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

Written by Dr. Janet Thode 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.

For example, Millipore Durapore PVDF 0.22 µm membranes are possessing 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.

Some research pointed to an interesting book [2], which brings light into the darkness. Although high filtration pressures initially lead to higher flow rates, they reduce the possibility of removing potential deposits, which - as time goes by - may lead to filter clogging. Thus, in sterile filtration purposes, where filtration efficiency is an important factor, differential pressures greater than 29 psi (2 bar) are not recommended. This limit can be found in the HIMA recommendations from 1982 [2], from which in the following year the bacterial challenge test as ASTM F838-83 arose.

So far the history. What’s the current situation?

According to the PDA technical report 26 [3], the same conditions as in routine production must be applied when performing the bacterial challenge test ("under simulated process conditions"). This means using the routine transfer pressure, but also applying a significantly increased pressure for a short time (which occurs during integrity testing) to cover this as well (more about this topic can be found here). Furthermore, for products that are not prone to filter blocking, bacterial retention studies with higher process pressures are certainly no problem from a regulatory point of view.

 

[1] Jornitz MJ, Jornitz MW, Meltzer TH (Eds) 2008, Filtration and Purification in the Biopharmaceutical Industry, New York: Informa Healthcare, 2nd edition, Volume 174, ISBN: 978-0-8493-7954-3

[2] Health Industry Manufacturers Association (HIMA) 1982, Microbiological Evaluation of Filters for Sterilizing Liquids, Document No. 3 Volume 4

[3] Antonsen HR et. al. 2008, Sterilizing Filtration of Liquids. Technical report no. 26: (revised 2008). PDA J Pharm Sci Technol. 62(5 Suppl TR26)