Filter Integrity Testing

A filter testing procedure will be developed to ensure that bacterial retentive air and liquid filters are integrity tested and replaced as necessary. This program will include those filters not directly in the process stream, such as vent filters on tanks and autoclaves, and compressed gas filters. This procedure will include filter integrity testing instructions, schedules, and acceptable test results. 

Filters that are directly in the process stream, such as product sterilizing filters and media sterilizing filters, will be tested before and after the processing of each batch and documented in the actual batch production records. 

The automatic filter integrity tester will be operationally qualified, and all test parameters and acceptable test results will be verified in the Operational and Performance Qualifications of the equipment, for example, the Sterilizing Filter and the Media Preparation System. 

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Filters used in the system (commonly at point of use) should be included in a routine filter integrity testing program. Establish the life cycle of the filters to maintain the system. 

Filter Integrity Test prior to and after Sterilization... 

Filter Integrity Test after Product Filtration... 

HEPA filter integrity testing is performed at 6-month intervals on level I and level II HEPA filters. HEPA filter testing includes Measuring (Machines, Eilters, Diffusers) Inlet and Outlet Air Velocity or Volume and Integrity Test of HEPA Filters Using Aerosol and Photometer. Refer to (provide reference to attachment no.). 

In modern freeze-drying systems, the filter integrity test is carried out automatically. All the relevant process parameters are documented by the control system of the unit. The important thing is to make sure that after every integrity test, the filter and the entire piping system are perfectly dry. This is effected by means of the installed liquid ring pump. 

When the filter integrity test fails, the sterile filtration process must be rejected. 

Once the materials have been sterilized, interventions near either the formulation or product contact surfaces/parts should be minimized. Direct handling of these materials should only be done with sterilized tools or implements nonsterile objects, such as operator gloves, should never directly contact a sterilized surface. Sampling, filter integrity testing, process connection, and other activities should all be designed to eliminate the need for personnel exposure to sterile items. 

Meltzer, T., Agalloco, J., et al. (2001), Filter integrity testing in liquid applications Revisited, Part 1, Pharm Technol, 25(10), and Part 2, Pharm Technol, 25(11). 

ISO 13408-1 First Edition, 1998-08-1, Aseptic Processing of Health Care Products, Part 1 General requirements Section 17.11.1 Investigation, m. pre- and post-filter integrity test data, and/or filter housing assembly ... 

The deficiencies and nonidealities that occur in bubble point testing should not be taken as contraindications of the usefulness of the method for in-process nondestructive filter integrity testing. It is in fact an extremely valuable in-process test. Its limitations should be understood and its value confined to comparing one filter with another of the same type. 

Qualification data (records) of the isolator should at least cover installation qualification (IQ), i.e., integrity and leakage test, filter integrity test, filter mounting integrity test, instrument check and calibration as well as functional check of all operating systems. 

The sterilization efficiency of the inlet venting Alters has to be assured by regular integrity tests. The filter integrity test should be performed automatically with the relevant data documented by the control system the principle is shown in Figure 20. The criteria for an integrity test given by the Parenteral Society [10] are summarized as ... 

The air quality class determines the type of HEPA filter (see Table 27.4) mounted in the inlet grid and the thereby raised air friction. All HEPA filters should be entered into a maintenance plan at least once a year a leakage test and a filter integrity test should be performed [5]. 

Filter tests must be performed by the manufacturer before release to the market and by the individual user also, to ensure that the membrane filter complies with the specifications, is undamaged, and is eventually placed correctly in the filter case by the user. As described before in this chapter, such a test should in fact be performed with Brevundimonas diminuta. However, in daily practice this is not possible for the user in the pharmacy, and thus test methods have been derived, which are based on the physical properties of the membrane filter. Such test methods are called filter integrity tests. 

In practice the filter integrity tests are performed with a dedicated filter test apparatus, suitable for the type and brand of membrane filter holders or filter candles in use. Most of the time all types of filter tests can be executed with this apparatus, and the results are printed or uploaded to a computer file, for control by a qualified operator and release of the tested filter. 

Qualification and validation can be outsourced. However, the responsibility remains in-house so the craitract-taker has to be approved according to current GMP requirements for outsourced activities [10]. For example, the following qualification and validation items can be outsourced LAF cabinets, safety cabinets, HVAC-systems, sterilisers, rinsing machines and devices for performing filter integrity testing. When tasks of qualification and validation are outsourced, internal approval of protocols, raw data and reports have to take place according to internal procedures. 

Filter integrity test passed using qualified device... 

Filter integrity testing equipment Usually, existing processes are validated retrospectively. Here a representative period is considered in which the process took place without adjustments, e.g. 3 years. 

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