General requirements: direct oral consumption of Chinese medicine tablets of crushing, sieving, packaging and other production plant should meet the requirements of 300,000 clean area. Specific requirements:
First, the management of clean plants and facilities: reference to the GMP inspection guidelines for Chinese medicine: 1101; 1102; 1103; 1301; 1401; 1501; 1502; 1503; 1504; 1601; 1602; 1701; 1801; 1903; 2402; 2701; 2802.
General requirements: direct oral consumption of Chinese medicine tablets, crushing, sieving, packaging and other production plants should meet the requirements of 300,000 clean area. > 1101 The inner surface of the clean room (area) is flat and smooth, free of cracks, with tight interfaces, free of particulate matter shedding, and resistant to cleaning and disinfection.
1. Check the clean room (area) construction acceptance documents, the material material is in line with the provisions.
2. Check the site, the clean room (area) is in line with the provisions.
1102 clean room (area) of the junction of the wall and the ground is curved or take other measures.
Check whether the junction of the clean room walls and the ground arc. If not curved, there should be appropriate measures.
Check the cleaning procedures, cleaning records, site cleaning.
1103 clean room (area) whether the use of non-shedding, easy to clean, easy to disinfect cleaning tools, its storage location is not easy to product contamination. Different clean room (area) cleaning tools are used across the region.
1. Check whether there are relevant documents and records, such as cleaning, disinfection requirements, use, storage and other management regulations.
2. Check the site; hygiene tools and storage is easy to product contamination.
1301 clean room (area) in a variety of pipes, lamps, air and other utilities are easy to clean.
Check the clean area piping, lamps, air intake and other public **** facilities are easy to clean, the site check whether clean.
1401 clean room (area) of the illumination and production requirements are compatible, whether the plant has emergency lighting facilities.
1. Check the completion of the clean area acceptance documents, the main studio of the illumination is 300 lux, the illumination of special requirements of the production process, whether to increase the local lighting or explosion-proof facilities.
2. Check whether the plant has sufficient emergency lighting facilities.
x1501 clean room (area) of the air is purified according to regulations.
1. According to the production requirements, check whether the corresponding clean room (area) has a cleanliness test report, test report data to meet the requirements.
2. Check the operation of the purification equipment on site, including differential pressure, temperature and humidity table shows whether the data meets the requirements.
3. Check the schematic diagram of the air supply, return and exhaust ducts if necessary.
1502 clean room (area) of the air is monitored according to regulations, air monitoring results are recorded and archived.
1. Check whether the enterprise clean room air monitoring cycle.
2. Whether according to the validation results in accordance with the specified period of monitoring, and record.
3. Monitoring results and records are archived.
1503 clean room (area) purified air circulation, whether to take effective measures to avoid contamination and cross-contamination.
1. Check whether the clean room is positive pressure.
2. Whether the return air is filtered and treated.
1504 air purification system is in accordance with the provisions of cleaning, repair, maintenance and record.
1. Check whether the enterprise according to the differential pressure record of the air purification system, the provisions of the primary and intermediate filters cleaning and high-efficiency filter replacement cycle.
2. Check whether the development of air purification system cleaning, disinfection and sterilization, repair and maintenance documents.
3. Check the records and whether they are performed as specified.
x1601 clean room (area) windows, canopy and into the indoor pipeline, air outlet, lamps and lanterns and walls or canopy connection parts are sealed.
1. Check the clean room (area) of the connection part of the sealing measures and whether the measures are effective.
2. Whether to carry out daily inspection and record.
1602 different clean levels of neighboring areas / rooms between whether there is an indication of the pressure difference between the device, static pressure difference is in line with the specified requirements.
1. Check the air cleanliness level of different neighboring rooms whether there is a device to indicate the differential pressure, indicating the static pressure difference is greater than 5Pa, clean room (area) and the outdoor atmosphere of the static pressure difference is greater than 10Pa.
2. Differential pressure indication device location is reasonable.
3. Differential pressure indicating device range accuracy meets the requirements.
1603 non-traumatic surface external Chinese medicine preparations and its special preparations of the production plant, whether the doors and windows can be airtight, if necessary, there are good dehumidification, exhaust, dust, cooling and other facilities.
1. Check whether the doors and windows of the production plant can be sealed.
2. Whether there are dehumidification, dust removal, cooling and other appropriate facilities.
1701 clean room (area) of the temperature and relative humidity in line with the requirements of the pharmaceutical production process.
1. Check the clean room (area) whether there is a temperature and humidity meter and records, whether the temperature is in the range of 18-26 ℃, the relative humidity is in the range of 45% ~ 65%.
2. Check whether the temperature and humidity of the Chinese medicine preparation plant with special temperature and humidity requirements meet the requirements of the production process.
x1801 clean room (area) of the pool, floor drains whether the drug contamination, aseptic operation of the 100-level clean room (area) whether the pool and floor drains.
1. Check the clean room floor drain material is not easy to corrode, whether the inner surface is smooth, not easy to scale; floor drain surface whether to add a sealing cover (generally stainless steel), and open convenient, whether to prevent wastewater, exhaust gas back up liquid sealing device.
2. Clean room and back to the water piping connected to the equipment, sanitary appliances and drainage equipment below the outlet part of the water seal device.
3. Aseptic operation of the 100 clean room (area) is set up in the pool, floor drain.
*1903 clean room (area) and non-clean room (area) is set up between the buffer facilities, clean room (area), human flow, logistics direction is reasonable.
1. Check the clean room (area) and non-clean room (area) is equipped with buffer facilities.
2. Clean room (area) people, logistics outlets are separated, whether the direction is reasonable.
2402 large amount of dust production clean room (area) by the dust trapping process is difficult to avoid cross-contamination, its air purification system is the use of return air. Non-sterile drug air cleanliness level of the same area, dust production of large operating room whether to maintain a relatively negative pressure.
1. Check the air purification system map, non-sterile drugs produce a large amount of dust clean room (area) by the dust capture can not avoid cross contamination, its air purification system is the use of return air.
2. Check the differential pressure indicator device, dust production of large operating room whether to maintain a relatively negative pressure.
3. Check whether the dust capture facility has an effective device to prevent air backflow.
2701 clean room (area) in the weighing room or preparation room clean level with the production requirements, whether the dust capture facilities, measures to prevent cross contamination.
1. Check the clean room (area) within the weighing room or preparation room clean level is consistent with the production requirements.
2. Whether there is a dust capture facilities, whether there is a device to prevent the backflow of outdoor air.
2802 biological assay, microbial limit checks are conducted in separate rooms,
Aseptic assay, microbial limit checks, microbial limit checks of the positive control, etc. are conducted in separate rooms.
Second, the management of locker rooms and work clothes: refer to the GMP inspection guidelines for Chinese pharmaceutical preparations:5101;5201;5203.
5101 Locker rooms, bathrooms and toilets are set up whether or not they have an adverse effect on the clean room (area).
Inspection site:
1. Changing rooms, bathrooms and toilets are appropriately located, whether the facilities are complete.
2. Whether the sanitary facilities have an adverse effect on the clean area.
5201 workwear selection and production operations and air cleanliness level requirements are consistent, and shall not be mixed. Whether the texture of the clean work clothes is smooth, does not produce static electricity, does not shed fibers and particles.
1. Check the documents.
1.1 different production operations and cleanliness level of the selection of workwear material is appropriate.
1.2 different clean areas of the work clothes are clearly differentiated, whether or not mixed.
2, check the scene: check the record of work clothes issued, whether or not a person to keep.
5203 Different air cleanliness levels used in the work clothes are cleaned, organized, disinfected or sterilized if necessary, whether to develop cleaning procedures.
Third, plant, equipment, container cleaning procedures, refer to the GMP inspection guidelines for Chinese pharmaceutical preparations: 4901; 4902; 4903.
4901 Whether according to the production requirements and air cleanliness level to develop plant cleaning procedures, the content of whether or not include; cleaning methods, procedures, intervals,
the use of detergents or disinfectants, cleaning tools and storage location. Cleaning methods and storage locations.
4902 Whether to make equipment cleaning procedures according to production requirements and air cleanliness levels, including: cleaning methods, procedures, intervals, the use of detergents or disinfectants, cleaning methods and storage location of cleaning tools.
4903 Whether the production requirements and air cleanliness level to develop cleaning procedures, including: cleaning methods, procedures, intervals, the use of detergents or disinfectants, cleaning methods and storage location of cleaning tools.
Check the documents:
1. Whether to develop plant, equipment, container cleaning procedures. The.
2. Whether the content meets the requirements.
3. Whether the project is specific, operable, including: cleaning scope, cleaning implementation conditions and procedures, cleaning equipment, facilities or appliances used, cleaning agents or disinfectants allowed to use and preparation methods, cleaning, disinfection frequency and methods, cleaning effect evaluation, cleaner, checker and so on.
Fourth, enter the clean room personnel management, with reference to the Chinese pharmaceutical GMP inspection guidelines: 5301; 5302; 5401; 5501.
5301 clean room (area) is limited to the region's production operators and approved personnel to enter, the number of personnel is strictly controlled, whether the temporary outsiders are guided and supervised.
1. Check the documents.
1.1 different cleanliness levels of the clean room (area) the number of operators and entry and exit procedures are clearly defined.
1.2 to enter the different clean levels of clean room (area) of foreign personnel (service, maintenance, inspection and guidance) whether there are provisions for approval, records, supervision and guidance.
2. On-site inspection.
2.1 Check whether the number of operators in accordance with the provisions.
2.2 Check whether the entry and exit records of foreign personnel and approval procedures are complete.
2.3 Supervision and guidance of outsiders is provided.
5302 into the clean area of the staff (including maintenance, auxiliary personnel) whether regular health and microbiological basics, clean operations and other aspects of training and assessment.
1. Whether to formulate the provisions of regular health education for the personnel.
2. Check whether the enterprise has a health training program, teaching materials.
3. Check the training, assessment records and training files.
V. Clean room disinfection management, with reference to the Chinese pharmaceutical preparations GMP inspection guide: 5501.
5501 clean room (area) is regularly disinfected, disinfectant is not on the equipment, materials and finished products to produce contamination, disinfectant varieties are regularly replaced to prevent the production of drug-resistant strains of bacteria.
1. Check the documents.
1.1 clean room (area) disinfection management procedures clearly stipulate the regular disinfection time, whether based on the validation results of the disinfection cycle.
1.2 disinfectant selection of equipment, materials and finished products whether the pollution.
1.3 whether there is a disinfectant varieties of regular replacement provisions.
Six, water cleaning: refer to the Chinese pharmaceutical preparations GMP inspection guide:3401.
3401 purified water preparation, storage and distribution of measures to prevent microbial growth and contamination.
1. Check documentation.
1.1 The process flow diagram of purified water and water supply pipe network diagram.
1.2 purified water standard operating procedures, process control procedures, including sampling and records.
1.3 drinking water, purified water internal control standards.
1.4 purified water source is in line with drinking water standards.
2. Check the site.
2.1 whether the preparation of purified water meets the requirements.
2.2 whether the storage of purified water meets the requirements.
2.2.1 storage tank is sealed, whether the inner surface is smooth, the top should be installed to clean the spray device.
2.2.2 storage tanks have a vent pipe, whether the vent is installed with a hydrophobic filter.
2.3 purified water distribution to meet the requirements.
2.3.1 distribution system piping and related components are kept inclined and have a discharge point so that the system is completely emptied when necessary.
2.3.2 Whether the design of the distribution system takes into account the location of the installation of each sampling valve.
2.3.3 Whether the distribution system for water circulation avoids low flow rates, and whether the length of the branch pipe is less than six times its diameter.
2.3.4 storage and distribution of the preferred method of circulation.