Dynamic Perfusion Delivers Highest Productivity in Smallest Footprint
Upstream Intensification for Challenging Modalities and Molecules
Established manufacturers are looking to single-use, flexible solutions when building new facilities or modifying existing operations. Their goal is to increase productivity across different modalities including difficult-to-express molecules. Meanwhile, early-stage drug development companies are looking for low upfront investment for their lower throughput products. With smaller bioreactor requirements that deliver higher productivity per batch, dynamic perfusion can be the answer in both cases.
The up to 5x higher volumetric productivity in DP allows for a modular approach and smaller bioreactor sizes (<2000 L) for faster build-up times.
DP enables 2-5 g/L per day with continuous harvest of product over 2 weeks, achieving up to 5x higher productivity than Fed-Batch.
Continuous harvest ensures optimal product stability and quality, which is critical for unstable molecules prone to degradation.
Intensified Seed Train and Production Options
Dynamic Perfusion Proves That Less Can Mean More
Up to 5x the Productivity in a 500 L Bioreactor
In dynamic perfusion, the product can be continuously harvested by microfiltration. This approach can be accomplished in smaller bioreactors, resulting in smaller footprint and as much as a 60% lower capex upfront investment. Productivity can be increased up to 5 times compared to standard fed-batch, while offering the flexibility to support multiple molecule pipelines, even for hard-to-express molecules.
Perfusion-Ready Biostat® RM
A Cost Effective Upstream Intensification Option
Implementing rocking motion bioreactor, with integrated perfusion membrane, in the N-1 seed train step is the most cost-effective opportunity for seed train intensification for high inoculum fed-batch process. Using the RM bioreactor manufacturers can
- Reduce both capital and consumable investment by >30%
- Achieve high cell densities at lower volumes to inoculate production bioreactor
- Increase productivity and overall facility throughput by 30-50% thus decreasing overall COGS by up to 50%
Perfusion-Ready Biostat STR®
Increased Flexibility by Implementing Dynamic Perfusion
Running a bioreactor in dynamic perfusion (DP) mode enables the use of smaller bioreactors, such as the Biostat STR® 500 L with integrated XCell ATF® technology, to run perfusion in microfiltration mode. Dynamic perfusion usually does not use cell bleeds, which results in increased viable cell density (VCD) as the product is harvested continuously for the next 15-20 days. This operation can lead to:
- Increased productivity up to 5 times
- Increased flexibility for executing multi-modality facility
- Additional benefits for difficult-to-express molecules (bispecifics and multispecifics)
Media Management
Ensuring Media Quality and Stability Is Critical for Intensification
Consistent cell culture performance in intensified processes is dependent on the media design, quality, and stability. In dynamic perfusion, fresh medium and feeds are added continuously over 15-20 production days, thus requiring smart media strategies. Consumables and equipment to handle these volumes are essential to support a smooth process flow, while reliable filters to avoid contamination and remove mycoplasma are critical for successful intensified processes.
Liquid Handling
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 Dynamic Perfusion
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 – and in the case of dynamic perfusion, 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 due to the complexity of operations, processes and data as well as the total cost of risk. Multivariate Data Analysis (MVDA) extracts meaningful information from large data sets, enabling 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 in dynamic perfusion. 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.
