maintenance，and disinfection or sterilization if necessary。
Article 72 Equipment should be established for use、Cleaning、Operation Procedures for Maintenance and Repair，And save the corresponding operation records。
Article 73 Equipment procurement shall be established and maintained、Install、Confirmed documents and records。
Section 2 Design and Installation
Article 74 Production equipment shall not have any adverse impact on the quality of drugs。The surface of production equipment in direct contact with drugs should be smooth、Smooth、Easy to clean or disinfect、Corrosion Resistance，No chemical reaction with drugs、Adsorb drugs or release substances into drugs。
Article 75 Weighing instruments with appropriate range and accuracy shall be equipped、Measuring tool、Instruments and Meters。
Article 76 Appropriate cleaning should be chosen、Cleaning equipment，And prevent such equipment from becoming a source of pollution。
Article 77 Lubricants used in equipment、Coolants, etc. must not cause contamination to medicines or containers，Food grade or equivalent lubricant should be used whenever possible。
Article 78 Procurement of production molds、Acceptance、Keeping、Maintenance、Corresponding operating procedures should be formulated for issuance and scrapping，Dedicated counter for safekeeping，And there are corresponding records。
Section 3 Maintenance and Repair
Article 79 The maintenance and repair of equipment shall not affect product quality。
Article 80 Preventive maintenance plans and operating procedures for equipment should be formulated，The maintenance and repair of equipment should have corresponding records。
Article 81 Equipment that has been modified or significantly repaired shall be re-confirmed，Can only be used for production if it meets the requirements。
Section 4 Use and Clean
Article 82 Major production and inspection equipment should have clear operating procedures。
Article 83 Production equipment should be used within the confirmed parameter range。
Article 84 Production equipment shall be cleaned in accordance with detailed operating procedures。
The operating procedures for cleaning production equipment should specify specific and complete cleaning methods、Cleaning equipment or tools、Name and preparation method of cleaning agent、Method to remove the previous batch of identifiers、Methods to protect cleaned equipment from contamination before use、Maximum storage time of cleaned devices、How to check the cleanliness of equipment before use，Enables operators to perform reproducible operations、Effective way to clean all kinds of equipment。
If you need to disassemble and assemble the equipment，The order and method of disassembly and assembly of equipment should also be specified；If you need to disinfect or sterilize the equipment，Specific methods of disinfection or sterilization should also be specified、Name and preparation method of disinfectant。When necessary，The maximum time allowed between the end of production and cleaning of equipment should also be specified。
Article 85 Cleaned production equipment shall be cleaned before cleaning、Store in dry conditions。
Article 86 Equipment and instruments used for drug production or testing，There should be usage logs，Record content including use、Cleaning、Maintenance and repair status and dates、Time、Name of the drug produced and tested、Specifications and batch numbers, etc.。
Article 87 Production equipment should have obvious status signs，Indicate the device number and contents (such as name、Specifications、batch number)；If there is no content, please indicate the clean status。
Article 88 Unqualified equipment should be moved out of the production and quality control area if possible，Before moving out，There should be an eye-catching status mark。
Article 89 The main fixed pipelines shall be marked with the name of the contents and flow direction。
Section 5 School Accurate
Article 90 Weighing instruments used for production and inspection shall be regularly inspected in accordance with operating procedures and calibration plans、Measuring tool、Instrument、Recording and controlling equipment and instruments for calibration and inspection，And save relevant records。The calibration range should cover the actual production and inspection range of use。
Article 91 Key weighing instruments used in production and inspection shall be ensured、Measuring tool、Instrument、Recording and control equipment and instruments are calibrated，The data obtained is accurate、Reliable。
Article 92 Measuring standard instruments shall be used for calibration，And the measuring standard instruments used shall comply with relevant national regulations。Calibration records should indicate the name of the measuring standard instrument used、No.、Calibration validity period and metrology certificate number，Ensure record traceability。
Article 93 Weighing Instruments、Measuring tool、Instrument、Equipment and instruments used for recording and control should be clearly marked，Indicate its calibration validity period。
Article 94 No use without calibration is allowed、Calibration validity period exceeded、Inaccurate weighing instrument、Measuring tool、Instruments and equipment for recording and control、Instrument。
Article 95 In production、Packaging、Using automatic or electronic equipment in the warehousing process，Calibration and inspection should be carried out regularly in accordance with operating procedures，Make sure it operates properly。Calibration and inspection should have corresponding records。
Section 6 Pharmaceutical water
Article 96 Pharmaceutical water should be suitable for its purpose，And comply with the quality standards and related requirements of the "Pharmacopoeia of the People's Republic of China"。Pharmaceutical water should at least be drinking water。
Article 97 Design of water treatment equipment and its delivery system、Install、Operation and maintenance should ensure that pharmaceutical water meets the set quality standards。Water treatment equipment must not be operated beyond its design capabilities。
Article 98 Purified water、The materials used in water for injection storage tanks and delivery pipelines should be non-toxic、Corrosion Resistance；The vent of the storage tank should be installed with a hydrophobic sterilizing filter that does not shed fibers；Pipeline design and installation should avoid dead ends、Blind leg。
Article 99 Purified water、Preparation of water for injection、Storage and distribution should prevent the growth of microorganisms。Purified water can be recycled，Water for injection can adopt a heat preservation cycle above 70℃。
Article 100 The quality of pharmaceutical water and raw water should be regularly monitored，And there are corresponding records。
Article 101 Purified water should be treated in accordance with operating procedures、Cleaning and disinfection of water for injection pipelines，And there are related records。It was found that microbial contamination of pharmaceutical water reached the warning limit、When correcting the deviation to the limit, it should be handled in accordance with the operating procedures。
Chapter 6 Materials and Products
Section 1 Original then
Article 102 Raw materials and excipients used in pharmaceutical production、Packaging materials in direct contact with drugs should comply with corresponding quality standards。The ink used for direct printing on medicines should comply with food standards。
Imported raw and auxiliary materials should comply with relevant national import management regulations。
Article 103 Operating procedures for materials and products should be established，Ensure correct receipt of materials and products、Storage、Issue、Use and Shipping，Prevent pollution、Cross contamination、Confusion and Error。
Materials and products should be handled in accordance with operating procedures or process procedures，With record。
Article 104 The determination and change of material suppliers shall be subject to quality assessment，Purchase only after approval by the quality management department。
Article 105 The transportation of materials and products should be able to meet their quality assurance requirements，Those who have special requirements for transportation，The transportation conditions should be confirmed。
Article 106 Raw and auxiliary materials、There should be operating procedures for the receipt of packaging materials and printed packaging materials that are in direct contact with drugs，All incoming materials should be inspected，To ensure consistency with the order，And confirm that the supplier has been approved by the quality management department。
The outer packaging of materials should have labels，And indicate the required information。When necessary，Should also be cleaned，Found that the outer packaging is damaged or other problems that may affect the quality of the materials，Should be reported to the quality management department for investigation and recording。
Every receipt should be recorded, including:
(1) The name of the material stated on the delivery note and packaging container；
(2)The name and/or code of materials used within the enterprise;
(3) Date of receipt;
(4) Name of supplier and manufacturer (if different)；
(5) Batch number identified by supplier and manufacturer (if different)；
(6) Total amount received and number of packaging containers;
(7) The batch number or serial number designated by the enterprise after receipt;
(8) Relevant instructions (such as packaging status).
Article 107 After receiving materials and producing finished products, they must be managed in a timely manner and in accordance with the inspection requirements，Until release。
Article 108 Materials and products shall be stored and transferred in batches in an orderly manner according to their nature，Issue and shipment should comply with the first-in-first-out and first-in-first-out principles。
Article 109 Using computerized warehousing management，There should be corresponding operating procedures，Prevent system failure、Confusion and errors in materials and products caused by special circumstances such as shutdown。
Identification using a fully computerized warehouse management system，Material、Product and other related information does not need to be marked in a written and readable manner。
Section 2 Raw materials
Article 110 Corresponding operating procedures should be formulated，Take appropriate measures such as verification or inspection，Confirm that the raw and auxiliary materials in each package are correct。
Article 111 Receive several batches of materials at one time，Sampling should be done in batches、Inspection、Release。
Article 112 Raw and auxiliary materials in the storage area should be appropriately labeled，And at least indicate the following:
(1) Specified material name and internal material code of the enterprise；
(2) The batch number set by the enterprise when receiving;
(3) Material quality status (such as pending inspection、Qualified、Unqualified、sampled)；
(4) Validity period or re-inspection period.
Article 113 Only raw materials and excipients that have been approved and released by the quality management department and are within the validity period or retest period can be used。
Article 114 Raw materials and excipients should be stored according to the validity period or retest period。During storage period，If special circumstances are found that have an adverse impact on quality，Should be retested。
Article 115 The ingredients shall be prepared by designated personnel in accordance with operating procedures，After checking the materials，Accurate weighing or measuring，And make a mark。
Article 116 Each prepared material and its weight or volume shall be independently reviewed by others，And there is a review record。
Article 117 All ingredients used in the production of the same batch of pharmaceuticals shall be stored in a centralized manner，And make a mark。
Section 3 Intermediate products and products to be packaged
Article 118 Intermediate products and products to be packaged shall be stored under appropriate conditions。
Article 119 Intermediate products and products to be packaged should have clear identification，And at least indicate the following:
(1) Product name and internal product code of the enterprise;
(2) Product batch number;
(3) Quantity or weight (such as gross weight, net weight, etc.);
(4) Production process (if necessary);
(5) Product quality status (if necessary，If pending、Qualified、Unqualified、sampled)。
Section 4 Packaging materials
Article 120 The management and control requirements for packaging materials and printed packaging materials that are in direct contact with drugs are the same as those for raw and excipient materials。
Article 121 Packaging materials shall be distributed by designated personnel in accordance with operating procedures，And take steps to avoid confusion and errors，Ensure the correct packaging materials are used for pharmaceutical production。
Article 122 Printing and packaging material design shall be established、Review、Approved operating procedures，Ensure that the printed content of printed packaging materials is consistent with that approved by the drug regulatory department，And create a special document，Save the original version of the printed packaging materials approved by signature。
Article 123 When the version of printing and packaging materials changes，Measures should be taken，Ensure that the printed packaging material used for the product is the correct version。It is advisable to take back the obsolete old printing templates and destroy them。
Article 124 Printing and packaging materials should be properly stored in a special area，Unauthorized personnel are not allowed to enter。Cut labels or other bulk printed packaging materials should be stored and transported in sealed containers，To prevent confusion。
Article 125 Printing and packaging materials should be kept by designated personnel，And distributed according to operating procedures and demand。
Article 126 Packaging materials or printed packaging materials in direct contact with drugs for each batch or each release，All should have identification marks，Indicate the name and batch number of the product used。
Article 127 Expired or discarded printing and packaging materials shall be destroyed and recorded。
Section 5 成 item
Article 128 Finished products must be inspected and stored before release。
Article 129 The storage conditions of finished products shall comply with the requirements for drug registration approval。
Section 6 Specially managed materials and products
Article 130 Narcotic drugs、Psychotropic drugs、Toxic drugs for medical use (including medicinal materials)、Radioactive pharmaceuticals、Pharmaceutical precursor chemicals and flammable、Acceptance of explosive and other dangerous goods、Storage、Management shall implement relevant national regulations。
Section 7 its him
Article 131 Unqualified Materials、Intermediate products、Each packaging container of products to be packaged and finished products should have clear and eye-catching signs，And keep it properly in the quarantine area。
Article 132 Unqualified Materials、Intermediate products、The handling of products to be packaged and finished products shall be approved by the person in charge of quality management，With record。
Article 133 Product recycling requires prior approval，And fully assess the relevant quality risks，Decide whether to recycle based on the assessment conclusion。Recycling should be carried out in accordance with predetermined operating procedures，And there are corresponding records。The validity period of the recycled products shall be determined based on the production date of the earliest batch of products in the recycling process。
Article 134 Preparation products shall not be reprocessed。Unqualified intermediate preparation product、Products to be packaged and finished products are generally not allowed to be reworked。Only if it does not affect product quality、Conform to corresponding quality standards，And based on reservation、After approved operating procedures and full assessment of relevant risks，Rework processing is only allowed。Rework should have corresponding records。
Article 135 Rework or reprocessing or recycling of finished products produced after merging，The quality management department should consider the need to conduct inspections and stability investigations of additional related items。
Article 136 Enterprises should establish operating procedures for drug returns，And there are corresponding records，The content should at least include: product name、Batch number、Specifications、Quantity、Return unit and address、Reason and date of return、Final processing opinions。
Returns of the same product, the same batch number, and different channels should be recorded separately、Storage and Handling。
Article 137 Only after inspection、Inspection and Investigation，There is evidence that the quality of the return is not affected，After evaluation by the quality management department in accordance with the operating procedures，The return may be considered for repackaging、Reshipment Sale。The factors considered in the evaluation should at least include the nature of the drug、Required storage conditions、Current status of drugs、History，And factors such as the time between shipment and return。Returns that do not meet storage and shipping requirements，Should be destroyed under the supervision of the quality management department。When you have doubts about the quality of the return，No reshipping。
Recycling of returns，Recycled products shall comply with predetermined quality standards and the requirements of Article 133。
The process and results of return processing should be recorded accordingly.
Chapter 7 Confirmation and Verification
Article 138 The enterprise shall determine the confirmation or verification work that needs to be carried out，To demonstrate that key elements of the operation can be effectively controlled。The scope and extent of validation or verification should be determined through a risk assessment。
Article 139 Enterprise’s Factory Building、Facilities、Equipment and inspection instruments should be confirmed，Proven production processes should be used、Operating procedures and inspection methods for production、Operation and Inspection，And maintain ongoing verification status。
Article 140 Documents and records for confirmation and verification shall be established，And can prove with documents and records that the following predetermined goals are achieved:
(1) Design confirmation should prove the factory building、Facilities、The equipment is designed to comply with the intended use and the requirements of this specification；
(2) Installation confirmation should prove the factory building、Facilities、The equipment is constructed and installed in compliance with design standards；
(3) Operation confirmation should prove the factory building、Facilities、The equipment operates in compliance with design standards；
(4) Performance confirmation should prove the factory building、Facilities、The equipment can continue to meet standards under normal operating methods and process conditions；
(5) Process verification should prove that a production process can continuously produce products that meet the intended use and registration requirements according to the specified process parameters。
Article 141 Before adopting new production recipes or production processes，The suitability for routine production should be verified。The production process uses the specified raw materials and equipment conditions，Should always be able to produce products that meet the intended use and registration requirements。
Article 142 The main factors affecting product quality，Such as raw materials、Packaging materials in direct contact with drugs、Production equipment、Production environment (or factory)、Production process、When inspection methods etc. change，Should be confirmed or verified。When necessary，Should also be approved by the drug regulatory department。
Article 143 Cleaning methods should be verified，Confirmed its cleaning effect，To effectively prevent contamination and cross-contamination。Cleaning verification should take into account equipment usage、Cleaners and disinfectants used、Sampling method and location and corresponding sampling recovery rate、Nature and limits of residues、Sensitivity and other factors of residue testing methods。
Article 144 Confirmation and verification are not one-time actions。After first confirmation or verification，Should be re-confirmed or re-validated based on product quality review analysis。Key production processes and operating procedures should be revalidated regularly，Ensure it achieves the expected results。
Article 145 Enterprises shall formulate a master verification plan，Describe the key information of the confirmation and verification work in the form of documents。
Article 146 Provisions should be made in the verification master plan or other relevant documents，Secure factory building、Facilities、Equipment、Inspection instruments、Production process、Operation procedures and inspection methods can remain stable。
Article 147 A confirmation or verification plan shall be developed based on the object of confirmation or verification，and reviewed、Approved。The validation or verification plan should clearly define responsibilities。
Article 148 Confirmation or verification shall be carried out in accordance with a predetermined and approved plan，With record。After the confirmation or verification work is completed，A report should be written，and reviewed、Approved。The results and conclusions of confirmation or verification (including evaluation and suggestions) should be recorded and archived。
Article 149 The process procedures and operating procedures shall be confirmed based on the verification results。
Chapter 8 File Management
Section 1 Original then
Article 150 Documentation is the basic element of the quality assurance system。Company must have written quality standards with correct content、Production prescription and process procedures、Operating procedures and records and other documents。
Article 151 Enterprises should establish operating procedures for document management，Design systematically、Formulated、Review、Approval and issuance of documents。Documents related to this specification shall be reviewed by the quality management department。
Article 152 The content of the document shall be consistent with the drug production license、Same requirements for drug registration and other related requirements，And help trace the history of each batch of products。
Article 153 Drafting of documents、Revised、Review、Approved、Replace or cancel、Copy、Storage and destruction shall be managed in accordance with operating procedures，With corresponding file distribution、Cancel、Copy、Destroy record。
Article 154 Drafting of documents、Revised、Review、Approvals should be signed and dated by the appropriate personnel。
Article 155 Documents shall be titled、Type、Purpose and file number and version number。The text should be accurate、Clear、Easy to understand，Cannot be ambiguous。
Article 156 Documents shall be stored in categories、Clearly organized，Easy to read。
Article 157 When copying original documents，No errors shall occur；Copied files should be legible。
Article 158 Documents shall be reviewed regularly、Revised；Revised document，Should be managed in accordance with regulations，Prevent misuse of older versions of files。Distribution、The document used should be the current version of the approval，Revoked or old versions of documents will be retained except for future reference，Not allowed on the job site。
Article 159 Every activity related to this Code shall be recorded，To ensure product production、Activities such as quality control and quality assurance can be traced。The record should have enough space to fill in the data。Records should be filled in promptly，True content，Clear handwriting、Easy to read，Not easy to erase。
Article 160 Records automatically printed by production and inspection equipment shall be used whenever possible、Charts and graphs, etc.，And indicate the name of the product or sample、Batch number and recording equipment information，The operator should sign the name and date。
Article 161 Records should be kept clean，Do not tear or modify at will。Any changes to the record should be signed with name and date，Making the original information legible，When necessary，The reason for the change should be stated。If the record needs to be re-transcribed，The original records shall not be destroyed，Should be saved as an attachment to the re-transcription record。
Article 162 Each batch of drugs shall have a batch record，Includes batch production records、Batch packaging record、Batch inspection records and drug release audit records and other records related to this batch of products。Batch records should be managed by the quality management department，Keep the medicine for at least one year after its expiry date。
Quality Standard、Process Specification、Operating Procedures、Stability inspection、Confirm、Verification、Changes and other important documents should be kept for a long time。
Article 163 If electronic data processing system is used、Photographic technology or other reliable means of recording data，There should be operating procedures for the system used；Records stake sports betting appstake betting appshould be checked for accuracy。
Using electronic data processing systems，Only authorized personnel may enter or change data，Changes and deletions should be recorded；Password or other means should be used to control system login；After key data input，Should be independently reviewed by others。
Electronically maintained batch records，Tape should be used、Microfilm、Paper copy or other method for backup，To ensure the security of records，And the data can be easily accessed during the storage period。
Section 2 Quality Standard
Article 164 Materials and finished products shall have approved current quality standards；When necessary，Intermediate products or products to be packaged should also have quality standards。
Article 165 The quality standards of materials should generally include:
(1) Basic information of materials:
1.The material name uniformly designated by the enterprise and the material code used internally；
2. Basis for quality standards;
3. Approved suppliers;
4. Actual samples or prototypes of printing packaging materials.
(2) Sampling、Inspection method or related operating procedure number；
(3) Qualitative and quantitative limit requirements;
(4) Storage conditions and precautions;
(5) Validity period or re-inspection period.
Article 166: Intermediate products purchased or exported and products to be packaged shall have quality standards；If the inspection results of the intermediate product are used for the quality evaluation of the finished product，Intermediate product quality standards corresponding to the finished product quality standards should be formulated。
Article 167 Quality standards for finished products should include:
(1) Product name and product code;
(2) Corresponding product prescription number (if any);
(3) Product specifications and packaging forms;
(4) Sampling、Inspection method or related operating procedure number；
(5) Qualitative and quantitative limit requirements;
(6) Storage conditions and precautions;
(7) Validity period.
Section 3 Process Specification
Article 168 Each production batch of each drug shall have a process procedure approved by the enterprise，Each packaging form of different drug specifications should have its own packaging operation requirements。The formulation of process specifications should be based on the registered and approved process。
Article 169 Process specifications shall not be changed at will。If you need to change，Should be revised in accordance with relevant operating procedures、Review、Approved。
Article 170 The content of the preparation process specification should at least include:
(1) Production prescription:
1. Product name and product code;
2. Product dosage form, specifications and batch size;
3.List of raw materials and auxiliary materials used (including those used in the production process，Materials that do not appear in the finished product)，State the designated name of each material、Code and usage；If the amount of raw materials and excipients needs to be converted，The calculation method should also be stated。
(2) Production operation requirements:
1.Description of the production location and equipment used (such as the location and number of the operating room、Cleanliness level、Necessary temperature and humidity requirements、Equipment model and number, etc.)；
2.Preparation of key equipment (such as cleaning、Assembly、Calibration、Sterilization, etc.) method or corresponding operating procedure number；
3.Detailed production steps and process parameter description (such as material verification、Preprocessing、The order of adding materials、Mixing time、Temperature, etc.)；
4. All intermediate control methods and standards;
5.Expected final production limit，When necessary，The production limit of intermediate products should also be stated，And the calculation method and limits of material balance；
6.Storage requirements for products to be packaged，include container、Labels and special storage conditions；
7. Things to note.
(3) Packaging operation requirements:
1.In terms of quantity of product in final packaging container、Packaging form expressed by weight or volume；
2.Complete list of all packaging materials required，Includes name of packaging material、Quantity、Specifications、Type and code for each packaging material related to quality standards；
3.Real samples or copies of printed packaging materials，And indicate the product batch number、Validity date printing location；
4.Notes that need to be explained，Includes inspection of production areas and equipment，Before the packaging operation begins，Confirm that the clearing of the packaging production line has been completed, etc.；
5.Instructions on packaging steps，Includes important auxiliary operations and precautions for the equipment used、Check packaging materials before use；
6.Detailed operations of intermediate control，Including sampling methods and standards；
7.Product to be packaged、Material balance calculation methods and limits for printing and packaging materials。
Section 4 Batch production record
Article 171 Each batch of products shall have corresponding batch production records，The production history and quality-related conditions of this batch of products can be traced。
Article 172 Batch production records shall be formulated based on the relevant contents of the currently approved process regulations。Records should be designed to avoid filling errors。Each page of the batch production record should be marked with the name of the product、Specifications and batch numbers。
Article 173 The original blank batch production record shall be reviewed and approved by the person in charge of production management and the person in charge of quality management。The copying and issuance of batch production records shall be controlled and recorded in accordance with operating procedures，Only one copy of the original blank batch production record can be issued for each batch of products。
Article 174 During the production process，Every operation should be recorded in time，After the operation is completed，Should be confirmed and signed by the production operator with name and date。
Article 175 The contents of the batch production record should include:
(1) Product name, specifications, batch number;
(2) Start of production and intermediate processes、Ending date and time；
(3) Signature of the person in charge of each production process;
(4) Signature of the operator of the production step；When necessary，There should also be the signature of the person who reviewed the operation (such as weighing)；
(5) The batch number and actual weighed quantity of each raw material and excipient (including the batch number and quantity of the input recycled or reworked products)；
(6) Related production operations or activities、Process parameters and control range，And the number of the main production equipment used；
(7) Record of intermediate control results and signature of operator；
(8) Output from different production processes and material balance calculation when necessary；
(9) Records of special problems or abnormal events，Include detailed description or investigation report of deviations from process procedures，and approved by signature。
Section 5 Batch packaging record
Article 176 Packaging of each batch of products or part of the products in each batch，There should be batch packaging records，In order to trace the packaging operations and quality-related conditions of this batch of products。
Article 177 Batch packaging records shall be formulated based on the packaging-related contents in the process specifications。The record should be designed to avoid filling errors。Each page of the batch packaging record should be marked with the name of the product being packaged、Specifications、Packaging form and batch number。
Article 178 Batch packaging records shall contain the batch number of the product to be packaged、Quantity and batch number and planned quantity of finished product。Audit of original blank batch packaging records、Approved、The requirements for copying and distribution are the same as the original blank batch production record。
Article 179 During the packaging process，Every operation should be recorded in time，After the operation is completed，Should be confirmed and signed by the packaging operator with name and date。
Article 180 The contents of the batch packaging record include:
(1) Product name、Specifications、Packaging form、Batch number、Production date and expiry date；
(2) Packaging operation date and time;
(3) Signature of the person in charge of the packaging operation;
(4) Signature of the operator of the packaging process;
(5) Name of each packaging material、Batch number and actual quantity used；
(6) Inspection records according to process regulations，Include intermediate control results；
(7) Details of packaging operations，Includes the numbers of the equipment and packaging production lines used；
(8) Actual samples of printing and packaging materials used，with batch number printed、Expiration date and other printed content；Printed packaging materials that are difficult to file with batch packaging records can be printed with copies of the above；
(9) Records of special problems or abnormal events，Include detailed description or investigation report of deviations from process procedures，and approved by signature；
(10) Names of all printed packaging materials and products to be packaged、Code，and distribution、Use、Quantity destroyed or withdrawn、Actual output and material balance check。
Section 6 Operating procedures and records
Article 181 The content of operating procedures shall include: title、No.、Version number、Issuing Department、Effective date、Distribution department and formulator、Reviewer、Approver’s signature and date，Title、Text and change history。
Article 182 Factory Building、Equipment、Material、Documents and records should have numbers (or codes)，And formulate operating procedures for numbering (or codes)，Ensure the uniqueness of the number (or code)。
Article 183 The following activities should also have corresponding operating procedures，The process and results should be recorded:
(1) Confirmation and verification;
(2) Assembly and calibration of equipment;
(3) Maintenance, cleaning and disinfection of plant and equipment;
(4) Training、Personnel-related matters such as dressing and hygiene；
(5) Environmental monitoring;
(6) Pest control;
(7) Change control;
(8) Deviation processing;
(9) Complaint;
(10) Drug recall;
(11) Return.
Chapter 9 Production Management
Section 1 Original then
Article 184 All pharmaceutical production and packaging shall be operated in accordance with approved process procedures and operating procedures and relevant records shall be kept，To ensure that drugs meet the required quality standards，And comply with the requirements for drug production license and registration approval。
Article 185 Operating procedures for dividing product production batches shall be established，The division of production batches should ensure the uniformity of product quality and characteristics in the same batch。
Article 186 Operating procedures for formulating drug batch numbers and determining production dates shall be established。Each batch of drugs should have a unique batch number。Unless otherwise legally required，The production date must not be later than the start date of the final mixing operation before the product is formed or filled (sealed)，Do not use product packaging date as production date。
Article 187 Each batch of products should be inspected for output and material balance，Ensure material balance meets set limits。Subject to discrepancy，Must find out the reason，After confirming that there is no potential quality risk，Only before processing as normal products。
Article 188 The production operations of drugs of different varieties and specifications shall not be carried out simultaneously in the same production operation room，Unless there is no possibility of confusion or cross-contamination。
Article 189 At every stage of production，Products and materials should be protected from microbial and other contamination。
Article 190: Drying materials or products，Especially high activity、During the production of highly toxic or highly allergenic materials or products，Special measures should be taken，Prevent the generation and spread of dust。
Article 191 All materials used during production、Containers and main equipment for intermediate products or products to be packaged、Necessary operating rooms should be labeled or otherwise marked with the names of products or materials in production、Specifications and batch numbers，If necessary，The production process should also be indicated。
Article 192 Containers、The markings used on equipment or facilities should be clear，The format of the logo should be approved by the relevant departments of the enterprise。Except for using text description on the logo，Different colors can also be used to distinguish the status of the marked object (such as pending、Qualified、Unqualified or cleaned, etc.)。
Article 193 Pipelines and other equipment connections that transport products from one area to another should be inspected，Make sure the connection is correct。
Article 194 The site must be cleared after each production，Ensure that no materials related to this production are left in the equipment and workplace、Products and Documentation。Before the next production starts，The previous clearance situation should be confirmed。
Article 195 Any deviation from process procedures or operating procedures should be avoided as much as possible。Once deviation occurs，Should be implemented in accordance with the deviation handling operating procedures。
Article 196 Access to the production plant shall be limited to approved personnel。
Section 2 Prevent contamination and cross-contamination during production
Article 197 Measures should be taken as much as possible during the production process，Prevent contamination and cross-contamination，For example:
(1) Producing different types of medicines in separated areas；
(2) Adopt staged production methods;
(3) Set up necessary air lock rooms and exhaust；Areas with different air cleanliness levels should have differential pressure control；
(4) The risk of pollution caused by untreated or insufficiently treated air re-entering the production area should be reduced；
(5) In production areas prone to cross-contamination，Operators should wear protective clothing specific for this area；
(6) Use proven or known effective cleaning and decontamination operating procedures for equipment cleaning；When necessary，Residues on equipment surfaces that are in direct contact with materials should be tested；
(7) Use closed system production;
(8) The air inlet of drying equipment should have an air filter，The exhaust should have a device to prevent air backflow；
(9) Fragile materials should be avoided during production and cleaning、Easy to peel、Mold-prone utensils；When using the screen，There should be measures to prevent contamination caused by screen breakage；
(10) Preparation of liquid preparations、Filter、Potting、Sterilization and other processes should be completed within the specified time；
(11) Ointment、Cream、Semi-solid preparations such as gels and intermediate products such as suppositories should specify storage periods and storage conditions。
Article 198 Measures to prevent contamination and cross-contamination shall be regularly inspected and their applicability and effectiveness evaluated。
Section 3 Production operations
Article 199 Inspections should be carried out before production starts，Make sure the equipment and workplace are free of products from the previous batch、Documents or materials unrelated to the production of this batch of products，The device is cleaned and ready for use。The inspection results should be recorded。
Before production operation，The name of the material or intermediate product should also be checked、Code、Batch number and identification，Ensure that the materials or intermediate products used in production are correct and meet the requirements。
Article 200 Intermediate control and necessary environmental monitoring shall be carried out，And record it。
Article 201 Each batch of drugs must be cleared by production operators after each production stage is completed，And fill in the clearance record。The clearance record includes: operating room number、Product name、Batch number、Production process、Clearing date、Inspection items and results、Signature of the person in charge of clearance and reviewer。Cleaning records should be included in batch production records。
Section 4 Packaging operation
Article 202 Packaging operating procedures should provide for reducing contamination and cross-contamination、Measures against risk of confusion or error。
Article 203 Inspection should be carried out before packaging，Securing the workplace、Packaging production line、Printing presses and other equipment are in a clean or ready state，No products left over from the previous batch、Documents or materials unrelated to the packaging of this batch of products。The inspection results should be recorded。
Article 204 Before packaging operation，You should also check that the packaging materials you receive are correct，Check the name of the product to be packaged and the packaging materials used、Specifications、Quantity、Quality status，And consistent with the process specifications。
Article 205 Each packaging operation site or packaging production line，There should be a label indicating the name of the product in the package、Specifications、Batch number and batch production status。
Article 206 When several packaging lines are packaging at the same time，Isolation or other effective measures to prevent contamination should be taken、Measures for cross-contamination or confusion。
Article 207 Ready-to-use repackaging containers should be kept clean before repacking，Avoid glass shards in containers、Contaminants such as metal particles。
Article 208 Product Packaging、A label should be attached promptly after sealing。When the label cannot be applied in time，Should be operated in accordance with relevant operating procedures，Avoid errors such as confusion or mislabeling。
Article 209 Information printed individually or online during the packaging process (such as product batch number or expiration date) shall be inspected，Make sure it’s correct，And record it。Such as manual printing，The frequency of inspections should be increased。
Article 210 Use cutting labels or print labels separately outside the packaging line，Special measures should be taken，Prevent confusion。
Article 211 Electronic code reading machines shall be inspected、Function of tag counter or other similar device is checked，Make sure it runs accurately。The inspection should be recorded。
Article 212 The printed or molded content on packaging materials should be clear，Not easy to fade and erase。
Article 213 Packaging period，The intermediate control inspection of products should at least include the following contents:
(1) Packaging appearance;
(2) Whether the packaging is complete;
(3) Whether the product and packaging materials are correct;
(4) Whether the printed information is correct;
(5) Whether the function of the online monitoring device is normal.
Samples should not be returned after being taken from the packaging production line，To prevent product mix-up or contamination。
Article 214 Products need to be repackaged due to abnormalities in the packaging process，Must undergo special inspection、Investigated and approved by designated personnel。Repackaging should be recorded in detail。
Article 215 During material balance inspection，Found products to be packaged、When there are significant differences in printing packaging materials and finished product quantities，Should be investigated，Before drawing a conclusion，Finished products shall not be released。
Article 216 At the end of packaging，The remaining packaging materials with printed batch numbers should be counted and destroyed by a dedicated person，With record。If printing and packaging materials without printed batch numbers are returned to the warehouse，Should be implemented in accordance with operating procedures。
Chapter 10 Quality Control and Quality Assurance
Section 1 Quality Control Laboratory Management
Article 217 Personnel of Quality Control Laboratory、Facilities、Equipment should be suitable for the nature of the product and the scale of production。
Enterprises are usually not allowed to conduct commissioned inspections，Those who really need to commission inspection，Should be in accordance with the provisions of the commissioned inspection part in Chapter 11，Entrust an external laboratory to conduct inspection，But it should be stated in the inspection report。
Article 218 The person in charge of quality control shall have sufficient qualifications and experience in managing laboratories，Can manage one or more laboratories in the same enterprise。
Article 219 The inspectors in the quality control laboratory should have at least a technical secondary school or high school degree or above in relevant majors，And have undergone practical training related to the inspection operations and passed the assessment。
Article 220 Quality control laboratories should be equipped with pharmacopoeia、Necessary reference books such as standard charts，And related standard materials such as standards or controls。
Article 221 The documents of the quality control laboratory shall comply with the principles of Chapter 8，And meet the following requirements:
(1) The quality control laboratory should have at least the following detailed documents:
1.Quality standard;
2. Sampling operating procedures and records;
3.Inspection operating procedures and records (including inspection records or laboratory work notebooks)；
4. Inspection report or certificate;
5.Necessary environmental monitoring operating procedures、Records and Reports；
6. Necessary inspection method verification reports and records;
7.Instrument calibration and equipment use、Cleaning、Maintenance operating procedures and records。
(2) The inspection record of each batch of drugs should include intermediate products、Quality inspection records of products to be packaged and finished products，All relevant quality inspection status of this batch of drugs can be traced；
(3) It is advisable to save certain data (such as inspection data) in a way that facilitates trend analysis.、Environmental monitoring data、Microbiological monitoring data of pharmaceutical water)；
(4) Except for information related to batch records，Other original data or records should also be saved，For easy reference。
Article 222 Sampling should at least meet the following requirements:
(1) Personnel from the quality management department have the right to enter the production area and storage area for sampling and investigation；
(2) Sampling should be carried out in accordance with approved operating procedures，Operating procedures should specify in detail:
1. Authorized sampler;
2. Sampling method;
3. Utensils used;
4. Sample size;
5. Method of dividing samples;
6. Type and status of sample container;
7.Disposal and labeling of remaining parts and samples after sampling；
8.Sampling Precautions，Includes precautions taken to reduce various risks arising from the sampling process，Especially the sampling of sterile or hazardous materials and precautions to prevent contamination and cross-contamination during the sampling process；
9. Storage conditions;
10. Cleaning methods and storage requirements for sampling equipment.
(3) Sampling methods should be scientific、Reasonable，To ensure the representativeness of the sample；
(4) The retained sample should be representative of the sampled batch of products or materials，Other samples can also be taken to monitor the most important aspects of the production process (such as the beginning or end of production)；
(5) Sample containers should be labeled，Indicate sample name、Batch number、Sampling date、Which packaging container is it taken from、Sampler and other information；
(6) Samples should be stored in accordance with specified storage requirements。
Article 223 The inspection of materials and products at different production stages shall at least meet the following requirements:
(1) Enterprises should ensure that drugs are fully inspected in accordance with registration-approved methods；
(2) Meet one of the following circumstances，Inspection methods should be validated:
1. Adopt new inspection methods;
2. The inspection method needs to be changed;
3.Using test methods not included in the Pharmacopoeia of the People's Republic of China and other legal standards；
4.Other inspection methods that require verification as specified by regulations.
(3) Inspection methods that do not require verification，Enterprises should confirm the inspection methods，To ensure the accuracy of inspection data、Reliable；
(4) Inspection should have written operating procedures，Specifies the method to be used、Instruments and equipment，The content of the inspection operating procedures should be consistent with the confirmed or verified inspection methods；
(5) Inspection should have traceable records and should be reviewed，Make sure the results are consistent with the records。All calculations should be strictly checked；
(6) Inspection records shall include at least the following contents:
1.Name of product or material、Dosage form、Specifications、Batch number or supply batch number，Indicate the name or source of the supplier and manufacturer (if different) if necessary；
2. Based on the quality standards and inspection operating procedures;
3.The model and number of the instrument or equipment used for inspection；
4.The preparation batch number of test solution and culture medium used for inspection、Source and batch number of reference substance or standard substance；
5. Information about the animals used for testing;
6.Inspection process，Including preparation of reference solution、Specific inspection operations、Necessary ambient temperature and humidity；
7.Inspection results，Including observations、Calculations and graphs or graphs，And the inspection report number based on it；
8. Inspection date;
9. Signature and date of the inspector;
10.Inspection、Calculate the signature and date of the reviewer。
(7) All intermediate controls (including intermediate controls performed by production personnel)，All should be carried out in accordance with the methods approved by the quality management department，Inspection should be recorded；
(8) Glass instruments for laboratory capacity analysis should be used、Reagent、Test solution、Quality inspection of reference materials and culture media；
(9) If necessary, experimental animals used for testing should be inspected or quarantined before use。Raising and management should comply with relevant experimental animal management regulations。Animals should be labeled，And the history of use should be saved。
Article 224 The quality control laboratory shall establish operating procedures for the investigation of excessive inspection results。Any inspection result exceeding the standard must be fully investigated in accordance with the operating procedures，And there are corresponding records。
Article 225 What the enterprise keeps in accordance with regulations、Materials used for drug quality traceability or investigation、Product samples are reserved samples。Samples used for product stability testing are not reserved samples。
The retained sample should at least meet the following requirements:
(1) Retained samples should be managed in accordance with operating procedures；
(2) The retained sample should be representative of the batch of materials or products being sampled；
(3) Samples of finished products:
1.Each batch of medicines should have samples；If a batch of medicines is divided into several times for packaging，Then each package should retain at least one finished product in the smallest commercial package；
2.The packaging form of retained samples should be the same as the commercial Stake Sports Bettingstake online sports bettingpackaging form of the drug，If the retained sample of the API cannot be packaged in commercially available packaging，Simulated packaging available；
3.The number of retained samples for each batch of drugs should generally be at least sufficient to ensure that two full inspections (except sterility inspection and pyrogen inspection, etc.) are completed in accordance with the registered and approved quality standards；
4.If it does not affect the packaging integrity of the retained sample，Visual inspection and observation of retained samples should be carried out at least once a year during the storage period，If anything unusual，A thorough investigation should be conducted and corresponding measures taken；
5. There should be records for sample observation;
6.Retained samples should be kept in accordance with the storage conditions approved by registration until at least one year after the expiry date of the drug；
7.If the enterprise terminates drug production or closes，The retained samples should be transferred to the authorized unit for storage，And inform the local drug regulatory department，So that retained samples can be obtained at any time when necessary。
(4) Sample retention of materials:
1.Each batch of raw materials and excipients used in preparation production and packaging materials in direct contact with drugs should have samples retained。Packaging materials in direct contact with drugs (such as infusion bottles)，If you have a sample of the finished product，No need to keep separate samples；
2.The sample volume of materials should at least meet the needs of identification；
3.Except raw and excipients with poor stability，Raw materials and excipients used in preparation production (excluding solvents used in the production process、Retained samples of gases or pharmaceutical water) and packaging materials in direct contact with pharmaceuticals should be kept for at least two years after product release。If the material has a shorter validity period，The sample retention time can be shortened accordingly；
4.Reserved samples of materials should be stored according to specified conditions，It should also be properly packaged and sealed if necessary。
Article 226 Reagents、Test solution、The management of culture media and test bacteria should at least meet the following requirements:
(1) Reagents and media should be purchased from reliable suppliers，Suppliers should be evaluated when necessary；
(2) There should be receiving reagents、Test solution、Medium record，When necessary，Should be in reagent、Test solution、Mark the date of receipt on the container of culture medium；
(3) It should be prepared in accordance with relevant regulations or instructions for use、Storing and using reagents、Test solution and culture medium。Special circumstances，Before receiving or using，The reagents should also be identified or otherwise tested；
(4) The test solution and prepared culture medium should be marked with the preparation batch number、Preparation date and compounder’s name，And have preparation (including sterilization) records。Unstable reagent、The test solution and culture medium should be marked with an expiration date and special storage conditions。Standard solution、The titrant should also be marked with the date of the last calibration and the correction factor，With standardized records；
(5) The prepared culture medium stake sports betting appstake betting appshould be checked for suitability，And there are related records。There should be media usage records；
(6) There should be various test bacteria required for inspection，And establish the storage of test bacteria、Passage、Use、Destruction operating procedures and corresponding records；
(7) The tested bacteria should be appropriately labeled，The content includes at least the name of the strain、No.、Generation、Passage date、Generation operator；
(8) The tested bacteria should be stored according to the prescribed conditions，The method and time of storage should not have an adverse effect on the growth characteristics of the tested bacteria。
Article 227 The management of standards or reference materials shall at least meet the following requirements:
(1) Standards or reference materials should be stored and used in accordance with regulations；
(2) Standards or controls should be appropriately labeled，Content including at least name、Batch number、Date of preparation (if any)、Validity period (if any)、First opening date、Content or potency、Storage conditions；
(3) If the enterprise needs to make its own working standards or controls，Quality standards and preparation of working standards or controls should be established、Identification、Inspection、Approved and Storage Operating Instructions，Each batch of working standards or controls should be standardized with legal standards or controls，And determine the validity period，It should also be proved through regular standardization that the potency or content of the working standard or reference substance remains stable during the validity period。The standardization process and results should have corresponding records。
Section 2 Material and product release
Article 228 Operating procedures for material and product approval and release shall be established separately，Clear the criteria for approval and release、Responsibilities，And there are corresponding records。
Article 229 The release of materials should at least meet the following requirements:
(1) The quality evaluation content of materials should at least include the manufacturer’s inspection report、Inspection status and results of material packaging integrity and sealing；
(2) The quality evaluation of materials should have clear conclusions，Released if approved、Failure or other decision；
(3) Materials should be signed by the designated person for approval。
Article 230 The release of products should at least meet the following requirements:
(1) Before approval，Quality evaluation should be conducted on each batch of drugs，Ensure that drugs and their production should comply with the requirements of registration and this specification，And confirm the following:
1. The main production processes and inspection methods have been verified;
2.All required checks completed、Inspection，And comprehensively consider the actual production conditions and production records；
3.All required production and quality controls have been completed and signed by the relevant supervisor；
4.The change has been processed in accordance with relevant procedures，Changes requiring approval from the drug regulatory authority have been approved；
5.All necessary sampling of changes or deviations has been completed、Check、Inspection and Audit；
6.All deviations related to this batch of products have been clearly explained or stated，Or it has been thoroughly investigated and dealt with appropriately；If the deviation also involves other batches of products，Should be processed together。
(2) The quality evaluation of drugs should have clear conclusions，Released if approved、Failure or other decision；
(3) Each batch of drugs shall be signed by the quality authorized person for approval and release；
(4) Vaccine products、Blood products、In vitro diagnostic reagents used for blood source screening and other biological products specified by the State Food and Drug Administration must also obtain batch release certificates before release。
Section 3 Continuous stability inspection
Article 231 The purpose of continuous stability inspection is to monitor the quality of marketed drugs during the validity period，To identify manufacturing-related stability issues of drug products (such as changes in impurity content or dissolution characteristics)，And confirm that the drug can be stored under the labeled storage conditions，Meet all requirements of quality standards。
Article 232: Continuous stability inspection mainly focuses on commercially available packaged drugs，But you also need to take into account the products to be packaged。For example，When the product to be packaged is before packaging is completed，Or transported from the production plant to the packaging plant，When long-term storage is needed，Should be under corresponding environmental conditions，Evaluate its impact on product stability after packaging。Also，Intermediate products with longer storage times should also be considered for inspection。
Article 233 There should be an inspection plan for continuous stability inspection，Results should be reported。Equipment used for continuous stability investigation (especially stability test equipment or facilities) should be confirmed and maintained in accordance with the requirements of Chapter 7 and Chapter 5。
Article 234 The time for continuous stability inspection should cover the validity period of the drug，The inspection plan should at least include the following contents:
(1) Each specification、Number of inspection batches for each production batch of drugs；
(2) Related physics、Chemistry、Microbiological and biological testing methods，Consider using a dedicated testing method for stability testing；
(3) Basis for inspection methods;
(4) Qualification standards;
(5) Description of container sealing system;
(6) Test interval (test time point);
(7) Storage conditions (the long-term stability test standard conditions specified in the Pharmacopoeia of the People's Republic of China that correspond to the labeled storage conditions of the drug should be adopted)；
(8) Inspection items，If the inspection items are less than those included in the finished product quality standard，The reason should be stated。
Article 235 The number of inspection batches and inspection frequency should be able to obtain sufficient data，For trend analysis。Normally，Each specification、Drug products in each inner packaging form，At least one batch should be inspected every year，Unless there is no production that year。
Article 236 Under certain circumstances，The number of additional batches should be increased in the ongoing stability investigation，Drugs that have undergone major changes or have major deviations in production and packaging should be included in the stability investigation。Also，Reprocess、Batch reworked or recycled，should also be considered for inclusion in the inspection，Unless it has been verified and checked for stability。
Article 237 Key Personnel，Especially the quality authorized person，Should understand the results of ongoing stability studies。When continuous stability inspection is not conducted at the manufacturer of the product to be packaged and finished product，There should be a written agreement between the relevant parties，The results of continuous stability inspections should be saved for review by the drug regulatory authorities。
Article 238 Results that do not meet quality standards or important abnormal trends should be investigated。For any confirmed results that do not meet quality standards or significant adverse trends，Companies should consider whether it may have an impact on already marketed drugs，Recall should be implemented when necessary，The investigation results and measures taken should be reported to the local drug regulatory department。
Article 239 It shall be based on all the data obtained，Including staged conclusions of the investigation，Write a summary report and save it。The summary report should be reviewed regularly。
Section 4 Change Control
Article 240 Enterprises should establish a change control system，Evaluate and manage all changes that impact product quality。Changes that require approval from the drug regulatory department shall be implemented only after approval。
Article 241 Operating procedures should be established，Specified raw and auxiliary materials、Packaging materials、Quality Standard、Inspection method、Operating Procedures、Factory、Facilities、Equipment、Instrument、Application for changes in production process and computer software、Evaluation、Review、Approval and Implementation。The quality management department should designate a dedicated person to be responsible for change control。
Article 242 All changes should be evaluated for their potential impact on product quality。Enterprises can change according to the nature of the change、Scope、Category the change to the degree of potential impact on product quality (e.g. major、Minor changes)。Verification required to determine changes、Additional testing and stability investigations should have scientific basis。
Article 243 After changes related to product quality are proposed by the applying department，Should be evaluated、Develop an implementation plan and clarify implementation responsibilities，Finally reviewed and approved by the quality management department。Change implementation should have corresponding complete records。
Article 244 Change of raw materials and auxiliary materials、Packaging materials in direct contact with drugs、Production process、Main production equipment and other major factors affecting drug quality，The quality of the drug product should also be evaluated for at least the first three batches after the change is implemented。If the change may affect the validity period of the medicine，The quality assessment should also include stability inspection of the drugs produced after the change is implemented。
Article 245 When changes are implemented，Should ensure that documents related to the change are revised。
Article 246 The quality management department shall keep documents and records of all changes。
Section 5 Deviation processing
Article 247 The heads of each department shall ensure that all personnel correctly implement the production process、Quality Standard、Inspection methods and operating procedures，Preventing deviations。
Article 248 Enterprises should establish operating procedures for handling deviations，Report of Specified Deviation、Record、Investigation、Processing and corrective actions taken，And there are corresponding records。
Article 249 Any deviation should be evaluated for its potential impact on product quality。Enterprises can decide based on the nature of the deviation、Scope、Category the deviation (e.g. major by the degree of potential impact on product quality、Minor deviation)，The assessment of significant deviations should also consider whether additional inspection of the product is required and the impact on the shelf life of the product，When necessary，Stability inspections should be conducted on products involving major deviations。
Article 250 Any deviation from the production process、Material balance limit、Quality Standard、Inspection method、Operating procedures and other situations should be recorded，And immediately report to the supervisor and quality management department，There should be clear instructions，Major deviations should be thoroughly investigated by the quality management department in conjunction with other departments，With investigation report。The deviation investigation report should be reviewed and signed by the designated personnel of the quality management department。
Enterprises should also take preventive measures to effectively prevent similar deviations from happening again。
Article 251 The quality management department shall be responsible for the classification of deviations，Save deviation survey、Processed files and records。
Section 6 Corrective and Preventive Actions
Article 252 Enterprises shall establish a system of corrective measures and preventive measures，Complaint、Recall、Deviation、Self-test or external inspection results、Investigate process performance and quality monitoring trends, etc. and take corrective and preventive actions。The depth and form of the investigation should be appropriate to the level of risk。Corrective and preventive action systems should improve product and process understanding，Improve products and processes。
Article 253 Enterprises should establish operating procedures for implementing corrective and preventive measures，The content includes at least:
(1) Complaints、Recall、Deviation、Self-test or external inspection results、Process performance and quality monitoring trends and quality data from other sources for analysis，Identify existing and potential quality issues。When necessary，Appropriate statistical methods should be used；
(2) Survey and products、Reasons related to process and quality assurance system；
(3) Determine the corrective and preventive measures required，Prevent the problem from happening again；
(4) Evaluate the rationality of corrective and preventive measures、Validity and Adequacy；
(5) All changes that occur during the implementation of corrective and preventive actions should be recorded；
(6) Ensure that relevant information has been passed to the quality authorized person and the person directly responsible for preventing the recurrence of the problem；
(7) Ensure that relevant information and its corrective and preventive measures have been reviewed by senior management。
Article 254 The implementation of corrective and preventive measures shall be documented，And saved by the quality management department。
Section 7 Supplier Evaluation and Approval
Article 255 The quality management department shall conduct quality assessment on all suppliers of production materials，Work with relevant departments to conduct on-site quality audits of the quality systems of major material suppliers (especially manufacturers)，And exercise veto power on suppliers whose quality assessment does not meet the requirements。
The determination of main materials should comprehensively consider the quality risks of the drugs produced by the enterprise、Factors such as the amount of materials and the impact of materials on drug quality。
Legal representative of the enterprise、The person in charge of the enterprise and personnel from other departments shall not interfere or hinder the quality management department from independently conducting quality assessments of material suppliers。
Article 256 Operating procedures for material supplier evaluation and approval shall be established，Clear supplier qualifications、Principles of selection、Quality assessment method、Evaluation Criteria、Material supplier approval process。
If quality assessment requires on-site quality audit，The content of the audit should also be clarified、Period、Composition and qualifications of auditors。Need to use samples for small batch trial production，The production batch size should also be specified、Production process、Product quality standards、Stability inspection plan。
Article 257 The quality management department shall designate a dedicated person to be responsible for material supplier quality assessment and on-site quality audit，Distribute approved list of qualified suppliers。The designated person should have relevant regulations and professional knowledge，Have sufficient practical experience in quality assessment and on-site quality audit。
Article 258 On-site quality audits shall verify the authenticity of supplier qualification documents and inspection reports，Verify whether inspection conditions are met。Should its personnel organization、Plant facilities and equipment、Material Management、Production process and production management、Quality control laboratory equipment、Instrument、File management, etc. to check，To fully evaluate its quality assurance system。On-site quality audit should have a report。
Article 259 When necessary，Small batch trial production should be carried out on the samples provided by the main material suppliers，And conduct stability inspections on trial production drugs。
Article 260 The quality management department’s evaluation of material suppliers should at least include: the supplier’s qualification certificate、Quality Standard、Inspection report、Enterprise inspection data and reports on material samples。Such as on-site quality audit and small batch trial production of samples，Should also include on-site quality audit report，As well as the quality inspection report and stability inspection report of the pilot product。
Article 261 Change of material supplier，New suppliers should be evaluated for quality；Change of main material supplier，Relevant verification and stability inspection of the product are also required。
Article 262 The quality management department shall distribute the approved list of qualified suppliers to the materials management department，The list contains at least the material name、Specifications、Quality Standard、Manufacturer name and address、Dealer (if any) name, etc.，And update in time。
Article 263 The quality management department shall sign a quality agreement with the main material suppliers，The quality responsibilities of both parties should be clearly stated in the agreement。
Article 264 The quality management department shall regularly conduct evaluations or on-site quality audits on material suppliers，Review and analyze material quality inspection results、Quality complaints and non-conformity handling records。If there are quality problems with the materials or production conditions、Craftsmanship、When there are major changes in key factors that may affect quality, such as quality standards and inspection methods，Relevant on-site quality audits should also be conducted as soon as possible。
Article 265 The enterprise shall establish quality files for each material supplier，The file content should include the supplier’s qualification certificate、Quality Agreement、Quality Standard、Sample inspection data and report、Supplier’s inspection report、On-site quality audit report、Product stability inspection report、Regular quality review analysis reports, etc.。
Section 8 Product quality review analysis
Article 266 Operating procedures should be followed，Carry out product quality review and analysis of all produced drugs by variety every year，To confirm that the process is stable and reliable，And raw and auxiliary materials、Applicability of current quality standards for finished products，Discover bad trends in time，Determine the direction of product and process improvement。Historical data from previous retrospective analyzes should be considered，Self-inspection of the effectiveness of product quality review analysis should also be conducted。
When there is a reasonable scientific basis，Quality review can be carried out according to the dosage form classification of the product，Such as solid preparation、Liquid preparations and sterile preparations, etc.。
The retrospective analysis should be reported.
Enterprises should at least review and analyze the following situations:
(1) All changes in raw materials and auxiliary materials used in products，Especially raw materials and excipients from new suppliers；
(2) Inspection results of key intermediate control points and finished products；
(3) All batches that do not meet quality standards and their investigation；
(4) All major deviations and related investigations、Effectiveness of corrective measures and preventive measures taken；
(5) All changes in production processes or inspection methods；
(6) All changes to approved or filed drug registrations；
(7) Results of stability investigation and any adverse trends；
(8) All returns due to quality reasons、Complaint、Recall and Investigation；
(9) Implementation and effects of corrective measures related to product processes or equipment；
(10) Newly approved and changed drugs，Work that should be completed after listing in accordance with registration requirements；
(11) Related equipment and facilities，such as air conditioning purification system、Water system、Confirmation status of compressed air, etc.；
(12) Performance of technical contracts for entrusted production or inspection。
Article 267 The results of the retrospective analysis shall be evaluated，Propose the evaluation opinions and reasons for whether corrective and preventive measures need to be taken or re-confirmation or re-validation is required，And in time、Complete the rectification effectively。
Article 268 When entrusting the production of drugs，There should be a written technical agreement between the entrusting party and the entrusted party，Specifies the responsibilities of all parties in product quality review analysis，Ensure product quality review analysis is conducted on time and meets requirements。
Section 9 Complaints and Adverse Reaction Reports
Article 269 An adverse drug reaction reporting and monitoring management system shall be established，Establish a specialized agency and assign full-time personnel to manage it。
Article 270 Adverse drug reactions should be actively collected，Adverse reactions should be recorded in detail、Evaluation、Investigation and processing，Take timely measures to control possible risks，And report to the drug regulatory department as required。
Article 271 Operating procedures should be established，Required complaint registration、Evaluation、Investigation and handling procedures，And stipulates the measures to be taken when complaints arise due to possible product defects，Including consideration of whether it is necessary to recall drugs from the market。
Article 272 There should be a dedicated person and sufficient supporting personnel responsible for investigating and handling quality complaints，All complaints、Investigation information should be reported to the quality authorized person。
Article 273 All complaints shall be registered and reviewed，Complaints related to product quality defects，Every detail of the complaint should be recorded in detail，And investigate。
Article 274 A batch of drugs is found or suspected to be defective，Consideration should be given to checking other batches of the drug，Find out if it is affected。
Article 275 Complaint investigation and handling should be recorded，And indicate the information of the relevant batch of products being checked。
Article 276 Complaint records shall be reviewed and analyzed regularly，In order to find the need to be alert、Recurring issues and possible recalls of medicines from the market，And take corresponding measures。
Article 277 Enterprises make production errors、Drug deterioration or other major quality issues，Corresponding measures should be taken in a timely manner，If necessary, it should also be reported to the local drug regulatory department。
Chapter 11 Consigned production and commissioned inspection
Section 1 Original then
Article 278 To ensure the quality of commissioned products and the accuracy and reliability of commissioned inspection，The entrusting party and the entrusted party must sign a written contract，Clearly specify the responsibilities of each party、Contents of commissioned production or commissioned inspection and related technical matters。
Article 279 All activities of commissioned production or commissioned inspection，Includes any proposed changes, technical or otherwise，All should comply with the relevant requirements for drug production licensing and registration。
Section 2 Client
Article 280 The entrusting party shall evaluate the entrusted party，Conditions to the trustee、Technical level、On-site assessment of quality management status，Confirm that they have the ability to complete the tasks entrusted to them，And can guarantee compliance with the requirements of this specification。
Article 281 The entrusting party shall provide all necessary information to the entrusted party，To enable the entrusted party to correctly implement the entrusted operations in accordance with drug registration and other statutory requirements。
The entrusting party shall make the entrusted party fully aware of various issues related to the product or operation，Includes products or operations on the trustee’s environment、Factory、Equipment、Potential hazards caused by personnel and other materials or products。
Article 282 The entrusting party shall supervise the entire process of entrusted production or inspection。
stake online sports bettingArticle stake sports betting app283 The client shall ensure that materials and products meet corresponding quality standards。
Section 3 Assignee
Article 284 The trustee must have sufficient factory buildings、Equipment、Knowledge and experience and people，Meet the requirements of the production or inspection work entrusted by the client。
Article 285 The entrusted party shall ensure that the materials provided by the entrusting party are received、Intermediate products and products to be packaged are suitable for their intended use。
Article 286 The entrusted party shall not engage in activities that have an adverse impact on the quality of the products entrusted to be produced or inspected。
Section 4 合 Same
Article 287 The contract signed between the entrusting party and the entrusted party shall specify in detail the respective product production and control responsibilities，The technical clauses should be prepared by people with pharmaceutical technology、Prepared by competent personnel with inspection expertise and familiarity with this specification。All commissioned production and inspection work must comply with the relevant requirements for drug production licensing and drug registration and must be agreed by both parties。
Article 288 The contract shall specify in detail the procedures for the approval and release of each batch of drugs by the quality authorized person，Ensure that each batch of products has been produced and inspected in accordance with the requirements for drug registration。
Article 289 The contract should stipulate who is responsible for purchasing materials、Inspection、Release、Production and quality control (including intermediate control)，It should also specify who is responsible for sampling and inspection。
In the case of commissioned inspection，The contract should stipulate whether the trustee takes samples in the client’s factory。
Article 290 The contract shall stipulate the production to be retained by the trustee、Inspection and shipping records and samples，The client should be able to access or inspect at any time；Complaint occurred、When it is suspected that the product has quality defects or is recalled，The client should be able to easily access all records related to evaluating product quality。
Article 291 The contract should clearly stipulate that the entrusting party can conduct inspections or on-site quality audits of the entrusted party。
Article 292 The entrusted inspection contract shall specify that the entrusted party is obliged to accept inspection by the drug regulatory department。
Chapter 12 Product Shipping and Recall
Section 1 Original then
Article 293 Enterprises should establish a product recall system，Quickly if necessary、Effectively recall any batch of products with safety hazards from the market。
Article 294 Products returned and recalled due to quality reasons，All should be supervised and destroyed in accordance with regulations，Except for cases where there is evidence proving that the quality of the returned product has not been affected。
Section 2 发 luck
Article 295 Each batch of products shall have a shipping record。According to shipping records，Should be able to trace the sales of each batch，It should be possible to recover everything in time if necessary，Shipping record content should include: product name、Specifications、Batch number、Quantity、Receiving unit and address、Contact information、Shipping date、Transportation methods, etc.。
Article 296: Only two batch numbers can be combined into one box for the odd packaging of pharmaceutical shipments，All batch numbers should be marked outside the combined box，And create a packing record。
Article 297 Shipping records shall be kept for at least one year after the expiry date of the drug。
Section 3 call Reply
Article 298 Recall operating procedures should be formulated，Ensuring the effectiveness of recall efforts。
Article 299 A dedicated person should be designated to organize and coordinate the recall work，And equipped with a sufficient number of personnel。The person responsible for product recalls should be independent from the sales and marketing department；If the person in charge of product recall is not the quality authorized person，The quality authorized person shall be notified of the recall handling status。
Article 300 The recall should be able to be initiated at any time，And implement it quickly。
Article 301 Decision to recall products from the market due to potential safety hazards，Should be reported to the local drug regulatory authority immediately。
Article 302 The person in charge of product recall should be able to quickly access the drug shipment records。
Article 303 Recalled products should be labeled，Alone、Properly store，Waiting for final decision。
Article 304 The progress of the recall shall be recorded，With final report。Product shipping quantity、The recalled quantity and quantity balance should be stated in the report。
Article 305 The effectiveness of the product recall system shall be evaluated regularly。
Chapter 13 Since Check
Section 1 Original then
Article 306 The quality management department shall regularly organize self-inspections of the enterprise，Monitor the implementation of this specification，Assess whether the enterprise meets the requirements of this specification，And propose necessary corrective and preventive measures。
Section 2 Since Check
Article 307 Self-inspection should be planned，For institutions and personnel、Plant and facilities、Equipment、Materials and Products、Confirmation and Verification、File Management、Production Management、Quality Control and Quality Assurance、Consigned production and commissioned inspection、Product shipment and recall items are inspected regularly。
Article 308 Independent personnel shall be designated by the enterprise、System、Comprehensive self-examination，Independent quality audits may also be conducted by external personnel or experts。
Article 309 Self-inspection should be recorded。There should be a self-inspection report after the self-inspection is completed，The content includes at least all the conditions observed during the self-test、Conclusions of the evaluation and recommendations for corrective and preventive actions。The self-inspection situation should be reported to the senior management of the enterprise。
Chapter 14 Attachment then
Article 310 This specification is the basic requirement for quality management of pharmaceutical production。For sterile drugs、Biological products、Special requirements for blood products and other drugs or production quality management activities，Separately formulated by the State Food and Drug Administration in the form of an appendix。
Article 311 Enterprises can adopt proven alternative methods，Meet the requirements of this specification。
Article 312 The meanings of the following terms in this specification (sorted by Chinese Pinyin) are:
(1) Packaging
All operating steps required to turn the packaged product into a finished product，Including repackaging、Labeling, etc.。But aseptic filling of products in aseptic production processes，And the filling of terminally sterilized products are not considered packaging。
(2) Packaging materials
Materials used in pharmaceutical packaging，Including packaging materials and containers in direct contact with drugs、Printing packaging materials，But does not include outer packaging materials used for shipping。
(3) Operating procedures
Approved to guide equipment operation、Maintenance and Cleaning、Verification、Environmental Control、General documents for pharmaceutical production activities such as sampling and inspection，Also known as Standard Operating Procedures。
(4) Products
Intermediate products including pharmaceuticals、Products to be packaged and finished products。
(5) Product life cycle
Product from initial research and development、All stages from listing to delisting。
(6) Finished product
Products that have completed all production steps and final packaging。
(7) Reprocessing
Part or all of a batch of intermediate products or products to be packaged that do not meet quality standards produced in a certain production process，Adopt different production processes for reprocessing，To meet predetermined quality standards。
(8) Products to be packaged
Products that have not yet been packaged but have completed all other processing steps。
(9) To be verified
Refers to raw materials、Packaging materials、Intermediate products、Products or finished products to be packaged，Use physical means or other effective means to isolate or distinguish them，Storage before release for use in production or marketing、Status waiting for release decision。
(10) Distribution
Refers to materials in the production process、Intermediate products、Product to be packaged、File、A series of operations that circulate production molds etc. within the enterprise。
(Eleventh) Re-inspection Period
Raw materials、After storing packaging materials for a certain period of time，To ensure it remains suitable for its intended purpose，The date determined by the enterprise to require re-inspection。
(12) Shipping
Refers to a series of operations by which an enterprise sends products to dealers or users，Includes distribution、Transportation, etc.。
(Thirteen) Rework
A batch of intermediate products or products to be packaged that do not meet quality standards produced in a certain production process、Return part or all of the finished product to the previous process，Using the same production process for reprocessing，To meet predetermined quality standards。
(14) Release
Conduct quality evaluation on a batch of materials or products，The operation of making an approval for use or placing on the market or other decision。
(15) Senior Management
Directing and controlling the enterprise at the highest level within the enterprise、Person with the authority and responsibility to mobilize resources。
(16) Process Regulations
A document or set of documents developed to produce a specific quantity of finished product，Includes production prescription、Production operation requirements and packaging operation requirements，Specifies the quantity of raw materials and packaging materials、Process parameters and conditions、Processing instructions (including intermediate controls)、Precautions, etc.。
(17) Supplier
Refers to the material、Equipment、Instrument、Reagent、Provider of services etc.，Such as manufacturer、Dealers, etc.。
(18) Recycling
At a specific production stage，Convert part or all of a batch or batches of previously produced products that meet the corresponding quality requirements，Operation to add to another batch。
(19) Computerized System
Integrated system for reporting or automatic control，includes data entry、Electronic processing and information output。
(Twenty) Cross-contamination
Different raw materials、Mutual contamination between excipients and products。
(Twenty-one) Calibration
Under specified conditions，Confirm measurement、Record、The indication of a control instrument or system (especially weighing) or the quantity represented by a physical measuring instrument，A series of activities related to the corresponding reference standard value。
(22) Phased production method
Refers to the shared production area，Concentrate the production of a certain product within a period of time，Reconcile the corresponding shared production area、Facilities、Equipment、Clean tools and utensils thoroughly，Change the way to produce another product。
(Twenty-three) Clean Area
Rooms (areas) that need to control the number of dust particles and microorganisms in the environment，its architectural structure、Equipment and its use should be able to reduce the introduction of contaminants into the area、Generation and retention。
(Twenty-four) Alert Limit
The key parameters of the system are outside the normal range，But the correction limit has not been reached，Need to be alert，Limit criteria that may require corrective action。
(Twenty-five) Correction Limits
The key parameters of the system exceed the acceptable standards，Limit criteria requiring investigation and corrective action。
(Twenty-six) Inspection results exceed the standard
All situations in which the inspection results exceed legal standards and standards set by the enterprise。
(Twenty-seven) batch
Produced by one or several processing processes、A certain quantity of raw materials and excipients with expected uniform quality and characteristics、Packaging materials or finished products。To complete certain production operation steps，It may be necessary to divide a batch of product into sub-batches，Finally merged into a uniform batch。In the case of continuous production，A batch must correspond to a defined quantity of product with expected uniform characteristics in production，A batch size can be a fixed quantity or the amount of product produced within a fixed period of time。
For example: solid for oral or external use、The homogeneous product produced by mixing semi-solid preparations at one time using the same mixing equipment before forming or packaging is a batch；Oral or external liquid preparations are a batch of homogeneous products produced by final mixing of the medicinal solution before filling (sealing)。
(Twenty-eight) batch number
A unique combination of numbers and/or letters used to identify a specific batch。
(Twenty-nine) Batch Records
Used to record the production of each batch of drugs、All documents and records of quality inspection and release audit，All historical information related to finished product quality can be traced。
(Thirty) Air Lock Room
An isolation space with two or more doors set between two or several rooms (such as between rooms with different cleanliness levels)。The purpose of setting up the air lock room is when people or materials enter and exit，Control air flow。The air lock room has a personnel air lock room and a material air lock room。
(Thirty-one) Enterprise
Unless otherwise stated in this specification，Enterprise refers specifically to pharmaceutical manufacturing enterprises。
(Thirty-two) Confirmation
Proof of factory、Facilities、A series of activities that allow equipment to operate correctly and achieve expected results。
(Thirty-three) Return
Activities to return medicines to enterprises.
(Thirty-four) Files
The documents referred to in this specification include quality standards、Process Specification、Operating Procedures、Record、Reports, etc.。
(Thirty-five) Materials
Refers to raw materials, auxiliary materials and packaging materials, etc.
For example: the raw materials of chemical preparations refer to raw materials；The raw materials of biological products refer to raw materials；The raw materials of traditional Chinese medicine preparations refer to traditional Chinese medicinal materials、Chinese medicine pieces and purchased Chinese medicine extracts；The raw materials of APIs refer to other materials other than packaging materials used in the production of APIs。
(Thirty-six) Material Balance
Comparison between the sum of the actual output or actual usage of a product or material and the collected losses and the theoretical output or theoretical usage，And consider the allowable deviation range。
(Thirty-seven) pollution
In production、Sampling、Pack or repack、During operations such as storage or transportation，Raw materials、Intermediate products、Product to be packaged、Finished product adversely affected by impurities or foreign matter with chemical or microbiological properties。
(Thirty-eight) Verification
Demonstrate any operating procedures (or methods)、A series of activities that enable a production process or system to achieve expected results。
(Thirty-nine) Printing and packaging materials
Refers to packaging materials with specific styles and printed content，such as printed aluminum foil、tag、Instructions、Paper boxes, etc.。
(Forty) raw and auxiliary materials
Except for packaging materials，Any material used in the production of pharmaceuticals。
(41) Intermediate products
Refers to products that have completed some processing steps，Needs further processing before becoming a product to be packaged。
(42) Intermediate control
Also called process control，Refers to ensure that products comply with relevant standards，Monitoring the process during production，Checks to make adjustments if necessary。Environmental or device controls may be considered part of intermediate controls。
Article 313 This specification shall come into effect on March 1, 2011。In accordance with the provisions of Article 9 of the "Drug Administration Law of the People's Republic of China"，The specific implementation methods and steps shall be stipulated by the State Food and Drug Administration。
