Improve Process Efficiency in Bioprocess Streams by Prefiltration Optimization and Bioburden Reduction
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The document discusses the performance and benefits of Milligard® PES filters in improving bioprocess filtration efficiency by acting as prefilters for sterilizing-grade filters. These filters are validated for bioburden reduction and significantly enhance throughput capacity while effectively removing particles from process streams. OPTIMIZING the ratio of prefilter to final filter can lead to cost-effective solutions due to improved filtration economics.
Improve Process Efficiency in Bioprocess Streams by Prefiltration Optimization and Bioburden Reduction
- 1. MerckMillipore.com The life science business of Merck operates as MilliporeSigma in the U.S. and Canada. Sherry Ashby Leon, Shannon Cleveland, Ravin Gami, Sal Giglia, Joseph Hersey, Nhung Nguyen, Andrew Koch, Songhua Liu Merck, Bedford MA, USA Introduction Membrane-based prefilters are an important component of many downstream operations. They are used to limit the variability of process streams by removing plugging contaminants thereby protecting sterilizing-grade filters and other unit operations. Some prefilters contribute to process safety by reducing bioburden in intermediate process steps where sterilizing grade filters are not required. Milligard® PES filters contain polyethersulfone (PES) membranes of different pore sizes for efficient particle removal from a broad range of process streams. These prefilters are compatible with caustic sanitization, gamma irradiation, autoclave and steam in place (SIP) sterilization methods. Table 1 lists the different pore sizes of Milligard® PES filters. This poster summarizes throughput and bacterial retention performance of Milligard® PES membranes in OptiScale® capsules challenged with different streams. Throughput capacity was determined either alone or with a downstream sterilizing-grade filter. © 2019 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved. Merck, Millipore, the vibrant M, Milligard, OptiScale, Durapore, and Millipore Express are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the property of their respective owners. Detailed information on trademarks is available via publicly accessible resources. MK_PS2745EN Ver 2.0 09/2019 Improve Process Efficiency in Bioprocess Streams by Prefiltration Optimization and Bioburden Reduction Application Milligard® PES Filter Bioburden Reduction Particle & Bioburden Reduction 1.2/0.2 µm nominal >6 LRV Brevundimonas diminuta 1.2/0.45 µm >6 LRV Serratia marcescens Particle Reduction 1.2/0.8 µm NA Table 1. Milligard® PES Filters Methods Throughput capacity studies The streams used in these studies were selected to represent a wide range of particle sizes and particle size distributions (Figure 1); they were concentrated to achieve a high degree of plugging (> 90% flux decay at < 1000 L/m2 of filtrate). Throughput capacity of final sterilizing grade filters was measured both with and without Milligard® PES prefilter protection. The effect of different prefilter to final filter area ratios on throughput capacity was explored at area ratios ranging from 0.5:1 to 3:1. Tests were performed at both constant pressure (10 psi) and constant flow (500 LMH final filter) operating conditions. The experimental setup is illustrated in Figure 2. Figure 1. Particle size distributions of model streams Bioburden reduction studies Bioburden reduction was evaluated using Milligard® PES 1.2/0.2 µm nominal and 1.2/0.45 µm membrane in OptiScale® capsules challenged at 2 psi with Soy peptone spiked with Brevundimonas diminuta or Serratia marcescens. Retention of these microorganisms was evaluated at different points of filter plugging. Figure 2. Experimental setup for throughput capacity tests Results Final filter protection and throughput Figure 3 illustrates the throughput capacity of a Durapore® 0.22 µm filter alone, and paired with a Milligard ® PES 1.2/0.2 µm nominal prefilter. The capacity of the combined prefilter/final filter train was almost 10 fold higher than that of the sterilizing filter alone. (b) 500 LMH constant flow(a) 10 psi constant pressure 0 500 1000 1500 2000 0 50 100 Throughput(L/m2offinalfilter) Time (min) with prefilter without prefilter 0 5 10 15 20 25 30 0 500 1000 1500 2000 Presuure(psi) Throughput (L/m2 of final filter) without prefilter with prefilter The impact of prefiltration on final filter throughput capacity for the 3 pore sizes of Milligard® PES filters, with 3 different particle size distribution streams, and 2 types of final filters (PVDF and PES) is summarized in Figure 4. These studies were performed at constant pressure of 10 psi. The magnitude of final filter throughput improvements was dependent on the filter pore size, challenge feed, and the type of sterilizing filter. As prefilters have lower unit costs than sterilizing filters, any improvement in capacity due to prefilters can result in dramatic improvements in filtration economics. Figure 3. Effect of Milligard® PES 1.2/0.2 µm nominal filters on capacity of Durapore® 0.22 µm filter: (a) 10 psi constant pressure (b) 500 LMH (final filter) constant flow. Figure 4. Final filter capacity improvement by prefiltration. % improvement is compared to stand-alone final sterilizing filter: (a) Durapore® 0.22 µm (PVDF) final filter; (b) Millipore Express® SHF (PES) final filter. (a) Durapore® 0.22 µm (PVDF) final filter (b) Millipore Express® SHF (PES) final filter Optimization of area ratio Increasing prefilter area will often improve final filter capacity. Optimizing the prefilter to final filter area ratio can result in a cost-effective filtration solution. Figure 5 shows an example of the capacity benefit of different area ratios. A theoretical model is available for efficient system sizing and optimization. 0 500 1000 1500 2000 2500 3000 0 1 2 3 4 Throughput(L/m2finalfilter) Area Ratio (Pre/Final Filter) Model Data Millipore Express® SHF only Figure 5. Effect of prefilter (Milligard® PES 1.2/0.2 µm nominal) to final filter (Millipore Express® SHF) area ratio on throughput capacity in Soy peptone at 10 psi constant pressure. Particle removal by prefilters Prefilters protect final filters and other unit operations by removing particles that would otherwise plug or contaminate downstream unit operations. Particle removal capability was quantified by measuring cumulative concentration of particles of different sizes in the Soy peptone challenge and filtrate solutions after processing through Milligard® PES filters. Most particles in this solution are smaller than 1.0 µm in size, with the highest concentration being at approximately 0.2 µm in diameter (Figure 1). Figure 6 shows that all Milligard® PES filters retained over 90% of the particles between 0.2 µm and 1.0 µm. Figure 6. Soy peptone particle retention by Milligard® PES filters. Bioburden reduction Prefilters can provide an increased level of process safety by reducing bioburden. Milligard® PES 1.2/0.2 µm nominal filters have been validated to demonstrate >6 log B. diminuta retention while the Milligard® PES 1.2/0.45 µm filters have been validated to demonstrate >6 log retention of S. marcescens. Figure 7 shows microorganism retention by ‘stand alone’ Milligard® PES 1.2/0.2 µm nominal and Milligard® PES 1.2/0.45 µm filters in the absence of a final sterilizing filter. The microorganism challenge level was > 107 cfu/cm2 and filtrate grab samples were collected at different points of filter plugging. As would be expected based on a retention mechanism based on size exclusion, microorganism retention was robust (no breakthrough) under all conditions. Figure 7. Log reduction values (LRV) as a function of filter plugging. (a) Milligard® PES 1.2/0.2 µm nominal filters challenged with B. diminuta; (b) Milligard® PES 1.2/0.45 µm filters challenged with S. marcescens. Data points indicate results from individual OptiScale® 25 devices; arrows indicate complete retention. Summary Milligard® PES filters are available in a range of pore sizes for processing different streams, are compatible with multiple sterilization methods, and have been validated to reduce bioburden. These filters: • Dramatically improve the throughput capacity of both PVDF and PES sterilizing-grade filters, significantly improving filtration economics. • Efficiently remove particulates from process streams. • Can be used ‘stand-alone’ to provide sustained bioburden reduction even under conditions of extreme filter plugging. (a) Milligard® PES 1.2/0.2 µm nominal filter retention of B. diminuta (b) Milligard® PES 1.2/0.45 µm filter retention of S. marcescens To quantify the particle removal capability of the prefilters, particle concentrations and size distributions of the challenge stream feeds and filtrates were measured using an optical particle counter (Liquilaz SO2). 0% 20% 40% 60% 80% 100% Particle sizes 0.2-1.0 µm ParticleRetention Milligard® PES 1.2/0.2 µm nominal Milligard® PES 1.2/0.45 µm Milligard® PES 1.2/0.8 µm 0 200 400 600 800 1000 1200 1400 1600 Soy Peptone Whey Soy T CapacityIncreasebyPrefiltration (%) Milligard® PES 1.2/0.2 µm nominal Milligard® PES 1.2/0.45 µm Milligard® PES 1.2/0.8 µm 0 50 100 150 200 250 300 350 400 Soy Peptone Whey Soy T CapacityIncreasebyPrefiltration(%) Milligard® PES 1.2/0.2 µm nominal Milligard® PES 1.2/0.45 µm Milligard® PES 1.2/0.8 µm 0 2 4 6 8 10 0 20 40 60 80 100 LRV % Flow Decay 0 2 4 6 8 10 0 20 40 60 80 100 LRV % Flow Decay