For pharmaceutical enterprises, high-quality construction of purified air-conditioning system can improve the stability and reliability of system operation and reduce investment costs; while stable operation and scientific maintenance of purified air-conditioning system can reduce its operating costs and improve business performance.
Drugs will be affected by temperature, humidity, external environment, personnel and product pollution in the production process. At the same time, with the improvement of international and domestic drug production regulations and standards, purification air-conditioning system has attracted more and more attention of drug regulators. Based on the author's many years'experience in the operation and management of purified air conditioning system in pharmaceutical enterprises, this paper points out the problems existing in the engineering design, construction and operation and maintenance management of purified air conditioning system, and puts forward corresponding suggestions for improvement.
1. System Selection
Purification air conditioning system is the key equipment to ensure the environment of pharmaceutical production. In actual operation, the unreasonable division of air conditioning system in the early stage leads to the risk of cross-contamination in pharmaceutical production, the fluctuation of room temperature and humidity is great, the system regulation is difficult, the energy consumption is high, and the cost of transformation and maintenance is high, which results in that the pharmaceutical production environment can not meet the requirements of pharmaceutical production management regulations. Drug quality risk. Therefore, in the design of purified air conditioning system, we should fully consider the above situation, and reduce and avoid similar situations.
The basic basis and principles for the division of air conditioning and purification systems in pharmaceutical manufacturing enterprises are as follows:
To avoid the risk of cross-contamination, it is necessary to classify products according to their categories.
(2) According to the different pharmaceutical production environment (clean level), rooms with different clean level should be divided into different air conditioning systems for control.
(3) The air conditioning system is divided according to the baseline of indoor temperature and humidity (such as 18-26 C, 45-60%) and the accuracy (such as (+0.5 C, +5%).
(4) The air conditioning system is divided according to the space (room orientation, floor) location, which facilitates the layout and installation of air ducts and the later operation and management.
_According to the harmfulness of toxic and harmful substances and the concentration of dust, air conditioning system is divided to avoid cross-contamination and improve the life of medium and high efficiency filters.
_Air-conditioning system is divided according to the operation time of air-conditioning and the usage of air-conditioning shifts in order to benefit the economy of operation.
_Air-conditioning systems are divided according to the different air flow patterns (laminar flow and turbulent flow) in rooms.
_The humidity and heat load of the room varies greatly, and the room which needs strict control of temperature and humidity in the area should be divided into zones to set up a system, or set up a local processing device (reheating system, zoning unit system, etc.).
_In order to operate and maintain conveniently, large air volume air conditioning system should be divided into different small systems according to the actual situation. Generally, it is advisable to use less than 40 000 m3/h air volume.
_According to the requirements of fire prevention zoning, the zoning of air conditioning system should meet the requirements of fire prevention zoning of buildings.
2. Air Volume Selection
In addition to meeting the requirements of temperature and humidity of clean room and preventing air pollution, the air supply volume of clean air conditioning system also needs to replace and dilute the pollutants in indoor air, maintain the clean level of the environment and ensure the reasonable flow direction of air. In the actual operation of the air conditioning system, there is room air insufficient leading to poor cleanliness, room air excessive leading to increased energy consumption, resulting in the system debugging air volume balance difficulties, poor system stability in operation. Therefore, when selecting and purchasing the air-conditioning unit system, the air supply quantity of the air-conditioning fan should be reasonably considered; the change of air supply quantity should be monitored regularly during the normal operation of the system to prevent the reduction of air supply quantity from affecting the cleanliness of the clean room.
3. Key Points of Air Conditioning Fan Selection
1) The total air supply capacity of the fan should meet the requirements of the lowest air exchange frequency (volume flow replacement frequency of the room within 1 hour). Typical values of cleanliness level and engineering experience rule are usually used to estimate the total air supply volume: C NC level space of FD A and ISPE (EU D level dynamic standard), 6-20 times/h; ISO8 level (EU C level dynamic standard) space, 20-40 times/h; ISO7 level (EU B level dynamic standard) space, 40-60 times/h; ISO5 level (EU A level) space, for one-way space. As far as flow is concerned, the number of ventilation has nothing to do with it; the velocity and form of air flow are very important.
2) Consider comprehensively the minimum air volume required for the removal of humid and heat sources in a room.
Usually it includes the following situations:
(1) The amount of air needed to remove the increment of heat generated by room equipment and personnel activities;
(2) The amount of air required for the increment of humidity and heat generated by cleaning activities;
(3) Different air volume is needed because of different air supply modes and efficiency;
(4) Operators'clothes (clean clothes or isolation clothes) need different air volume;
(5) The different process flow and particle formation rate lead to the need for more air flow in power plant.
Different air volume is required for different exhaust modes and locations of rooms.
3) The air volume required to meet the required pressure difference is usually less than 1) and 2).

4) Choose fan direct connection mode as far as possible to reduce belt maintenance; Choose fan frequency converter to save energy and operate economically.

4. Common Conditions of Reducing Air Supply Volume and Treatment Methods
1) The wear and slippage of fan belt results in the reduction of fan output; the wear belt is replaced to tighten the belt tension.
2) Breakage and leakage of the soft connection between the air duct and the static pressure box; maintenance and replacement of the soft connection.
3) Air leakage at the interface of the air supply pipeline; glass glue seal or re-connect the sealing gasket at the air leakage.
4) Initial and intermediate-effect air filters are blocked and the air supply is insufficient; the pressure difference before and after the filters is monitored and the filters are replaced in time.
5) High efficiency filters are blocked and the air can't be delivered; the air volume and pressure difference of the tuyere are checked regularly, and the reasonable replacement period is determined according to the use situation.
6) The return air and exhaust filter of the system are blocked, the air pressure in the room is high, and the air can not go out; the filters are cleaned and replaced regularly.
7) Change of the position of the air supply valve in operation causes the valve to close and cannot supply air; after air volume adjustment, lock and fix the opening of the valve, affix the position marking and periodically inspect.
5. Pollutant Control
According to the different process and attributes of drugs, drugs need to be produced in different areas with different cleanliness levels. Relevant laws and regulations on drug production management at home and abroad, as well as the quality management documents of drug production promulgated by them, specify the number of air suspended particles in the pharmaceutical production environment.
The factors affecting cleanliness of clean rooms are composed of two parts: exogenous pollutants and endogenous pollutants. Exogenous pollutants include the introduction of air supply into the clean room and the immersion of pollutants in the envelope of the clean room. Endogenous pollutants include dust production by workers, dust production in equipment and product production process. Controlling dust particle pollution is an important function of purifying air conditioning system to ensure the purity, homogeneity and quality of drugs. The inadequate maintenance and management of air-conditioning system will lead to production stoppage and drug scrap from time to time, which should be paid enough attention by air-conditioning system maintenance and management personnel.
The control measures of pollutants in clean rooms are as follows:
The primary and intermediate filters of air conditioning should be cleaned or replaced regularly, and the chassis or air supply pipes should be cleaned regularly.
(2) Regular leakage detection of high efficiency filters, timely replacement of air volume reduction or damage.
(3) Clean room doors and windows, walls, floors, roof crevices should be sealed, access to the clean room pipeline connection sealed, to prevent exogenous sources of pollution into the clean room.
(4) Clean room personnel wear suitable dust-free work clothes, standardize operation and reduce unnecessary actions.
_Reduce the dust production of indoor materials, select the production process and equipment in closed mode.
Materials and articles entering the clean room should be cleaned, materials that do not easily produce dust should be used, and unnecessary moving routes should be reduced.
_Clean all kinds of equipment and facilities in clean rooms regularly to prevent the generation and retention of pollutants.
6. Differential Pressure Control
The pressure difference of clean room is to maintain a certain static pressure difference between rooms of different cleanliness levels or between rooms of different cleanliness levels at the same level. Its purpose is to protect the cleanliness of clean room from contamination of adjacent rooms when normal work or air balance is temporarily destroyed. It is also clearly stipulated in domestic and foreign drug production regulations. Control is a very important link in the purification air-conditioning system.
In the operation of purifying air conditioning system in pharmaceutical enterprises, there are often situations such as high or low pressure difference, large fluctuation, and even reverse air flow in the clean room, which bring about the quality risk of pharmaceutical production.
According to many years'experience, the main influencing factors of pressure difference in clean room are inadequate management and maintenance, unreasonable system design, insufficient investment, resulting in poor stability of pressure difference in clean air conditioning system, which requires frequent adjustment of fan parameters, as well as supply, return and exhaust valves.
The factors affecting the pressure difference in the clean room and the corresponding measures are as follows:
1) The change of resistance of air filter in purified air-conditioning system causes the change of air supply volume, which results in the change of indoor pressure difference. The primary, middle and high efficiency filters can be replaced regularly, or the variable frequency air supply fan can be used to control the speed of the fan by the difference between the actual air supply volume and the set air supply volume, so as to ensure the constant air supply volume.
2) The opening and closing of the clean room door will cause fluctuation of the pressure difference in the clean room. Reduce the number of opening and closing doors and close them at will; Buffer chamber or air lock room can be set; Residual pressure valve can be installed to change the opening of residual pressure valve by balancing pressure block, so as to realize the control of pressure difference in clean room.
3) Through the differential pressure transmitter to detect the indoor pressure, and control the opening of the air supply or return valve, to achieve the control of the pressure difference in the clean room.
4) Excessive air leakage in the windows and doors of the room results in too low pressure difference. It can regularly repair the enclosure structure and the sealing strip of the door to ensure good air tightness.
7. Temperature and relative humidity control
In the clean room, if the temperature is too low, it is not easy to work normally; and if the temperature is too high, perspiration will increase the pollution of the clean room; while for materials sensitive to temperature and relative humidity, temperature and relative humidity need to be strictly controlled, otherwise the product quality can not be guaranteed. Therefore, it is an important capability of air conditioning system to ensure that the temperature and relative humidity of clean room meet the technological requirements. Usually there are many factors that cause the air temperature and relative humidity of clean room not to meet the requirements. We should take different measures to deal with them.
1) There are many and large heating equipments in some pharmaceutical factories. If only the number of ventilation is determined, the temperature in the clean room will often exceed the standard. For example, through the fan filter unit (FFU) to achieve A level of purification area, it is necessary to configure air conditioning units alone or use secondary cooling (heating) mode of air supply branch pipe to control room temperature.
2) There are problems in the design, installation and commissioning of refrigerated water pipeline, which results in uneven flow distribution of refrigerated water and difficulty in temperature and humidity control of air-conditioning units when multiple air-conditioning units are used in parallel. Therefore, pipeline modification or water balance commissioning should be carried out.
3) The equipment maintenance is not in place, which leads to the temperature and relative humidity exceeding the range when the air-conditioning system is running. For example, surface cooler scaling and fin dust accumulation lead to low heat transfer efficiency, pipeline blockage lead to insufficient water flow, excessive temperature of chilled water supply, insufficient pressure of steam supply, poor water drainage of steam condensate, etc., maintenance management and implementation should be strengthened.
8. Design of Purification Air Conditioning Unit
Purification air-conditioning unit is a kind of equipment which can realize refrigeration, heating, dehumidification, humidification and purification through air purification and heat and humidity treatment. The improper design and selection of the unit will cause great trouble to the use of purification air-conditioning system. In the selection and confirmation of air conditioning units, attention should be paid to the possible problems, so as to reduce the troubles of later commissioning and operation.
1) insufficient maintenance space. For example, the distance between the two sides of the surface cooler and the heater is insufficient, so the maintenance of the heat exchanger needs to remove the box and related components to maintain.
2) The function interval is insufficient and no other remedial measures are taken, such as the short distance between the air supply section and the effective filter section of the fan, and the absence of a flow equalizer, which results in the extremely uneven air filtration speed of the whole section of the intermediate filter at the outlet of the fan, affects the filtering effect and shortens the service life of the filter.
3) The large wind speed on the windward side of the box results in the drifting of the condensate plate behind the surface cooling section. If the design of the baffle is unreasonable, the problem will be more serious. Therefore, the wind speed on the windward side of the surface cooler should be controlled at 2-2.5m/s as far as possible.
4) The overall sealing performance of the unit is poor. If the power cable of the air conditioning unit passes through the chassis, the sealing at the connection with the chassis plate is not strict, or even no treatment is done. Therefore, strict quality control is required in unit acceptance. Normally, the standard requirement of "Combined Air Conditioning Unit" [4] is that when the static pressure of the purified air conditioning box is 1000Pa, the air leakage rate in the box shall not exceed 2%.
5) The design of condensate water system is unreasonable, and the condensate water can not be stored in the water storage bend or discharged from the box, which not only affects the inner surface of the air conditioning unit, but also affects the life of the filter, as well as the heat and humidity treatment. Usually, the height of condensate plate is 50% higher than the negative static pressure (water column height) of the unit, and the gradient of condensate pipe is more than 0. 3%, the height of water storage bend water seal is 2 times of the maximum negative static pressure of the unit, and the total height of water storage bend is 4 times of the maximum negative static pressure of the unit.
6) The design of the drainage outlet of the surface cooler is unreasonable and the water stored cannot be discharged cleanly, which causes the surface cooler to freeze and crack, and makes it difficult to maintain and replace. It is suggested that when using air conditioning units in the north, after stopping the use of chilled water, disconnect the inlet and outlet pipes of chilled water and use compressed air to clean the surface cooler for water storage; if there is still some chilled water, appropriate amount of ethylene glycol solution can be filled in the surface cooler to prevent freezing.

9. Energy-saving operation management
In pharmaceutical manufacturing enterprises, the energy consumption of air-conditioning system is about 20%-30% of the total energy consumption of the whole enterprise, which shows that energy saving of air-conditioning is a very important work. Because the daily management and maintenance of air-conditioning is not in place, there are many hidden waste phenomena of air-conditioning energy. From the perspective of improving business performance, it is of great practical significance to realize energy-saving operation of air-conditioning. The energy consumption of HVAC system mainly depends on the determination of the cooling and heat load of air conditioning system and the reasonable operation parameters of air conditioning system. Through good operation and maintenance management, the energy consumption of purified air conditioning system can be reduced completely.
1) Because the air supply volume and pressure loss of air conditioning fans change with the increase of resistance of primary, middle and high efficiency filters, in order to maintain the cleanliness of the room, fresh air, supply air and return air need to be consistent. Therefore, frequency conversion fans are installed in the air conditioning system, which can be purified by changing the frequency of the fans and constant air volume and variable air pressure. At the same time, it can meet the requirements of energy saving.
2) Pressure test, cleaning and descaling of air conditioning system should be carried out before operation every year to prevent heat transfer efficiency from decreasing and increase operation cost.
3) Regular replacement of primary and intermediate filters in air conditioning system to reduce the waste of fan power.
4) Increase the use of outdoor fresh air in transitional season to regulate indoor temperature and humidity.
5) On the premise of meeting the requirements of temperature and humidity in clean areas, the temperature and humidity control values should be increased (in summer) or decreased (in winter).
10. Conclusion
Purification air conditioning system is a key system in pharmaceutical production. Through the analysis of the exposed problems in the system selection, air volume selection, pollutant control, pressure difference control, temperature and relative humidity control, and the structure of the purification air conditioning unit, the paper puts forward some suggestions on the design, type selection, construction and operation management of the purification air conditioning system, so as to achieve the goal. Purification air-conditioning system runs stably and reliably, reduces the system investment cost and operation cost, and improves the business performance of enterprises.
Author: Liu Xuejun, Power Equipment Department of Huarun Zizhu Pharmaceutical Co., Ltd.