103.0 High Efficiency Filter DOP Leak Detection

Key words High efficiency filter DOP leak detection PAO generator Photometer

  High Efficiency Filter DOP Leak Detection Method - Application in Pharmaceutical Enterprises

Abstract : This article describes the original, detection method, result judgment and processing of the leak detection of high efficiency filter DOP in pharmaceutical companies . Leak detection cycle and other issues, and discuss the issues related to DOP leak detection and the differences between the standards.

  High efficiency filter (HEPA) generally refers to a particle size greater than or equal to 0.3um particle collection efficiency of 99.97% The above filter is usually used as a filter device at the end of a clean room in 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.

1 High-efficiency filter leak detection purpose

  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 presence of HEPA filters and their presence in the installation by checking the tightness of the HEPA filter and its connection to the mounting frame. Sink and take appropriate remedial measures to ensure the cleanliness of the area.

2 DOP leak detection principle

  HEPA filters usually leak in PAO dust filter upstream of the generator, using a luminometer (Photometer) aerosol concentration downstream of the filter is detected to determine whether 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, people have a suspicion of carcinogenicity, are often DOS (Dioctylsebaeate aliphatic dioctyl sebacate), also known as [sebacate di (2-ethylexyl) ] and (polyaphaolefin poly-a-olefin) or the like instead of PAO DEHS, but 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 PAO generator can be divided into two types: heat generation and cold generation. The heat generator uses the principle of evaporation condensation. The aerosol particles that are atomized are evaporated by the heater and condense into tiny droplets under certain conditions, removing excessive and large after leaving too small droplets of about 0.3um DOP mist into the air duct, the particle size distribution in the 0.1 ~ 0.3um. The cold generator refers to the use of compressed air to bubble in the liquid, and the multi-disperse DOP aerosol in the state of being splashed by the laskin nozzle has a large distribution particle size of about 0.65 um . Cold DOP is often used when scanning filters for leak detection .

  There are two kinds of detection instruments, one is an aerosol photometer , and the other is a particle counter . The commonly used detection instrument in high-efficiency filter leak detection is an aerosol photometer ( hereinafter abbreviated as photometer ) , which is a kind 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, it is the concentration of test value reflects the number of particles in the gas stream! Pill "# $ and predetermined particle size range, high sensitivity, suitable for all aerosol dust source, a larger choice, but in the high Less use of filter leak detection, the two instrument test results are difficult to quantitatively compare.

3 detection methods

  To 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 ) , 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 20Pa working pressure, At a gas flow rate of 50 to 2025 f3/min , a polydisperse submicron oil aerosol at a concentration of 10 to 100 μg/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) .

3.1 Introduction of PAO aerosol on the upstream side of HEPA to be tested

  For HEPA in HVAC system, aerosols can be introduced directly from the negative pressure side of the system fan to achieve a uniform concentration when the aerosol reaches HEPA . If the HEPA is introduced from the air duct, it should be at least 10 times the wind from HEPA. Introduce the tube at the diameter 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, HEPA on the clean bench , the aerosol is introduced directly from the negative pressure side of the system fan.

3.2 Aerosol photometer initialization, setting 100% , 0 % reference standard value

  Initialize and set the alarm value according to the operation requirements of the aerosol photometer. UPSTREAM upstream of the sampling tube and sampling port to the measured concentration of the aerosol upstream. According to the requirements of aerosol generator operation, adjust the concentration of aerosols generated so that the upstream aerosol concentration reaches 10 to 20 μg/mL .

3.3 Scan leak detection

  Remove the HEPA diffuser plate and scan the entire filter surface, between the filter and the frame, between the frame and the frame, and between the frame and the static pressure tank. 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. The lines should be heavy .

  Stack. During the test, if there is an alarm sound ( that is, %LEAKAGE ( leakage rate ) exceeds 0.01% ) , there is a leak. The leak was scanned and inspected after plugging or fastening with silicone. Check a filter for about 5 minutes . During the test, the concentration of the upstream aerosol should be confirmed frequently. Note that protective masks and protective eye masks should be provided during the test.

4 result determination and processing

  High efficiency filter leakage rate should be less than or equal to 0.01% . If HEPA is in the process of detection, %LEAKAGE for all points ( Leakage rate % ) No more than 0.01%, it is judged passing the HEPA, if one percent more than 0.01%, as unqualified, and the mark out point, need repair or replacement. 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 , and the area of ​​all leaks cannot be greater than 5% of the total area , otherwise it must be replaced.

5 high efficiency filter leak detection cycle

The FDA recommends in the guideline for the production of sterile drugs that leak detection should be conducted semiannually in the workshop of the aseptic preparations, and China recommends in the guideline for high standards inspection that it is usually conducted once a year. The ISO14644 leak test for installed HEPA has a recommended interval of 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 also include HEPA used in drying tunnels and dry ovens .

6 Question Discussion

6.1 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 are: DOP method, which is less sensitive than the particle counting method by photometric detection, the relevant standards can be seen in the United States IEST-RP-CC001 , particle counting method, particle counters as testing instruments, using monodispersed or Polydisperse aerosol, high sensitivity, Mostly used for ultra-efficient filters, Relevant standards can be seen in IEST-RP-CC007; particle size penetration method ( MPPS ) using particle counter as a test Measuring instruments, the use of aerosols with the former, this law is the EU EN1822 standards, and the particle counting method is the difference, the particle size of the filter easy to penetrate as a test particle size; Sodium flame method, this method uses flame The photometer responds to the flame chromaticity of NaCL combustion. The relevant standards can be seen in our country's "High Efficiency Air Filter GB13554-92 ", which has low sensitivity and NaCl is harmful to the quality of microelectronic products. It 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.

6.2 Aerosol photometers and particle counters

The instrumentation can use an aerosol photometer or a particle counter. Particle counters detect the distribution of the number of particles, often as "grain /L " The unit indicates that the photometer measures the mass concentration of the particles and is expressed in “ mg/L ”. Particles with a large number of distributions do not have the same particle size as those with a large concentration, because the relationship between particle size and weight is cubic, and particles with a large particle size account for a greater proportion of the concentration distribution. Therefore, when measuring filter efficiency, the results obtained using a particle counter and a photometer will be different. With particle counter In contrast, the photometric sensitivity and accuracy are slightly worse, so it is not used 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.

6.3 leak detection standards

  Different criteria are also different in the determination of leak detection results. U.S. predetermined IEST-RP-CC034 C,. D stage leak detection efficiency filter transmittance 0.3um, scanning photometer leak detection method) of 0.01. The European Union EN1822 stipulates that the leak detection test is acceptable if the local transmission rate of the tested filter does not exceed the specified local value. The local transmittance of the H13 -level high-efficiency filter corresponds to 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 “Guidelines for Design of Cleanrooms GB50073-2001 and High Efficiency Air Filters GB13554-92 ” stipulates the use of atmospheric dust or other aerosols, and the leakage concentration measured by particle counters for high-efficiency filters. The penetration rate should not be more than 2 times the filter's factory qualified penetration rate . For the leak test of pharmaceutical company HEPA , in the actual test, if there is a leak, the photometric count value will obviously increase, and it is easy to judge that the high efficiency filter leakage rate standard is set to be less than or equal to 0.01% and does not affect the actual leak detection.

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