N-1 Perfusion Equals Lower COGS, Higher Titer
N-1 Perfusion High Inoculum Fed-Batch Is a Logical First Step Toward Intensification
With increasing development cost (>30%) and reduction in sales (<50%) biomanufacturers need to increase productivity of their facility to reduce overall COGS to stay competitive. Intensifying their seed train, especially the N-1 step, is one of the most adapted and logical change that the manufacturers can implement.
N-1 perfusion can lead to 2x higher titer, reduce the overall USP duration and increase throughput by 20–50%.
Thanks to increased throughput, the impact of additional media requirements on cost or facility setup is mitigated.
N-1 leads to an easy retrofit in existing Fed-Batch facilities without changing the Fed-Batch strategy in the main bioreactor.
With higher throughput and increased productivity, N-1 perfusion reduces cost per gram by 30–50% compared to traditional Fed-Batch.
Intensified Seed Train Options
N-1 for High-Performing High Inoculum
In the N-1 perfusion high inoculum fed-batch process, the production bioreactor is seeded at a higher density, accelerating cell growth. Biomanufacturers can leverage this benefit in two ways:
- Achieve the same titer as standard fed batch in 40% fewer days, increasing throughput
- Deliver almost double the titer in the same time as standard fed batch operations
Sartorius is the only company offering N-1 seed train intensification options for both rocking motion and stirred tank bioreactors.
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%
Intensification Made Simpler with Perfusion-Ready Biostat STR®
Sartorius Biostat STR® bioreactors are available with integrated XCell ATF® technology, enabling an easy switch form batch to perfusion processes in any stage of the seed train. Implementing intensification or perfusion in the seed train achieves a higher N-1 cell density that, in turn, enables a higher inoculation cell density of the N bioreactor. This provides considerable benefits:
- Easy retrofit in the current fed-batch facility
- Increased titer (up to 2 times)
- Reduced COGS (up to 50%)
- Increased overall facility throughput >50%
Ensuring Media Quality and Stability Is Critical for Intensification
Running the N-1 seed train step in perfusion mode 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.
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
2D Single-Use Bags
Storage to Support the Media Volume Required for N-1 Perfusion
N-1 perfusion requires more cell culture medium, so 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 PE 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 N-1 perfusion 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
Ensuring Quality and Safety of Cell Culture Medium
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.
Implementing N-1 Perfusion Process at a Biosimilars Manufacturer
This webinar presents how Intas Pharmaceutical, a leading biosimilars product manufacturer, targeted seed train intensification as a viable entry point to explore intensified manufacturing.
- Discover the value of seed train intensification in manufacturing scenarios.
- Learn about the various approaches that can be taken to intensify the seed train
The Why, How, and When to Implement Process Intensification
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.
Whitepaper: Intensifying Upstream Processing - Implications for Media Management
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.
Process Data Analytics
Assurance through Multivariate Data Analytics
Customers rely on enhanced approaches to 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® 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 N-1 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.
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.