Category: Manufacturing and Bioprocessing
Purpose: The purpose of this study was to compare hold-up volumes of pleated and stacked disc filters after two different filter draining procedure to identify ‘best practice’ for maximizing product recovery.
Methods: The hold-up volumes of a range of market-leading commercially available capsule filters containing pleated polyether sulfone (PES) and polyvinylidene fluoride (PVDF) sterilizing-grade membranes were compared following filter draining and after blow-down through the filter inlet with a short pressure hold above the filter’s bubble point specification. The holdup volumes of pleated capsule filters were compared to Millipak® Final Fill stacked disc filters following blow-down. A minimum of three replicate filters were tested for each condition.
Filter drain hold-up volumes were determined by weighing each dry unit then filling the filters with water. Fittings were removed so the liquid downstream of the filters could drain by gravity. Filters were then inverted to allow upstream liquid to clear, and the drained filters were weighed: hold-up volumes were calculated as the difference between the weight of the dry and drained filters
The hold-up volumes following blow-down were determined after connecting an air source to the inlet of pre-wet filters and applying pressure to exceed the filter’s bubble point specification by 20 psi for one minute. After blow-down, the filters were disconnected and weighed: hold-up volumes were the difference between the dry and blown-down filters.
Results: Filter hold-up volume is dependent on the method of blow-down: more liquid is removed if the filter is blown down with air rather than simply allowed to drain by gravity. Figure 1 shows the hold-up volumes of pleated filters following a gravity drain and following blow down at 20 psi above the filter’s bubble point specification for 1 minute.
Figure 1. Mean hold-up volume of pleated PES (blue) and PVDF (yellow) filters following a filter gravity drain (dashed lines) or a 1-minute blow-down with air at 20 psi above the filter’s bubble point specification (solid lines). Each value represents the mean and SD from three replicate filters.
For all pleated filters, across all filtration areas, blowing the filter down with air at pressures above the filter’s bubble point reduced the hold-up volume as compared to gravity drain alone. The benefits of blow down are particularly important for filters containing PES membrane as, following gravity drain, these filters have higher hold-up volumes than filters of similar membrane area containing PVDF membrane.
Figure 2 shows the hold-up volumes of the stacked disc filters, overlaid on the hold-up volumes of the pleated filters, following blow-down above the filter’s bubble point.
Figure 2. Mean hold-up volume of pleated filters compared to stacked disc filters (Millipak® Final Fill filters) following a 1-minute blow-down with air at 20 psi above the bubble point of the membrane. Each value represents the mean and SD from three replicate filters.
After blow-down, the stacked disc format filters had substantially lower hold-up volumes than pleated filters for any given filtration area. Although, this differential is particularly noticeable with larger filtration areas, even across smaller filtration areas, the hold-up volumes of the stacked disc format filters are 1.5-5 times lower than those of pleated filters.
Less Hold-up Means Improved Economics - Although blow-down procedures improve product recovery for both pleated and stacked disc filters, the benefits of this added step have profound benefits with stacked disc filters, especially when considering the losses from larger area capsule filters containing pleated membrane. Figure 3 illustrates the potential revenue impact for medicinal products at different price points. All costs are based on product recovery following blow-down for 1 min at 20 psi above the filter’s bubble point specification.
Figure 3: Comparison of revenue impact to manufacturer for medicinal products at different price points due to hold-up volume (after blowdown) in PVDF pleated filters (~900 cm2) and stacked disc filters (~1000 cm2).
The economic benefits of reduced hold-up volume and improved product recovery is highly dependent on the dollar value of the medicinal products being processed. As the cost of the medicinal product increases, the benefit differential between filter formats also increases, with maximum benefit of stacked disc filters aligning with high cost products.
Conclusion: Implementation of a filter blow-down minimizes hold-up volume as compared to a gravity drain procedure, for both pleated and stacked disc filters. For any given filter membrane area, the stacked disc filter format of Millipak® Final Fill filters resulted in the lowest hold-up volume and highest product recovery. For high value medicinal products, the specialized filter format and modified blow-down procedure could translate to substantial economic benefits for production processes.