This correlation verifies the integrity test limits the filters have to pass. Oct 17, 2017 a filter integrity test is a critical unit operation commonly employed in the pharma industry. The most common integrity test for uf membrane assemblies is the airwater diffusion test. Intrusion test is an insitu integrity test for hydrophobic.
Seitz bubble point test xlii appalachian state university. The pressure hold, forward flow, and pressure decay tests are variations of the diffusion test. How to make a diffusion test program in filter integrity. How to make diffusion test program in filter integrity test. Disconnect the integrity testing apparatus from the filter housing. L where q is the permeation flow rate, a is the membrane area. The most widely used nondestructive integrity test is the bubble point test. Enhanced aerosol test for assessing filter integrity emd. Water intrusion integrity testing of hydrophobic membrane filters. The test methods could be bubble point, diffusion or pressure hold.
There are many standards that outline the frequency of testing and guidelines for the actual tests to be carried out. Diffusion flow too low to measure on small discs cant scale up disc flow to cartridge flow accurately filter mfr certifies cartridge membrane bp min. Taken those specific needs into account, this unit offers the following main features. If a diffusion test is started, for example, no diffusion will take place. Filter integrity testing can be conducted manually or via an automated. Pdf filter integrity testing fda guideline on sterile. Available in either a standalone or networkable configuration, the integritest 4 instrument offers. Because the measurement is upstream of the filters, any risk to downstream sterility is eliminated. The stringent requirements of the pharmaceutical industry dictate that nondestructive filter integrity testing must be performed in each sterilizing. In particular, integrity tests enable users to verify that no filter damage has. Feb 20, 2018 for accurate, reproducible, reliable automatic integrity testing of liquid or gas filters.
Probably the most commonly applied nondestructive integrity test for membrane filters is the gasliquid diffusion test, with air and water often used as the gasliquid pair. Thoroughly wet the filter with appropriate test fluid, typically water for hydrophilic membranes or an alcoholwater mixture for hydrophobic membranes. The post filtration integrity test is a must, pre filtration integrity testing is recommended. Filter integrity testing fda guideline on sterile drug products. Integrity testing sterilizing filters after a batch has been filtered can detect if the integrity of the filter has been compromised during the process. Because the maximum diffusion rate is the criterion for evaluating whether a filter passes or fails its integrity test, in this case a pass evaluation may be displayed.
Figure 1 water intrusion test setup introduction cartridge installation prior to any integrity test procedure, the membrane cartridge filter must be sealed in the housing. G difficult to perform insitu particle counter downstream of filter. Because of the amount and variability of gas flow through large area membrane filters, flaws. Filter integrity testing troubleshooting guidelines. Manual bubble point of a filter housing system consult factory for pressure hold procedure wetting hydrophobic filters must be wet with a low surface tension fluid such as 60% isopropyl alcohol 60% ipa before they can be integrity tested with the bubble point or diffusion test.
The diffusion test measures the rate of gas transfer through a filter to be tested. Incase a sterilizing grade filter which is used for filtration of nitrogen, compressed air carbon dioxide in vial filling room, fails in integrity test post, inform the production manager and quality assurance. A filter integrity test is a critical unit operation commonly employed in the pharma industry. Physical integrity testing of a process filter should be conducted before use where process conditions permit. Diffusion tests with automatic filter wetting water intrusion test wit wit on huge housings 39. Instead, the integrity of the closed tubing will be tested. This integrity test, typically either a diffusion test or bubble point, is performed on an integrity test system in the manufacturing area with the values recorded as part of the quality program. Sterilizing grade filters require testing to assure the filters are integral and fulfill their purpose. Detecting a failed filter alerts operators to a problem immediately after batch processing, eliminating delay and allowing rapid reprocessing. Because of the amount and variability of gas flow through large area membrane filters, flaws can be masked which.
The pressure hold test is a variant of the diffusive airflow test. High sensitivity binary gas integrity test for membrane. The purpose of this document is to present the collected best methodspractices to give filter end users the best possible chance of performing a successful wit. The rate of gas diffusion through the liquid follows ficks law, remodelled by reti. Water intrusion integrity testing of hydrophobic membrane. At differential gas pressures below the bubble point, gas molecules migrate through waterfilled pores of a wetted membrane following ficks law of. Integrity tests, like the bubble point, diffusive flow or pressure hold test, are nondestructive tests, which are correlated to a destructive bacteria challenge test. The integritest 4 instrument is an easytouse, portable, fullyautomated integrity test system.
Because filter integrity testing is a critical step in the manufacturing of sterile drug products, it is required by regulatory bodies. Biopharmaceutical division discover the more in millipore. The four integrity test steps are implemented upstream and downstream of the filtration unit in order to be able to detect any possible changes in filter element properties and thereby supply positive results to confirm the success of the filtration step. The filter needs to be moistened with a liquid just like in the bubble point test. Regulated industries such as pharmaceutical, medical device and nuclear require cleanroom certification so filter testing is a necessity. Users can conduct bubblepoint, diffusion, enhanced bubble. Pressure hold test is a nondestructive integrity test based upon the diffusive flow forward flow of a cartridge. Technical brief microfluor ii filter cartridge integrity testing introduction the integrity test is the end users method to confirm the structural integrity of a membrane filter before and after use. This segment is also expected to witness the highest growth during the forecast period. Integrity testing offers nondestructive methods for proving the capability of a. The integrity test is a nondestructive method for the end user to confirm the structural integrity of a lifeassure pda series filter before and after use.
Integrity testing sterilizing filters is a fundamental requirement of critical process. Regulatory agencies require integrity testing of sterilizing grade filters. To detect different pore sizes, the diffusion test pressure for a filter with a given pore size e. Continuous and controlled performance of the filter elements is one of the critical parameters for the process of bioproduction. The water intrusion test is widely used in the pharmaceutical industry to test the integrity of tank, autoclave and lyophilizer vent filters. The filter may be wet by flowing 60% ipa through the vented filter housing or by soaking the filter in 60% ipa for 5 minutes. Diffusion test forward flow test and pressure hold test the diffusion test takes advantage of the natural diffusion of gas molecules according to ficks law. Slowly increase pressure on the upstream side of the filter to the r ecommended test pressur provided by the manufacturer. The single point diffusion test as usually performed is capable of detecting a flaw of 5 to 10. For production operators, supervisors, and validation managers who need to perform onsite filter integrity tests, the integritest 5 instrument is a solution that is easy to learn and gives you the confidence and assurance you need for your test results.
We have 2 sartorius sartocheck 4 plus manuals available for free pdf download. For accurate, reproducible, reliable automatic integrity testing of liquid or gas filters. Bubble point is based on the fact that liquid is held in the pores of the filter by surface tension and capillary forces. Some plants will also integrity test after a run, but before cleaning, to ensure that the run was successful or during production. There are also two methods solely for the use of hydrophobic. To achieve dependable retention, an integrity test can be applied to ensure the absence of oversize pores or defects that can compromise the retention capability of the filter. Palltronic aquawit iv filter integrity test system youtube. Filter integrity testing in the pharmaceutical process. Integrity testing methods integrity testing merck millipore. Dec 19, 2017 the water intrusion test is widely used in the pharmaceutical industry to test the integrity of tank, autoclave and lyophilizer vent filters. The most commonly applied nondestructive integrity test for membrane filters, especially virus filters, is the gasliquid diffusion test.
Saves operator time, delivers a fullycontrolled test sequence enables accurate and reliable testing. Data sheetdata sheet easytouse, portable, networkable, and fullyautomated integrity test systems that offer reliable, repeatable measurements fast. With the outlet valve closed, an entire system is brought to the test pressure typically 1030 psig. Sartocheck 5 plus filter integrity tester keeps your risk. Integrity testing of microfiltration membranes pda. By meeting the present fda definition, the sterilizing filter is conventionally classified as 0. The larger the flaw or a combination of flaw, the higher the diffusive flow. If the pressure is relieved upstream, then the downstream pressure will create backpressure across the membrane and thus irreversibly damage it. Airwater binary gas integrity test for sterilizing and virus. The global filter integrity test market size was estimated at usd 58. Airwater binary gas integrity test for sterilizing and. The minimum pressure required to force liquid out of the pores is a measure of the pore diameter see formula. Test its integrity by performing a simple handheld bubble point measurement.
If the cartridge integrity test will be conducted when the filter is installed in the process system, but the filter requires wetting with a fluid different from the normal process fluid to be filtered, the user may wet the filter in a. Based on type, the market is segmented into the diffusion test, water flow integrity test, and bubble point test. Continuous and controlled performance of the filter elements is one of the critical parameters for. Integrity tests are required by regulatory authorities. There are three integrity test methods used to verify the performance of wettable. Integrity testing of hydrophilic membrane filters reva page 3 refer to figure 1, which represents a typical layout for an integrity test system. Diffusion test and bubblepoint test complete test this test method is a combination of the diffusion and the b. An in specification result confirms the porosity of the filter membrane and that the cartridge is structurally integral. Integrity testing of hydrophilic membrane filter reva page 2 note.
Diffusive flow, pressure hold, and bubble point are acceptable physical integrity tests. Prewetting hydrophilic membranes for integrity testing. There are three types of nondestructive testing the bubble point test, the diffusion test, and the waterflow integrity test for hydrophobic filters hydrocorr test. There are a variety of methods of integrity testing, including the diffusion test and the pressure hold test. The diffusion test and the bubble point test are established, nondestructive test methods. Dec 17, 2015 how to make diffusion test program in filter integrity test. Derived from these challenge tests, specific integrity test limits are established, which are described and documented within the filter manufacturers literature. Water test waterbased integrity test basis ahydrophobic polymers repel water awater intrusion pressure the minimum pressure necessary to force water into the largest pores of a hydrophobic membrane. The methods are detailed in liquid integrity tests and aerosol integrity test. Individual filter products integrity test value applied safety margin nonsterile. In this case, the filter cant be used in production anymore and has to be replaced. Intrusion test is an insitu integrity test for hydrophobic filters. Integrity testing of microfiltration membranes pda journal.
The rate of gas diffusion through the liquid follows ficks law, remodelled by reti 1977. Integrity testing of filters is cen tral to the practice. This ensures the end user that the product they receive will conform to the retention requirements. To further reduce the risk of operator errors when selecting a program the use of the barcode scanner can be set to mandatory. Using a highly accurate gauge, the upstream pressure change due to gas diffusion through the filter in monitored over time. The integrity of these filters and their ability to retain bacteria are traditionally correlated to a nondestructive integrity test, current methods require the use of solvents ethanol, isopropanol, freon to wet the membranes in order to perform bubble point and diffusion integrity tests and the use of these solvents poses several problems.
The pore size of a filter qualified for trial in a sterilization thus is designated by its performance characteristics. The pressure hold test, also known as pressure decay, is dependent on the specified diffusional flow and volume upstream of the filter and downstream of system valve v1. This measurement is taken from the downstream side of the filter housing where a flexible piece of tubing has. Failure mode effects analysis for filter integrity testing. Integrity tests, such as the diffusive flow, pressure hold, bubble point, or water intrusion tests, are nondestructive tests, which are correlated to the destructive bacteria challenge test with 107cm 2 diminuta.
Jan 01, 2008 because filter integrity testing is a critical step in the manufacturing of sterile drug products, it is required by regulatory bodies. These are the main times when a filter should be integrity tested. Filter manufacturer s testing instructions or recommendations may be used as a basis for a validated method. Operator certification course integrity testing methodology. Pdf to ensure that sterilizing grade filters in aseptic processing. However, the bubble point test depends on a subjective visual. To soak a filter cartridge, immerse the cartridge outlet end up in a cylinder of 60% ipa until the core completely fills with fluid. Therefore, filter manufacturers specify the diffusive flow integrity test limits as maximum allowable diffusion value. Apr 01, 2020 based on type, the market is segmented into the diffusion test, water flow integrity test, and bubble point test. The diffusion test in combination with the bp test provides decisive information for the acceptance of a filter element in sterile filtration. Such filter tests are called integrity tests and are performed. Alcohol test issues a alcohol water mixtures are often used due to.