Membrane Prefilters Improve Sterilizing Filter Capacity and Process Economics in Bioprocessing
Prefilters
Particulate impurities in complex bioprocessing stream can impact downstream purification operations leading to early plugging of sterilizing grade membrane filters, limiting concentration of fluids due to high turbidity1 or interfering with chromatographic separation.
Prefilters can be implemented at different steps in bioprocessing to remove particulates, or for bioburden or contamination control, and improve processing efficiency. This technical article will focus on capacity performance improvements in sterilizing filters when Milligard® PES prefilters are upstream. Specifically:
Materials and Methods
Fluid Streams
Filtration studies were performed with four model streams, selected to represent the range of particle sizes that might be present in different process feeds, Figure 1.
Figure 1.Particle size distributions of the challenge streams. Particle sizing was performed with Malvern MasterSizer and PMS Liquilaz.
Throughput performance
Water permeability of Milligard® PES filters was measured at 10 psi and 21-25oC. Throughput testing of all filtration trains was performed using OptiScale® 25 capsules (3.5 cm2) at a prefilter:final filter area ratio of 1:1. All tests were run at constant trans-membrane pressure differential of 10 psi until permeability of the filtration train was reduced by 90% compared to the water permeability (90% flow decay). During testing, temperature, pressure, and filtrate volume data were collected as a function of time. Differences less than 20% are not considered statistically significant.
Filtration Trains Tested
For more details, read our Tech Note.
Benefits of Milligard® PES Prefilters on Sterilizing Filter Throughput Capacity
Improved filtration train performance was assessed with Millipore Express® SHF sterilizing filters and Milligard® PES 1.2/0.2 μm nominal and 1.2/0.45 μm prefilters upstream. Millipore Express® SHF filters contain a single layer of 0.2 µm polyethersulfone (PES) membrane and are typically used in sterile filtration applications requiring high flux such as buffer filtration or for filtration of non-plugging streams.
Performance benefits of filtration trains using Milligard® PES 1.2/0.8 μm filters was assessed with Millipore Express® SHC filters; these filters contain an onboard 0.5 µm PES membrane prefilter upstream of the 0.2 µm sterilizing membrane. Millipore Express® SHC filters are recommended for sterile filtration of more plugging streams, such as process intermediate filtration. Figure 2 summarizes the study results.
Figure 2.Relative throughput of (A) Millipore® Express SHF filters or (B) Millipore Express® SHC sterilizing filters with Milligard® PES filters upstream. Capacity was assessed at 90% flow decay for the filtration train and is relative to the sterilizing grade filter capacity without a prefilter.
The presence of Milligard® PES prefilters significantly improved sterilizing filter capacity in all model streams, with the clearest benefit in streams that contained smaller sized particles, Soy Peptone and Whey. For the Soy T stream that contains larger sized particles, Milligard® PES filters offered modest capacity improvements.
In summary, implementing Milligard® PES prefilters upstream of a sterilizing filter can markedly improve filter capacity with improvements dependent on the feed stream characteristics, the prefilter pore size and the final sterilizing filter.
Benchmarking performance of Milligard® PES with other prefilters
All our prefilters efficiently reduce particulates in bioprocessing fluid streams. Our portfolio includes:
- Milligard® PES: gamma, autoclave/SIP compatible PES membrane prefilters that deliver reliable particle removal from most fluid streams.
- Milligard®: autoclave/SIP compatible prefilters containing cellulose esters on a polyester web, suitable for sterilizing filter protection.
- Polysep™II: autoclave/SIP compatible prefilters containing mixed cellulose esters and glass microfibers, with high dirt holding capacity for more challenging streams.
For protection of Millipore Express® SHF sterilizing filters, the results in Figure 3A show that Milligard® PES 1.2/0.2 µm nominal filters provide similar performance benefits to Polysep™ II filters in most streams, and better performance benefits than Milligard® filters in all streams tested.
Similarly, Milligard® PES 1.2/0.45 µm prefilters showed equivalent performance to Polysep™ II prefilters in three of the four model streams, Figure 3B.
Results with Milligard® PES 1.2/0.8 µm filters showed less differentiated performance of the filtration trains: equivalent performance was observed in all model streams (data not shown).
Figure 3.Relative throughput of filtration trains containing Millipore Express® SHF membrane filters with competitive filters and Milligard® PES 1.2/0.2 µm nominal (A) or Milligard® PES 1.2/0.45 µm (B) prefilters upstream. Performance of other filtration trains were benchmarked against Milligard® PES filters.
In summary, when used upstream of Millipore Express® filters, Milligard® PES prefilters offer opportunities for marked improvements in filtration train capacity performance. The extent of the benefit is dependent on the fluid stream characteristics, the prefilter pore size and the downstream sterilizing filter.
Case Study: Economic Benefits of Prefiltration
Experimental results confirm the benefits of prefiltration for maximizing the throughput capacity of sterilizing-grade filters. This increased capacity will reduce filtration area requirements and translate to lower filtration costs.
To quantify the benefits, we analyzed the performance of Milligard® PES 1.2/0.2 µm nominal filters upstream of sterilizing grade Millipore Express® SHF filters in the Soy Peptone stream. The analysis, expressed as a filter cost per volume of fluid filtered, is shown in Figure 4. Implementing Milligard® PES can significantly improve process economics by reducing the number of sterilizing filters needed for processing.
Figure 4.Filtration cost comparisons for filtration trains with Millipore Express® SHF sterilizing filters with Milligard® PES 0.2/1.2 µm nominal filters upstream.
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References
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