Concentrated Fed-Batch for Increased Productivity and Flexibility
Intensification With Flexibility for Higher Facility Throughput Requirement
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.
Intensified Seed Train and Production Options
Concentrated Fed-Batch for Concentrated Impact
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.
Perfusion-Ready Biostat® RM
The Patented Rocking Motion Bag with Integrated Perfusion Membrane
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.
- 25% reduction in costs per batch compared to a standard perfusion enabled stirred tank seed train.
- Increase titer by 30% or more
- Reduce upstream seed train days
Perfusion-Ready Biostat STR®
Increased Productivity and Flexibility with Biostat STR®
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:
- Increased facility throughput up to 4 times
- Increased productivity per batch with up to 4 times titer increase
- Potential shorter batches that further increase throughput and flexibility
Media Management
Ensuring Media Quality and Stability Is Critical for Intensification
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.
Single-Use Mixing
The Flexsafe® Pro Mixer Saves Time Without Compromising Control
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.
- Saves time with fast powder dissolution
- Preserves quality of shear sensitive fluids through low shear mixing and high torque
- Designed for rapid set-up and efficient changeover (in less than 10 minutes) reducing risk of damage and loss from product mishandling
- Includes full material characterization and safety evaluation
Single-Use Bags
2D Single-Use Bags
Storage to Support the Media Volume Required for Concentrated Fed-Batch
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.
3D Single-Use Bags
Self-Deploying and Filling 3D Single-Use Bags for Pallet Tanks
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.
Virus Filtration
Ensuring Quality and Safety of Cell Culture Medium
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.
Sterile Filtration
Cost Efficient Media Filtration with High Mycoplasma Retention
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.
注目の資料
ホワイトペーパー： Intensifying Upstream Processing - Implications for Media Management
プロセス強化（PI）により、創薬のスピードアップ、生産性・柔軟性・品質の向上が可能です。これらの利点がある一方で、PIは必要とする培地の容量を増加させるといった問題とアップストリームプロセスでこれらをどのように管理するのかという課題をもたらす場合もあります。このホワイトペーパーは、プロセス強化に伴う培地容量の増加をふまえた確実な導入戦略をたてるために役立ちます。
Process Data Analytics
Assurance Through Multivariate Data Analytics
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.
MVDA
SIMCA® Ensures Process Health and Manufacturing Success
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.
Online MVDA
SIMCA®-Online Integrates Real-Time Monitoring and Controls
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.
