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.
Sartorius Biostat® STR bioreactors are ATF-compatible simplifying the switch to perfusion thus offering an easier intensified implementation
Perfusion enabled seed train with Sartorius Biostat® RM or STR at N-1 stage results in HCD inoculation producing higher titers
4Cell® XtraCHO media system for small and large scale production contains CHO media and feeds, optimized for protein manufacturing
Economical seed train with perfusion enabled RM200, ideal media management with mixers, bags and filters ensures quality and consistency
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 Easier by Implementing ATF
Sartorius Biostat® STR bioreactors are compatible with the leading alternating tangential flow (ATF) perfusion device in mAb production: the XCell ATF® System (scalable to 5000 L) from Repligen. This allows a seed train step intensification that, in microfiltration mode, achieves a higher cell density for bioreactor inoculation. Using the current STR in your seed train one can switch from fed batch to perfusion mode without investing into a new STR.
- 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. These ready-to-use bags have “plug and play” compatibility with Sartorius´ Biostat® STR bioreactors.
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.
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.
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.