Concentrated Fed-Batch
Concentrated fed-batch (CFB) is the upstream process intensification that can have the greatest impact on productivity compared to standard fed-batch, producing up to four times the titer and 3-4 times higher throughput. Concentrated fed-batch is the ideal option for converting stainless-steel to single-use operations and for blockbuster drugs. Considering the increasing trend towards throughput of less than 500 kg per year, concentrated fed-batch offers the flexibility to have a multiproduct high throughput facility to satisfy productions of multiple drugs within the same single-use facility.
CFB enables higher viable cell densities in the production bioreactor, resulting in up to 4x increase in product titer compared to Fed-Batch.
CFB increases throughput by up to 3x, creating the flexibility needed for high throughput facilities (>500 kg/yr) to meet market demands.
With a smaller footprint, single-use facilities are more sustainable, and they offer greater adaptability and flexibility.
Options for stirred tank and rocking motion bioreactors
For the larger volumes needed to increase cell density
Ensuring quality, safety, and efficacy at all times
Up to 4x Productivity, Even in Small Volumes and Different Modalities
Concentrated fed-batch (CFB), combined with N-1 intensification in the seed train, achieves a 4-5 fold increase in productivity by running the production bioreactor in concentrated mode. The product and cells are returned to the bioreactor, hence concentrated, reaching high cell densities and titers, until the final harvest, which is performed in batch mode. The alternating tangential flow filter used in ultrafiltration mode is critical to remove spent media during that process. With up to 4 times titer over standard fed-batch and 3-4 times the throughput, CFB is an attractive alternative for both multiproduct single-use facilities or those with high drug demands.
A rocking motion perfusion system is an optimal solution consisting of a rocking motion single-use bag with an integrated perfusion membrane. Thanks to the unique design, a separate cell separation device is not required. Using the rocking motion perfusion bioreactor in the N-1 seed train step is a cost-effective way to establish intensified upstream seed train. This leads to increased productivity and potential reduction in seed train steps.
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Sartorius Biostat STR® bioreactors with integrated XCell ATF® technology simplify perfusion processes. Using the ATF in ultrafiltration mode enables complete retention of cells in the production bioreactor, leading to concentrated product and resulting in much higher titers than with traditional fed-batch. Implementing this mode of operation within the intensified seed train can result in:
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Concentrated Fed-Batch requires a larger amount of cell culture medium than in standard fed-batch. Ensuring consistent cell culture performance in intensified processes is dependent on the media design, quality, and stability. Consumables and equipment to handle these volumes are equally essential to support a smooth process flow. A reliable filter to avoid contamination and remove mycoplasma is also critical for successful intensified processes.
Explore the implications of media management in an intensification strategy in this webinar featuring Sartorius experts.
Flexsafe® Pro Mixer is an efficient, single-use mixer for 50 L up to 3000 L. It provides the high levels of control that are essential for cGMP biomanufacturing.
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With concentrated fed-batch running in perfusion mode, there is a greater demand for cell culture medium. It is for this reason that consumables and equipment to handle these volumes are essential for a smooth process flow. Sartorius Flexsafe® 2D Single-Use Bags ensure the stability and integrity of the medium, allowing excellent, reproducible cell growth. The superior strength of the polyethylene film reduces risk of damage, while its flexibility enables consistent performance and easy handling.
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Liquid medium must be prepared and safely stored to be ready whenever it is needed. To meet the significant cell culture media requirements of concentrated fed-batch and support smooth process flow, larger scale liquid storage is often required. Flexsafe® 3D Single-Use Bags, designed for storage applications in pallet tanks, are easy to use and allow excellent and reproducible cell growth. With a self-deploying accessory, the bag can be filled with no operator manipulation.These ready-to-use bags have “plug and play” compatibility with Sartorius Biostat STR® bioreactors.
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Companies are looking more and more for virus removal filters for media for risk mitigation purposes. Virosart® Media filters, provide high virus clearance safety and show superior capacities for media used for mAbs and recombinant proteins.
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Sartopore® 2 XLM sterile filters are used for cost-efficient media filtration with outstanding high throughput. They feature a 30% larger surface area and optimized pre-filter layers which results in a higher flow rate and higher throughput. The Sartopore® 2 XLM is an advanced 0.1 µm rated filter with high mycoplasma retention.
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Key Note Presentation at BPI Amsterdam - Miriam Monge, Head of Marketing Single-Use Technologies at Sartorius, was giving an overview of upstream and downstream Process Intensification, including cost & facility footprint implications of various process intensification scenarios.She discussed how the selection of given process strategies directly impacts environmental sustainability in biomanufacturing in terms of CO2, water and electricity usage and showed how single-use technologies can further drive environmental sustainability in biomanufacturing.Download eBook
Change can be risky, but also beneficial. Watch this video to learn about the benefits of using PI to overcome common challenges in biomanufacturing. Sartorius experts describe how PI components can help organizations implement changes gradually that will contribute to lower COGS, a smaller facility footprint, higher productivity, and faster time to market.
Process intensification (PI) enables faster drug development and increased productivity, flexibility, and quality. But with these benefits, PI can also introduce the challenge of increased media volumes and how to manage them in upstream processes. This whitepaper helps ensure your implementation strategy accounts for the increased media volume associated with process intensification.
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Customers rely on enhanced data analytics for process intensification. This is due to the increased complexity of processes, operations, and data, as well as the total cost of risk. Multivariate Data Analysis (MVDA) extracts meaningful information from large data sets. It enables scale-up and batch-to-batch comparison investigations to improve the quality, safety, and efficacy of a drug product.
SIMCA® is an advanced data analytics solution to gain actionable information from large quantities of data, ensuring consistent processes and product quality. SIMCA® analyzes incoming raw materials and determines how they may affect cell growth, viability, productivity, and quality – which is critical for concentrated fed-batch. This robust multivariate engine will compare batch-to-batch quality and identify sources of any variation, accessible through an intuitive interface and easy-to-read interactive visualizations.
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Multivariate real-time monitoring is important, especially in intensified processes. While SIMCA® creates a digital fingerprint of a process as reference, SIMCA®-online uses real-time measurements to assess operations based on this fingerprint – essentially verifying if the current batch fingerprint matches or not. If there are derivations from the reference, the process can be adapted immediately. This automated corrective action keeps quality consistent, maximizes efficiency and reduces costs.
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Sartorius' experts sharing best practices and addressing critical questions.
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