High-efficiency filter DOP leak detection The original, detection method, result judgment and processing, and leak detection cycle of high efficiency filter DOP in pharmaceutical companies, and the related issues of DOP leak detection and the differences between standards.
High-efficiency filter (HEPA) generally refers to a filter with a particle size greater than or equal to 0.3 um particles with a capture efficiency of 99.97% or more. It is usually used as a terminal filtration device in a cleanroom of a pharmaceutical company to provide clean air. Whether the cleanroom can achieve and maintain the cleanliness level of the design is to a certain extent related to the performance of the HEPA filter and its installation. Therefore, it is one of the important means to ensure the clean environment of the workshop that the high-efficiency filter in the cleanroom is tested for leak detection to ensure that it meets the requirements. The FDA also pointed out in the guidelines for the production of sterile drugs that leak detection should be performed after the installation of high-efficiency filters to check the tightness of filter gaskets, frames, and filter media, etc. A high-efficiency filter leak test was performed.
The filtration efficiency of the HEPA filter itself is generally detected by the manufacturer, and the filter filtration efficiency report sheet and the qualification certificate are attached at the factory. For pharmaceutical companies, high efficiency filter leak detection refers to the on-site leak detection of high-efficiency filters and their systems after installation. The main task is to check the small pinholes and other damages in the filter media, such as frame seals, gasket seals, and filters. Leaks on the frame. The purpose of leak detection is to detect the leaks in the high-efficiency filter itself and in the installation by checking the tightness of the high-efficiency filter and its connection to the mounting frame, and to take appropriate remedial measures to ensure the cleanliness of the area.
DOP leak detection principleLeak detection of high-efficiency filters usually uses DOP generators to generate dust upstream of the filter. Photometers (photometers) are used to determine the aerosol concentrations upstream and downstream of the filter to determine if the filter leaks. The purpose of dust emission is that the dust concentration in the upstream of the high-efficiency filter is relatively low, and only the particle counter is used to detect it without generating dust. It is difficult to find a leak and it is necessary to supplement the dust to clearly and easily detect the leak.
Artificial aerosol DOP has a history of nearly 40 years. For some time, due to its suspected carcinogenic effect on humans, DOS (Dioctylsebaeate dioxin) is also known as DEHS [di(2-ethylexyl)sebacate] and Instead of PAOs (polyaphaolefin polyalphaolefins), the experimental method is still called "DOP method". Atmospheric dust may not be used as a leak detector because the concentration of the atmospheric dust varies with the location and time, and sometimes it is relatively large and sometimes low. The FDA pointed out that when performing leak detection, the selected aerosol should meet certain physical and chemical requirements and should not use aerosols that would cause microbial contamination and cause microbial growth.
The DOP generator can be divided into two types: heat generation and cold generation. The heat generator utilizes the principle of evaporation condensation. The aerosol particles that are atomized are evaporated by the heater and condense into tiny droplets under certain conditions. After the droplets are too small, about 0.3 μm of mist-like DOP is left into the air passage, and the particle size distribution is 0.1 to 0.3 μm. The cold generator refers to the use of compressed air to bubble in the liquid, and the multi-dispersed DOP aerosol in the state of being splashed by the laskin nozzle. The maximum distribution particle size is about 0.65 um. Cold DOP is often used when 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 commonly used detection instrument for high-efficiency filter leak detection is an aerosol photometer (abbreviated hereafter as a photometer), which is a type of forward-scattering linear photometry. It consists of a vacuum pump, a light scattering chamber, a photomultiplier tube, a signal processing converter and a microprocessor. The working principle is that when the air flow is pumped by the vacuum pump to the light scattering chamber, the particulate matter therein scatters the light to the photomultiplier tube. In a photomultiplier tube, light is converted into an electrical signal that is amplified and digitized and analyzed by a microprocessor to determine the intensity of scattered light. By comparison with the signal generated by the reference substance, the mass concentration of the particulate matter in the gas can be directly measured, so its use is very extensive. The particle counter, whose test value reflects the number of particles in the gas stream, has a particle size range and a high sensitivity. It is applicable to all dust aerosols and has a large selection but is highly efficient. Less use of filter leak detection, the two instrument test results are difficult to quantitatively compare.
High efficiency filter DOP leak detection methodTo determine whether the HEPA filter itself and its installation have significant leakage, the following locations must be tested on the site: the filter media of the filter; the filter media of the filter and the inside of the frame; the filter frame gasket and filter The support group is between the support frames; the support frame and the wall or ceiling.
DOP leak detection materials, instruments are: dust source (PAO solvent), TDA-6C aerosol generator, aerosol photometer.
The aerosol generator used by our company is ATI TDA-6C. Handheld Laskin nozzle type aerosol generator. It uses air directly without compressed gas as power. Under the working pressure of 20Pa, when the gas velocity is 50~2025f3/min, a polydisperse submicron oil aerosol with a concentration of 10~100ug/mL can be generated. The aerosol photometer used was an ATI 2H photometer with a dynamic measurement range of 0.00005~120ug/L and a sampling flow rate of 1F3/min (28.3L/min).
Introduce PAO aerosol on the upstream side of HEPA to be tested. For HEPA in HVAC system, aerosol can be introduced directly from the negative pressure side of the system fan to achieve even concentration of aerosol when reaching HEPA. For introduction, it should be introduced at a distance of at least 10 times the diameter of the wind pipe from HEPA, and minimize turning (American Society for Environmental Science and Technology). Under normal circumstances, maintain the upstream aerosol to the required concentration, and the concentration fluctuation can be within a certain range. For laminar flow hoods and HEPA on the clean bench, the aerosol is introduced directly from the negative pressure side of the system fan.
The aerosol photometer initializes, sets the 100%, 0% reference standard value to carry on the initialization according to the aerosol photometer operation request, sets up the warning value. Connect the UPSTREAM sampling tube to the upstream sampling port and measure the upstream aerosol concentration. According to the operational requirements of aerosol generators, the concentration of aerosols generated was adjusted so that the upstream aerosol concentration reached 10-20 ug/mL.
Scan leak detection Remove the HEPA diffuser plate and scan the entire filter surface, between the filter and the bezel, between the bezel and the bezel, and between the bezel and the static pressure box. The sampling head is approximately 1 inch (approximately 2.54 cm) from the filter surface during scanning and the scanning speed does not exceed 5 cm/s. The scans are reciprocated back and forth in a straight line, and the lines should overlap. During the test, if there is an alarm sound (ie %LEAKAGE (leakage rate) exceeds 0.01%), there is a leak. The leak was scanned and inspected after plugging or fastening with silicone. Check that a filter is approximately 5 minutes. During the test, the concentration of upstream aerosol should be confirmed frequently. Note that protective masks and protective goggles should be provided during the test.
DPF Leak Detection Method Decision and Processing of High Efficiency FilterHigh efficiency filter leakage rate should be less than or equal to 0.01%. If HEPA is in the testing process and %LEAKAGE (% leakage rate) does not exceed 0.01% at all points, the HEPA is judged to be acceptable. If there is a point that exceeds 0.01%, it is judged to be unqualified and the point is marked. Need to be repaired or replaced. Leakage of HEPA filters can be repaired with special glue, but the area of ​​a single leak cannot be greater than 1% of the total area. The area of ​​all leaks cannot be greater than 5% of the total area, otherwise it must be replaced.
High efficiency filter leak detection cycleThe FDA recommends in the guideline for the production of sterile drugs that leak detection should be conducted semi-annually in the workshop of the aseptic preparations. Our country recommends in the GMP inspection guide that it is usually conducted once a year. ISO14644 For leak detection with installed HEPA, the recommended maximum time interval is 24 months. DOP leak detection should be performed after HEPA installation or replacement. When the environmental monitoring shows that the air quality is deteriorating, or when the product sterility test fails, or the media simulation filling test fails, leak detection can be performed as part of the deviation investigation. Filters that need to be leak tested include HEPA used in drying tunnels and dry ovens.
Discussion on DOP Leak Detection Method of High Efficiency Filter
High efficiency filter efficiency and leak detection High-efficiency filter The filter efficiency refers to the efficiency of the filter itself, which varies with the standards and test methods performed. The current test methods for the efficiency of high-efficiency filters include the DOP method, which is not as sensitive as the particle counting method with photometric detection. The relevant standards can be seen in the United States IEST-RP-CC001; the particle counting method uses the particle counter as the testing instrument, using monodispersed or Multi-dispersed aerosol, high sensitivity, used for ultra-high efficiency filter, related standards can be seen IEST-RP-CC007; the most easily penetrated particle size method (MPPS), using particle counter as a detection instrument, using the same aerosol, this The method is defined by the EU EN1822 standard. The difference with the particle counting method is that the particle size that is the most easily penetrated by the filter is used as the particle size for the test; the sodium flame method uses the flame photometer and the flame color of the NaCL is burned. In response, the relevant standards see China's "high-efficiency air filter GB13554-92", the sensitivity is low, and NaCl is harmful to the quality of microelectronic products, and has not been used abroad.
For pharmaceutical companies, the leak detection of high-efficiency filters is mainly on-site leak detection. The DOP method can be used to identify problems that may exist in the filter itself and in the transportation and installation process. Aerosol photometers and polydisperse aerosols are often used because they are more economical and meet the requirements than monodisperse aerosols.
The instrumentation can use an aerosol photometer or a particle counter. Particle counters detect the distribution of particles, often expressed in "grain/L" units, while photometers measure the mass concentration of particles and are expressed in "mg/L". The particles with the largest number of distributions and the particles with the maximum concentration distribution are not in the same particle diameter, because the relationship between the particle diameter and the weight is cubic, and the particles with large particle diameters occupy a larger proportion in the concentration distribution. Therefore, when measuring filter efficiency, the results obtained using a particle counter and a photometer will be different. Compared with particle counters, photometric sensitivity and accuracy are somewhat poorer, so they are not designed to detect high-efficiency filters and ultra-efficient filters above H13. For on-site leak detection of high-efficiency filters in pharmaceutical companies, luminometers are widely used because they are easy to use, easy to determine test results, and sensitive to leak detection.
Leak detection standard Different criteria are also different in the determination of leak detection results. The United States IEST-RP-CC034 specifies that the C, D-class high-efficiency filters have a leak detection rate of 0.3 um on site and a photometric scanning leak detection method of 0.01. The European Union EN1822 stipulates that the leak detection test is acceptable if the local transmittance of the tested filter does not exceed the specified local value. The local transmittance of the H13 grade high-efficiency filter is 0.25%, but note that the transmittance here is It was measured with a 0.3 μm monodisperse phase DOP test. In China, the leak test of installed filters in the “Design Code for Cleanroom Buildings GB50073-2001 and High Efficiency Air Filter GB13554-92†stipulates the use of atmospheric dust or other aerosols, and the leakage concentration measured by a particle counter for high-efficiency filters. The penetration rate should not be more than 4 times the filter's factory qualified penetration rate. For the leak test of HEPA, a pharmaceutical company, in actual tests, if there is a leak, the photometric count value will obviously increase and it will be easy to judge. The leakage rate of high-efficiency filter is set to 0.01% or less and does not affect the actual leakage detection.
This article applies articles from Shenzhen Junda