Secondly, the 2010 version of the GMP since March 1, 2011, to combine the requirements of the new version of the GMP. Attached below are the contents of the plant and facilities, I hope it will be useful to you.
Specification for Quality Management of Pharmaceutical Manufacturing (Revised 2010)
(Ministry of Health Decree No. 79)
Chapter IV Plant and Facilities
Section I. Principles
Article 38 The siting, design, layout, construction, renovation and maintenance of the plant must be in accordance with the requirements of pharmaceutical production, and should be able to maximize the avoidance of pollution, cross-contamination, confusion and error. contamination, confusion and errors, and facilitate cleaning, operation and maintenance.
Article 39 should be based on the plant and production protection measures should be considered in a comprehensive site selection, plant should be located in the environment should be able to minimize the risk of contamination of materials or products.
Article 40 Enterprises should have a clean production environment; the plant's ground, pavement and transportation should not cause pollution to the production of drugs; production, administration, living and auxiliary areas of the overall layout should be reasonable, and shall not interfere with each other; the plant and the plant people, logistics direction should be reasonable.
Article 41 The plant shall be properly maintained, and ensure that the maintenance activities do not affect the quality of medicines. The plant shall be cleaned or disinfected as necessary in accordance with detailed written operating procedures.
Article 42 There shall be proper lighting, temperature, humidity and ventilation in the plant to ensure that the quality of the products manufactured and stored, and the performance of the relevant equipment, are not directly or indirectly affected.
Article 43 The design and installation of the plant and facilities should be able to effectively prevent insects or other animals from entering. Necessary measures should be taken to avoid the use of rodenticides, insecticides, fumigants and other contamination of equipment, materials, products.
Article 44 shall take appropriate measures to prevent the entry of unauthorized personnel. Production, storage and quality control areas should not be used as a direct route for non-staff in the area.
Article 45 As-built drawings of plants, utilities, fixed piping after construction or remodeling shall be kept.
Section II Production Area
Article 46 In order to reduce the risk of contamination and cross-contamination, the plant, production facilities and equipment shall be reasonably designed, laid out and utilized in accordance with the characteristics of the pharmaceutical products to be produced, the process and the corresponding requirements of the cleanliness level, and in accordance with the following requirements:
(1) Comprehensive consideration shall be given to the characteristics of the pharmaceutical products, the process and the intended use of factors such as determining the Plant, production facilities and equipment, multi-product **** the feasibility of use, and have the appropriate assessment report;
(2) the production of special nature of drugs, such as highly allergenic drugs (such as penicillin) or biological products (such as BCG vaccine or other drugs prepared with active microorganisms), must be used in a dedicated and independent plant, production facilities and equipment. Penicillin drugs dust-producing operation area should maintain a relatively negative pressure, exhaust to the outdoors should be purified and comply with the requirements, the exhaust port should be away from the air inlet of other air purification system;
(c) the production of β-lactam structure of drugs, sex hormones contraceptives must be used in dedicated facilities (such as independent air purification system) and equipment, and with the production of other medicines production area (d) The production of certain hormones, cytotoxicity, highly active chemicals should use special facilities (such as independent air purification systems) and equipment; under special circumstances, if special protective measures and the necessary verification, the above pharmaceutical preparations can be phased through the production of the same production facilities and equipment;
(e) For the above paragraph (ii), (iii), (iv) of the air purification system, the exhaust air shall be purified;
(vi) pharmaceutical production plant shall not be used for the production of non-pharmaceutical products that adversely affect the quality of pharmaceutical products.
Article 47 The production area and storage area shall have sufficient space to ensure orderly storage of equipment, materials, intermediate products, products to be packaged and finished products, to avoid confusion and cross-contamination of different products or materials, and to avoid omissions or errors in production or quality control operations.
Article 48 should be based on the variety of drugs, production operation requirements and external environmental conditions, such as the configuration of air-conditioning purification system, so that the production area is effectively ventilated, and temperature, humidity control and air purification and filtration, to ensure that the production of drugs in accordance with the requirements of the environment.
The pressure difference between the clean area and non-clean area, between different levels of clean area should be not less than 10 Pascal. If necessary, the same cleanliness level of different functional areas (operating rooms) should also maintain an appropriate pressure gradient between.
Oral liquids and solid preparations, cavity drugs (including rectal drugs), epidermal drugs and other non-sterile preparations for the production of exposed process areas and their direct contact with the final processing of pharmaceutical packaging materials exposed process areas, should be referred to the "sterile drugs" appendix in the requirements of the D clean area set up, the enterprise can be based on the product Enterprises can adopt appropriate microbial monitoring measures for this area according to the standards and characteristics of the product.
Article 49 The inner surface of the clean area (walls, floor, ceiling) should be flat and smooth, no cracks, tight interfaces, no particles off, to avoid the accumulation of dust, to facilitate effective cleaning, and should be disinfected when necessary.
Article 50 of the design and installation of various pipelines, lighting facilities, air vents and other utilities should be avoided in parts that are not easy to clean, should be as far as possible in the outside of the production area for its maintenance.
Article 51 The drainage facilities shall be of appropriate size and installed to prevent backflow. Open ditch drainage should be avoided as far as possible; when unavoidable, the open ditch should be shallow to facilitate cleaning and disinfection.
Article 52 The weighing of raw and auxiliary materials for preparations shall normally be carried out in a specially designed weighing room.
Article 53 of the dust-producing operations room (such as dry materials or products, sampling, weighing, mixing, packaging and other operations room) should be maintained at a relatively negative pressure or to take special measures to prevent the spread of dust to avoid cross-contamination and facilitate cleaning.
Article 54 for pharmaceutical packaging plant or area should be reasonably designed and layout to avoid confusion or cross-contamination. If there are several packaging lines in the same area, there should be segregation measures.
Article 55 The production area should have appropriate lighting, visual operation area lighting should meet the operational requirements.
Article 56 The production area may have an intermediate control area, but the intermediate control operation shall not bring quality risks to the drugs.
Section III Warehousing Area
Article 57 The warehousing area shall have sufficient space to ensure orderly storage of raw and auxiliary materials, packaging materials, intermediate products, products to be packaged and finished products to be inspected, qualified, unqualified, returned or recalled and other types of materials and products.
Article 58 The design and construction of the storage area shall ensure good storage conditions with ventilation and lighting facilities. Warehousing area shall be able to meet the storage conditions of materials or products (such as temperature and humidity, avoiding light) and the requirements of safe storage, and inspection and monitoring.
Article 59 Highly active materials or products and printed packaging materials shall be stored in a safe area.
Article 60 The receiving, issuing and shipping area shall be able to protect the materials or products from the influence of external weather (such as rain or snow). Receiving area layout and facilities should be able to ensure that the arrival of materials before entering the storage area can be necessary to clean the outer packaging.
Article 61 If a separate segregated area is used for storage of materials to be inspected, the area to be inspected shall be clearly marked and access shall be restricted to authorized personnel only.
Non-conforming, returned or recalled materials or products shall be stored in a segregated area.
If an alternative to physical segregation is used, the method shall be equally safe.
Article 62 There shall normally be a separate material sampling area. The level of air cleanliness in the sampling area shall be consistent with the production requirements. If samples are taken in other areas or by other means, it should be possible to prevent contamination or cross-contamination.
Section IV Quality Control Area
Article 63 The quality control laboratory shall normally be separated from the production area. Laboratories for bioassay, microbiology and radioisotopes shall also be separated from each other. /> Article 64 The laboratory shall be designed so as to ensure that it is suitable for its intended use and is capable of avoiding confusion and cross-contamination, and there shall be adequate areas for sample disposal, storage of samples for retention and stability checks, and record keeping.
Article 65 If necessary, a special instrument room should be set up so that highly sensitive instruments are protected from static electricity, vibration, moisture or other external factors.
Article 66 The laboratories dealing with biological samples or radioactive samples and other special items shall comply with the relevant state requirements.
Article 67 The laboratory animal room shall be strictly separated from other areas, and its design and construction shall comply with the relevant state regulations, and have independent air treatment facilities as well as special access for animals.
Section V Auxiliary Areas
Article 68 The setting of the lounge shall not adversely affect the production area, storage area and quality control area.
Article 69 Changing rooms and lavatories shall be convenient for personnel to enter and exit, and be appropriate for the number of users. Washroom shall not be directly connected with the production area and storage area.
Article 70 of the maintenance room should be as far away as possible from the production area. Stored in the clean area of the maintenance of spare parts and tools should be placed in a special room or tool cabinet.
Chapter 5 Equipment
Section 1 Principles
Article 71 The design, selection, installation, modification and maintenance of equipment must be consistent with the intended use, and should minimize the risk of contamination, cross-contamination, confusion and error, and to facilitate the operation, cleaning, maintenance, and, if necessary, disinfection or sterilization.
Article 72 shall establish the use of equipment, cleaning, maintenance and repair of the operating procedures, and keep the appropriate operating records.
Article 73 shall establish and maintain equipment procurement, installation, confirmation of documents and records.
Section II Design and Installation
Article 74 The production equipment shall not have any adverse effect on the quality of drugs. The surface of the production equipment in direct contact with pharmaceutical products shall be flat, polished, easy to clean or disinfect, corrosion-resistant, and shall not chemically react with the pharmaceutical products, adsorb the pharmaceutical products or release substances into the pharmaceutical products.
Article 75 shall be equipped with scales, gauges, instruments and meters of appropriate range and accuracy.
Article 76 Appropriate washing and cleaning equipment shall be selected and such equipment shall be prevented from becoming a source of contamination.
Article 77 The lubricants, coolants, etc. used in the equipment shall not contaminate the medicines or containers, and lubricants of edible grade or equivalent grade shall be used as far as possible.
Article 78 of the production of mold procurement, acceptance, storage, maintenance, issuance and scrapping should be formulated accordingly operating procedures, set up special cabinets for safekeeping, and have the appropriate records.
Section III maintenance and repair
Article 79 The maintenance and repair of equipment shall not affect product quality.
Article 80 shall formulate preventive maintenance program and operating procedures for equipment, maintenance and repair of equipment should have the appropriate records.
Article 81 of the renovation or major maintenance of equipment should be reconfirmed to meet the requirements before being used in production.
Section IV Use and Cleaning
Article 82 The main production and inspection equipment should have clear operating procedures.
Article 83 The production equipment shall be used within the confirmed parameters.
Article 84 Production equipment shall be cleaned in accordance with the operating procedures detailed.
Operational procedures for cleaning production equipment shall specify specific and complete cleaning methods, equipment or tools for cleaning, names of cleaning agents and methods of preparation, methods for removing markings from previous batches, methods for protecting cleaned equipment from contamination prior to use, the maximum time limit for storage of cleaned equipment, and methods for checking the state of cleanliness of the equipment prior to use, so as to enable the operator to clean all types of equipment in a reproducible and effective manner. all types of equipment in a reproducible and effective manner.
If it is necessary to disassemble the equipment, it should also specify the order and method of disassembly of equipment; if it is necessary to disinfect or sterilize the equipment, it should also specify the specific method of disinfection or sterilization, the name of the disinfectant and the preparation method. If necessary, should also specify the equipment production to the end of the maximum permissible time interval before cleaning.
Article 85 The production equipment that has been cleaned shall be stored in clean and dry conditions.
Article 86 of the equipment and instruments used for the production or inspection of drugs, there should be a logbook, the record includes the use, cleaning, maintenance and repair, as well as the date, time, the production and inspection of the name of the drug, specifications and batch number.
Article 87 of the production equipment should have a clear state identification, labeled with the equipment number and contents (such as name, specifications, batch number); there is no content should be marked clean state.
Article 88 of the substandard equipment if possible should be moved out of the production and quality control area, before moving out, there should be a conspicuous status marking.
Article 89 The main fixed piping should be labeled with the name and flow direction of the contents.
Section V Calibration
Article 90 The production and inspection scales, gauges, meters, recording and control equipment and instruments shall be calibrated and inspected regularly in accordance with operating procedures and calibration plans, and relevant records shall be kept. The range of calibration shall cover the actual production and inspection of the scope of use.
Ninety-one shall ensure that key scales, gauges, meters, recording and control equipment and instruments used for production and inspection are calibrated, and the resulting data are accurate and reliable.
Article 92 should be calibrated using measurement standards, and the measurement standards should be used in accordance with relevant state regulations. Calibration records should be marked with the name of the measuring instruments used, number, calibration period and measurement of the certificate of conformity number, to ensure the traceability of the records.
Article 93 of the scales, gauges, meters, equipment used for recording and control, and instruments should be clearly marked, indicating the validity of its calibration.
Article 94 shall not be used without calibration, beyond the validity period of calibration, out of calibration of the scale, gauge, instrumentation, as well as equipment and instruments for recording and control.
Article 95 in the production, packaging, warehousing process using automatic or electronic equipment, should be in accordance with operating procedures for regular calibration and inspection to ensure that its operational function is normal. Calibration and inspection shall have the appropriate records.
Section VI Pharmaceutical Water
Article 96 The pharmaceutical water shall be suitable for its purpose, and in accordance with the "Chinese People's **** and the State Pharmacopoeia" of the quality standards and related requirements. Pharmaceutical water should be used at least drinking water.
Article 97 The design, installation, operation and maintenance of water treatment equipment and its delivery system shall ensure that pharmaceutical water meets the set quality standards. The operation of water treatment equipment shall not exceed its design capacity.
Article 98 of the purified water, water for injection tanks and piping materials used should be non-toxic, corrosion-resistant; tanks should be installed in the air vent does not shed fibers of the hydrophobic sterilizing filters; piping design and installation should be avoided, dead ends, blind tubes.
Article 99 of the purified water, water for injection preparation, storage and distribution should be able to prevent the growth of microorganisms. Purified water can be used cycle, water for injection can be used above 70 ℃ insulation cycle.
Article 100 The pharmaceutical water and raw water quality should be regularly monitored, and have the appropriate records.
Article 101 should be in accordance with operating procedures for purified water, water for injection pipeline cleaning and disinfection, and have the relevant records. Pharmaceutical water microbial contamination found to reach the alert limit, corrective limit should be handled in accordance with operating procedures.