Recent advances in harvest clarification for antibodies and related products

Gupta, Abhinav; Amara, John P.; Gousseinov, Elina; Cacace, Benjamin

doi:10.1016/b978-0-08-103019-6.00006-0

Cited by 9 publications

(12 citation statements)

References 49 publications

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Section: Resultsmentioning

confidence: 99%

“…Impurity levels and composition of HCCFs vary depending on the design of upstream processing (e.g., cell line, fermentation conditions) and cell clarification [ 12 , 13 , 14 ]. In the case of an expected or measured low impurity level, a reduction in the regeneration frequency should be considered.…”

Section: Resultsmentioning

confidence: 99%

“…A reduction in regeneration frequency from each cycle to every 7th cycle for the optimal conditions detected in Section 3.4.1, leads to an additional increase in productivity of 11.8 ± 6.5%. A reduction in regeneration frequency can be achieved, e.g., when the number of impurities in the HCCF is comparatively low [12][13][14]. Impurity levels and composition of HCCFs vary depending on the design of upstream processing (e.g., cell line, fermentation conditions) and cell clarification [12][13][14].…”

Section: Influence Of Regeneration Frequency and Duration On Producti...mentioning

confidence: 99%

“…A reduction in regeneration frequency can be achieved, e.g., when the number of impurities in the HCCF is comparatively low [12][13][14]. Impurity levels and composition of HCCFs vary depending on the design of upstream processing (e.g., cell line, fermentation conditions) and cell clarification [12][13][14]. In the case of an expected or measured low impurity level, a reduction in the regeneration frequency should be considered.…”

Section: Influence Of Regeneration Frequency and Duration On Producti...mentioning

confidence: 99%

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Scalable, Robust and Highly Productive Novel Convecdiff Membrane Platform for mAb Capture

et al. 2022

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The recombinant monoclonal antibody capture step represents the current bottleneck in downstream processing. Protein A resins are diffusion-limited chromatography materials which require low flow rates to achieve a binding capacity above 30 g L−1 with the result of low productivity. Here, we present a novel chromatography membrane combining superior binding capacities with high flow rates for high productivity while achieving comparable product quality as state-of-the-art protein A resins. Further, we demonstrate full scalability of this convecdiff technology with experimental data demonstrating suitability for bioprocessing at different scales. This technology results in more than 10-fold higher productivity compared to Protein A resins, which is maintained during scale up. We demonstrate the influence of residence times, feed titers and the cleaning regime on productivity and indicate optimal utilization of the convecdiff membrane based on feed titer availability. The underlying high productivity and short cycle times of this material enable the purification of monoclonal antibodies with 10-times less chromatography material used per batch and utilization of the membrane within one batch. Provided in disposable consumables, this novel technology will remove column handling in bioprocesses and resin re-use over multiple batches.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Influence Of Regeneration Frequency and Duration On Producti...mentioning

confidence: 99%

Section: Influence Of Regeneration Frequency and Duration On Producti...mentioning

confidence: 99%

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Scalable, Robust and Highly Productive Novel Convecdiff Membrane Platform for mAb Capture

et al. 2022

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“…The intermittent discharge of the solids from the centrifuge poses a challenge for the high cell-density feed stream as the intervals between subsequent discharges become too short, leading to frequent separation space disruption, resulting in overall lower process recoveries and increased centrate turbidities. 13,14,17,19 Continuous solids-discharging centrifugation provides a solution for clarifying high cell-density mammalian cell cultures. Recent work by Ardarion et al compared Westfalia's stainless steel continuous discharge centrifuge with an intermittent discharge centrifuge for clarification of high cell-density [11-14% packed cell volume (PCV)] mammalian cell culture and reported a >10% increase in yield, lower turbidity, and reduced secondary-stage filter fouling.…”

Section: Introductionmentioning

confidence: 99%

Single‐use centrifugal separator enables intensification of the clarification process in biomanufacturing of recombinant proteins

Agarwal

Thwin

Kumaar

2023

J of Chemical Tech & Biotech

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BACKGROUND:The need to produce more biologics at lower costs and hence intensify bioprocessing has significantly improved upstream productivity (cell culture titers ≥3 g L −1 and cell densities ≥20 × 10 6 cells mL −1 ), shifting the economic and production bottleneck to downstream manufacturing. The first downstream unit operation is the clarification of the cell culture broth to remove various insoluble (such as cells and cell debris) and soluble (such as host cell DNA and proteins) contaminants, producing a feed stream suitable for further downstream purification. The high cell-density cultures obtained in modern intensified bioprocessing have made legacy single-use clarification trains (based primarily on depth filtration of the cell culture broth) ineffective and impractical, significantly increasing the economic and material burden of the clarification process.RESULTS: We have developed and characterized approaches that enable intensification of the clarification operation, by increasing process capacities while reducing material requirements and footprint, for single-use manufacturing facilities. These approaches are based on primary clarification using the Alfa Laval CultureOne™ centrifuge (a continuous solid discharge discstack centrifuge with a single-use flow path) followed by secondary clarification using single-use disposable depth filters. We show that these intensified clarification trains are suitable for processing high cell-density cultures (6-12% packed cell volume) with significantly high yields (≥90%) and impurity clearance, along with reduced operating costs (30-60% savings).CONCLUSION: Incorporating a single-use continuous discharge centrifuge into the clarification train enables clarification of high cell-density cultures in single-use manufacturing facilities and enhances process economic and environmental sustainability.

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Cost‐efficient cell clarification using an intensified fluidized bed centrifugation platform approach

Saballus,

Filz,

Pollard

et al. 2023

Biotech & Bioengineering

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The intensification of industrial biopharmaceutical production and the integration of process steps pave the way for patients to access affordable treatments. The predominantly batchwise biomanufacturing of established cell clarification technologies, stainless steel disc stack centrifugation (DSC) and single‐use (SU) depth filtration (DF), pose technological and economical bottlenecks, that include low biomass loading capacities and low product recoveries. Therefore, a novel SU‐based clarification platform was developed combining fluidized bed centrifugation (FBC) with integrated filtration. The feasibility of this approach was investigated for high cell concentration with more than 100E6 cells/mL. Furthermore, scalability to 200 L bioreactor scale was tested for moderate cell concentrations. In both trials, low harvest turbidities (4 NTU) and superior antibody recoveries (95%) were achieved. The impact on the overall economics of industrial SU biomanufacturing using an up‐scaled FBC approach was compared with DSC and DF technologies for different process parameters. As a result, the FBC showed to be the most cost‐effective alternative for annual mAb production below 500 kg. In addition, the FBC clarification of increasing cell concentrations was found to have minimal impact on overall process costs, in contrast to established technologies, demonstrating that the FBC approach is particularly suitable for intensified processes.

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Recent advances in harvest clarification for antibodies and related products

Cited by 9 publications

References 49 publications

Scalable, Robust and Highly Productive Novel Convecdiff Membrane Platform for mAb Capture

Scalable, Robust and Highly Productive Novel Convecdiff Membrane Platform for mAb Capture

Single‐use centrifugal separator enables intensification of the clarification process in biomanufacturing of recombinant proteins

Cost‐efficient cell clarification using an intensified fluidized bed centrifugation platform approach

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