The Experts below are selected from a list of 14853 Experts worldwide ranked by ideXlab platform
Peter L. Roberts - One of the best experts on this subject based on the ideXlab platform.
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Virus Inactivation in albumin by a combination of alkali conditions and high temperature.
Biologicals : journal of the International Association of Biological Standardization, 2011Co-Authors: Peter L. Roberts, John More, Jackie Rott, David Roger LewinAbstract:Non-enveloped Viruses such as HAV and B19 are of potential concern in plasma products. In the case of albumin, pasteurisation at 60 °C for 10 h is generally used for Virus Inactivation. However this procedure is only partially effective against some non-enveloped Viruses. Using a range of non-enveloped Viruses i.e. HAV, SV40, CPV, treatment at a high pH of about 9.5 and a temperature of 60 °C for 10 h was found to be effective for Virus Inactivation. These extreme conditions caused no increase in aggregate composition of the albumin. In addition the albumin composition was stable over a period of at least 6 months. The ligand binding properties of the albumin, as determined using the dye phenol red, were also not affected by this treatment. This procedure has the potential for increasing the spectrum of Viruses inactivated by the 60 °C pasteurisation step.
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Virus Inactivation in a factor viii vwf concentrate treated using a solvent detergent procedure based on polysorbate 20
Biologicals, 2009Co-Authors: Peter L. Roberts, David Lloyd, Philip J MarshallAbstract:Treatment with solvent/detergent is a widely used method for ensuring the Virus safety of plasma products. In the present study, Virus Inactivation by a novel solvent/detergent combination, i.e. TnBP (tri-n-butyl phosphate) and polysorbate 20 during the manufacture of the factor VIII/VWF concentrate Optivate® has been investigated. The Inactivation of most enveloped Viruses was rapid, i.e. >5 log in 2 min, although the Inactivation of vaccinia Virus was slower, i.e. 4 log in 1 h. Virus Inactivation was effective over a wide range of conditions, i.e. solvent/detergent concentration, protein concentration and temperature, irrespective of whether tested individually or in combination. This confirms the effectiveness and robustness of this alternative version of the solvent/detergent procedure, and allows appropriate control limits to be set for this manufacturing step. Polysorbate 20 provides an alternative to the non-ionic detergents currently in use with the solvent/detergent procedure.
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Virus Inactivation in a factor VIII/VWF concentrate treated using a solvent/detergent procedure based on polysorbate 20
Biologicals : journal of the International Association of Biological Standardization, 2008Co-Authors: Peter L. Roberts, David Lloyd, Philip J MarshallAbstract:Treatment with solvent/detergent is a widely used method for ensuring the Virus safety of plasma products. In the present study, Virus Inactivation by a novel solvent/detergent combination, i.e. TnBP (tri-n-butyl phosphate) and polysorbate 20 during the manufacture of the factor VIII/VWF concentrate Optivate® has been investigated. The Inactivation of most enveloped Viruses was rapid, i.e. >5 log in 2 min, although the Inactivation of vaccinia Virus was slower, i.e. 4 log in 1 h. Virus Inactivation was effective over a wide range of conditions, i.e. solvent/detergent concentration, protein concentration and temperature, irrespective of whether tested individually or in combination. This confirms the effectiveness and robustness of this alternative version of the solvent/detergent procedure, and allows appropriate control limits to be set for this manufacturing step. Polysorbate 20 provides an alternative to the non-ionic detergents currently in use with the solvent/detergent procedure.
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Virus Inactivation by solvent/detergent treatment using Triton X-100 in a high purity factor VIII.
Biologicals : journal of the International Association of Biological Standardization, 2008Co-Authors: Peter L. RobertsAbstract:Virus Inactivation by solvent/detergent treatment using 0.3% tri-n-butyl phosphate and 1% Triton X-100 in the high purity factor VIII concentrate Replenate has been investigated. A wide range of model enveloped Viruses were confirmed to be inactivated by >4 to >6 log after 30 min at 22 degrees C under standard conditions. Using Sindbis as a representative enveloped Virus, the effect of various parameters on the Inactivation process was tested. Virus Inactivation was confirmed to be effective in different batches of product and was not influenced by changing the process conditions with regard to protein and salt concentration or pH. Virus Inactivation was effective even at a temperature as low as 4-5 degrees C. Although solvent/detergent concentration was the most critical parameter, a concentration as low as 0.15% TnBP/0.5% Triton X-100 was still completely effective. At a lower concentration an extended incubation period was required. These studies demonstrate the robustness of this solvent/detergent procedure based on Triton X-100 and allow suitable process limits to be set for this manufacturing step.
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Virus Inactivation by protein denaturants used in affinity chromatography.
Biologicals : journal of the International Association of Biological Standardization, 2007Co-Authors: Peter L. Roberts, David LloydAbstract:Virus Inactivation by a number of protein denaturants commonly used in gel affinity chromatography for protein elution and gel recycling has been investigated. The enveloped Viruses Sindbis, herpes simplex-1 and vaccinia, and the non-enveloped Virus polio-1 were effectively inactivated by 0.5 M sodium hydroxide, 6 M guanidinium thiocyanate, 8 M urea and 70% ethanol. However, pH 2.6, 3 M sodium thiocyanate, 6 M guanidinium chloride and 20% ethanol, while effectively inactivating the enveloped Viruses, did not inactivate polio-1. These studies demonstrate that protein denaturants are generally effective for Virus Inactivation but with the limitation that only some may inactivate non-enveloped Viruses. The use of protein denaturants, together with Virus reduction steps in the manufacturing process should ensure that viral cross contamination between manufacturing batches of therapeutic biological products is prevented and the safety of the product ensured.
Thierry Burnouf - One of the best experts on this subject based on the ideXlab platform.
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single use technology for solvent detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Elizabeth M Goodrich, Jessica Shea, Eric Youssef, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
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Single-use technology for solvent/detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Jessica Shea, Eric Youssef, Goodrich Elizabeth M, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
Patricia Greenhalgh - One of the best experts on this subject based on the ideXlab platform.
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Continuous In-Line Virus Inactivation for Next Generation Bioprocessing.
Biotechnology journal, 2018Co-Authors: Christopher Gillespie, Lori Mullin, Melissa Holstein, Kristen Cotoni, Ronald Tuccelli, John Caulmare, Patricia GreenhalghAbstract:Viral Inactivation plays a critical role in assuring the safety of monoclonal antibody (mAb) therapeutics. Traditional viral Inactivation involves large holding tanks in which product is maintained at a target low pH for a defined hold time, typically 30-60 min. The drive toward continuous processing and improved facility utilization has provided motivation for development of a continuous viral Inactivation process. To this end, a lab-scale prototype viral Inactivation system was designed, built, and characterized. Multiple incubation chamber designs are evaluated to identify the optimal design that enables narrow residence time distributions in continuous flow systems. Extensive analysis is conducted supporting rapid low pH viral Inactivation and included evaluations with multiple Viruses, a range of pH levels, buffer compositions, mAb concentrations, and temperatures. Multiple test conditions are evaluated using the in-line system and results compared to traditional batch-mode viral Inactivation. Comparability in kinetics of Virus Inactivation suggests equivalency between the two approaches.
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single use technology for solvent detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Elizabeth M Goodrich, Jessica Shea, Eric Youssef, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
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Single-use technology for solvent/detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Jessica Shea, Eric Youssef, Goodrich Elizabeth M, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
Yao Ting Hsieh - One of the best experts on this subject based on the ideXlab platform.
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single use technology for solvent detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Elizabeth M Goodrich, Jessica Shea, Eric Youssef, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
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Single-use technology for solvent/detergent Virus Inactivation of industrial plasma products
Transfusion, 2016Co-Authors: Yao Ting Hsieh, Lori Mullin, Patricia Greenhalgh, Michael Cunningham, Jessica Shea, Eric Youssef, Goodrich Elizabeth M, Thierry BurnoufAbstract:BACKGROUND Virus Inactivation of plasma products is conducted using stainless-steel vessels. Single-use technology can offer significant benefits over stainless such as operational flexibility, reduced capital infrastructure costs, and increased efficiency by minimizing the time and validation requirements associated with hardware cleaning. This study qualifies a single-use bag system for solvent/detergent (S/D) Virus Inactivation. STUDY DESIGN AND METHODS Human plasma and immunoglobulin test materials were S/D-treated in Mobius single-use bags using 1% tri-n-butyl phosphate (TnBP) with 1% Triton X-100 or 1% Tween 80 at 31°C for 4 to 6 hours to evaluate the impact on protein quality. Volatile and nonvolatile organic leachables from low-density polyethylene film (Pureflex film) used in 1-L-scale studies after exposure to S/D in phosphate-buffered saline were identified compared to controls in glass containers. Virus Inactivation studies were performed with xenotropic murine leukemia Virus (XMuLV) and bovine viral diarrhea Virus (BVDV) to determine the kinetics of Virus Inactivation, measured using infectivity assays. RESULTS S/D treatment in Mobius bags did not impact the protein content and profile of plasma and immunoglobulin, including proteolytic enzymes and thrombin generation. Cumulative leachable levels after exposure to S/D were 1.5 and 1.85 ppm when using 0.3% TnBP combined with 1% Tween 80 or 1% Triton X-100, respectively. Efficient Inactivation of both XMuLV and BVDV was observed, with differences in the rate of Inactivation dependent on both Virus and S/D mixture. CONCLUSION Effective S/D Virus Inactivation in single-use container technology is achievable. It does not alter plasma proteins and induces minimal release of leachables.
Alois Jungbauer - One of the best experts on this subject based on the ideXlab platform.
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A narrow residence time incubation reactor for continuous Virus Inactivation based on packed beds
New biotechnology, 2019Co-Authors: Jure Sencar, Duarte L. Martins, Nikolaus Hammerschmidt, Alois JungbauerAbstract:Abstract A narrow residence time distribution (RTD) is highly desirable for continuous processes where a strict incubation time must be ensured, such as continuous Virus Inactivation. A narrow RTD also results in faster startup and shut down phases and limits the broadening of potential disturbances in continuous processes. A packed bed reactor with non-porous inert beads was developed to achieve narrow RTDs. The performance was defined as the ratio between the onset of the cumulative RTD and the median residence time (tx%/t50%). Laboratory-scale packed columns were used to study the influence of the column parameters on the RTD. A larger column with a void volume of 0.65 L and a length of 89 cm, packed with beads in a size range of 125 to 250 μm, achieved t0.5%/t50% >0.93 across flow rates from 0.1 to 9.8 mL/min. The RTD was significantly narrower than the RTDs of other reactor designs, such as the Coiled Flow Inverter and Jig in a Box. The pressure drop remained under 3 kPa for all tested flow rates. Fluorescent nanoparticles (30 and 200 nm) were used to mimic Viruses. These two sizes showed less than 2% difference in terms of t1%/t50% and t0.01%/t50% scores. These results indicated that Viruses travelled through the column at rates independent of size. This proposal of packed beds as incubation chambers for continuous Virus Inactivation is simple, scalable, and can be realized as single-use devices. Due to the low pressure drop, the system can be easily integrated into a fully continuous process.
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Continuous Solvent/Detergent Virus Inactivation Using a Packed-Bed Reactor
Biotechnology journal, 2019Co-Authors: Duarte L. Martins, Jure Sencar, Nikolaus Hammerschmidt, Björn Tille, Johanna Kinderman, Thomas R. Kreil, Alois JungbauerAbstract:Continuous Virus Inactivation (VI) remains one of the missing pieces while the biopharma industry moves toward continuous manufacturing. The challenges of adapting VI to the continuous operation are two-fold: 1) achieving fluid homogeneity and 2) a narrow residence time distribution (RTD) for fluid incubation. To address these challenges, a dynamic active in-line mixer and a packed-bed continuous Virus Inactivation reactor (CVIR) are implemented, which act as a narrow RTD incubation chamber. The developed concept is applied using solvent/detergent (S/D) treatment for Inactivation of two commonly used model Viruses. The in-line mixer is characterized and enables mixing of the viscous S/D chemicals to ±1.0% of the target concentration in a small dead volume. The reactor's RTD is characterized and additional control experiments confirm that the VI is due to the S/D action and not induced by system components. The CVIR setup achieves steady state rapidly before two reactor volumes and the logarithmic reduction values of the continuous Inactivation process are identical to those obtained by the traditional batch operation. The packed-bed reactor for continuous VI unites fully continuous processing with very low-pressure drop and scalability.
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Continuous Virus Inactivation: How to Generate a Plug Flow.
Biotechnology journal, 2018Co-Authors: Alois JungbauerAbstract:To realize continuous integrated manufacturing of biopharmaceuticals, all steps of production have to be operated in a continuous mode. Virus Inactivation is a crucial step in this process, and due to standard procedures and a fixed residence time, it is particularly challenging to realize. Two articles in this issue present possible solutions to this problem.
