Business Line (Mr. Zeng)
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2019-02-15 15:22:50 Editor： jushong shares 0
With the implementation of the new version of GMP, pharmaceutical manufacturers have begun a new round of workshop renovation and upgrading. The quality of medicines is directly related to personal health. Therefore, it is necessary not only to control the number of bacteria and dust particles in the drug workshop, but also to prevent pollution, mixed drugs and mistakes in the production process. The key points to be aware of in the clean room design and clean room management of the pharmaceutical industry are particularly important!
(Good Manufacturing Practice) (G o o d M a n u f a e t u r i n g Practice abbreviated as G M P ) is an internationally recognized and widely adopted standard for the management of pharmaceutical production quality in the pharmaceutical industry. Before June 30, 2004, all pharmaceutical preparations and APIs in the country must meet the G M P requirements and obtain the G M P certificate.
1.1 Plant design
The design of the clean workshop is a highly technical work. The cleanliness of the air in the clean room of the pharmaceutical industry is divided into four grades, as shown in Table 1.
The design of the plant must be designed in accordance with the G M P and other regulations, from the overall layout of the pharmaceutical factory, the partition distribution, the internal process flow, and the air purification level. Emphasis is placed on measures to prevent contamination, mixed drugs and errors in the production of pharmaceuticals.
The pharmaceutical factory should choose areas with good atmospheric conditions, less air pollution, and no soil pollution. The water source should be sufficient and clean, and the quality of the pure water or water for injection can be guaranteed to meet the standards stipulated by the Pharmacopoeia, and the power supply is sufficient, the communication is convenient, and the traffic is convenient. Convenient transportation. The plant area is divided according to production, administration, living and auxiliary areas. The production area is strictly separated from the living area, and the administrative area must be separated from the production area by a certain distance.
The layout of the workshop should meet the requirements of the production process. The flow of chemicals, raw materials, raw materials, raw materials, and packaging should be separated. There must be sufficient space and space to arrange and store materials neatly and reasonably. Raw materials and materials in the human control area, cleaning rooms and intermediates, semi-finished products storage room. Drugs that are confusing or cross-contaminated in different formulations may not be operated or stored in the same room at the same time. The general production area is a non-clean area, and the control area refers to an area below 100,000. The cleanliness of the clean area is 10,000 or 100. The clean room should be equipped with sanitary passages and living facilities that are compatible with the cleanliness level. The doors with different cleanliness levels should be closed and leveled, and the doors should be opened in a high level.
According to the production process of different products, the room separation and process layout of the clean workshop should strictly comply with the G M P requirements to ensure the cleanliness requirements of the production workshop.
1.2 Purification air conditioning system design
The air-conditioning system should be combined with the process layout, and the system should be divided according to indoor temperature, humidity and cleanliness. Some products should be strictly separated at different stages, such as blood preparations. Before and after inactivation, the flow of people and logistics should be separated, and the air-conditioning system should be independent; A system can not be used in the production of different products of blood preparations. The cleanliness level 10, 1 0 0 0 level area generally controls the temperature between 18 and 25 degrees, and the relative humidity is between 45% and 60%. When the production process has special requirements on temperature and humidity, it should be determined according to the process requirements.
The clean room is mainly controlled by living particles, bacteria and viruses. The dust particle attached to it is generally 0.5 to 5 μm. Therefore, the clean room uses a sub-high efficiency filter as the end filter. The purification system is to send the air sent to the room as follows: Fresh air ~ coarse filter "mixed with return air ~ table cold one heating ~ humidification ~ fan one silencer one medium effect filter ~ high efficiency filter, according to the clean level Different, the air supply should reach the corresponding number of air changes, the number of air changes in level 10 should reach vertical laminar flow of 0.3 m/s, horizontal laminar flow o, 4 m/s, and 1 0 0 0 0 2 0 times / h, 10 0 0 0 0 class air exchange times 1 5 times / h. In actual design, generally 10 0 level air change times are 300 to 4 00 times / h, 10 0 0 0 level is 5 0 - 8 0 times / h, 10 0 0 0 0 level is 2 0 - 50 times / h. When designing system air volume wind pressure, the minimum air exchange times under the final resistance of the system should be met, and the inverter fan can be used.
The arrangement of the air-conditioning purification machine room is easy to close to the clean area, so that the ventilation route is the shortest. The surface decoration of the air supply duct, the return air duct and the return air duct should be compatible with the entire air supply and return air system, and it is easy to remove dust. To clean the new air duct and return air main pipe of the air conditioning system, a closed regulating valve is required. For the suction of the blower and the need to adjust the air volume, a regulating valve is required. For the exhaust system, a regulating valve, a check valve or a closed valve is required. The total duct must pass through the floor and the duct through the firewall, and a fire damper must be provided. Pressure taps are required before and after the intermediate and efficient air filter. The air conditioning system should be cleaned regularly. The air filter resistance should be checked frequently. The coarse and medium efficiency filters should be cleaned and replaced frequently to prevent cross-contamination. Cleaning the air-conditioning system should pay attention to:
Unless the various polluting air streams are filtered and meet the requirements, different polluted air streams cannot be mixed together;
2. For workshops producing highly toxic, strong allergenicity, high bioactivity or dust particles, a separate air-conditioning system should be set up. 3. If the return air is filtered or adsorbed, cross-contamination cannot be avoided. The system should be designed to be DC;
Fourth, the clean room airflow should be designed as follows to send the lower side return air mode, and ensure the indoor airflow direction and uniform airflow. When there is a laminar flow hood in the room, its position should be as far as possible from the return air outlet. The process with high cleanliness should be placed on the upwind side of the room, and the equipment that is likely to cause pollution should be close to the return air outlet. The clean room should strictly control the positive and negative pressure. The static pressure difference between clean areas with different air cleanliness and between clean and non-clean areas should not be less than 5 P a , and the static pressure difference between clean area and outdoor should not be less than 10 P a . A differential pressure gauge should be installed in the clean room between the different levels to monitor the positive pressure in the room. The noise level in the clean room should not exceed 75 d oB during dynamic testing and the noise control design must not affect the clean room conditions.
Clean technology plays an important role in the pharmaceutical industry. However, if there is no scientific management, the clean room will not achieve the expected results, and even cause the installation and damage of facilities and equipment. Personnel entering the clean area should wear appropriate clean clothes according to different cleanliness levels, with the principle of not dusting, non-shedding fibers, and covering all hair. The clean area should be disinfected regularly, installed with UV lamp, UV sterilization for surface sterilization, clean room still requires gas sterilization, commonly used 40% formaldehyde fumigation, or ozone generator disinfection, etc. Use alternately every 3 months.
According to reports, most of the accidents in the quality of various drugs are caused by human error, not the cause of the process. Therefore, the design of the clean room is only the first step in implementing the G M P requirements, and management is the top priority. No matter how reasonable the engineering design is, if there is a lack of scientific and strict management, the management and operators cannot abide by the standard operating procedures (SO)P. Even if it is a perfect design, it cannot fully play the role of clean technology. Guarantee the quality of medicines. Grasping management is to manage the personnel. Only the pharmaceutical manufacturers can voluntarily follow the S O P from top to bottom, and the quality of the drugs can be guaranteed.