<scp>Single‐use</scp> centrifugal separator enables intensification of the clarification process in biomanufacturing of recombinant proteins
Bibliographic record
Abstract
Abstract 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 × 106 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 disc‐stack 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. © 2023 Society of Chemical Industry (SCI).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".