Pdf filter integrity testing fda guideline on sterile. G difficult to perform insitu particle counter downstream of filter. Total suspended solids by membrane filtration millipore. Total suspended solids by membrane filtration millipore analysis performed by oilfield labs of america closely follows the prescribed methodologies prescribed in nace standard 0173 methods for determining.
Pdf ppt doc filter validation sterile protocol fda guide. The membrane filtration sterility test is the regulatory method of choice for filterable pharmaceutical products. Astm d6908 03 standard practice for integrity testing of. Millipore catalogue integrity testing methods pressure. A typical fourstep integrity test procedure algorithm is figure 1. Integrity testing sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. Oct 17, 2017 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. Integrity testing is used critically at the end of an aseptic filtration process to determine the filters functional integrity and, therefore, the sterility of the filtered fluid. The integrity tests used during this validation study were the forward flow and water intrusion tests. There are three types of nondestructive testing the bubble point test, the diffusion test, and the waterflow integrity test for hydrophobic filters hydrocorr test. Millipore filter integrity test methods free download as pdf file. Global availability allows these methods to be easily transferred to any laboratory, anywhere in the world.
For example, high gas flow at low pressure is observed with either bubble point or diffusion tests. Features integrity testing of hydrophobic membrane fdters sartorius replaces solventbased testing with new water pressure integrity test. Integrity testing of hydrophobic membrane filters sciencedirect. Use of these procedures on other types of filters such as polypropylene or glass fiber cartridges will not give consistent or accurate results. The water intrusion test is widely used in the pharmaceutical industry to test the integrity of tank, autoclave and lyophilizer vent filters. The hydrocorr test specifications are correlated to the bacterial challenge test.
Get a free demo of our palltronic flowstar iv filter integrity test instrument unique design the palltronic flowstar iv filter integrity test instrument is a highly sensitive measurement instrument which is designed for use in all locations including the laboratory or inside the process suite or cleanroom. Designed with process scaleup and applications development in mind. 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. An in specification result confirms the porosity of the filter membrane and that the cartridge is structurally integral. Millipore and customer specific filter testing information can be easily entered onsite. Contamination monitoring product guide devices and systems for industrial qc sample. The purpose of this document is to present the collected best methods practices to give filter end users the best possible chance of performing a successful wit. 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. Air filtration also needs a filter integrity test method to guarantee the sterility of critical parameters. 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.
Ultrafiltration uf is a membranebased separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove lowmolecularweight lmw impurities or exchange buffers. Integritest 4 filter integrity test instrument xit4s0001. Millipore value millipore contamination analysis kit consists of assorted millipore filtration products suited for contamination measurement and control. This, in combination with an eventbased capture of the flow curve, gives you the most reliable, sustainable method of bubble point testing.
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. 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. Seitz bubble point test xlii appalachian state university. Automated integrity test systems are very sensitive to temperature changes. Integrity testing integrity testing methods integrity testing sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. All integrity test procedures outlined below should be followed when performing integrity testing of membrane filters only. Although the procedures for millipore testing are usually very well written and precise, there is still occasionally reason to question the results. Integritest 4n integrity test instrument network and administrator manual, 0101797pu. A target product is retained by the membrane while lowermw. A combination of a unique approach to quality risk management as well as optimal data integrity, intuitive usability and minimized risk factors for health, safety and environment hse set a new standard for filter integrity test devices. The forward flow integrity test in the forward flow test, a filter is wetted with a suitable test liquid and a predetermined gas pressure.
Water intrusion integrity testing of hydrophobic membrane. If the filter is not installed correctly, water or air may bypass the filter membrane and give an incorrect test value. Procedure for the determination of particulate contamination of hydraulic fluids by the particulate count method arp 1953. Thus, forward flow, bubble point and pressure hold integrity test methods are suitable for sterilizing membrane filters with pore sizes ranging from.
Use of this procedure on other types of filters such as polypropylene or fiberglass depth media cartridges will not give consistent or accurate results. Trends in manufacturing of sterile medicinal products by. The nominal mw limit of uf membranes ranges from 1,000 da 1 kda to 1,000,000 da 1,000 kda. Upstream pressure decay measurements are used to determine the actual downstream. Please join randy wilkins, technical consulting team manager at merck millipore, for this webinar highlighting best practices and key considerations for performing filter integrity tests. 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. Absolute ratings can only be applied to membrane filters see definition below due to the requirement of a definable pore. Biopharmaceutical division discover the more in millipore. Water intrusion integrity testing of hydrophobic membrane filters. 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. Considerations in preuse poststerilization integrity. 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. Pdf filter integrity testing fda guideline on sterile drug. Typical bubble point values for microfilters range between 3,000 mbar and 4,000 mbar and, in ultrafiltration, can go up as high as 8,000 mbar.
It also demonstrates a simple low cost method of testing that does not required spending thousands of euros on complicated electronic. Acceptance test procedures and standards to ensure clean fuel system components. Such a filter can be integrity tested using a nondestructive test method and the data can be used to determine the actual size of the largest pore. Before sterilization, a preuse test will confirm that a filter is installed properly and was not damaged during shipment or handling. Filtration is a common method of sterilizing drug product solutions. For processes requiring inseries integrity testing e. Understanding terminology in regards to filter ratings. Inline integrity testing of the filter before the process avoids potential time loss and rejected. Filter integrity testing fda guideline on sterile drug products. Integrity testing methods integrity testing emd millipore. Test results can be printed using the builtin printer. Palltronic flowstar iv integrity test instrument pall shop. Gross failure is typical of truly non integral filters. There is a method for checking these filter element properties throughout the course of the processthe filter integrity test.
Bubble point integrity test introduction there are 3 major tests used to determine the integrity of a membrane filter. The rugged, ergonomic design of the system enables users to easily carry the integritest 4. It ensures that the membrane is integral, and that the cartridge is not damage or installed incorrectly. Principles of steaminplace jeanmarc cappia a millipore corpora tion steaminginplace sip is a. Global filter integrity testing market is expected to reach usd 86. Insert the syringe male luer into the acro 50 vent filter, and orient the outlet in. Bubble point filter integrity testing syringe filter duration. Jul 28, 1998 in the case of integrity testing of hydrophobic filters using the water flow test technique, the upstream side of a dry hydrophobic filter is exposed to water at a constant pressure equal to, or slightly below, the minimum intrusion pressure required for the filter, and a measurement of the water flow rate into the filter housing is made. A number of regulatory guidelines recommend preuse integrity testing of critical sterilizing liquid filters for aseptic processing. The unsurpassed quality and consistency of results they provide has led to the creation of many sample preparation methods specifying millex filters. This is done to ensure that the filter meets specification, is properly installed and intact during filtration, and to confirm the rating of the filter. Verifying the integrity of a membrane fi lter ensures that it is truly removing all contaminants at its rated pore size.
Biopharmaceutical manufacturing downstream processing sterile filtration integrity testing c189432integrity assurance with ease and confidence the integritest 5 is an easytouse, portable, and fullyautomated instrument that verifies the integrity of filters or processing equipment. Because water flow through an integral filter is minimal, it can be used in place after sip. Millipore s water flow integrity test hydrocorr meets fda requirements for integrity tests of sterilizinggrade cartridges. Hplc is very sensitive, quantitative, accommodating of sample reactivity or volatility, and compatible with high. Standard practice for integrity testing of water filtration. Filter integrity testing systems sartocheck 3 plus 319 description this unit supports all established integrity test methods and is characterized by its intuitive and easy handling.
Any integrity test is meaningful only when it can be correlated to specific microbial retention characteristics. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, 18ffdg and 11cpib. Millipore testing is a very popular method of measuring and verifying part cleanliness. Prove the filter removes bacteria from the stream per astm 83805. The hydrocorr test is a highly sensitive, nonalcohol, water flow integrity test for hydrophobic membrane filters. Fill a 10 ml or larger syringe with a fresh solution of 6040 isopropanolwater. The integritest 4 instrument features a graphical user interface with touchscreen menus and toolbars. Bubble point test, the forward flow test, and the pressure hold test. All major filter suppliers recommend the forward flow test as the method of choice for integrity testing of filter cartridge or capsule assemblies. All three tests are based on the same physics, the flow of a gas through a liquidwetted membrane under applied gas pressures.
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. Test to determine the functional performance of a filter system. Global filter integrity testing market by test type. Diffusion specification at 680 mbar 10 psi test pressure for a 0. Find msds or sds, a coa, data sheets and more information. The individual graphs for a waterwet integrity test can now be compared to the product wet test and a possible shift evaluated. There are 3 major tests used to determine the integrity of a membrane filter. It is a nondestructive test that has been correlated to bacteria retention and validates the performance of the filter cartridge. Integrity test is really means of fiber repair procedure. Prove the sterilization method is effective and does not compromise the filter.
Preuse post sterilization integrity testing pupsit. Bubble point method an integrity test kit is available to aid in this test. Water intrusion test for filters millipore corporation. In addition to classical contamination monitoring methods gravimetric, microscopic, colorimetric, chromatographic separation methods, such as high performance liquid chromatography hplc, have become popular in industrial qc testing. Successful filter integrity testing using water intrusion test. Printed test results can be customized to include operator, batch, or other desired data. The forward flow test is the filter integrity test that is most common in pharmaceutical manufacturing. Integritest 4n integrity test instrument central instrument management tool installation and operators manual. Follows similar procedures to hydrophilic membranes. Compatibility of the filter under actual use conditions should be demonstrated which may be done by integrity testing the filter before and after exposure to the expected process conditions. Total suspended solids by membrane filtration millipore summary. What are the effects of temperature on automated integrity testing. Water intrusion integrity testing of hydrophobic membrane filters instructions the integrity test procedure outlined below should only be used for hydrophobic membrane filters.
Total suspended solids by membrane filtration millipore analysis performed by oilfield labs of america closely follows the prescribed methodologies prescribed in nace standard 0173 methods for determining quality of subsurface injection water using membrane filters appendix csupplementary suspended solids test methods. Integrity tests, such as the diffusive flow, pressure hold, bubble point. Millipore test kit is recommended for ensuring conformance to cleanliness standards popularly known as the millipore value. Note that integrity testers should be programmed to reflect the filters they are testing and that all integrity testers work with all manufacturers filters. This booklet is designed to provide a basic understanding of methods for testing the integrity of millipore membrane. Filter integrity testing in the pharmaceutical process. Integrity testing of hydrophilic membrane filters reva page 3 refer to figure 1, which represents a typical layout for an integrity test system. Integritest 4 series automated filter integrity test. Integrity test is very essential to evaluate whether the moduleelements present state is good or it is going to end of life. This booklet is designed to provide a basic understanding of methods.
Solventbased integrity testing of hydrophobic filters used in pharmaceutical and biological applications is difficult to perform in situ following sterilization because of the risk of downstream solvent contamination. The user, through its own analysis and testing, is solely responsible for making the. Validation of sterilising and virally retentive filters michael payne knowledge development manager. Membrane filtration sterility test merck millipore. 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 methods integrity testing sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. Ai di r usionan bubd blepoint testsa e r normalyolnly complted when ue ing s piloandtp ro ductcaleioequnpmisent. Oct 19, 2017 pdf ppt doc pharmaceutical filter validation sterile protocol fda guide with filter validation ppt,filter validation pdf, brevundimonas diminuta filter validation, filter validation millipore, filter validation fda, pharmaceutical sterile filtration validation protocol, bacterial retention testing of sterilizinggrade filters, sterile filtration definition.
Automatic integrity test instrument qualification millipore validation engineers, familiar with the operation, can provide onsite assistance with performing installation qualification iq and operational qualification oq. Validation of sterilising and virally retentive filters. Identify, quantify, and assess impact of compounds that migrate from filter to process stream. The sartocheck 3 plus is not encumbered by the 21 cfr part 11 code as it is a paper based system and does not store test results electronically. The procedure is described in the blog millipore testing. Operator certification course integrity testing methodology hydrophobic filter integrity testing. 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. Millipore catalogue integrity testing methods free download as pdf file. Prove the filter does not adversely affect the process stream.
The test is very useful for out to in flow style element like dow and hyflux. Integritest 4 filter integrity test instrument cas find msds or sds, a coa, data sheets and more information. Millipore waterbased test for hydrophobic filters tests on a wide range of filters including disks, cartridges and tff filters, virus, and asymmetric membrane filters. Millipore filter integrity test methods flow measurement. The test is particularly suitable for samples containing preservative, bacteriostatic or fungistatic compounds, which inhibit microbial growth of potential contaminants.