30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Armin Hauk, Elke Jurkiewicz, Ina Pahl, Thomas Loewe, Roberto Menzel
This publication describes the development of an experimental set-up and testing protocol to test the hypothesis that filters used for sterile filtration can act as scavengers of leachables. The filter materials polyethersulfone (PESU) and cellulose acetate (CA) were tested. These membrane materials are used commonly in downstream operations during biopharmaceutical manufacturing. A solution containing a mixture of eight typical leachables was filtered through the respective filter and the eluate was monitored by HPLC-UV in order to quantify these leachables model compounds (LMC). The results show that substances are efficiently scavenged from an aqueous solution depending on their molecular structure and the filter type used. A mass balance was established by recovering the LMCs from the filters by rinsing the membranes with an organic solvent. Breakthrough curves were determined experimentally and substance specific filter capacities for the individual LMCs are presented. The surface specific filter capacity for the different LMCs range from <0.7 to 45 μg/cm2
. An extrapolation of these filter scavenging capacities to process conditions, where the filtration areas can be many square-meters in size, gives indication that the potential removal of expectable process-related leachables during filtration in downstream processing should not be underestimated. The capacity of a filter for the leachable bDtBPP, which is known to inhibit cell growth, was determined in samples after a buffer sterile-filtration using a standardized cell-culture test with CHO cells. The specific filter capacity of bDtBPP obtained with the cell-culture test was nearly identical to the analytically derived result. As outlook, the scavenger effect of a filter is demonstrated for media solutions containing buffer and model proteins.