Good production practice (as revised in 2010)
(Released January 17, 2011, the Ministry of health, the 79th since March 1, 2011) Chapter I General provisions
First to standardize the drug production and quality management, in accordance with the People's Republic of China pharmaceutical administration law and the People's Republic of China pharmaceutical administration law implementing regulations, development of this specification. Enterprise II pharmaceutical quality management system should be established.
This system should cover all factors affecting the quality of medicines, including ensuring the quality of drugs in accordance with the intended purpose of organized and planned activities.
Article III of the code as part of the quality management system, are basic requirements for pharmaceutical production management and quality control, designed to minimize the drug production process contamination, cross-contamination and confusion, errors and other risks to ensure sustained and stable produce in line with the intended use and drug registration requirements.
Fourth Enterprise shall strictly implement this specification, honest and trustworthy, against any false, deceptive practices.
Chapter quality management
Article fifth Enterprise meets the requirements of drug quality management the quality objectives should be established, information pertaining to the drug registration safe, effective and quality control of all requirements, systematically implementing a pharmaceutical production, control and product release, storage, and shipment of the entire process, ensuring that the production of medicines in accordance with its intended use and the registration requirements.
Sixth senior management should ensure that established quality objectives, at different levels, as well as suppliers, distributors should be participatory and bear their respective responsibilities.
Seventh Enterprise shall be equipped with adequate, meet the requirements of the personnel, premises, facilities and equipment, and provide the conditions necessary to attain the quality objectives.
Section II quality assurance Eighth quality assurance is part of the quality management system.
Enterprises must establish a quality assurance system, while establishing a complete file system, to ensure the effective operation of the system.
Nineth quality assurance system should ensure that:
(A) drug design and development reflect the requirements of this international standard;
(B) production management and quality control activities are consistent with the requirements of this specification;
(C) management responsibilities;
(D) the procurement and use of raw materials and packaging materials are correct;
(E) effective control of intermediate products;
(Vi) verification, validation implementation;
(G) production strictly in accordance with the statutes, inspection, testing, and review;
(H) each batch of product by the qualified person approved release;
(IX) in the storage, shipment and subsequent operation of adequate measures to ensure the quality of medicines in the process;
(J) in accordance with test procedures, checks on a regular basis to assess the validity and applicability of the quality assurance system.
Tenth GMP basic requirements:
(A) the development, production, and systematically review and prove its sustainable steady produce in line with the requirements of the product;
(B) the production process and significant changes are validated;
(C) equipped with the resources required, including at least:
1. have the appropriate qualifications and training of qualified personnel;
2. adequate plant and space;
3. the applicable equipment and maintenance support;
4. the right of starting materials, packaging materials and labels;
5. the approved processes and procedures;
6. appropriate storage conditions.
(D) accurate and understandable language should be used to develop operating rules;
(E) the operator training, in accordance with the practice for correct operation;
(F) the production process should be documented, deviations are investigated and documented;
(VII) batch records and shipping records to be able to trace the complete history of the product, and keep it and easy to read;
(H) reduce quality risks in the course of shipment;
(I) establishing drug recall system to ensure any recalled product shipped sales;
(J) the investigation leads to drug complaints and the reasons for quality defects and to take measures to prevent recurrence of similar quality.
Section III quality control
11th quality control including the corresponding organizational structure, file system, as well as sampling, inspection, material or products prior to release to complete the necessary testing to confirm their quality meet the requirements.
12th quality control of the basic requirements:
(A) shall be equipped with adequate facilities, equipment, equipment and trained personnel, quality control effectively and reliably completed all related activities;
(B) should have approved rules for raw materials, packaging materials, intermediate products, bulk products and finished product sampling, inspection and testing, as well as the stability of the product and, if necessary, environmental monitoring, to ensure compliance with the requirements of this international standard;
(C) by authorized personnel in accordance with the method of raw materials, packaging materials, intermediate products, bulk products and finished goods samples;
(D) the test methods should be validated or confirmed;
(E) sampling, inspection and testing shall be recorded, the deviation should be investigated and documented;
(Vi) materials, intermediate products, bulk products and finished products must be checked according to quality standards and inspection and records;
(G) material and packaging of the finished product shall have a sufficient number of samples, for the necessary inspection or testing; in addition to the final packaging of the finished product, a sample packaging should be identical to the final packaging of the finished product.
Fourth day of quality risk management
13th quality risk management is used throughout the product life cycle perspective or review, risk assessment, control, communication, audit quality system procedures.
14th for quality risk assessment based on scientific knowledge and experience in order to ensure product quality.
15th quality risk management process is the approach it adopted, measures, form, and formation of a document should be commensurate with the risk level.
Chapter III organization and personnel
16th Enterprise shall set up fitting in with the production management and organization chart. Enterprises should set up an independent quality control Department, quality assurance and quality control responsibilities.
Quality management departments can set up quality assurance and quality control departments. 17th quality control departments should be involved in all quality-related activities is responsible for auditing all files associated with this specification.
Quality assurance Department personnel shall not delegate responsibilities to personnel in other sectors. 18th Enterprise shall be equipped with a sufficient number and with the appropriate qualification (including qualifications, training and experience) management and operations personnel, should clearly establish the responsibilities of each sector and each post. Job responsibilities may not be missing, cross responsibilities should be clearly defined.
Too many responsibilities should not be borne by everyone.
All personnel should be clear and understood responsibilities, familiar with the requirements associated with their duties and receive the necessary training, including training and continued training. 19th duties usually may not be delegated to others.
Absolutely necessary to entrust, its functions could be entrusted with a very qualified designated person.
Section II key personnel
20th key enterprises should be full-time personnel, shall at least include the heads of the enterprises, production management, head of quality management and qualified person. Head of quality management and production management person in charge shall not be concurrently with each other. Head of quality management and qualified person can concurrently.
Procedures should be established to ensure that qualified person independent performance of their functions, without interference of business owners and others.
Head of 21st Enterprise Business owners is the primary responsibility of pharmaceutical quality, overall responsibility for the daily management of enterprises.
To secure your enterprise to achieve quality objectives and in accordance with the specification requirements for drug production, business owners should be responsible for providing the necessary resources, planning, organization and coordination, quality assurance management independent in the performance of their duties.
The 22nd head of production management
Head of production management should have at least Bachelor's degree in pharmacy or related (or intermediate professional titles or licensed pharmacist qualification), have engaged in drug production and quality management for at least three years of practical experience, including at least one year of experience in pharmaceutical production and management, have received professional training associated with the product.
(B) main responsibilities:
1. ensure that medicines in accordance with the approved procedures, storage, in order to ensure the quality of drugs;
2. ensure strict implementation of the procedures associated with the operation;
3. ensure that the batch production records and batch packaging records through a designated person auditing to the quality control Department;
4. ensure that the maintenance of plant and equipment, to keep it in good running condition;
5. ensure the completion of all the necessary validation work;
6. ensure that production-related personnel after the necessary training and continuing training, and training contents should be adjusted according to actual needs.
The 23rd head of quality management
Head of quality management at least has a Bachelor's degree in pharmacy or related (or intermediate professional titles or licensed pharmacist qualification), with at least five years ' practical experience of drug production and quality control, with at least one year of drug quality management experience, have received professional training associated with the product.
(B) main responsibilities:
1. to ensure that raw materials, packaging materials, intermediate products, bulk products and finished products meet the requirements of approved by the registration and quality standards;
2. ensure that the product prior to release to the batch record review;
3. ensure that all necessary tests;
4. Approves the quality criteria, methods of sampling, testing and other quality control procedures;
5. review and approval of all quality-related changes;
6. ensure that all significant deviations and excessive testing results have been investigated and are processed in a timely manner;
7. approve and supervise the commissioning inspection;
8. the maintenance of plant and equipment, to keep it in good running condition;
9. ensure the completion of all the necessary confirmation or verification, audit and confirmation or validation protocols and reports;
10. ensure that complete a self-test;
11. evaluate and approve suppliers of materials;
12. to ensure that all quality-related complaints have been investigated, and handled correctly and timely;
13. ensure the continuing stability of finished product tours, provide stability data;
14. ensure the completion of retrospective analysis of product quality;
15. to ensure that quality control and quality assurance have been necessary training and continuing training, and training contents should be adjusted according to actual needs.
24th head of the head of production management and quality control typically has the following responsibilities:
(A) review and approval process, procedures and other documents;
(B) supervision of the plant health situation;
(C) ensure that key equipment have been identified;
(D) ensure the complete production process validation;
(E) ensure that all relevant personnel have been with the necessary induction training and continuing training, and training contents should be adjusted according to actual needs;
(Vi) approve and monitor contract manufacturing;
(G) to identify and monitor the storage of materials and products;
(IX) monitor implementation of this specification;
(J) monitor the factors affecting product quality.
25th quality Attorney
Qualified person should have at least Bachelor's degree in pharmacy or related (or intermediate professional titles or licensed pharmacist qualification), with at least five years ' practical experience of drug production and quality control, engaged in drug production process control and quality inspection work.
Qualified person should possess the necessary professional knowledge and training associated with the product release, the independent exercise of their duties.
(B) main responsibilities:
1. participation in the enterprise quality system is established, the internal self test, and external quality audit, validation, and quality management activities such as adverse drug reaction reporting and product recall;
2. assume the role of product release, ensures that each batch has been release product production, tests are in line with relevant laws and regulations, drug registration requirements and quality standards;
3. prior to the product release, qualified person must be issued in accordance with the requirements of the aforementioned 2nd release an audit trail, and incorporated into the batch record.
Section III training
26th Enterprise shall designate a Department or person responsible for training management, shall have the production management Director or head of the quality control review or approve training programmes or plans, training records should be kept. 27th and drug production and quality of all personnel should be trained, the content of the training should be commensurate with the job requirements.
In addition to the theoretical and practical training of this specification should also have related legislation, job duties, skills training, and periodic evaluation of the effects of training.
28th high risk operation areas (such as highly active, toxic, infectious, highly sensitized recipients of materials production area) staff should receive specialized training.
Fourth person health
29th all personnel should receive training in hygiene requirements, health enterprises shall establish personnel procedures, minimize the risk of contamination to personnel on drug production. Article 30th personnel hygiene procedures should include health, hygiene, and dress-related content. Production and quality control personnel should understand the relevant personnel of health rules.
Enterprises should take measures to ensure the implementation of hygienic practice for. 31st enterprises shall manage the health, and health records.
Direct contact with the pharmaceuticals production staff should undergo a medical examination beforehand, at least once a year after health checks.
32nd enterprises shall take appropriate measures to avoid superficial wounds, suffering from a communicable disease or other potentially contaminated medicine diseases of workers engaged in direct contact with the pharmaceuticals production.
Article 33rd visitors and untrained personnel are not allowed in production and quality control areas, exceptional circumstances needed to enter, advance guidance on issues such as personal hygiene, dressing. 34th article of any persons entering the production area shall be in accordance with the provisions of clean clothes.
Selection, style and dress in work clothes and work and air cleanliness levels to adapt.
35th into the clean production area personnel shall not make up and wearing jewelry.
36th production areas, storage areas should be prohibited from smoking and diet, prohibit the storage of food, beverages, cigarettes and drugs for personal use, not for production use.
37th operations personnel should avoid direct contact with bare hands pharmaceuticals, packing materials and equipment surfaces in contact directly with the drug.
Fourth plant and facilities
Article 38th plant siting, design, layout, construction, renovation and maintenance of pharmaceutical production requirements must be met, should be able to the maximum to avoid contamination, cross-contamination, confusion and error, easy cleaning, operation, and maintenance.
39th based on plant and production of protective measures should be considered site selection, plant environment should be able to minimize the material or product contamination risk.
40th enterprises shall have clean production environment; plant on the ground, the roads and transportation should not pollute the pharmaceutical production; production, administration, and support the overall layout should be reasonable, shall not hinder each other; people in the factory and plant, logistics to be reasonable. 41st workshop should be properly maintained, and to ensure that maintenance activities do not affect the quality of medicines.
Shall, in accordance with a detailed written operating procedures to clean the plant or the necessary disinfection.
42nd workshop should have proper lighting, temperature, humidity and ventilation, and to ensure the production and storage of product quality and performance will not be affected, directly or indirectly related equipment. 43rd workshop, facility design and installation should be able to effectively prevent insects or other animals.
Shall take the necessary measures to avoid the use of rodenticides, insecticides, smoke agent on device, item, product contamination. 44th article should take appropriate measures to prevent unauthorized persons from entering.
Production, storage and quality control areas should not serve as a non-staff direct access to this area.
45th article should save the plant, utilities, fixed pipelines constructed or reconstructed as-built drawings.
Section II production areas
Article 46th in order to reduce the risk of contamination and cross-contamination, plants, production facilities and equipment should be based on the production of pharmaceuticals properties, process and design, layout, and cleanliness level required to use and comply with the following requirements:
(A) should take into account drug characteristics, process and intended use and other factors, identifying plants, production facilities and equipment product feasibility of sharing, and there is a corresponding assessment reports; (B) the production of special drugs, such as the highly sensitized recipients of drugs (such as Penicillins) or biological (such as Bacillus Calmette-Guerin or other microorganisms preparation of pharmaceutical products), must be dedicated and independent buildings, production facilities and equipment.
Penicillin class drug produced dust volume big of operation regional should keep relative negative pressure, row to outdoor of exhaust should after purification processing and meet requirements, row outlet should away from other air purification system of into outlet; (three) production beta-the lactam structure class drug, and sex hormone class contraceptive drug must using dedicated facilities (as independent of air purification system) and equipment, and and other drug production district strictly separate;
(D) the production of certain hormones, cell toxicity class, highly reactive chemicals shall use special facilities (such as independence air purification system) and equipment under special circumstances, such as to take special protective measures and after the necessary validation, these drugs may be available through a staged production with the same production facilities and equipment;
(E) above (b), (c), (d), air cleaning system, the exhaust should undergo purification treatment;
(F) drug production plant may not be used for the production of pharmaceutical quality adversely affects non-medicinal products.
47th production areas and storage areas should have sufficient space to ensure orderly storage of equipment, materials, intermediate products, bulk products and finished products, to avoid confusion, cross contamination of different products or materials, avoid omission or error in the production or quality control operations.
48th article should be according to the varieties of medicines, production requirements and configure external environmental conditions such as air conditioning and cleaning system, make the production zone effective ventilation, and temperature and humidity control and air purification filters, ensure production environment meets the requirements. Clean area and clean area, between different levels of pressure difference between the clean area shall not be less than 10 Pascal.
If necessary, the functional areas of the same cleanliness level (operational) should keep a proper pressure differential between gradients.
Oral liquid body and solid preparations, and cavity road medication (containing rectal medication), and epidermal topical drug, non-no bacteria preparations production of exposed process regional and directly contact drug of packaging material eventually processing of exposed process regional, should reference "no bacteria drug" Appendix in the d level clean district of requirements set, enterprise can according to products of standard and characteristics on the regional take appropriate of microbial monitoring measures.
49th clean area on the inner surface (walls, floors, and ceilings) should be smooth, free from cracks and close interface, no particles fall off, avoid dust, easy and effective cleaning and, if necessary, should be disinfected.
50th all plumbing, lighting, ventilation and other public facilities should be designed and installed to avoid difficult to clean the parts, should be outside of the production area as much as possible to be maintained. 51st drainage facilities shall be suitable for, and install the device to prevent intrusion.
Should be avoided as far as possible open drainage; inevitable, open drains should be light, easy to clean and disinfect.
52nd preparations weighing raw materials usually should be carried out in the weighing room specifically designed.
53rd among the dust-producing operations (such as raw material or product sampling, weighing, blending, and packaging operations) should remain relatively negative pressure or special measures, prevent the spread of dust, avoid cross-contamination and facilitate cleaning. 54th for pharmaceutical packaging plant or area should be reasonable design and layout, to avoid any confusion or cross-contamination.
Like region, several packing lines, should have such measures.
55th production areas should have an appropriate level of lighting, Visual area lighting should meet operational requirements.
56th production can be set up in the region control area in the Middle, but no quality risk to drug control operations.
Section III storage area
57th storage area should have enough space to ensure orderly storage of quarantine, qualified, unqualified, return or recall of raw materials, packaging materials, intermediate products, bulk products and finished products, such as various types of materials and products. 58th article storage area design and construction must ensure good storage conditions, and has ventilation and lighting.
Storage areas should be able to meet the material or product storage conditions (such as temperature, humidity, light) and safe storage requirements, and inspection and monitoring.
59th highly active materials or products, as well as printing and packaging materials should be stored in a secure area. 60th reception, distribution and delivery area should be able to protect materials, products from outside weather conditions (rain, snow) effects.
Reception area layout and facilities should be able to ensure the delivery of materials in outer packaging can be necessary when entering the storage area clean.
61st separate quarantine stores quarantined items, Holding Area should have a striking identity and access limited to authorized personnel only.
Failed, return or recall of materials or products should be stored in isolation.
If alternative physical isolation by other methods, the method should have the same level of security. 62nd should normally be a separate item sampling area. Air cleanliness level in the sampling area should be consistent with the production requirements.
As in other areas or other means of sampling should be able to prevent contamination or cross-contamination.
Fourth section, quality control 63rd quality control laboratories should normally be separated from production areas.
Biological assays, micro-organisms and radioisotope laboratory should be separated from each other.
64th laboratories should be designed to ensure that it is suitable for intended use and to avoid confusion or cross-contamination should have enough area to sample handling, sampling and storage of stability samples and record keeping.
The 65th when necessary, should set up special equipment rooms, protect sensitive instruments from electrostatic interference, vibration, moisture or other external factors.
66th processing biological samples or radioactive samples laboratory for special items shall conform to the national requirements.
67th experimental animal room should be strictly separated from other regions, its design and construction shall conform to the relevant regulations of the State, and separate air handling facilities as well as dedicated lanes for animals.
Fifth section auxiliary
68th lounge set should not be adversely affected, storage and quality control areas. 69th dressing rooms and toilet facilities should be easy to access and adapt with the number.
Lavatories shall not directly connected with the production area and storage area. 70th maintenance should be as far away from the production area.
Kept in repair of spare parts and tools within the clean area, should be placed in a special room or tool Cabinet.
The fifth chapter equipment
71st equipment design, selection, installation, and maintenance must be consistent with its intended use, should as far as possible to reduce pollution, the risk of cross-contamination, confusion and error, easy to operate, clean and maintain, and, if necessary, disinfected or sterilized.
72nd shall establish equipment use, cleaning, maintenance and repair procedures, and save the log.
The 73rd article should establish and maintain equipment purchase, installation, confirmation of documents and records.
Section II design and installation 74th production equipment may not have any adverse impact on quality.
Direct contact with the pharmaceuticals production equipment surfaces should be flat, smooth, easy to clean and disinfect, corrosion shall not react with the drug releasing substances, adsorption of drugs or to drugs.
75th should be equipped with appropriate range and precision of weighing, measuring, instruments and meters.
The 76th article should select the appropriate cleaning, cleaning equipment, become a source of pollution and to prevent such equipment.
77th devices of lubricants, coolants, of pharmaceutical products or containers shall not be polluted, and should as far as possible using the food grade level or equivalent lubricant.
78th production tooling procurement, acceptance, storage, maintenance, release and scrapping it shall develop appropriate procedures, set up special counters kept and have corresponding records.
Section III maintenance and repair
79th equipment maintenance and repair must not affect product quality.
80th equipment preventive maintenance program should be developed and procedures, equipment maintenance and repair should have the appropriate records.
81st modification of or major repairs of equipment should be conducted to confirm, meets the requirements before they can used in the production.
Fourth section using and cleaning
82nd of the main production and test equipment shall have a clear operating rules.
83rd production equipment should be confirmed within the parameters of the use.
84th article should be in accordance with the detailed procedures for the operation of cleaner production equipment.
Production equipment clean of operation should provides specific and full of clean method, and clean with equipment or tool, and clean agent of name and preparation method, and removal Qian a times identifies of method, and protection has clean equipment in using Qian from by pollution of method, and has clean equipment most long of save time, and using Qian check equipment clean status of method, makes operation who can to can reproduce of, and effective of way on various equipment for clean. If disassembly is required equipment, should also provide the order of disassembly and Assembly of equipment and methods if disinfection or sterilization of equipment is required, and should also provide specific disinfection or sterilization method, name of the disinfectant and the preparation method.
If necessary, should also provide equipment to clean the longest interval allowed before the end time.
85th cleaning production equipment should be clean and stored under dry conditions.
86th for production or inspection of equipment and instruments, should be using a log record includes the use, cleaning, maintenance and repair, as well as date, time, the production and inspection of drug name, specification, and lot number, etc.
87th production equipment should have a clear identity, indicating the device number and contents (such as name, size, lot number); no content shall be indicated in a clean state.
88th article not qualifying equipment if possible should be moved out of production and quality control areas, before move out, there should be an eye-catching logo.
89th main fixed pipework should be clearly indicate the content name and direction.
The fifth calibration 90th shall be in accordance with procedures and calibration program for production and testing on a regular basis weighing, measuring, instruments, recording and control devices and instruments are calibrated and checked, and preserve relative record.
Calibration range should cover the actual use for production and testing.
91st article should ensure that the production and inspection of critical weighing, measuring, instruments, recording and control equipment, and Instrumentation Calibration and concluded that the data are accurate and reliable. The 92nd article should be calibrated using standards of measurement, and the standards of measurement used shall conform to the relevant provisions of the State.
Calibration of standards of measurement for record shall be indicated in the name, number, number, validity of calibration and measurement certificates, ensure that traceability record.
93rd weighing, measuring, instrument, used to record and control devices and instruments should be clearly labeled, indicating the calibration validity.
94th article more than inaccurate calibration period, shall not be used without calibration, weighing, measuring, instruments and equipment, apparatus for recording and control. The 95th in the production, packaging, storage automatic or electronic devices that are used in the process, should be carried out according to the guideline periodically calibrations and checks to ensure its normal operation function. Calibration and check the corresponding record should be.
Sixth section for pharmaceutical use 96th pharmaceutical water should be suitable for its purpose, and in accordance with the People's Republic of China Pharmacopoeia quality standards and requirements.
Pharmaceutical water should be at least of drinking water. 97th water treatment equipment and its transportation system design, installation, operation and maintenance shall ensure that pharmaceutical water reaches the set quality standards.
Water treatment equipment not in excess of the design capacity.
98th purified water, WFI storage tank and pipeline materials used should be nontoxic, corrosion; tank vents should be installed does not shed fibers hydrophobic bacterial filter; piping should be designed and installed to avoid dead ends, pipe. 99th purified water, water for injection preparation, storage and distribution should be able to prevent microbial growth.
Purified water cycle, water for injection 70 deg heat circulation.
100th pharmaceutical water and raw water quality should be monitored on a regular basis, and to maintain appropriate records. 101th shall in accordance with the rules of purified water, water for injection piping for cleaning and disinfection, and related records.
Discover pharmaceutical water microbiological pollution reaches alert limit deviation limit should be dealt with in accordance with the rules.
The sixth chapter of materials and products
First principles 102th drugs used in the production of raw materials, packaging materials in direct contact with drugs shall meet appropriate quality standards.
Drug use for direct printing on ink should conform to the standard requirements.
Imports imports of raw materials shall conform to the relevant State regulations.
103th material and product handling procedures should be established to ensure correct of materials and products receiving, storage, distribution, use and delivery, to prevent contamination and cross-contamination, confusion and error.
Handling of materials and products shall be in accordance with the rules or procedures to perform and record.
104th material determination and change of the supplier shall carry out quality assessment, and approved by the quality control Department before they can purchase.
105th material and product shipping should be able to meet the requirements of its quality assurance, have special requirements for the transport, the transport conditions should be confirmed.
106th of raw materials, direct contact with the drug packaging materials received and printed packaging materials should be operating rules, all of the delivery item shall be checked to ensure that consistent with the order, and verify that the vendor has been approved by the quality control Department. Packaging materials should have a label, and indicate the provision of the information.
If necessary, should also be clean, find packaging damage or other problems that may affect quality, should be reported to the quality control Department to investigate and record.
Each time you receive should be recorded, including:
(A) Note on the delivery and packaging the name of the item;
(B) internal use item name and (or) code;
(C) the date of receipt;
(D) supplier and manufacturer (if different) name;
(E) the supplier and manufacturer (if different) identifying lot number;
(Vi) total received quantity and packaging containers;
(G) after receiving a designated lot number or serial number;
(H) instructions (such as packaging).
107th material shall, without delay after receiving and finished production according to the quarantine management until the release.
108th batch storage of materials and products should be ordered according to its nature and working capital, payment and shipping shall comply with FIFO and peri first out principle.
109th use computerized warehouse management, shall have the corresponding operation, preventing downtime due to system failure, caused by exceptional circumstances, such as material and product of confusion and error.
Identification by using a fully computerized warehouse management system, materials, products, and other related information need not be in writing to be read out.
Section II material
110th should develop appropriate procedures and take appropriate measures such as checking or inspection, recognizing that every package of raw materials is correct.
111th received several batches of materials should be according to the sampling, testing and release.
112th raw materials in the storage area should be properly labeled, and indicate at least the following elements:
(A) specify the name of the item and the item code within the enterprise;
(B) set by the enterprise receiving the batch number;
(C) the quality status on material (such as quarantine, qualified and unqualified, sampling);
(D) the expiry or retest date.
113th released only with the approval of the quality control Department and the expiry or retest date within the raw materials to be used. 114th storage of raw materials should be in accordance with the expiry or retest date.
Storage period, if found any adverse effects on the quality of the special circumstances, shall reinspect.
115th article should be determined by the designated officer the ingredients according to the guideline, check items, accurate weighing or measuring, and make a good logo.
The 116th in the preparation of each item and its weight or volume should be independently reviewed by others, and review the records.
117th for the same drug in the production of all the ingredients should be centrally located and well identified.
Section III intermediate and bulk products
118th intermediate and bulk products should be stored under appropriate conditions.
119th intermediate and bulk products should be clearly labeled, and indicate at least the following elements:
(A) the product name and product code within the enterprise;
(B) the batch number;
(C) the quantity or weight (such as gross weight, net weight, etc);
(D) the production process (if necessary);
(E) the product quality status (and, if necessary, such as quarantine, qualified and unqualified, sampled).
Fourth section packaging materials
120th of direct contact with the drug packaging material and printing management and control requirements of the packing material with the same raw materials.
121th packaging material should be issued by the person according to the guideline, and take measures to avoid confusion and errors, ensure that packaging materials for pharmaceutical production is correct.
122th printing and packaging materials should be established to design, review, approval procedures, ensure printing and packaging materials printing and unanimously approved by the pharmaceutical supervisory and administrative departments, and the establishment of specialized documents, saving printing and packaging materials approved by the signature of the original sample. Version changes of the 123th printing and packaging materials, measures should be taken to ensure correct version of products used in printing and packaging materials.
Yi reclaims the legacy print templates and be destroyed. 124th printing and packaging materials should be properly stored in dedicated areas, and unauthorized persons are not permitted.
Cut labels or other bulk printing and packaging materials shall be placed in a closed container storage and transport, to prevent confusion.
125th printing and packaging materials should be kept by hand, and according to the guideline of and demand for payment.
126th/or issue at a time of direct contact with the drug or printed packaging materials packaging materials, shall have identification signs, indicating the name and batch number of the product.
127th outdated or obsolete printed packaging materials shall be destroyed and records.
Fifth Festival products
128th storage of finished products should be quarantined before being released.
129th finished product storage conditions shall meet the approval requirements for registration of pharmaceuticals.
Sixth special management of materials and products
130th of narcotic drugs, psychotropic substances, toxic drugs for medical use (including herbs), radioactive pharmaceuticals, drugs type of precursor chemicals and flammable, explosive and other dangerous goods acceptance, storage, management shall implement the relevant provisions of the State.
The 131th substandard materials, intermediate products, bulk products and finished products on each packaging shall be clearly visible signs, and in the area of preservation.
The 132th substandard materials, intermediate products, bulk products and finished products should be approved by the head of the quality control and record. 133th products subject to prior approval and the related quality risks are adequately assessed, based on the assessment findings to decide whether recovery. Recycling should be carried out according to the rules, and have the appropriate records.
Recycling products should be in accordance with the recovery in the earliest production date of validity of the product. 134th drug product may not be reworked. Unqualified agents of intermediate products, bulk products and finished products shall not be reprocessed. Only do not affect the product quality, meet appropriate quality standards, and according to the book, approved procedures and related risk fully assessed only allowed rework process.
Rework should be recorded accordingly.
135th of reworked or reprocessed or recycled after merging production of the finished product, quality control Department shall take into account the need for additional testing of relevant projects and stability. 136th enterprises shall establish drug return procedures, and to maintain appropriate records, which shall at least include: product name, lot number, size, quantity, return address and return reasons and date, final disposal.
Returns of the same product on the same lot different channels should be recorded, stored and processed. 137th only after inspection and testing and investigation, there is evidence that the return is not affected, and according to operating rules evaluation by the quality management Department, should be considered to return new packaging, a new ship sales. Evaluation of the factors to be considered shall include at least the drug properties, the required storage conditions, status, history of medicine, and the interval between shipment and return, and other factors. The returned goods do not meet the requirements for storage and transport, shall be destroyed under the supervision of the quality control Department.
To return quality case of doubt shall not be shipped back.
Returns for recycling, recycled products should meet the pre-determined quality standards and 133th requirements.
Returns processing processes and results should be recorded.
The seventh chapter of validation and verification 138th Enterprise shall determine the need for confirmation or verification, to prove that the key elements of the action can be effectively controlled.
Scope and extent of validation or verification should be determined through risk assessments.
139th business premises, facilities, equipment and testing equipment shall be subject to confirmation, should be used after validation of production processes, procedures and test methods of production, operation and inspection, and to maintain the authentication status.
140th shall establish a validation and verification of documents and records, and can prove with documents and records meet the following goals:
(A) the design validation shall demonstrate buildings, facilities, designed in accordance with the intended purpose of the equipment and this norm requirements;
(B) the installation confirmation should prove that buildings, facilities, construction and installation of the equipment in accordance with design criteria;
(C) operational qualification should show that the operation of the plant, facility, equipment comply with the design standards;
(D) performance verification should show that the plant, facility, equipment, methods and process conditions can continue normal operation in accordance with standards;
(V) process validation should show a production process in accordance with the established process parameters can produce in line with the intended use and registration requirements of the product. 141th before using a new recipe and production craft production, should verify its applicability of conventional production.
If necessary, should also be approved by the pharmaceutical supervisory and administrative departments. 143th cleaning methods should be validated and confirmed its cleansing effect in order to prevent contamination or cross-contamination.
Cleaning validation should consider the use of equipment, detergents and disinfectants used, the sampling method and location and the corresponding sampling rate, remnants of nature and limits, sensitivity testing of residues and other factors. Validation and verification of the 144th article is not a one-time act. Confirmed for the first time or after validation, based on analysis of product quality review should be carried out to confirm or verify.
Critical production processes and procedures should be periodically verified to ensure that it can achieve the desired results.
145th enterprises should develop a validation master plan, to file format validation and verification of critical information.
146th validation master plan or in other relevant documents should be provided to ensure that buildings, facilities, equipment, testing equipment, production processes, procedures and test methods to maintain sustainable and stable. 147th article should be based on confirmation or verification of object develop confirmed or verified programmes, and review and approval.
Confirm or verify that the programmes should be clear responsibilities. 148th in confirmation or verification should be predetermined and approved programmes, and record. Upon completion of the validation or verification, shall write a report and review and approval.
Confirmation or validation of findings and conclusions (including evaluation and recommendations) should be recorded and archived.
149th article should be based on the results of the confirmation process and procedures.
The eighth chapter document management
First principles 150th files are fundamental elements of the quality assurance system.
Enterprise must have a written quality standards, prescription and production processes, procedures and records and other documents. 151th enterprises shall establish document management procedures, system design, development, review, approval and issuance of documents.
Files associated with this specification should be examined by the quality control Department.
152th file content should be associated with pharmaceutical production license, drug registration requirements and help to trace back the history of each batch of products.
153th articles document the drafting, revision, review, approval, replaced or revoked, replication, storage and destruction shall be in accordance with practice management, and there are corresponding documents, undo, copy, destruction of records.
154th document drafting, revision, review, approval, shall be signed and dated by the appropriate personnel. 155th documents shall clearly indicate the topic, type, purpose, and number and version number of the file.
Text should be accurate, clear, and easy to understand, not ambiguous.
156th file classification should be stored, organized, and easy to access.
157th original file copy, shall not give rise to any mistakes; copies of documents should be clearly visible. 158th file shall regularly review, revision after revision, should be managed in accordance with regulations, prevent the misuse of the old version of the file.
Distribution and use of the documents should be approved by the existing text, retired or older version of the file besides filed away for future reference, and not at the work site. 159th to the specifications relating to each activity should be recorded to ensure the production, quality control and quality assurance and other activities can be traced back. Records there should be enough space to fill in the data.
Records should be completed in a timely manner, true, clear and easy to read, easy to erase.
The 160th article should as far as possible production and testing equipment automatically records, maps, and graphs, such as, name, batch number and indicate the product or sample and record the device information, name and date of action people should endorsements. 161th records should be kept clean and not torn or arbitrarily alter. Records to fill in names and dates of any change should be endorsed, and the original message is still clearly visible, if necessary, should indicate the reason for this change.
Records as necessary to copy, the original records be destroyed should be saved as an attachment again transcription records. 162th each batch of medicines has batch records, including batch production records, batch packaging records, inspection records and drug release of audit records and other records relating to this product.
Batch records should be managed by the quality control Department is responsible for, at least until after the drugs period of validity for one year.
Quality standards and process regulations, operating rules, stability, verification, validation, change, and other important documents should be saved for a long time.
163th articles such as the use of electronic data processing system, photography, or other reliable way to record data, should be systematic practice for recording accuracy should be checked.
Use of electronic data processing system, only authorized personnel may enter or change data, change, and delete records; should login using a password or other means to control system; after key data entry, should be reviewed by independent of others.
Electronically save the batch record, tape, microfilm, paper copies of backups or other methods in order to ensure the security of records, and the data is easy to access in the shelf life.
Section II quality standard
164th materials and finished products should be approved by existing quality standards when necessary, intermediate or bulk products should have quality standards.
165th material quality standards should generally include:
(A) items of basic information:
1. Enterprise Unified the specified item name and item code for internal use;
2. based on the quality standard of;
3. approved supplier;
4. the samples or samples of the printed packaging materials.
(B) the method of sampling, inspection, or related procedures number;
(C) qualitative and quantitative limits requirements;
(D) the storage conditions and notes;
(E) the expiry or retest date.
166th purchased or exports of intermediate products and bulk product quality standards if the inspection result of intermediate products for quality evaluation, you should set that correspond to intermediate products and finished product quality standards quality standards.
167th finished product quality criteria should include:
(A) the product name and product code;
(B) the corresponding product prescription number (if any);
(C) the product specification and packaging;
(D) the method of sampling, inspection, or related procedures number;
(E) qualitative and quantitative limits requirements;
(F) the storage conditions and notes;
(G) the expiry date.
Section III procedure specification 168th each drug should be approved by the company for each production batch processes, different specifications of pharmaceuticals packaging for each packaging shall have their own operational requirements.
Process should be made according to the registration approval process. 169th process shall be arbitrarily changed.
If you need to change, and should be in accordance with the relevant procedures for the operation of the revision, review, approval.
170th preparation process should include at least:
(A) the production of prescription:
1. product name and product code; 2. product dosage form, specifications and quantities;
3. the list of raw materials (including the production process used, but does not appear in the finished product), clarify the amount of each item of the specified name, code, and if consumption of raw materials when the required conversion should also be calculated.
(B) production requirements:
1. Description of the production sites and the equipment used (such as number and operations, cleanliness level, the necessary temperature and humidity requirements, equipment type and number);
2. preparation of key equipment (such as cleaning, Assembly, sterilization, calibration, etc) the methods used or the appropriate operation number;
3. detailed description of the production steps and the process parameters (such as the reconciliation of materials, pretreatment, joined the order of items, mixing time, temperature, etc);
4. all the intermediate control methods and standards;
5. it is expected that the yield limits and, if necessary, should also indicate the production of intermediate products limited, and the material balance calculation and limits;
6. bulk product storage requirements, including containers, labels and special storage conditions;
7. Notes notes.
(C) packaging operation requires:
1. in the final container product quantity, weight or volume of packing;
2. a complete list of all the packaging materials required, including the name of the packaging material, quantity, specification, type and quality standards-related code of each packaging material;
3. samples of the printed packaging materials or copy and print position indicate the product batch number, validity period;
4. instructions the notes, including the inspection of production areas and equipment in the packaging before the operation began, confirm the clearance of packaging line has been completed;
5. Description of the procedure, including important complementary actions and used equipment considerations, packaging materials before using the check;
6. the detailed operation of the control, including the methods and criteria for sampling;
7. bulk product, printed packaging materials the material balance calculation methods and limits.
The fourth batch production records
171th each batch of product shall have a corresponding batch records, dating the product manufacturing and quality-related situations. 172th batch production records should be based on the existing approval process-related content. Records should be designed to avoid filling out the mistake.
Batch production records should mark each page of product names, size and lot number. 173th original blank batch production records shall be subject to production management and head of quality management for review and approval.
Batch production record of copying and distribution should be controlled and recorded according to the guideline, the production of each batch of products can only be issued a copy of the original blank batch records.
174th in the production process, carrying out each operation shall be recorded in a timely manner, after the end of the operation, production operators should confirm the names and dates and endorsements.
175th batch production records should include:
(A) the product name, size, lot number;
(B) the production and operation to begin in the middle and the end date and time;
(C) the signature of each production process;
(D) the signatures of the production steps, if necessary, should also have operations (such as weight) the signatures of the review;
(E) the lot number of each raw material and the number of actual weight (including put into recycling or remanufacture of processing the batch number and the quantity of the product);
(F) the related manufacturing operations or activities, process parameters and control, as well as the number of the main production equipment;
(G) the signatures of the records and operations of the control results;
(H) the yield derived from different manufacturing processes and material balance calculation, if necessary;
(I) record for special problems or unusual events, including deviations from the detailed description of the process specification deviation or investigation reports, and approved by the signature.
The fifth batch packaging records
176th each batch of product or packaging of some products with each batch, batch packaging record should, in order to trace the product packaging operations as well as quality-related conditions. 177th batch packaging record should be based on process specification and packaging-related content. Records should be designed to avoid filling out the mistake.
Each page of a batch packaging record should be marked the packaging product name, size, packaging and lot number. 178th batch packaging record should be packaging the product lot number, quantity, as well as finished product batch number and plan number.
Original blank batch packaging records reviewed, approved, copy and the issuance of the same requirements as the original blank batch records.
179th in the packaging process, carrying out each operation shall be recorded in a timely manner, after the end of the operation, it should be confirmed and endorsed by the wrap operation name and date.
180th batch packaging records include:
(A) the name, specifications, package, batch number, date of production and expiry date;
(B) the packing date and time;
(C) packaging operation signature;
(D) packaging operation signatures;
(E) the name of each packaging material, batch number and the quantity actually used;
(F) according to the procedures carried out by inspection records, including process control results;
(VII) details of packaging operations, including used equipment and packaging line number;
(VIII) samples of the printed packaging materials used, and bearing the batch number, expiry date and other print content; not easy to batch packaging records archive of printed packaging materials can be printed copies of such content;
(I) record for special problems or unusual events, including deviations from the detailed description of the process specification deviation or investigation reports, and approved by the signature;
(X) the names of all printed packaging materials and packaging products, code, as well as the issuance, use, destruction or return of the amount, actual production and material balance checks.
Sixth section procedures and records
181th procedures should include: title, number, version number, the issuing sector, effective date, the distribution sector and the development of people, checker and approver signature and date, title, body, and change history.
182th plant, equipment, materials, documents and records should be numbered (or code), and compiled numbers (or code) operation procedure, make sure the numbers (or code) is unique.
183th following activities should have appropriate procedures, processes and results should be recorded:
(A) validation and verification;
(B) the Assembly and calibration of equipment;
(C) plant and equipment maintenance, cleaning and disinfection;
(D) training, dressing and hygiene and other personnel-related matters;
(E) environmental monitoring;
(Vi) pest control;
(G) change of control;
(VIII) deal with deviations;
(I) the complaint;
(J) the drug recalls;
Nineth part production management
184th all drug manufacturing and packaging shall be in accordance with the approved procedures and operation procedures and related records, to ensure that medicines reach the required quality standards and meet the requirements of drug production licenses and registration approval.
185th Division should be established product operation for the production batch, Division of production batches should be able to ensure that the same batch of product quality and characteristics of homogeneity. The 186th article should establish preparation of drug batch number and production date code. Each batch of the drug shall prepare a unique lot number.
Except where otherwise legal requirements, production date must not be later than the product or packaging (sealed) before finally mixing operation start date may not be packing date as the date of manufacture. 187th should check that the output of each batch of products and material balance, ensure the material balance is in setting limits.
If there are differences, you must identify the reasons, after making sure that no potential quality risk, shall not be processed according to normal products.
188th in the same production simultaneously to different varieties and specification of drug manufacturing operation, unless there is no possibility of confusion or cross-contamination.
189th in every phase of production, should be protected from microbial and other contamination of products and materials.
190th in the dry material or products, especially high-activity, high toxicity or high-sensitive materials or products in the production process, should take special measures to prevent the emergence and spread of dust.
191th used during the production of all materials, intermediate products or containers of bulk product and main equipment, necessary actions should be labeled identity or otherwise marked in the production of product or item name, specification, and lot number, if necessary, shall be indicated in the production process. 192th containers, equipment or facilities used by the logo should be clear and concise, identifying format should be approved by related departments. In addition to using the text on the label stated, can also use different color markers (such as quarantine, qualified and unqualified, or cleaning, etc).
193th should check the product from one region into another region of pipes and other devices are connected, make sure that the connection is correct. 194th should be cleared after the end of each production, ensure equipment and workplaces are not left with the documents related to the materials, products and production.
Next time before you start, previous clearance should be confirmed. 195th should be avoided as far as possible any deviated from procedures or operating procedures deviation.
If there is a deviation, should be dealt with in accordance with the deviation procedures implemented.
196th production plants should be limited to authorized personnel only.
Section II to prevent contamination and cross-contamination in the production process
197th production process should take measures to prevent contamination or cross-contamination, such as:
(A) the production of different kinds of medicines in a delimited area;
(B) the stage of production;
(C) set up necessary between the air lock and ventilation air cleanliness level should be pressure difference control in different areas;
(D) shall reduce the untreated or inadequately treated air is once again risk of pollution entering the production area;
(V) easy to produce cross-contamination in production areas, operators should wear dedicated protective clothing in the region;
(Vi) using proven or known effective cleaning and decontamination procedures for equipment cleaning, if necessary, should be in direct contact with the material surface residues were detected;
(VII) a closed system;
(H) air of drying equipment should have air filters, exhaust air should prevent air backflow devices;
(I) manufacturing and cleaning process should avoid the use of fragile, easy to desquamation, moldy devices when using a screen, there should be measures to prevent pollution caused by their screen fault;
(X) preparation of liquid preparations, filtering, potting, sterilization processes should be completed within a specified time;
(11) ointment, cream, gel, semi-solid dosage forms and suppositories should provide storage and storage conditions of intermediate products.
198th article should be checked on a regular basis to prevent contamination or cross-contamination and assessing their suitability and effectiveness of the measures.
Section III operation 199th production checks should be carried out before the start, ensuring that equipment and workplaces do not have legacy product, files, or batch production related materials, equipment is cleaned and ready state.
Inspection results should be recorded.
Before the operation, should also be checked material or intermediate product name, code, lot number, and mark, make sure the right materials or intermediate products used in production and meet the requirements.
Article No. 200 controls should be carried out and the necessary environmental monitoring and recording. Article No. 201 each completion of the production of each batch of drugs must be cleared by production personnel, and fill in the clearing record. Clearance records include: operation number, product name, batch number, production processes, the clearance date, examinations and results, head of clearing and checking signatures.
Clear record should be included in the batch production record.
Fourth section packaging operations
Article No. 202 packing procedures should provide for reducing pollution and the risk of cross-contamination, confusion or error measures. Article No. 203 packaging check should be carried out before the start, ensure that the workplace, packaging lines, printing machines and other equipment are clean or stand-by status, Supreme group of legacy products, file has nothing to do with this batch of product or packaging materials.
Inspection results should be recorded.
Article No. 204 before packaging operations, should also examine the use of packaging materials are correct, nuclear treatment of packaging products and packaging materials used by name, size, quantity, quality, and consistent with the procedures.
No. 205 of each packing or packaging production line, shall be marked with an identification of packaging product name, size, lot number and batch production.
Article No. 206 when a number of packaging the packaging line at the same time, isolation or other effective should be taken to prevent contamination, cross-contamination or mix of measures.
Article No. 207-packing containers in front of the packaging should be kept clean and avoid glass containers, metal particles and other pollutants. Article No. 208 products packaging, shall, without delay after sealing labeling.
Delay when labeling should be in accordance with the relevant procedures for the operation of the action in order to avoid confusion or errors such as mislabeled. No. 209 single printing or packaging process printed information online (such as lot number or expiry dates) shall be checked to ensure that it is correct, and be recorded.
Such as hand-print, check the frequency should be increased.
Article No. 210-cutting label or on the packaging line separate printing labels, special measures should be taken to prevent confusion. Article No. 211 should be on electronic reading machine function, label counters or similar devices are checked to ensure its accurate operation.
Examination should be documented.
No. 212 packaging materials printed or molded piece of content should be clear, resists fading and erasing.
Article No. 213 during packaging, product control and inspection shall include at least the following elements:
(A) the packaging appearance;
(B) the integrity of the packaging;
(C) the products and packaging materials are correct;
(D) the printed information is correct;
(E) online monitoring device for proper functionality.
After the samples removed from the packaging line should not be returned, in order to prevent confusion or contamination. Article No. 214 packaging anomalies arise that need to be repackaged products shall be subject to special inspection, investigation and approval by the designated officer.
Repackaging should be recorded in detail.
Article No. 215 in the examination of material balance, find bulk product, printed packaging materials and finished products when there is a significant difference in the number, should be investigated, not before coming to a conclusion, products shall not be released. Packing at the end of Article No. 216, printed the lot number of the remaining packaging material shall be destroyed by the person responsible for all counts and records.
Will not print a return batch printing and packaging materials, shall be executed in accordance with the rules.
The tenth chapter of quality control and quality assurance
Section management of quality control laboratories
No. 217 quality control laboratory personnel, facilities, equipment should be commensurate with the nature and the scale of production.
Businesses often are not permitted to delegate inspection, commissioning inspection requirements shall be as provided for in the commissioning inspection section in the 11th chapter, and commissioned an external laboratory for testing, but should be included in the inspection report indicated.
Article No. 218 the management of laboratory in charge of the quality control shall have sufficient qualifications and experience, you can manage one or more of the same enterprise Labs.
No. 219 of quality control laboratories of inspection personnel should at least have the relevant professional college or high school education, and of the examination related to the practice and training and pass the examination.
No. 220 quality control laboratories should be equipped with Pharmacopoeia, the necessary tools such as standard, as well as standards or control, and other related standards.
File No. 221 of quality control laboratories shall comply with the principles of the eighth chapter, and meet the following requirements:
(A) quality control laboratories should have at least the following documents:
1. quality standards;
2. sampling procedures and records;
3. inspection procedures and records (including test record or laboratory notebook);
4. the inspection report or certificate;
5. the necessary procedures for environmental monitoring, recording and reporting;
6. test method validation reports and records as are necessary;
7. instrument calibration and equipment use, cleaning, maintenance procedures and records.
(B) each batch of drug test records shall include intermediate products, bulk products and finished products inspection record, dating to the drug quality inspection of all relevant circumstances;
(C) facilitate trend analysis methods should be adopted to save some data (such as testing data, microbial monitoring data for environmental monitoring data for pharmaceutical use);
(D) apart from information associated with batch record information, should also be saving the other primary sources or records, to facilitate inspection.
Article No. 222 sampling shall meet the following requirements at least:
(A) quality management departments have access to production areas and storage areas for sampling and surveys;
(B) shall, in accordance with the approved rules of sampling procedures should be specified in detail:
1. sampling of authorized people;
2. the sampling method;
3. the apparatus;
4. the sample size;
5. the sampling methods;
6. store sample container type and status;
7. rest after sampling and sample handling and identity;
8. sampling considerations, including for reducing the risk of sampling a variety of preventive measures taken, especially aseptic or hazardous material sampling and cautions to prevent contamination or cross-contamination during sampling;
9. storage conditions;
10. cleaning and storage requirements for sampling devices.
(C) the sampling method should be scientific and reasonable, to ensure the representativeness of the sample;
(D) samples should be representative of the sampled lot of products or materials, but also extracted other samples to monitor the most important link in the production process (such as the beginning or end of production);
(E) the sample containers should be labeled, indicating the sample name, batch number, sampling date, from which containers, samples and other information;
(F) samples should be in accordance with the storage requirements preservation.
Article No. 223 materials and to produce a product test shall at least comply with the following requirements:
(A) the Enterprise shall ensure that medicines in accordance with approved methods to inspect;
(B) in accordance with any of the following circumstances, the test method shall be verified:
1. introduction of new testing methods;
2. test methods need to change;
3. adoption of the People's Republic of China Pharmacopoeia and other legal standard does not include test methods;
4. the regulations of other validated testing methods.
(C) does not require validated testing methods, Enterprise testing methods should be confirmed, to ensure that the data is accurate and reliable;
(D) the inspection should have written operating procedures, provisions of the methods, apparatus and equipment, test procedures shall be consistent with confirmed or validated testing methods; (E) the inspection should have a traceable record and shall review and ensure that the results are consistent with the records.
All terms shall be subject to strict checks;
(F) inspection records shall include at least the following:
1. product or item name, the dosage form, specifications, lot number, or lot number delivery and, if necessary, indicate the supplier and manufacturer (if different) name or source;
2. in accordance with quality standards and inspection procedures;
3. the instrumentation for the test or the model and serial number of the device;
4. preparation of the test solution and culture medium for the test batch, the source of reference standards or reference and batch number;
5. inspection and animal-related information;
6. the inspection process, including the reference solution preparation and testing of the specific operations, the necessary environment of temperature and humidity;
7. test results, including observations, calculations and map or graph, and based on the test report number;
8. test date;
9. signature of Inspector and date;
10. inspection, review officer's signature and date is calculated.
(VII) all intermediate controls (including the control carried out by production staff), shall, in accordance with the method approved by the quality control Department, testing shall be recorded;
(VIII) should be laboratory volumetric glassware, reagents, test and reference substance and medium quality checks; (I) when necessary, the use of laboratory animals for testing prior to use inspect or quarantine. ¡¡Feeding and management in accordance with the relevant provisions on administration of laboratory animals.
Animals should be identified and use history should be saved. No. 224 quality control laboratory examination results exceeding investigation procedures should be established.
Any test results exceeded must be in accordance with the rules carry out a full investigation, and to maintain appropriate records. Article No. 225 enterprise in accordance with the regulations, for drug quality traceability investigation materials, products or samples for samples.
Not part of the sample the sample used for product stability.
Sampling shall meet the following requirements at least:
(A) shall, in accordance with practice for the management of samples;
(B) the samples should be representative of the sampled batches of materials or products;
(C) the retention samples of the finished product:
1. keeping samples of each batch of the drug shall; if a batch of drugs into several packages, each package should be retained at least a minimum, packing of finished products for sale;
2. sample packaging format should work with commercial packaging form of the same drug, bulk drug samples cannot be sold in packaging, simulation package can be used;
3. samples of each batch of drugs generally should at least be able to ensure that the quality standards approved by the registered two-test (such as sterility and pyrogen);
4. If it does not affect sample packaging integrity, save the sampling period should be at least a year to conduct a Visual observation, if there are any, should be a thorough investigation and take the appropriate measures;
5. the observation shall be recorded;
6. the sample shall register the storage conditions of the approved at least until after the drugs period of validity of one year;
7. termination of drug production or closed, samples should be forwarded to the authorized units to save, and inform the local drug regulatory authorities in order to ready access to samples, if necessary.
(D) the material retention sample: 1. preparations used for the production of each batch of raw materials and packaging materials shall have direct contact with drugs.
Packaging materials in direct contact with drugs (such as bottles), such as keeping samples of finished products has been, it is not alone;
2. material retention sample should at least meet identified needs; 3. Apart from the less stable raw materials, and raw materials used for production (not including solvents, gases that are used in the production process or pharmaceutical use) and direct contact with the drug to samples of packaging materials should be kept for at least two years after product release.
If a shorter valid period for the item, the sampling time can be shortened accordingly;
4. material retention sample should be in accordance with the provisions of the conditions of storage, if necessary, should also be properly packaged sealed.
Article No. 226 reagent solution, media and management of test organism shall at least comply with the following requirements:
(A) the reagents and culture media should be purchased from reliable suppliers, when necessary, to assess suppliers;
(B) should have received reagent solution, media records and, if necessary, reagents, test should be marked on the container of the liquid, medium date of receipt; (C) shall, in accordance with the relevant regulations or instructions for use preparation, storage and use of reagent solution and culture medium.
Exceptional circumstances, prior to receiving or use, shall identify the reagents or other examination; (D) and preparation of culture media should be noted the preparation of test solution batch preparation, preparation date, and name of the person, and preparation (including sterilization) record. Unstable reagents, test and the validity of the medium should be marked and special storage conditions.
Standard, titration of liquid should also mark the last time the date and the correction factor, and standardized records; (E) preparing medium should be checked for applicability and related records.
Should have medium used records;
(Vi) should have the kinds of bacteria required to test and set up save the test organism, passage, use, destruction of operating procedures and the appropriate records;
(G) identification of the test organism shall be an appropriate, should at least include the strain name, number, time, date of passage, the passage of operator;
(H) the test organism shall be in accordance with the provisions of the conditions of storage, storage and time should not be adverse impact on growth characteristics of the test organism.
Article No. 227 of standards or reference management shall meet the following requirements at least:
(A) the standards or control, shall be stored and used in accordance with regulations;
(B) the standards should have appropriate identification or reference, should at least cover the name, batch number, manufacturing date (if applicable), expiry date (if any), date of opening for the first time, content or potency, and storage conditions; (Three) enterprise as needed homemade work standard products or control products, should established work standard products or control products of quality standard and preparation, and identification, and test, and approved and storage of operation, each batch work standard products or control products should with statutory standard products or control products for standard of, and determine validity, also should through regularly standard of proved work standard products or control products of effect price or content in validity within keep stable.
Standardized processes and results should be recorded.
Section II material and product release
Article No. 228, respectively, established material and product approval procedures, clear approval criteria, responsibilities, and to maintain appropriate records.
Article No. 229 release materials shall meet the following requirements at least:
(A) material quality evaluation shall include at least the manufacturer's inspection report, item packaging integrity and sealing of the inspection and testing results;
(B) the material quality of the conclusions of the assessment should be clear, such as approval, disqualification or other decisions;
(C) the release of materials should be ratified by the signature of the designated officer.
No. 230 product release should at least comply with the following requirements:
(A) prior to the approval, should be carried out on each batch of drug quality assessment to ensure drugs and their production should be subject to registration and this specification and confirm the following:
1. the main production process and test method validation;
2. complete all required inspections, tests, and considering the actual conditions of production and production records;
3. all the necessary production and quality control have been completed and signed by the supervisor;
4. changes in accordance with the relevant procedures have been processed, changes that need to be approved by the pharmaceutical supervisory and administrative departments have been approved;
5. to change or deviation has completed all necessary sampling, inspection, examination and audit;
6. all deviations from this batch has a clear explanation or statement, or has been thoroughly investigated and appropriate treatment of such deviations also covers other batches of products, should be dealt with together.
(B) drug quality assessment shall have clear conclusions, such as approval, disqualification or other decisions;
(C) each batch of drug shall be signed by the qualified person approved release;
(D) the vaccine products, blood products, blood source screening of in vitro diagnostic reagents and other biological products as prescribed by the State food and Drug Administration prior to release lot release certificate shall be obtained.
Section III sustainable mission
Article No. 231 in the continuing validity of the purpose of the stability study is to monitor the quality of medicines already on the market, to detect drug stability problems associated with production (such as impurities or dissolution characteristics of change), and drugs in the labeled storage conditions, in line with the requirements of the quality standards. No. 232 continues investigation of the stability of the main commercial packaging for pharmaceuticals, but also need to take into account when packaging products. For example, when the bulk product is complete before packing, transport or from the production plant to the packing plant, requiring long-term storage shall be in the appropriate environmental conditions, and assess their impact on the stability of packaged products.
In addition, consideration should be given to surveying the intermediate products stored for a long time. No. 233 last stability programme of investigation should be investigated, the results should be reported.
For continuous study of the stability of the equipment (especially the stability test equipment or facilities) in seventh and fifth chapter request to confirm and maintain.
Article No. 234 steady review of time drugs period of validity should be covered, inspection programme shall include at least the following: (a) each specification, every production lot inspection batch number of the drug;
(B) the relevant physical, chemical, microbiological and biological testing methods, stability could be considered exclusive to inspect;
(C) test methods;
(Iv) eligibility criteria;
(E) description of the container closure systems;
(F) test intervals (time points);
(G) the storage conditions (should be used corresponds to the drug label storage condition of the People's Republic of China Pharmacopoeia standard conditions of long-term stability test);
(H) the inspection item, if the test project contains items less than the quality standards, it shall explain the reasons. Article No. 235 inspection batch number and frequency of inspection should be able to get enough data, for the purpose of trend analysis.
Typically, every size, every packaging form of the drug, at least once a year a batch should be investigated unless there was no production. Article No. 236 in some cases, in the ongoing investigation of the stability of an additional batch number, such as significant changes or production and packaging have a significant deviation of the drug should be included in the stability study.
In addition, rework, reprocessing or recovery of batch, should also be considered for inclusion in the review unless it is validated and stability. Article No. 237 of key personnel, especially qualified person, should be aware of continued study of the stability of results.
When the steady review is not bulk product enterprise of production and when there should be a written agreement between the parties, and shall save the stability study results for drug supervision and management review. No. 238 does not meet the quality standards should be the results of abnormal or important trend for investigation.
Does not meet the quality standards of any confirmed or significant negative trend, companies should consider whether it might affect drug already on the market and, if necessary, should recall, survey results, and shall report on the measures taken by the local Drug Administration Department. Article No. 239 should be in accordance with the access to all data, including the stage conclusion of investigation, written report and save it.
Should periodically audit summary report.
Fourth quarter change control No. 240 enterprises shall establish a change control system, for all the changes that impact product quality assessment and management.
Changes that need to be approved by the pharmaceutical supervisory and administrative departments shall be approved to be implemented. Article No. 241 shall establish procedures, provides raw material, packaging material, quality standards, test methods, procedures, premises, facilities, equipment, instruments, production technology and change in computer software applications, assess, review, approval and implementation.
Quality Management Department shall designate a person responsible for the change control. Article No. 242 changes should evaluate the potential impact on product quality. Enterprises can change with the nature, scope, potential impacts on product quality and minimize the change category (primary, secondary, subject to change).
Judge changes required for validation, additional testing and stability should be based on science. No. 243 product quality-related after the changes proposed by the requisitioning departments shall be subject to assessment, develop implementation plans and clear implementation responsibilities, and ultimately by the quality control Department for approval.
Changes should be in place for the corresponding full records. Article No. 244 changes in raw materials, direct contact with the drug packaging materials, production technology, production equipment, as well as other major factors that affect drug quality, and after the change should be implemented initially at least three batches of the drug quality assessment.
If the change may affect the validity of the drug, after the implementation of the evaluation should also include the change production drug stability test.
Article No. 245 changes implemented, should ensure that files have been associated with the change amendments.
Section No. 246 quality control departments should save all changed files and records.
Fifth section deviation handling
No. 247 correctly heads of departments shall ensure that all personnel, production, quality standards, inspection methods and procedures to prevent deviations.
Article No. 248 deviation handling procedures should be established, provides error reporting, recording, investigation, and corrective measures taken, and to maintain appropriate records. No. 249 any deviation should assess the potential impact on product quality.
Business can bias the nature, scope, potential impacts on product quality and minimize the deviation classification (such as major and minor deviations), the material discrepancy between the assessment should also consider the need for additional testing and the impact of the expiration date, if necessary, on products of major deviations should be stability. No. 250 of any deviation from the production process, material balance limits, quality standards, inspection methods, procedures and other conditions should be recorded and immediately report to the Manager and the quality assurance Department, there should be clear instructions, significant deviations should be thoroughly investigated by the quality control Department, in conjunction with other departments and investigation reports.
Deviation survey report shall be signed by the designated person auditing and quality management Department.
Enterprises should take preventive measures to prevent recurrence of similar errors.
Article No. 251 classification of the quality control Department is responsible for deviation, save the deviation surveys, processing of documents and records.
Sixth corrective and preventive measures Section No. 252 enterprises shall establish corrective and preventive action system, complaints, recalls, deviations, the self test or the external examination results, technical performance and quality monitoring trends, investigate and take corrective and preventive measures. Investigation depth and should be commensurate with the level of risk.
Corrective and preventive action system should be able to improve product and process understanding, improve products and processes.
Article No. 253 enterprises operation shall establish and implement corrective and preventive measures, including at least: (A) complaints, recalls, deviations, the self test or the external examination results, process performance and quality monitoring trends and analyze the quality of data from other sources, identify existing and potential quality problems.
If necessary, the appropriate statistical methods should be adopted;
(B) investigation and reasons related to products, processes and quality assurance systems;
(C) determine the corrective and preventive measures to be taken to prevent the problem from happening again;
(D) assess the rationality and effectiveness of corrective and preventive actions and adequacy;
(E) to implement corrective and preventive measures for all changes that occurred in the process should be recorded;
(F) ensure that the relevant information had been passed to the qualified person and head directly to prevent from happening again;
(G) ensure that the relevant information and its corrective and preventive measures for review by senior management.
Article No. 254, implementation of corrective and preventive actions shall be documented and retained by the quality control Department.
Seventh day supplier assessment and approval
No. 255 of quality control departments should be conducted for all production material supplier for quality assessment, in conjunction with the relevant departments of the major material suppliers (particularly by producers) quality audit of quality system and quality assessment does not meet the requirements of suppliers to exercise the right of veto.
Determination of main material production the quality of medicines should be considered enterprise risk, the amount of material and material effects on the quality of drugs and other factors.
Legal representative of the enterprise, business leaders and officials from other departments shall not interfere with or hinder the quality assessment of the quality management Department materials suppliers independent.
Section No. 256 material supplier assessment and approval procedures should be established, clear supplier qualification, selection principles, quality assessment, evaluation standards, material supplier approval procedures. Such as quality assessment quality audit, should also be explicit content, the cycle, the composition of the audit and the audit qualification.
Sample small batch trial production is needed, it should also be clear production quantity, production processes, product quality standards, the stability programme. Article No. 257 quality management Department shall designate a person responsible for the item vendor quality assessment and quality auditing, distribute the approved supplier list. Designated personnel shall have relevant regulations and expertise, have sufficient practical experience in quality assessment and quality auditing.
No. 258-site quality audit shall verify the vendor qualification documents and test the truth of the report, verify the availability of test conditions. Of its people, institutions, facilities and equipment, materials, production processes and production management, quality control, laboratory equipment, apparatus, document management, check such things as, in a comprehensive assessment of its quality assurance system.
On-site quality audits shall be reported.
Article No. 259, if necessary, should be the main vendor-supplied samples of materials for small batch production, stability and the production of drugs. Article No. 260 in quality management assessment of the material suppliers shall at least include: proof of qualification of suppliers, quality standards, inspection reports, business item sample test data and reports.
As on-site quality audits and small batch production of the sample should also include on-site quality audits as well as the stability of products quality inspection reports and inspection reports.
Section No. 261 change material suppliers, the qualitative assessment of new suppliers should be changing major material suppliers, products also need to be related validation and stability.
Article No. 262 quality control departments should be circulated to the materials management Department approved supplier list, this list should at least cover the items name, specifications, quality standards, the manufacturer's name and address, distributor (if any) name, and update.
No. 263 quality control departments should work with the main material supplier quality agreements, agreements should specify the responsibility of quality of both parties. Article No. 264 quality management for suppliers of materials should be regularly evaluated or on-site quality audits, retrospective analysis of quality test results, complaints about the quality and substandard treatment records.
Material quality problems or conditions of production, processing, quality standards and testing methods may affect the quality of key factors, such as when a major change occurs, related site quality audit should be carried out as soon as possible.
Article No. 265 enterprises should be established for each material supplier quality archives, archive should include the vendor's qualification documents, quality, quality standards, samples and test data and reports, inspection reports, on-site quality audits of suppliers reporting, product stability reports, periodic quality review analysis report.
Eighth section analysis of the product quality review No. 266 shall be in accordance with operating rules, all drugs produced annually according to the variety of product quality review analysis to confirm that the process is stable and reliable, as well as the applicability of current quality standards for raw materials, finished products, adverse trends in a timely manner, determine the direction of the product and process improvement.
Retrospective analysis of previous historical data should be considered, it should self test the validity of retrospective analysis on product quality.
When you have a reasonable scientific basis, quality review can be classified according to the dosage form of the product, such as solid dosage forms, liquid dosage forms and sterile preparation, and so on.
Retrospective analysis should be reported.
At least the following circumstances should be reviewed:
(A) all changes to products used in raw materials, in particular from new suppliers of raw materials;
(B) the critical control points and finished in the middle of the test results;
(C) all batch does not meet the quality standards and their investigation;
(D) all significant deviations and related investigations, corrective action taken and the effectiveness of preventive measures;
(E) the production or test methods all change;
(F) registration all changes that have been approved or registered;
(VII) stability study results and any adverse trends;
(H) all returns due to quality, complaints, recalls and investigations;
(IX) associated with the product or device implementation and effectiveness of corrective measures;
(J) and change of the approved new drugs, in accordance with the registration requirements listed should be done after work;
(11) the equipment and facilities, such as air purification systems, water systems, compressed air and other recognized State;
(12) contract manufacturing or inspection of the technical contract conditions.
Section No. 267 evaluation of the results should be reviewed, it raised the possible need for corrective and preventive measures or to confirm or verify the assessment and the reasons for, and the timely and effective completion of the rectification.
When production is Article No. 268, the principal and the agent shall have a written technical agreement between the parties, provide product quality review analysis of each party's responsibilities, ensure product quality review analysis on time and in conformity with the requirements.
Nineth day complaints and adverse reaction reports
Section No. 269 drug adverse reaction reporting and monitoring system should be established, and establish an organization and equip fulltime staff responsible for the management.
Article No. 270 should collect adverse drug reaction adverse reactions should be recorded in detail, assessment, investigation and treatment, and to take timely measures to control possible risks, and report to the pharmaceutical supervisory and administrative departments in accordance with the requirements.
Article No. 271 shall establish procedures requiring registration, evaluation, investigation and complaint handling procedures, and provisions for possible product defect complaints made by the measures taken, including considering whether it is necessary to recall the drug.
Article No. 272 should have special and adequate support staff is responsible for the investigation and handling of complaints all complaints and investigations information should be communicated to the qualified person.
Section No. 273 all complaints should register and review, and product defect-related complaints, shall make a detailed record various details complaint and investigation.
Article No. 274 finds or suspects that a batch of drugs was flawed, you should consider checking other batches of the drug, identify whether it is affected.
Article No. 275 complaints investigation and treatment should be recorded and annotated check relevant product information.
No. 276 should be reviewed on a regular basis complaints records to discover needs vigilance, repeated and may need to withdrawal from the market of drugs problems, and take the appropriate measures.
Article No. 277 enterprises production mistakes, medicine, deterioration or other significant quality problems, shall promptly take the appropriate measures, if necessary, should also be reported to the local drug regulatory authorities.
Delegate to a 11th chapter, production and inspection
Article No. 278 to ensure that commissioned the production of product quality and commissioned a test of accuracy and reliability, the principal and the agent must sign a written contract, clearly defined responsibilities, delegate or delegate inspection and related technical matters.
Article No. 279 delegate or delegate inspection activities, including technical or any other proposed changes, shall comply with the licensing and registration requirements.
Section II client
Article No. 280 principals shall assess the trustee, the trustee for on-site examination on the conditions, technical level and quality of, verify that it has the ability to complete commissioned work, and to ensure compliance with the requirements of this specification.
No. 281, the principal shall provide the trustee with all necessary information, to enable the trustee to follow drug registration and other operations commissioned by the correct implementation of the statutory requirements.
Principal Trustees should be made fully aware of problems associated with the product or operations, including product or operation on the Trustees of the environment, plant, equipment, personnel, and other materials or products may cause hazards.
Article No. 282 principal should be entrusted with production or inspection to supervise the whole process.
Article No. 283, clients should ensure that materials and products meet appropriate quality standards.
Section III trustee
Article No. 284 trustees must have a sufficient number of plant, equipment, knowledge and experience, as well as personnel, production or inspection work commissioned to meet client requirements.
Article No. 285 trustee where our clients should make sure that the received material, intermediate products and packaging product is suitable for its intended use.
Article No. 286 delegate trustee shall not engage in production or inspection activities that adversely affect the quality of the product.
Fourth quarter contract Article No. 287 clients between the Trustees and signed the contract should be specified in detail the individual product production and control duties, the technical provisions should be made by pharmaceutical technology, testing expertise and person who is familiar with the norms of the development.
Contract manufacturing and inspection must be consistent with the work of the pharmaceuticals production license and drug registration requirements and agreed to by the parties.
Article No. 288 contract should be specified in detail procedures for approved qualified person releasing each batch of drugs to ensure that each batch of product has been completed in accordance with the requirements for registration of pharmaceuticals production and testing.
No. 289 articles should provide that where the contract is responsible for the procurement of materials, production and quality control, testing, release (including control), should also provide that where responsible for sampling and inspection.
In the case of the commissioning inspection, contract should provide for the trustee at the client's plant sampling.
Provisions No. 290 contracts should be retained by the consignee of the production, testing and shipping records and samples, clients should be able to easily scan or check occurred when complaints, suspected of quality defects or product recalls, clients should be able to easily view all the records associated with the evaluation of the quality of products.
No. 291 contracts should be specified that the principal can be entrusted to inspection or quality audit.
Article No. 292 commissioning inspection contract should make clear the agent shall have a duty to accept the pharmaceutical supervisory and administrative department.
12th chapter product shipment and recall
Article No. 293 product recall system should be established and, if necessary, can be quickly and effectively to any withdrawal from the market of unsafe products.
No. 294 returns due to quality reasons and recalled products, shall, in accordance with the provisions for the monitoring of the destruction, except as evidence that the returned product is not affected.
Section II shipped No. 295 of each batch of products shall be shipped records.
According to shipping records, should be able to trace each batch of product sales, and when necessary can all recover in time, shipped a record shall include: the product name, lot number, quantity, specification and receiving units and address, contact information, the date of shipment, modes of transport, and so on.
Article No. 296 drug packaging only two batches for a fraction of the shipping box, collection box shall be indicated in all batches, and establish a record of collection boxes.
No. 297 shipped record shall be kept for at least until after the drugs period of validity for one year.
Section III recall
Article No. 298 recall procedures should be developed, ensuring the effectiveness of recalls. No. 299 shall designate a person responsible for organizing the recall work, and is equipped with a sufficient number of personnel.
Head of product recall should be independent of the sales and marketing departments as head of product recalls is not a qualified person, you should inform the qualified person handling of recalls.
Article No. 300 recalls should be able to start at any time and quickly implemented.
Article No. 301 unsafe decided to withdrawal from the market of the product, should be reported immediately to the local drug regulatory authorities.
Article No. 302 heads of product recall should be able to quickly access to the drug shipment records.
Article No. 303 has recalled products should be identified and separate, properly stored, waiting for the final decision. No. 304 recalled the progress should be recorded and a final report.
Product shipment quantity, has recalled the number amount balance should be explained in the report.
Article No. 305 should regularly assess the effectiveness of product recall system.
The 13th chapter self test
No. 306 quality management departments shall regularly organize enterprise performing a self-test, monitoring the implementation of this specification, evaluation of compliance with the requirements of this specification, and to propose necessary corrective and preventive measures.
No. 307 self-test should be planned, to agencies and personnel, plant, and facilities, equipment, materials and products, validation and verification, file management, production management, delegate to a quality control and quality assurance, production and testing, product shipment and recall items such as checks on a regular basis.
No. 308 should be designated by the enterprise personnel to conduct independent, systematic and comprehensive self test or by an external independent quality audit or a specialist. No. 309 self test should be recorded. After the self test is completed should have a self test report should at least cover the self test observed in all cases, evaluation conclusions and make recommendations for corrective and preventive actions.
Self test shall be reported to senior management.
14th chapter supplementary articles Article No. 310 of the code for the basic requirements of GMP.
For sterile drug products, biological products, blood products, such as pharmaceuticals or special requirements for production and quality management activities, formulated by the State food and Drug Administration Appendix separately.
Article No. 311 validated alternative methods can be used, meet the requirements of this specification.
No. 312 standard the following terms (sorted in Hanyu Pinyin) are:
(A) packaging Bulk product into finished all the steps required, including packaging, labeling, etc.
Aseptic filling of sterile products in the production process, as well as the filling is not regarded as packaging for terminally sterilized products.
(B) packaging material
Drug packaging materials, packaging materials and containers including direct contact with the pharmaceuticals, printing and packaging materials, but does not include the use of packaging materials.
Approved to guide the equipment operation, maintenance and cleaning, verification, environmental control, sampling and inspection of pharmaceutical manufacturing activities as common files, also known as standard operating procedure.
Including pharmaceutical intermediates, bulk products and finished products.
(V) the product life cycle
Product research and development, from the initial listing until the withdrawal of all stages.
All production steps and the final packaged product.
A production process that does not conform to the quality standards of a number of intermediate products or bulk product in part or in whole, and processed using different production processes to meet pre-determined quality standards.
(H) the products to be packaged
Wraps yet but have completed all other processing of products.
(I) to be inspected
Raw materials, packaging materials, intermediate products, bulk products or finished products, the physical means or other effective way to isolate or distinguish them, before allowing for feed production or sale store, waiting for the decision to release State.
(J) the issuance
Production process materials, intermediate products, bulk products, documents, molds used in the internal circulation of a series of operations.
(11) the retest
Storage of raw materials, packaging materials after a certain time, in order to ensure that it still applies to the intended use, determined by the business need a new test date.
(12) the shipment
Refers to send the product to the dealer or user of a series of actions, including distribution, transport and so on.
(13) the rework
A production process that does not conform to the quality standards of a number of intermediate products or bulk product and finished product part or all of the operations before returning to, using the same production for further processing in order to meet pre-determined quality standards.
Quality evaluation of the number of items or products make use or operation of the market or other decisions.
(15) top management
In the enterprise at the highest level of command and control, has the power to mobilize resources and responsibilities of the staff.
For the production of a certain number of finished products made of one or a set of files, including the prescription, production operations and packaging operations requirements, provision of raw material and packaging material quantities, process parameters and conditions, processing instructions (including controls), considerations, and so on.
(17) the supplier
Means materials, equipment, instruments, reagents, and service providers, such as producers, distributors, etc.
At a specific point in the production stage, will be produced before a number or batch of products that meet the appropriate quality requirements in part or in whole, added to another batch operation.
(19) the computerized system
For reporting or automatic control of the integrated system, including data entry, electronic processing and the output.
Different raw materials, auxiliary materials and product contamination.
(21) the calibration
Under the stated conditions, determine the measurement, recording, control instrument or system of values (especially weight) or material measure represented by the measure, and the corresponding reference to the relationship between the value standards of a series of activities.
(22) the stage of production
The total production area, concentrated production of a product for some time, and then on the corresponding share in the production areas, facilities, equipment and utensils, clean thoroughly, replace the production of another product.
(23) the clean area
Need to control the amount of dust particles and microorganisms in the environment room (area), their building structure, equipment and its use should be able to reduce pollutants in the region introduced, and retention.
(24) the alert limit
The key parameters of the system beyond the normal range, but does not meet the deviation limits need to be alerted to, and may be required to take corrective measures standard.
(25) the deviation limits
The key parameter is within the acceptable standard, standard of the need to investigate and take corrective action.
(26) results exceeded the
Test results exceed the statutory standards and enterprise standards of all cases.
(27) One or several processes, with expected uniform quality and characteristics of a number of raw material, packaging material or finished product. For the completion of certain production steps, it may be necessary to divide the product into several sub eventually merged into a single homogeneous batch.
In the continuous case, must have expected production determination of uniform characteristics correspond to the quantities of products, the bulk can be a fixed amount or fixed volume of products produced during the period.
For example: solid, semi-solid preparations in oral or topical or subdividing the former uses the same hybrid device produced by a mix of homogeneous products; oral or topical preparations with liquid filling (sealed) before finally mixing liquid for homogeneous products produced by batch.
(28) the batch number
Used to identify a specific batch of unique numbers and (or) combination of letters.
(29) the batch record
For descriptions of each batch of drugs production, quality inspection and release, examine all documents and records, can be traced back the history of all quality-related information.
(30) between the air lock Set between two or more rooms (such as between the different levels of cleanliness rooms) with two or more doors, isolated space. Set the air lock between the aim of personnel or materials when access, to control the air flow.
Personnel air lock between the lock and the vapor lock.
If there are no special instructions in this specification, and enterprises in particular to drug manufacturers.
Prove that buildings, facilities, equipment functions correctly and a series of activities to achieve the desired results.
(33) the return
Drugs returned to the enterprise's activity.
(34) the file
Files referred to in this specification, including quality standards, processes, procedures, records, reports, and so on.
(35) the item
Of raw materials, auxiliary materials and packaging materials, etc.
For example: chemical raw material for pharmaceutical preparation refers to active pharmaceutical ingredients; biological material refers to the material; traditional Chinese medicine preparation material refers to traditional Chinese medicine, Chinese herbal medicine and purchased Chinese medicine extract API raw material is used for raw material in production of other materials except for the packaging material.
(36) the material balance
Actual yield of products or materials, or the actual amount and collected losses and compared with the theoretical yield, or amount of theory, taking into account the permissible deviation.
(37) the pollution
During production, sampling, packaging or repackaging, storage or transportation during the operation, raw materials, intermediate products, bulk products and finished products are chemical or microbiological characteristics of adverse effects of impurities or foreign bodies.
(38) validation Any operating procedures (or methods), the production process or system, a series of activities to achieve the expected results.
(39) the printing and packaging materials
Packaging material with a specific style and print content, such as printing and foil, labels, brochures, cartons, etc.
(40) the raw material
Apart from the packaging material, any material used in the production of medicines.
(41) the intermediate
Refer to complete processing procedures product, needs further processing to become a party to bulk product.
(42) control Also known as process control, to ensure that the product complies with the relevant standards, to monitor the production process, so that if necessary, for adjustment of the examination.
To the environment or equipment can be controlled as part of the control. No. 313 standard come into force on March 1, 2011. In accordance with the People's Republic of China Law on drug management article Nineth, specific implementation measures and procedures prescribed by the State food and drug administration.