Recently, I've been asked if I know why the ASTM F838 bacterial challenge test sets a maximum pressure of 30 psi (= 2.07 bar). Should this limit not be exceeded as no retention capability of the filter upwards can be provided? The answer to this question is a clear no. Filter membranes are still bacteria-retaining even at much higher pressures. For example, Millipore Durapore PVDF 0.22 µm membranes are possesing a water-wetted bubble point of 3.45 bar, which correlates with bacterial retention (see also our blog article "How is the filter’s bacterial retention capability connected with its integrity?"). So this is not the reason.
For pharmaceutical companies that manufacture their products under aseptic conditions, sterile filtration is the last step before filling. The validation of the manufacturing process also includes the step of sterile filtration. Accordingly, it must be demonstrated by filter validation that the filter is able to retain bacteria and thus ensure the sterility of the product. This evidence is provided by a bacterial challenge test according to ASTM F838-15a. But, before this bacterial challenge test can be performed, it must be checked by a viability test that the product solution has no negative effect on the bacterium used in the bacterial challenge test. That sounds complicated? It shouldn’t - just imagine what would happen if your product solution is killing the test bacteria... You wouldn’t know if you get a sterile filtrate in the bacterial challenge test due to the fact that the filter did a good job or due to the fact that your product solution already killed the bacteria.
Sterile filters are used in pharmaceutical production, in particular in aseptic manufacturing of parenterals. As part of filter validation, evidence must be provided that the filter used for sterile filtration is able to retain bacteria and potential undesirable components such as particles or fibers, thereby ensuring the sterility of the product. The corresponding test is the bacterial challenge test according to ASTM F838-15a. Therefore, the filter is flown with a defined number of particularly small bacteria (Brevundimonas diminuta) in solution and subsequently, the filtrate is examined for bacterial growth. A sterile filtrate shows that the filter is able to retain > 107 CFU/cm2 filter surface area and is therefore suitable for its intended use.
In this blog article the influence of filter integrity test parameters on bacterial retention will be discussed.
Sterile filters can be used during the manufacture of parenteralia for example. If the product is is a protein solution two filtration steps are required for aseptic preparation. First a bioburden reduction filtration and directly before filling a sterile filtration.