Filter Integrity Testing in the Pharmaceutical Process Environment - Automating filter integrity testing helps to ensure that GMP sterility requirements are met. - BioPharm International


Filter Integrity Testing in the Pharmaceutical Process Environment
Automating filter integrity testing helps to ensure that GMP sterility requirements are met.

BioPharm International
Volume 19, Issue 6

Figure 1. Process integration of a filter integrity tester
Air filters are sterile barriers that typically are sterilized prior to the test step (Process step 1 in Figure 1), at the same time the production system is sterilized. They can no longer be removed for the test or during the test, but may only be accessed from the non-sterile process direction. Since the sensitive measurands (diffusion, bubble point or water intrusion value) can already be determined within the upstream volume, no contact or inflow to the sterile area is necessary and process-relevant sterile barriers remain intact.

Table 1. Typical limit values for different filter types
All of these test methods give results as either a flowrate (diffusion test, water intrusion test, water flow test) or a pressure value (bubble point test, pressure drop test) which has to be compared to the given limit value of the tested filter element in order to pass the test. These limit values are supplied either by the filter manufacturer as part of the validation documents of the filter element, or are determined during a validation process for customer-specific parameters and correlate to a destructive bacteria challenge test.7 Table 1 shows a typical set. Short test descriptions appear in the glossary.


Figure 2. Standard integrity test algorithm 11
The test algorithm described by Figure 1 consists of several steps to be performed by an automated integrity tester (Figure 2). An automated integrity tester therefore needs to be able to handle pressurized air or WFI, in order to pressurize the filter cartridge with the appropriate media. Based on this requirement, hardware such as valves, pressure transducers, and flowmeters are standard components of a today's integrity tester. Typically these parts are controlled by micro-controller-based hardware and run by proprietary firmware (GAMP class 2 or 3).8 Since integrity testers are not only used in a well-defined laboratory environment, but also installed in a rough production process, the integrity tester manufacturer has taken these conditions into consideration. Hardware components should be made of appropriate materials (stainless steels are favored) and have the needed process reliability. Software has to cover the normal operating conditions, and also be able to detect critical changes of process parameters such as temperature or supply media (pressurized air). Often, these requirements are met by an automated functionality test or separate software control loops within the test procedure.

To meet the needs of process integration, most of the available integrity testers have interfaces in order to use additional external hardware. External valves mounted on the filter housing can be handled directly, or controlled by sending commands via a PLC interface. External sensors can be connected in order to perform the measurement directly at the filter housing, because long tubing lengths could interfere with the accuracy of the measurement.

Filter Integrity
Because the WIT and WFT test use WFI as penetration media for the filter membranes, additional dedicated equipment has been developed by most of the integrity test manufacturers. A trolley equipped with a stainless steel vessel stores the needed water volume under sterile conditions. A PLC allows automated CIP or even SIP procedures for the vessel, with valves permanently connected.

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