N-1 Perfusion | Sartorius

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.

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Flexible Process Intensification to Meet Biopharma Challenges

In this webinar, Sartorius experts present the latest PI technologies,  including advanced Biostat® bioreactors integrated with PAT functionality controlled by the Biobrain® automation platform.

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Up to 2x higher titer and as much as 50% increase in throughput

N-1 perfusion can lead to 2x higher titer, reduce the overall USP duration and increase throughput by 20–50%.

Increased throughput outweighs additional media investments

Thanks to increased throughput, the impact of additional media requirements on cost or facility setup is mitigated.

Easy retrofit in existing facilities

N-1 leads to an easy retrofit in existing Fed-Batch facilities without changing the Fed-Batch strategy in the main bioreactor.

Lower COGS compared to Fed-Batch

With higher throughput and increased productivity, N-1 perfusion reduces cost per gram by 30–50% compared to traditional Fed-Batch.

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Intensified Seed Train Options

Options for stirred tank and rocking motion bioreactors

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Media Management

For the larger volumes needed to increase cell density

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Process Control and Data Analytics

Ensuring quality, safety, and efficacy at all times

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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%​

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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%


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Media Management

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.


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The Missing Link in Your PI Plan

Explore the implications of media management in an intensification strategy in this webinar featuring Sartorius experts.

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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

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Single-Use Bags

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.

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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

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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. ​

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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.

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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

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Featured Assets

Impact on Cost, Facility Footprint and Environmental Sustainability in Biomanufacturing

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.
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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.

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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.

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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.

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White Paper

Intensifying Upstream Processing and the Implications for Media Management

PDF | 4.4 MB
Article

(Re)Defining Process Intensification

PDF | 343.7 KB
Poster

Scalability of Cost Effective 2D Rocking Motion Bioreactors with Internal Filter Membrane for Perfusion Processes.

PDF | 502.9 KB
Success Story

Improve Productivity and Reduce Risk with Biostat® RM

PDF | 199.6 KB
Article

Enabling Broader Adoption of Process Intensification in Biopharma

PDF | 671.0 KB
Article

Seed Train Process Intensification Strategy Offers Potential for Rapid, Cost-Effective Scale-Up of Biosimilars Manufacturing

PDF | 1.6 MB
Success Story

N-1 Perfusion High Inoculum Fed-Batch for Reduced COGS and Easy Retrofit

PDF | 318.4 KB
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Process Intensification Webinar Series

Sartorius' experts sharing best practices and addressing critical questions.

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