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. In addition to filter integrity tests this instrument is also capable of checking unknown volumes e. In manufacture of heat labile sterile drug products, the final step involves filtration through sterilizing grade filters. Test results are automatically printed using the builtin thermo printer.
The integrity of other filters should be confirmed at appropriate intervals. Preuse, poststerilization filter integrity testing for single. Palltronic aquawit iv filter integrity test system youtube. Filter media hollow fiber membrane hfm storage temperature above 32 f 0 c do not freeze the hollow fiber membrane hfm is a collection of small porous tubes that can be damaged by dropping or freezing. Integrity test measurements depend on the surface area of the filter, the polymer of the membrane, the wetting fluid, the pore size of the membrane, and the gas used to perform the test.
We have 2 sartorius sartocheck 4 plus manuals available for free pdf download. A broad issue for singleuse filter users and suppliers across north america and europe is the preuse integrity testing of sterilizing filters in singleuse systems. Functionality test programs in the test program, the procedural steps and the parameters are set down for the filter integrity test. Many users now use this parameter or a combination of bubble point and 10 lpm to determine an elements fitness for reuse. A guide for selecting the correct filter integrity test. Pda points to consider relating to eu gmp annex 1 changes. Wetting fluids may have different surface tensions, which can depress or elevate the bubble point pressure. Selecting the right filter integrity test instrument is an important task. This sop shall be is applicable for hvac system, laminar air flow stations and air handlers of process equipment. Keep in mind, the least likely reason for an integrity failure is a nonintegral cartridge.
The water intrusion test is widely used in the pharmaceutical industry to test the integrity of tank, autoclave and lyophilizer vent filters. Slowly increase pressure on the upstream side of the filter to the r ecommended test pressur provided by the manufacturer. There are three integrity test methods used to verify the performance of wettable. 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. The global filter integrity test market size was estimated at usd 58. For bidirectional protection, a small, sterile vent filter can be installed directly in the test line between an integrity tester and filter cartridge housing. Iii foreword the purpose of the nebb procedural standards for certified testing of cleanrooms is to establish a uniform and systematic set of criteria for the performance of cleanroom testing and certification.
Using a highly accurate gauge, the upstream pressure change due to gas diffusion through the filter in monitored over time. Prewetting hydrophilic membranes for integrity testing. When the designated pressure is reached on the pressure gauge a spurt of. Most manufacturers, including graver technologies, conduct an integrity test on each universal segment andor finished cartridge prior to release to provide assurance that the cartridge will. Water intrusion integrity testing of hydrophobic membrane. Seitz bubble point test xlii appalachian state university. Sterilizing grade filters require testing to assure the filters are integral and fulfill their purpose. Procedural standards for certified testing of cleanrooms 2009 third edition national environmental balancing bureau 8575 grovemont circle gaithersburg, maryland 20877 3019773698 3019779589 fax. Bubble point test procedure a forward bubble point integrity test is a procedure which measures the pressure needed to be applied to the upstream side of a filter causing bulk or open pore flow through the largest pores of a wetted filter. A novel nondestructive integrity test for microporous and ultraporous membranes has been developed that is far more sensitive to detecting defects than a conventional gasliquid diffusion test. Regulatory agencies require integrity testing of sterilizing grade filters. Where the claimed purpose of the filter is to sterilize, pre and post filtration integrity tests should be performed.
The integrity of the sterilised filter should be verified before use and should be confirmed immediately after use cases in eu where major deficiencies assigned to manufacturers based on failure to pupsit. The flowstar iv instrument introduces many new features, enabling users to reliably and reproducibly test even more filters and in less time, saving time and. Feb 27, 2019 equally, once the unit is installed in the users production site, the test should be performed promptly to verify the integrity of the filter as well as the installation. The procedures and apparatus to characterize other parameters, of concern in cleanrooms and clean zones used for specific products or processes, are discussed elsewhere in other documents prepared by isotc 209 for example, procedures for control and measurement of viable materials iso 14698, testing. An in specification result confirms the porosity of the filter cartridge. Integrity tests are required by regulatory authorities. Multipoint diffusion testing offers the ability to test the filter s performance and, especially, to plot the entire diffusive flow graph through the bubble point. Integrity testing fit for use focus on these 3 elements of validation sterile filter master extractables plan prove the stream does not adversely impact the filter. Cartridge integrity test bubble point refer to figure 1, which represents a typical layout for an integrity test system. An additional port allows the connection of an external printer. One method used widely to check integrity of a filter is the bubble point test. A filter integrity test is a critical unit operation commonly employed in pharma industry. For both of the most commonly used filter integrity it tests, the forward flow test and the bubble point. There is a method for checking these filter element properties throughout the course of the processthe filter integrity test.
Successful wetting for filter integrity testing in volume. Note not all cleanroom parameter test procedures are shown in this part of iso 14644. Integrity test water or solvent v q, l q, l sterilization method, effects on filter integrity v q q leachables v extractables v q q chemical compatibility, effects on filter integrity v q q bacteria retention in product v bacteria retention in water, saline lactose broth slb q, l q with integrity test correlation in water or solvent. The dispersed oil particulate dop scan testing, also known as filter integrity testing, or leak testing, is one of the most quoted methods by industry standards. Propanol2, methanol, tert butyl alcohol, or a mixture of one of these and water. Industry, based on knowledge of integrity failures. Push the air from the syringe out, until the pressure gauge reaches 60psi for 0.
Detecting a failed filter alerts operators to a problem immediately after batch processing, eliminating delay and allowing rapid reprocessing. Membrane filters have been used successfully for many years to remove yeast, bacteria and particulate from fluid streams. Disconnect the integrity testing apparatus from the filter housing. Integrity tests, like the bubble point, diffusive flow or pressure hold test, are nondestructive tests, which are correlated to a destructive bacteria challenge test. Place the end of the silicone tubing into the beaker so that it is submerged in the water. Pressure hold test is a nondestructive integrity test based upon the diffusive flow forward flow of a cartridge. Dec 06, 2017 one of the best ways to test the nondestructive integrity test is the bubble point test. Integrity testing of membrane filters integrity testing ensures that membrane filters are removing their target microbial contaminants and that there is no bypass occuring due to the filters or housing components. A programmed test program can be loaded into the test unit and the test will be run independently.
Filter integrity testing troubleshooting guidelines. The integrity test is a nondestructive method for the end user to confirm the structural integrity of a lifeassure bna045 or bna065 series filter cartridge before and after use. Filter integrity testing fda guideline on sterile drug products. To ensure that sterilizing grade filters in aseptic processing worked as required, such filters are integrity tested. Integrity testing sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. Oct 16, 2014 here i present an engineering approach for preuse poststerilization integrity testing that already has been implemented on several production sites. The data from the testing is provided on a label on every filters stating test airflow, resistance to. Published values selection of the proper integrity test value is critical. 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.
The automated test instruments that are used for filter integrity testing have been improved during the over 40 years that filter integrity testing has been performed. Prove the filter removes bacteria from the stream per astm 83805. Standard operating procedure to test the integrity of hepa filters installed in hvac air handling system by hepa filter integrity testing using pao aerosols. The subject has received considerable discussion lately, with differences in regulatory requirements and risk assessments being considered. Pdf filter integrity testing fda guideline on sterile drug products doc ppt a filter integrity test is a critical unit operation commonly employed in the pharma industry. It is a nondestructive test that has been correlated to bacteria retention and validates the performance of the filter cartridge. If appropriate, remove the filter cartridge from the housing used for wetting the cartridge, drain all excess wetting solution from cartridge and install it into the housing used for the integrity testing. Sartorius sartocheck 3 plus operating instructions manual pdf. The sartocheck 5 plus is the only vhp compatible filter integrity tester on the market. Open the air vent of filter housing so that air is removed form the vent and close the air vent when water for injection or iso propyl alcohol droplet starts oozing out.
The optional accessory kit for external venting consists of a venting valve and a blocking valve and includes a pressure sensor that is identical to the one used inside the sartocheck 5 plus. An informed, balanced choice will support the seamless integration of the instrument into critical processes and provide troublefree operation for years to come. This measurement is taken from the downstream side of the filter housing where a flexible piece of tubing has. The technology to perform a post sterilization preuse filter integrity test is available. A post sterilization integrity test provides meaningful data about filter integrity, pall biotech therefore advocates and supports the application as recommended by the above guideline. Sartocheck 5 plus filter integrity tester sartorius.
Follow filter integrity test to inspect filter to detect possible damage. Pdf filter integrity testing fda guideline on sterile. The methods are detailed in liquid integrity tests and aerosol integrity test. It is a critical step that must be correctly performed to ensure product quality. Furthermore, the multipoint diffusion test enables the establishment of an improved statistical base to determine the product wet versus waterwet limits. Integrity testing methods integrity testing merck millipore. Because the measurement is upstream of the filters, any risk to downstream sterility is eliminated. A typical fourstep integrity test procedure algorithm is figure 1. 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. Use of a hydrophobic protective filter in the test line. Integrity testing of hepa filters cleanroom technology. An automatic filler integrity testing machine was validated by challenging the units ability to differentiate between integral intact and nonintegral filters using a manual method as a standard. Preparation, use, and integrity testing of pall ultipor vf. Integrity testing is recommended in the pall biotech instructions for use usd 2441a.
Saves operator time, delivers a fullycontrolled test sequence enables accurate and reliable testing. Validation of an automated filter integrity tester for use in. In situ aerosol filter testing is a black art to many, but the new isoen146443 test methods standard incorporates two in situ test methods that are discussed here by neil stephenson of dop solutions. Thoroughly wet the filter with appropriate test fluid, typically water for hydrophilic membranes or an alcoholwater mixture for hydrophobic membranes. Pupsit of product filters pda ptc ap part 1, section vi, topic j annex 1, 2008. If the filter is not installed correctly, water or air may bypass the filter membrane and give an incorrect test value.
Under this process, the fluid is held in the pores of the filter by capillary forces and surface tension. Sartorius sartocheck 4 plus manuals manuals and user guides for sartorius sartocheck 4 plus. Operator certification course integrity testing methodology. Feb 20, 2018 for accurate, reproducible, reliable automatic integrity testing of liquid or gas filters. Preparation for preuse integrity testing while water as a wetting fluid may be acceptable for performing a preuse integrity test, there can be process benefits from the use of alcohol. Oct 19, 2017 the individual graphs for a waterwet integrity test can now be compared to the product wet test and a possible shift evaluated. However, the bubble point test depends on a subjective visual. Article 25 integrity test time after the sterilization filter is used, the integrity of the filter must be checked and recorded immediately with appropriate method. Integrity testing is a critical quality assurance process when using hydrophilic membrane filter cartridges in applications requiring bioburden control. Validation of an automated filter integrity tester for use. 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.
Sop for dop testing of hepa filters filter integrity testing. The test is recommended to be repeated at regular time intervals to verify the continued efficiency of the filter. Connect the compressed air supply to the inlet of integrity testing instrument. Connect the filter housing inlet to outlet of integrity testing instruments. This correlation verifies the integrity test limits the filters have to pass. Preuse, poststerilization filter integrity testing for. Successful filter integrity testing using water intrusion test. Integrity is tested according the pressuredrop method, for which the correlation to the integrity test value is explained in pda technical report 26 1. Integrity testing lifeassure bna045 and bna065 series filter. Performing filter integrity tests is a requirement by regulatory agencies fda, eu when a product is labeled sterile. Prior to use of the sterilization filter, a risk assessment shall be carried out to determine whether the integrity test is to be implemented before or after sterilization. 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. Accessory kit for external venting prevents backflow. The integrity of the sterilised filter should be verified before use and should be confirmed immediately after use also confirmed in pi 0076 why preuse, poststerilisation.
To lay down the procedure for dop testing integrity testing of hepa filter. There are also two methods solely for the use of hydrophobic. Processing and hold time limits, including the time limit for sterilizing filtration. Continuous and controlled performance of the filter elements is one of the critical parameters for the process of bioproduction. An indication of an improperly prewet filter is an improved integrity test value upon subsequent retest. Such filter tests are called integrity tests and are performed. One of the best ways to test the nondestructive integrity test is the bubble point test. By definition all hepa filters are individually certified as to conformance with their target efficiency and higher efficiency filters are 100% scanned for leaks. Integrity testing sterilizing filters after a batch has been filtered can detect if the integrity of the filter has been compromised during the process. Page 6 preparation, use, and integrity testing of pall ultipor vf dv20 filter cartridges and capsules 3.
Pdf ppt doc filter validation sterile protocol fda guide. During the integrity test, whether manually or using an integrity test instrument like the sartocheck 4 plus, potential false filter integrity test failures can occur. Instead of blocking the process line, filter integrity is performed in a filters housing in situ on an automated test bench off line. Diffusion test and bubblepoint test complete test this test method is a combination of the diffusion and the b. Filter integrity testing can be conducted manually or via an automated integrity. The palltronic flowstar iv instruments and palltronic aquawit iv systems represent the latest generation of bestinclass integrity test equipment. Laboratories ul also provides guidance as to hepa filter testing. Identify, quantify, and assess impact of compounds that migrate from filter to process stream. Oct 17, 2017 a filter integrity test is a critical unit operation commonly employed in the pharma industry. Fda guidelines require integrity testing of filters used in the processing of sterile solutions such as large volume paren terals lvps and small volume parenterals svps.
An automatic filler integrity testing machine was validated by challenging the units ability to differentiate between integral intact and nonintegral filters using a. 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. The individual graphs for a waterwet integrity test can now be compared to the product wet test. Biopharmaceutical division discover the more in millipore. To confirm that the filter used is integral, postuse integrity test is made obligatory by. The basic principles of filter integrity testing bubble point test are explained. The nature of bubble point test practically all that is done is the most significant pore size of the filter. Filter integrity testing in the pharmaceutical process. Successful wetting for filter integrity testing in. Water test resistance to water intrusion force water under pressure onto the surface of the filter. Pdf filter integrity testing in liquid applications.