Filter leak test case and application (2)

HEPA is a kind of filter which has a collection efficiency of more than 99.97% for particles with a particle size greater than or equal to 0.3um It is usually used as the end filtration device in the clean workshop of pharmaceutical enterprises to provide clean air Whether the clean room can reach and maintain the designed cleanliness level is related to the performance and installation of the filter to a certain extent Therefore, it is one of the important means to test the filter in the clean workshop to ensure that it meets the requirements The FDA also pointed out in the aseptic drug production guidelines that the leak test should be carried out after the filter is installed to check the tightness of the filter gasket, frame and filter material For the aseptic preparation production workshop, the filter leak test should be carried out regularly 1 The principle of DOP leak detection is that the Pao generator is usually used to generate dust upstream of the filter, and the photometer is used to detect the aerosol concentration upstream and downstream of the filter to determine whether there is leakage The purpose of dust generation is because the concentration of dust particles upstream of the filter is relatively low Only when particle counter is used to detect without dust generation, it is difficult to find any leakage Only when dust generation is supplemented can leakage be found obviously and easily The artificial aerosol DOP has a history of nearly 40 years For a period of time, because it is suspected to have carcinogenic effect on human beings, it is often replaced by the DOS (dioctylsebacate dioctyl sebacate) or dehs (DI (2-ethylxyl) sebacate) and Pao (polyaphaolefin polyolefin), but the experimental method is still called "DOP method" Because the concentration of atmospheric dust varies with place and time, sometimes it is larger, sometimes it is lower, so it is generally not used for leak detection FDA points out that the selected aerosol should meet certain physical and chemical requirements during leak detection, and should not use the aerosol that will cause microbial pollution and microbial breeding Pao generator can be divided into two types: thermal generator and cold generator The thermal generator uses the principle of evaporation and condensation to evaporate the aerosol particles which are atomized by heater, and condense them into small droplets under specific conditions After removing the large and small droplets, it leaves about 0.3um mist DOP into the air duct, with the particle size distribution of 0.1-0.3um The cold generator is a kind of multiphase DOP aerosol with the particle size of about 0.65um, which is produced by bubbling compressed air in liquid and splashing through Laskin nozzle There are two kinds of detection instruments, one is aerosol photometer, the other is particle counter The commonly used detection instrument in filter leak detection is aerosol photometer It consists of vacuum pump, light scattering chamber, photomultiplier, signal processing converter and microprocessor Its working principle is: when the air flow is pumped into the light scattering chamber by a vacuum pump, the particles in the chamber scatter the light photomultiplier tube In photomultiplier tubes, light is converted into electrical signals, which are amplified and digitized and then analyzed by microprocessor to determine the intensity of scattered light Compared with the signal generated by the reference material, it can directly measure the mass concentration of particulate matter in the gas, so it is widely used The particle counter, whose test value reflects the concentration of the number of particles in the air flow, has a high sensitivity and can be applied to all dust source aerosols There is a large choice, but it is seldom used in filter leak detection The test results of the two instruments are difficult to be compared quantitatively 2 The filter efficiency of the filter itself for leakage detection is generally tested by the manufacturer, and the filter efficiency report and qualification certificate are attached at the factory For pharmaceutical enterprises, filter leak detection refers to the on-site leak detection after the filter and its system are installed, mainly to check the small pinholes and other damages in the filter material, such as frame seal, gasket seal and the leak on the filter frame The purpose of leak detection is to check the tightness of the filter and its connection with the installation frame, find out the defects in the filter itself and installation in time, and take corresponding remedial measures to ensure the cleanliness of the area 3 Detection method to determine whether there is obvious leakage in the filter itself and its installation, the following parts must be tested on site: filter material of filter; connection between filter material and its frame; between the gasket of filter frame and filter group support frame; between support frame and wall or ceiling DOP leak detection materials and instruments include: dust source (PAO solvent), aerosol generator, aerosol photometer 3.1 Pao aerosol shall be introduced at the upstream side of HEPA to be tested For HEPA in HVAC system, in order to make the concentration of aerosol reach HEPA uniform, the aerosol can be directly introduced from the negative pressure side of the system fan If it is to be introduced from the air duct, it shall be introduced at the place 10 times less than the diameter of the air duct from HEPA, and the turning shall be minimized (American Society of environmental science and Technology) Generally, keep the upstream aerosol to reach the required concentration, and the concentration fluctuation in a certain range For HEPA on laminar flow hood and super clean platform, aerosol is directly introduced from the negative pressure side of the system fan 3.2 initialize and set 100% and 0% reference standard values of aerosol photometer according to the operation requirements of aerosol photometer Connect the upstream sampling tube with the upstream sampling port to measure the concentration of the upstream aerosol Adjust the aerosol concentration according to the operation requirements of the aerosol generator to make the concentration of the upstream aerosol reach 10 ~ 20ug / ml 3.3 scanning Leak Detection remove the diffuser of HEPA, and scan the sealing of the whole filter surface, between the filter and the frame, between the frame and the frame, and between the frame and the static pressure box When scanning, the distance between the sampling head and the filter surface is about 1 inch (about 2.54cm), and the scanning speed is not more than 5cm / s Scanning shall be conducted back and forth in a straight line, and the lines shall be heavy Stack During the detection, if there is an alarm sound (i.e the% leakage rate exceeds 0.01%), it indicates that there is leakage The leakage shall be blocked with silica gel or tightened before scanning and inspection Check a filter for about 5min During the test, always confirm the concentration of the upstream aerosol Pay attention to wearing protective mask and eye mask during the test 4 The filter leak detection cycle FDA recommends that the aseptic preparation workshop should be leak detected once every half a year in the aseptic drug production guidelines, and it is generally recommended once a year in the GMP Inspection Guidelines in China The recommended time interval for leak detection of installed HEPA in ISO14644 is 24 months DOP leakage detection shall be carried out after HEPA installation or replacement When the environmental monitoring shows that the air quality deteriorates, or the sterility test of the product fails, or the simulated filling test of the medium fails, the leakage can be detected as a part of the deviation investigation Filters to be leak tested also include HEPA for drying tunnels and ovens 5 The leakage rate of filter should be less than or equal to 0.01% In the process of HEPA detection, if the% leakage (leakage rate%) of all points does not exceed 0.01%, then the HEPA is qualified; if the% of one point exceeds 0.01%, it is unqualified, and the point is marked out, which needs to be repaired or replaced Special glue is allowed to repair the leakage of filter material, but the area of single leakage shall not be greater than 1% of the total area, and the area of all leakage shall not be greater than 5% of the total area, otherwise it must be replaced 6 Problem discussion 6.1 filter efficiency and leak detection filter efficiency refer to the efficiency of the filter itself, which varies with the standards and test methods implemented At present, the test methods for filter efficiency are: DOP method, which is not as sensitive as particle count method, and the relevant standards can be seen in the United States, iet-rp-cc001; particle count method, which uses particle counter as the detection instrument, uses single dispersion or multi dispersion aerosol, with high sensitivity, and is mostly used for super filter, and the relevant standards can be seen in iet-rp-cc007; Zui MPPs, which uses particle counter as detection instrument, uses the same aerosol as before This method is European Union EN1822 The difference between the standard and the particle count method is that the particle size of the filter Zui which is easy to penetrate is used as the particle size for testing; the sodium flame method adopts the flame photometer to respond to the flame chroma of NaCl combustion For the relevant standards, see "air filter gb13554-92" in China, with low sensitivity, and NaCl is harmful to the quality of microelectronic products, which has not been used abroad For pharmaceutical enterprises, the filter leak detection is mainly on-site leak detection Through DOP method, the possible problems of filter itself, transportation and installation process are found Aerosol photometer and multi divergent aerosol are often used because they are more economical and convenient than monodisperse aerosol 6.2 aerosol photometer and particle counter detector can use aerosol photometer or particle counter Particle counter detects the number distribution of particles, which is usually expressed in "particle / L" units, while photometer detects the mass concentration of particles, which is expressed in "mg / L" The particle size of Zui is not the same as that of Zui with large concentration, because the particle size and weight are in the third power, and the particle with large size takes a large proportion in the concentration distribution Therefore, when measuring the efficiency of the filter, the results obtained by using particle counter and photometer will be different Compared with the particle counter, the sensitivity and accuracy of the photometer are slightly poor, so it is not necessary to detect filters and ultrafilters above grade H13 For the field leak detection of filters in pharmaceutical enterprises, the photometer is widely used because of its convenience in use, easy to judge the detection results and sensitive to leak detection 6.3 in the determination of leak detection results, different standards are also different According to the American iest-rp-cc034, the field leakage detection transmissivity of class C and D filters is 0.3um, and the photometer scanning method is 0.01 European Union EN1822 stipulates that the leakage test is qualified as long as the local transmittance of the filter under test does not exceed the specified local value The corresponding local transmittance of grade H13 filter is 0.25% However, it should be noted that the transmittance here is obtained by 0.3um single dispersion phase DOP test According to the "code for design of clean building GB50073-2001 and air filter gb13554-92" on leakage test of installed filter in China, it is specified to use atmospheric dust or other aerosols, and use particle counter to measure the leakage concentration For filter, the penetration rate shall not be greater than twice of the qualified penetration rate of filter For the leakage test of HEPA in pharmaceutical enterprises, if there is any leakage in the actual test, the photometer value will be significantly increased, which is easy to judge The filter leakage rate standard is set as less than or equal to 0.01%, which does not affect the actual leakage test Shanghai Sujing Industry Co., Ltd if you have any need, you can pass with us at any time Thank you very much for your support and look forward to cooperating with you Thank you & bestragard! Suing Jinghua