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GMP cleanroom high efficiency filter leak detection purpose principle and cycle
GMP cleanroom high efficiency filter leak detection purpose principle and cycleGMP clean room is a space where air cleanliness reaches a specified level for human production activities and is widely used in pharmaceutical, medical, cosmetic, food, and electronic industries.Its function is to control the contamination of living particles (e.g. single-celled algae, bacteria, protozoa, bacteria, and viruses, etc.) and particulates (dust particles) to achieve a sterile and clean environment, therefore high-efficiency filters are widely used in pharmaceutical GMP cleanroom, cosmetic GMP cleanroom, food QS cleanroom, electronic cleanroom and other GMP cleanrooms to ensure the purification requirements of the production process. High-efficiency filters (HEPA) are generally filters with a particle size greater than or equal to 0.3um with a capture efficiency of 99.97% or more and are usually used as end filtration devices in GMP cleanrooms to provide clean air, whether the GMP cleanroom can achieve and maintain the designed cleanliness level is to a certain extent related to the performance of the HEPA filter and its installation. Leak testing of cleanroom HEPA filters to ensure that they meet the requirements is therefore an important means of ensuring a clean environment in the cleanroom. The FDA also points out in the guide of sterile drug production that leak tests should be conducted after the installation of a high-efficiency filter to check the sealing of the filter gasket, frame and filter material, etc. For sterile preparation production workshops, leak tests of high-efficiency filters should be conducted regularly. I. Selection of high-efficiency filters Due to the different characteristics of clean rooms, the choice of high-efficiency filters should first be determined by the level of the clean room, the degree of sterility, temperature, and humidity, the degree of fire resistance, anti-corrosion, and other different requirements. Such as the following 100 levels to choose class A or B, more than 100 levels need to choose class C filter; high temperature and high humidity conditions should be selected metal divider and metal frame of the filter; anti-corrosion requirements should be selected plastic divider and plastic frame of the filter; fire requirements, all the materials of the filter should be non-combustible, etc. In practice, conventional filters refer to the high-efficiency air filter standards in the A class and B class, they are the most commonly used in the design of GMP clean plant high-efficiency filters, generally less than or equal to 100,000 can choose A class; 10,000 ~ 100 can choose B class. All conventional high-efficiency filters, for ≥ 0.5μm particles, can be calculated according to the efficiency of 5 "9" which is 0.9999. High-efficiency filters are mainly used to filter air-suspended particles below 0.3um, as the end filter of various filtration systems. The selection of air filter configuration for a clean room clean area is generally based on the clean room level requirements. The filtration efficiency of the high-efficiency filter itself is generally tested by the manufacturer, and the filter filtration efficiency report sheet and certificate of conformity are attached to the factory. For GMP cleanrooms, high-efficiency filter leak detection refers to the on-site leak detection after the installation of high-efficiency filters and their systems, mainly to check small pinholes and other damages in the filter material, such as frame seals, gasket seals, and leaky seams on the filter frame. The purpose of leak detection is to detect defects in the HEPA filter itself and in the installation by checking the tightness of the HEPA filter and its connection to the installation frame, etc., and to take corresponding remedial measures to ensure the cleanliness of the area. The DOP generator can be divided into two types: the hot generator is using the principle of evaporation and condensation, and the atomized aerosol particles are evaporated with a heater and condensed into tiny droplets under specific conditions, leaving about 0.3um of foggy DOP into the duct after removing the oversized and undersized droplets, with a particle size distribution of 0.1 to 0.3um. the cold generator is using compressed air to drum bubbles in the liquid, splashing through the Laskin nozzle to produce a polydisperse phase DOP aerosol in the material state, with a maximum distribution particle size of around 0.65um. Cold DOP is often used for scanning filters for leak detection. There are two types of detection instruments, one is an aerosol photometer and the other is a particle counter. The common detection instrument used in leak detection of high-efficiency filters is an aerosol photometer (hereinafter referred to as photometer), which is a pre-scattering linear photometer, consisting of a vacuum pump, light scattering chamber, photomultiplier tube, signal processing converter, and microprocessor. Its working principle is that when the airflow is pumped by the vacuum pump to the light-scattering chamber, the particulate matter in it scatters light to the photomultiplier tube. In the photomultiplier tube, the light is converted into an electrical signal, which is amplified and digitized and then analyzed by the microprocessor to determine the intensity of the scattered light. By comparison with the signal generated by the reference substance, the mass concentration of the particulate matter in the gas can be measured directly, making it very versatile. Particle counters, on the other hand, whose test value reflects the concentration of the number of particles in the gas stream! and specifies the particle size range, its sensitivity is high, it applies to all dust sources aerosols and has a large choice, but it is less used in leak detection of high-efficiency filters and it is difficult to compare quantitatively the test results of the two instruments. II. Principle of the DOP leak detection method Leak detection of high-efficiency filters is usually carried out by using a DOP generator to generate dust upstream of the filter and a photometer to detect the concentration of aerosols upstream and downstream of the filter to determine whether there is a leak in the filter. The purpose of dust generation is to detect leaks with a particle counter without dust generation because of the low concentration of dust particles upstream of the HEPA filter, and additional dust generation is required clearly and easily detect leaks. The artificial aerosol DOP has been around for nearly 40 years, but for some time now it has been replaced by DOS (Dioctylsebaeate sebacate), also known as DEHS [di(2-ethyl hexyl)sebacate] and PAO (polyaphaolefin), due to suspected carcinogenic effects on humans, but the experimental method is still called the "DOP method". The FDA points out that when leak detection is carried out, the aerosol selected should meet certain physical and chemical requirements and should not be used to cause microbial contamination and microbial growth. III. Leak detection method of DOP for high-efficiency filters To determine whether there are obvious leaks in the HEPA filter itself and its installation, the following places must be tested on site: the filter material, the connection between the filter material and the inside of its frame, between the gasket of the filter frame and the support frame of the filter group; between the support frame and the wall or ceiling. Introduce PAO aerosol on the upstream side of the HEPA to be tested. For HEPA in HVAC systems, to achieve a uniform concentration of aerosol when it reaches the HEPA, introduce the aerosol directly from the negative pressure side of the system fan or, if introduced through the duct, at least 10 times the diameter of the duct from the HEPA, with minimal bends (American Society for Environmental Science and Technology). In general, it is sufficient to keep the upstream aerosol at the required concentration and to keep the concentration fluctuating within a certain range. For HEPA on laminar flow hoods and ultraclean tables, aerosols are introduced directly from the negative pressure side of the system fan. The initialization of the aerosol photometer, setting of 100% and 0% reference standard values Initialisation and setting of alarm values according to the operational requirements of the aerosol photometer. Connect the UPSTREAM sampling tube to the upstream sampling port and measure the upstream aerosol concentration. Adjust the aerosol concentration occurring by the aerosol generator operating requirements so that the upstream aerosol concentration reaches 10~20ug/mL. IV. Scanning leak detection Remove the diffuser plate of the HEPA and scan the entire filter face, between the filter and the frame, between the frame and the frame, and between the frame and the static pressure box. Scanning is performed with the sampling head approximately 1" (approx. 2.54cm) from the filter face and at a speed of no more than 5cm/s. Scanning is performed in a straight line back and forth with overlapping lines. During the test, an alarm (i.e. %LEAKAGE (leakage rate) exceeding 0.01%) indicates a leak. After the leak has been plugged with silicone or tightened, a scanning tour is carried out. The inspection of a filter takes about 5 min. During the test, the concentration of upstream aerosols should be confirmed frequently, and it should be noted that protective masks and eye protection should be worn during the test. V. High-efficiency filter DOP leak detection method results in determination and processing The leakage rate of the HEPA filter should be less than or equal to 0.01%. If the HEPA in the detection process, all points of %LEAKAGE ( leakage rate %) are not more than 0.01%, the HEPA is judged to be qualified, if there is a % more than 0.01%, it is judged to be unqualified, and the point will be marked out and need to be repaired or replaced. The leak of the HEPA filter media is allowed to be repaired with special glue, but the area of the single leak cannot be greater than 1% of the total area, and the area of all leaks cannot be greater than 5% of the total area, otherwise, it must be replaced. VI. Leak detection cycle for high-efficiency filters The FDA in its guidelines for sterile pharmaceutical production recommends that leak detection be carried out once every six months for sterile preparation production plants, while China in its GMP inspection guidelines recommends that leak detection be carried out once a year. |
