Filter validation

Multiple use of sterile filters?

Written by Dr. Janet Thode on . Posted in Filter validation

 

Some time ago, I received a very interesting request that I’d like to use as an opportunity for writing this blog article.

 

The question

According to the draft of the revised Annex 1 "Manufacture of Sterile Medicinal Products" of the EU GMP guidelines, sterile filters should be discarded after having been used. Multiple use is excluded, with the exception that a use for more than one working day has been validated. This phrasing is not quite unambiguous. So how should we interpret the following requirement "Liquid sterilizing filters should be discarded after the processing of a single lot. The same filter should not be used for more than one working day unless such use has been validated." (8.89)?

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Influence of polysorbate 20 on the filter integrity test of a PVDF sterile filter

Written by Gastautor on . Posted in Filter validation

As part of the release testing of parenteral pharmaceuticals, sterility of the pharmaceuticals must be ensured after filling. Since a direct check of every filled vial or every syringe cannot be performed, the sterile filters are checked for their integrity, more precisely for their pore diameter, instead. According to the specifications of the WHO, a pore diameter of maximum 0.2 µm is allowed for sterile filtration [1]; accordingly, filtration with a sterile filter possessing a pore diameter of 0.2 µm or less results in a sterile filtrate.

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Why should a maximum pressure of 30 psi be applied to the bacterial retention test?

Written by Dr. Janet Thode on . Posted in Filter validation

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.

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Modified bacterial challenge tests - what to do in case of bactericidal product solution?

Written by Dr. Janet Thode on . Posted in Filter validation

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 F838-20. 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...

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How is the filter’s bacterial retention capability connected with its integrity?

Written by Dr. Janet Thode on . Posted in Filter validation

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 F838-20. 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.

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Validation of bacterial retention - thought about filter integrity test parameters?

Written by Dr. Janet Thode on . Posted in Filter validation

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.

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