In pharmaceutical plants, compressed air is mainly used in filling machines for liquid formulations, pelletizers in solid formulations, blenders, filling machines, packaging machines, printing machines and extraction tanks for extraction processes. In addition, compressed air Test gas can be used in the experiment, material handling, drying, purging, pneumatic instruments, automatic control of gas. There are two kinds of commonly used compressed air, one is a general oil-lubricated compressed air system for the instrument's pneumatic components, not in direct contact with the drug and the other oil-free compressed air system and direct contact with drugs. As the quality of the compressed air directly contacted with the drug production directly affects the quality of the product, the most commonly used by the drug manufacturers is the oil-free compressed air system. In order to ensure the quality of compressed air, compressed air to take strict purification measures is particularly important. At the same time compressed air system to be verified to prove that the system meets production requirements and passed the GMP certification inspection.
1 Compressed air 1.1 Definition Compressed air, compressed by external forces. Compressibility of the air by the air compressor to make their own mechanical work volume reduction, the pressure increased after the air is called compressed air.
1.2 Principle Air occupies a certain space, but it does not have a fixed shape and size. When pressure is applied to the air in a closed container, the volume of air is compressed and the internal pressure is increased. When the force is withdrawn, the air will return to the original volume under the effect of internal pressure. If there is a movable object in the container, the object will be pushed out by the pressure of the air in the container when the air returns to its original volume.
1.3 Features The role of compressed air is an important source of power. Compared with other energy sources, it has the following clear features: Transparent and easy to transport No special harmful properties No fire risk, not afraid of overload, can work in many adverse environments Air everywhere on the ground are inexhaustible.
Compressed air is widely used in production and daily life. For example: the ball into the compressed air, the more gas the more hard football; tire into the compressed air tires can withstand a certain weight; in large cars, with compressed air switch car □ and brake hydraulic press using compressed air to pressurize the water ; In the factory, the compressed air is used to start the gas hammer in KTR station, it can start hoisting drilling; used for pipeline liquid and granular objects. Atmospheric atmospheric pressure is 0.1MPa after compressing the air compressor to achieve the desired pressure.
Compressed air is the second largest power source next to electricity and a source of process gas with various uses. Its application range covers petroleum, chemical industry, metallurgy, electric power, machinery, light industry, textile, automobile manufacturing, electronics, food , Medicine, biochemistry, national defense, scientific research and other industries and departments.
2 Compressed air for medical use 2.1 Gas source requirements for pharmaceutical production Generally speaking, the quality level of gas source used for drug production should meet the requirements of 2001 (1) and the general requirements for compressed air quality standard (GB / T132771991), that is dew point ~ 40C solid particles Diameter 0.1xm, oil content 0.1mg / m3 Compressed air quality standards and quality level stage, this stage contains three precision filters and a refrigeration dryer.
Table 1 shows the requirements. 3.1 The demand for compressed air Table 1 Compressed air quality standards and quality levels prescribed amount of air depends on the consumer of air. Grading Pressure Dew point (degree of wet / dry) / c Residual dust content (mg / m3) Residual oil content (mg / m3) (achieved by the dryer) (achieved by the filter) (achieved by the filter ) Class 1 -700.1 (corresponding to a particle size of 0.1 m) 0.13 -2050 (corresponding to a particle size of 5 is calculated by adding all the equipment and processes such as connected air consumption, etc. In addition, leakage, wear and future use Gas plus must also be taken into account. Test the current air demand is to connect all the air consumption of equipment together. The supply of compressed air to meet the current conditions of use on the basis of the same time to expand the regulation of 2.2 compressed air mixed Moderate margin due to the influence of foreign matter is considered in the device Compressed air is mixed with foreign matters such as lubricating oil, water vapor and dust, which may easily cause adverse effects as follows: Oil vapor mixed in compressed air accumulates to a certain extent It will form a source of flammable and explosive, while the lubricant will form an organic acid vaporized, easy to corrode the compressed air pipeline inner surface and pneumatic components.
Mixed with small particles (such as dust, rust, etc.) easily damaged Pneumatic components blocked the throttle even more serious is the material can cause serious pollution.
The moisture mixed in the compressed air will be saturated with water droplets under a certain temperature and pressure. When the compressed air is in contact with the material, the quality of the material will be greatly affected.
Compressed air temperature can also cause air pressure system seals, hose materials, such as membrane aging.
Therefore, when compressed air is transported to the point of use, it must be subjected to the requirements of GMP such as cooling, degreasing, water removal and solid particle removal.
3 Pharmaceutical compressed air purification system Compressed air purification system can also be said that the process of air pressure post-processing system as shown in Figure 1. Compressed air from the compressor out through a simple process into the compressed air tank, after the buffer began to enter the compressed air after-treatment compressed air purification system processes. 2 compressor compressor The entire process by the intake system, the host, the gas supply system, oil and gas separation system.
Intake system air through the filter through the butterfly valve to the compressor host suction port this process for the intake process. Intake system mainly consists of filters and butterfly valves.
3.2. Oil and gas separation system After entering the separator mixed gas separation, the compressed air supply users.
3.3 Oil-water separator Oil-water separator, used to separate condensed water in the compressed air and oil and other impurities, the compressed air to be initially purified. Oil-water separator works: When the compressed air into the oil-water separator resulting in rapid changes in the flow and speed and then rely on the role of inertia; the density of compressed air than large droplets and water droplets isolated. After the compressed air enters the separator body from the inlet, the airflow is blocked by the baffle to be folded backwards and then upward to generate a circular revolution. This allows water droplets and oil droplets in the centrifugal force and inertial force separated from the air and precipitated in the bottom of the body, regularly open the bottom of the valve □ can discharge oil droplets, water droplets. After the initial purification of air from the outlet to the gas tank.
C-class centrifugal oil and water separator filtration accuracy of 3xm, water removal rate> 99%, except for the oil mist rate of 40%, mainly used as a rear cooler separator and the dryer pre-dryer filter.
3.4 Freeze-Dryer Freeze-Dryer Working Principle: After the moist and high temperature compressed air flows into the pre-cooler, it flows into the heat exchanger and exchanges heat with the cold air discharged from the evaporator so that the compressed air entering the evaporator Lower temperature.
After the heat exchanger, the compressed air flows into the evaporator and exchanges heat with the refrigerant through the heat exchanger of the evaporator. The heat in the compressed air is taken away by the refrigerant. The compressed air rapidly cools and the moisture in the humid air reaches the saturation temperature. Water condensation by the formation of water droplets through a unique gas-water separator rotating ice at high speed due to the role of centrifugal force and air separation, separation of water drained from the automatic drainage valve. After cooling the air pressure dew point of the lowest up to 2C. After cooling the cold air flow through the air heat exchange with the entrance of high temperature damp hot air heat exchange by the cold air due to the absorption of the inlet air heat to enhance the temperature, At the same time, the compressed air is heat-exchanged again with the high-temperature refrigerant through the secondary condenser of the refrigeration system, so that the outlet temperature is fully heated to ensure that the outlet air line does not dew.
At the same time make full use of the export of cold air to ensure that the refrigeration system to ensure the quality of the outlet air quality of the condensate.
3.5 Main Line Filter The T-Air Line Filter filters out as little as 1 xm of liquid and solid particles to a minimum residual oil content of only 5x10-7 with traces of moisture, dust and oil mist. For adsorption dryer rear A-class filter before the pre-treatment for further improve air quality.
3.6 Oil mist filter A-class ultra-efficient oil filter can filter out as little as 0.01 xm of liquid and solid particles, reaching a minimum residual oil content of only 10+, almost all of the water, dust and oil are removed. After used in a dryer, it ensures that there is no oil in the air.
3.7 Air Terminal Sterilization Precision Filter Air precision filter as a high-precision end-end filter, its role is to ensure that filtered air to achieve sterile requirements. Air end sterilization bacteria filter material for the PTFE membrane and PTFE membrane, with strong hydrophobic, high filtration accuracy (filtration precision 001ixm, in addition to the oil mist rate of 99.9999%), low pressure drop, high temperature , Long life and other characteristics, is to filter out bacteria and bacteriophages in the air ideal and reliable filtration equipment.
3.8 Compressed air storage and transportation For the filtration and purification of compressed air storage and transportation, the compressed air tank to reduce the flow pulsation and storage of compressed air, compressed air can compensate for varying degrees of instantaneous consumption to avoid Frequent fluctuations and start-up of compressed air, with the role of water removal, sewage, etc., between the compressor and drying equipment, purification equipment and network equipment should be set between the gas tank.
Conveyor pipe in the specific use should meet the national standard Compressed Air Station Design Code (GB50029-2003) in the pipeline requirements For the smaller water vapor content of the pipeline cut-off valve □ should adopt a stainless steel valve for the compressor, gas tank , Freeze dryer, gas distributor must be stainless steel pipe: For dry and decontamination pipes less than 1ixm dust, stainless steel pipes are used to ensure the quality of the compressed and dried compressed air. The compressed air system in the pharmaceutical industry is generally made of 316L stainless steel sanitary pipes. 3.9 Compressed air pipe sterilization Pure steam generator pipe and compressed air pipe connection. Close (except compressed air furthest point of use) Each compressed air Use a point valve □ to open the compressed air fugacity valve □ Start the pure steam generator to open the pure steam valve □ Pass the pipe to the compressed air system Steam disinfection 30min. Disinfection 30min, open the use of each point valve empty blowing 30min. 4 purified compressed air validation 4.1 Installation Confirmation Installation confirmation is to check and confirm the installation of the device meets the design requirements, equipment information and documents meet GMP management requirements.
4.1.1Power supply 380 ± 10%) V, 50Hz, insulation resistance> 1MQ and good grounding.
4.1.2safety valve installation evaluation criteria should be verified with records. Pressure greater than 0.8MPa automatic pressure relief.
4.1.3 compressed air storage tank Confirmed compressed air storage tank should obtain the Municipal Quality and Technical Supervision pressure vessel license and valid period.
4.1.4 Installation and evaluation of filter installation criteria C-level centrifugal oil and water separator installation 3ixm, T-level air line filter 1 xm, A-level super-efficient degreasing filter 4.1.5 pipeline connected correctly by the system Process 圄 Check the use of welding connections, may not use threaded connections.
4.1.6 pipe installation Pipeline installation and compressed air delivery pipelines and sampling points indicate a consistent and strong and no leakage.
4.1.7 System valves on the pipeline switch flexible, non-leak sanitary 316L stainless steel ball valve.
4.1.8 pipe material 4.1.9 pipe welding must be used automatic welding. At the same time, the number of endoscope detection tests must be not less than 20% of the total welding points, the welding position should be marked on the welding 并 and documented. Welder requirements must provide welder qualification certificate.
4.1.9Pipeline finish requirements of 0.6xm (the construction side must provide proof).
4.1.10 gas point number in accordance with the system gas point 圄 paper check the actual gas point and 圄 paper is consistent.
4.1.11 Compressed air pipeline pressure test, passivation 4.1.12.1 Pipeline pressure test design pressure of more than 115% pressure test, dwell time is not less than 60min. Pressure loss is less than 0.03MPa. 4.1.12.2 pipe passivation purified water pre-rinse i Will passivation pipe to be connected with a tank and a water pump into a circulation path, in the tank filled with sufficient purified water, pump to be recycled, not less than 15min after the open branch drain valve, discharge while cycling.
Lye cleaning: The NaOH with purified water dubbed 2% NaOH solution main pipeline pump circulation not less than 45min branch pipe soak 1h after discharge.
Rinse i Add purified water to the tank Start the pump, open the drain valve and drain while flushing for at least 30 minutes until the conductivity of each outlet matches the conductivity of the water in the tank.
Passivation with 20% nitric acid solution, pump the main pipe circulation not less than 60min branch pipe soak 2h after discharge.
Flush with purified water again to the outlet of the conductivity and the tank water conductivity.
4.2 Confirmation of Operation Check compressed air system equipment operation and compressed air system operation should meet the production requirements. Verify that the device is ready for performance testing.
4.2.1 Compressor operation evaluation criteria Normal start-up operation without abnormal sound.
4.2.2 Air compressor automatic unloading system In automatic operation, filling the gas tank (3m3) for 1min; will lead to the point of use of the valve □ closed, the device is turned on under load in the gas system to be gas Device uninstall downtime.
4.2.3 freeze-drying operation evaluation criteria Smooth operation without abnormal sound.
4.2.4 Valves and Valves Evaluation Standard Valve □ Normal opening and closing, the pipeline leak.
4.2.5 Each gas supply point gas evaluation criteria The gas supply point should be normal.
4.2.6 Air filter Goodness of cilantro test using automatic filter Integral Tester on the use of filtered compressed air filter point detection test results are less than the factory diffusion flow standard 30mL / min 4.3 Confirmation of Performance Check the compressed air system At full load, check the air quality at each point of use to verify that water, oil, cleanliness, and microbial performance indicators are up to design requirements during normal operation of the compressed air system.
Table 2 shows the qualified standards for the performance of compressed air.
4.3.1 Moisture Detection Using Draeger compressed air quality detector, open the compressed air pipeline valve, the outlet connected to the pressure reducing valve, adjust the pressure reducing valve knob, the pressure maintained at about 0.3MPa; the valve lock, connect the compression Air quality detector with Opener Opens both ends of the Dräger water test tube Insert the test tube holder and start timing Ice test tube through 10min After reading out the moisture content of compressed air should be less than 100mg / m3, the water test pass .
4.3.2 After the oil detector 1125s removed, the tubing at the indicated point at the break point so that the liquid in the ampoule through the indicator layer of about 10mm actually wait 1min after the observation of compressed air oil content should be less than 0.1mg / m3 If the ampoule No color change, the oil test pass If the ampoule color becomes revealing, the oil test failed.
4.3.3 Check the number of dust particles at the point of use of compressed air valve □ appropriate step-down dust particle detector measuring period set to 60s, interval time 60s. The detector probe set in the cleanser self-cleaning 23min, Then align the compressed air outlet for direct testing and readings.
4.3.4 Detection of Bacterioplankton Table 2 Check of Compressed Air Performance Qualified Standard Test Item Qualified Standard Moisture Content 100mg / m3 Oil Content 0.1mg / m3 Dust Particles Grade A Grade Grade B Grade Grade C Grade D Grade Grade Particle Concentration> 0.5m Particle concentration> 5.0m Particle concentration> 0.5m Particle concentration> 5.0m Particle concentration> 0.5m Particle concentration> 5.0m Particle concentration> 0.5m Particle concentration> 20,000 pieces / m3 Microorganism (planktonic bacteria) A grade area B grade area C grade area D grade area<1CFU / m3 Carry the compressed air of each gas point separately to the pressure regulating valve, setting pressure is 0.1MPa, empty row for 5min; Air access stainless steel isolation device, the stainless steel isolation device to cover the airborne dust sampler, open the airborne dust sampler sampling volume of 1m3. After extracting the gas sample of the culture dish placed in 3035C culture for 3 days , Observe the growth of microorganisms.
4.3.5 Sediment bacteria test Refer to the test method for sedimentation bacteria in the clean room (area) of the pharmaceutical industry (GB / T162942010) 4, sterilize 23 times with 70% ethanol near the test site to ensure that the test environment has 2 clean testers, Air point of use after treatment with UV lamp 1h sterilized plastic bags tie vent, plastic bags containing nutrient agar medium Petri dishes 2 thorns with pressure reducing valve to adjust the compressed air pressure 0.3MPa, do Static test blowing medium 30min, 7C incubated for 5 days, colony count.
5 Conclusion As a special product of drugs, and people's lives and health is closely related to the State Food and Drug Administration for the pharmaceutical industry has formulated strict quality specifications. Compressed air as the key medium in the pharmaceutical industry, we must regularly check the compressed air pipeline system, the compressed air filter and respiratory filter for the integrity test of parsley, mixed with compressed air in the oil vapor, moisture, microorganisms Conduct testing to ensure the compressed air quality meets GMP requirements. 7 IS0B57312001 Compressed air Part 1: Pollutants and cleanliness level CB / T132771S91 - Compressed air quality class for general use CB500292003 Compressed air station design specification CB / T162942010 Test methods for settling bacteria in the clean room (area) of pharmaceutical industry Tone management.
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