Single Pass Tangential Flow Filtration (SPTFF) of monoclonal antibodies: Experimental studies and theoretical analysis

Jabra, Mario G.; Lipinski, Ann M.; Zydney, Andrew L.

doi:10.1016/j.memsci.2021.119606

Cited by 15 publications

(16 citation statements)

References 13 publications

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“…Such setup enables truly continuous ultrafiltration and diafiltration (UF/DF) which eliminate the recirculation tank in the traditional batch process. [ 20–23 ]…”

Section: Resultsmentioning

confidence: 99%

“…In this case and related study, [ 20 ] higher feed pressure was observed to decrease VCF. Theoretical modeling [ 21 ] shows that higher feed pressure increases the retentate flow rate more than the permeate flow rate, which lowers the VCF. To find the appropriate feed pressure for ILC, the correlation between feed pressure and VCF was studied.…”

Section: Resultsmentioning

confidence: 99%

“…Such setup enables truly continuous ultrafiltration and diafiltration (UF/DF) which eliminate the recirculation tank in the traditional batch process. [20][21][22][23] Different from the traditional TFF process that uses a transmembrane pressure (TMP) as the control variable, the ILC process is controlled by feed pressure. Higher feed pressure has two opposite effects on the ILC step.…”

Section: Ilc and Ildfmentioning

confidence: 99%

“…In the past 10 years, the above hurdles have been cleared gradually. With the emergence of new enabling technologies, such as continuous chromatography, [11][12][13] continuous virus inactivation (VI), [14][15][16][17] continuous virus filtration (VF), [18,19] in-line concentration (ILC), [20,21] and in-line diafiltration (ILDF), [22,23] as well as the development of various in-line and on-line PAT tools, [24][25][26][27] integrated continuous downstream processes become possible.…”

Section: Introductionmentioning

confidence: 99%

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Converting a mAb downstream process from batch to continuous using process modeling and process analytical technology

Chen

Shi

et al. 2022

Biotechnology Journal

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The biopharmaceutical market is driving the revolution from traditional batch processes to continuous manufacturing for higher productivity and lower costs. In this work, a batch mAb downstream process has been converted into an integrated continuous process with the combination of multiple techniques. For process intensification, two batch mode unit operations (protein A capture chromatography, ultrafiltration/diafiltration) were converted into continuous ones; for continuity, surge tanks were used between adjacent steps, and level signals were used to trigger process start or stop, forming a holistic continuous process. For process automation, manual operations (e.g., pH and conductivity adjustment) were changed into automatic operation and load mass was controlled with process analytical technology (PAT). A model-based simulation was applied to estimate the loading conditions for the continuous capture process, resulting in 21% resin capacity utilization and 28% productivity improvement as compared to the batch process. Automatic load mass control of cation exchange chromatography (CEX) was achieved through a customized in-line protein quantity monitoring system, with a difference of less than 1.3% as compared to off-line analysis. Total process time was shortened from 4 days (batch process) to less than 24 hours using the continuous downstream process with the overall productivity of 23.8 g mAb per day for the bench-scale system. Comparable yield and quality data were obtained in three test runs, indicating a successful conversion from a batch process to a continuous process. The insight of this work could be a reference to other similar situations.

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“…Such setup enables truly continuous ultrafiltration and diafiltration (UF/DF) which eliminate the recirculation tank in the traditional batch process. [ 20–23 ]…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Ilc and Ildfmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Converting a mAb downstream process from batch to continuous using process modeling and process analytical technology

Chen

Shi

et al. 2022

Biotechnology Journal

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show abstract

“…Jabra et. al, considered such variables to model and predict output concentrations within a different set of inlet flow rates (Jabra et al, 2021). While accounting for system variations at low flow rates such as the range in question within this paper is possible, doing so would require a battery of additional studies and severely increase the complexity of the model.…”

Section: Discussionmentioning

confidence: 99%

Challenges in Predictive Modeling of Single Pass Tangential Flow Filtration for Continuous Biomanufacturing

Fuchs

Bhawnani

Sripada

et al. 2022

Preprint

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Opportunities for process intensification and increased productivity have made the field of Continuous Biomanufacturing an area of high interest and active research. Within the purification train of producing biologics, Tangential Flow Filtration (TFF) is typically employed after chromatographic separations, to increase drug substance concentration, making the process more economical and further meeting dosage specifications. In a batch operation, concentration occurs via recirculation of the feed material where desired output concentration is attained through multiple pump-passes over the TFF membrane, while steadily excluding the buffer. Single-Pass Tangential Flow Filtration (SPTFF) enables continuity of this process by achieving similar concentration factors through a single – pass over these membranes while operating at low feed flow rates. Our work elucidates the development of a mechanistic process model to predict SPTFF performance across a relatively wide design space using a first principles approach. The developed model is found to be accurate for a range of high feed flow rates but is inaccurate at flow rates below 25 L/m2/hr. At very low flow rates, small differences in the mass transfer coefficient have been observed to significantly alter the prediction of the retentate concentration. We thus describe the challenges in predictive process modeling of SPTFF in antibody biomanufacturing.

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Predictive modeling of single pass tangential flow filtration for continuous biomanufacturing

Fuchs

Bhawnani

Sripada

et al. 2023

Biotechnology Progress

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Opportunities for process intensification have made continuous biomanufacturing an area of active research. While tangential flow filtration (TFF) is typically employed within the biologics purification train to increase drug substance concentration, single‐pass TFF (SPTFF) modifies its format by enabling continuity of this process and achieving a multifold concentration factor through a single‐pass over the filtration membranes. In continuous processes feed concentration and flow rate are determined by the preceding unit operations. Therefore, tight control of SPTFF output concentration must be achieved through precise design of the membrane configuration, unlike TFF. However, predictive modeling can be utilized to identify configurations that achieve a desired target concentration across ranges of possible feed conditions with minimal experimental data, hence enabling accelerated process development and design flexibility. We hereby describe the development of a mechanistic model predicting SPTFF performance across a wide design space using the well‐established stagnant film model, which we demonstrate is more accurate at higher feed flow rates. The flux excursion dataset was generated within time constraints and with minimal material consumption, showing the method's ability to be quickly adapted. While this approach eliminates characterizing complex physicochemical model variables or the need for users with specialized training, the model and its assumptions become inaccurate at low flow rates, below 25 L/m2/h, and high conversions, above 0.9. As this low flow rate, high conversion operating regime is relevant for continuous biomanufacturing, we explore the assumptions and challenges involved in predicting and modeling SPTFF processes, while suggesting added characterization to gain further process insight.

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Single Pass Tangential Flow Filtration (SPTFF) of monoclonal antibodies: Experimental studies and theoretical analysis

Cited by 15 publications

References 13 publications

Converting a mAb downstream process from batch to continuous using process modeling and process analytical technology

Converting a mAb downstream process from batch to continuous using process modeling and process analytical technology

Challenges in Predictive Modeling of Single Pass Tangential Flow Filtration for Continuous Biomanufacturing

Predictive modeling of single pass tangential flow filtration for continuous biomanufacturing

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