Process Intensification | Sartorius

Process Intensification

Modify. Intensify. Amplify.

As biopharmaceutical manufacturers and CDMOs face growing pressure to increase throughput and lower costs in order to stay competitive, process intensification (PI) seems the natural solution – but many feel implementing that level of change is an unrealistic expectation. Sartorius helps manufacturers balance today’s demands with tomorrow’s discoveries, intensifying key processes to experience the benefits of PI now while building for the future.

Sartorius offers various intensified solutions that can be applied to both upstream and downstream unit operations that will result in increased overall productivity of your process or facility. Our technologies, which include high-throughput tools for process development and scalable, flexible manufacturing solutions, combined with our team of expert application scientists, help manufacturers succeed in their PI journey. 

What is the Definition of Process Intensification?

Process intensification is a holistic framework to maximize overall productivity of the unit operation(s), or the manufacturing process, or the facility output for biomanufacturing.

Why Intensify a Bioprocess? 

  • Faster drug development 

  • Achieve up to 4x increase in titers in upstream processing 

  • Increase productivity in downstream by up to 50x  

  • Reduce chromatography resin volume and costs by up to 80% 

  • Applicable to any process irrespective of molecule 

Featured eBook 

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Top Considerations for Choosing Process Intensification Strategies

Get expert insights into the multifold benefits of process intensification for biologics manufacturing. 

  • Learn about different technological and strategic options for your business 
  • Understand how PI can help you increase productivity, shorten timelines, reduce footprint, lower costs, or add flexibility 
  • Get insights into how ideal strategies can differ based on modalities produced  

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Increase Productivity

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Producing Diverse Molecules at Various Volumes

For biopharmaceutical manufacturers to stay competitive while delivering multiple specialized products in smaller batches or blockbuster-level volumes, they must achieve the highest levels of productivity possible. Unfortunately, many are operating within existing stainless-steel facilities built for large volumes, and they cannot compete with facilities that employ single-use solutions and other intensified technologies. 

Concentrated Fed-Batch Fuels Productivity

Intensifying seed train operations is one way to see immediate impact on upstream productivity.

Concentrated fed-batch enables manufacturers to achieve productivity levels up to four times that of standard fed-batch operations. Enabling concentrated fed-batch capabilities is one way Sartorius helps bring process intensification technologies into existing systems or when planning new facilities.  

  • The Biostat STR® single-use bioreactor with integrated XCell ATF® technology and advanced PAT tools for process analytics and control enables perfusion from 50 L to 2000 L.

Explore Concentrated Fed-Batch     Consult Our Experts

Increasing Productivity with Process Intensification

The biopharma industry wants the capability to increase biomanufacturing productivity on demand. See why process intensification is the best way to achieve this goal.

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Reduce Cost of Goods

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Manufacturing Complex Products While Controlling Costs

In the past 10 years, the average annual peak sales per molecule has decreased by 50% while average annual costs to develop each molecule increased by 30% – this introduces a mission-critical need to reduce COGS. Manufacturers that currently rely on fed-batch operations have an opportunity to introduce technologies that can quickly modify their existing upstream processes to bring larger gains in productivity and ultimately reduce production costs.

N-1 Supercharges the Seed Train to Bring Costs Down

Implementing N-1 perfusion in the seed train can result in a 30-50% reduction in cost/g compared to standard fed-batch operations and is a key example of process intensification. Sartorius is the only company offering two flexible N-1 seed train intensification options for rocking motion and stirred tank bioreactors along with state-of-the-art integrated analytical tools:

  • The Biostat® RM rocking motion bioreactor with single-use Flexsafe® RM bags, integrated perfusion membrane and in-line analytical & automation tools.
  • The Biostat STR® single-use bioreactor with integrated XCell ATF® technology, PAT and automation tools can accommodate 50  L to 2000 L.
  • The 4Cell® XtraCHO media system optimized for CHO-DG44 cells.

Explore N-1 Perfusion     Consult Our Experts

Increase Flexibility

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Gaining Flexibility in Your Operations

As medicines become more specialized, the number of low-volume batches and variables in manufacturing processes will increase significantly. Analyses of commercial R&D pipelines between now and 2025 indicate more than 80% of candidates would require production of less than 500 kg per year to meet demand. To keep up with these trends, manufacturing operations need to manage higher throughput of individual therapies as well as accommodate different modalities within the same facility.

Intensified Bioprocessing Made Possible with CFB

​Sartorius can help introduce concentrated fed-batch (CFB) technology, enabling manufacturers to achieve throughput 3-4 times higher than standard fed-batch. This supports intensified bioprocessing and the flexibility biomanufacturers require to remain competitive:

  • The perfusion-enabled Biostat STR® and Biostat® RM bioreactors with integrated PAT automation tools establish a fully flexible intensified seed train.

Explore Concentrated Fed-Batch     Consult Our Experts

Reduce Footprint

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Accommodating a Modular Mindset

Traditional upstream operations that rely on fed-batch processes simply cannot support the diversity of modalities resulting from innovations in protein-based medicines. Meanwhile, specialized medicines mean smaller throughput requirements, with almost 60% of drugs requiring 300 kg/year throughput or less to satisfy patient demands. Given these trends, manufactures are looking for flexible smaller modular Single Use perfusion based facilities to support this diversity in modalities and enable faster changeovers between multiple products.

Perfusion-Based Process for Modular Design

Manufacturing multiple modalities relies on introducing perfusion-based technologies that require smaller bioreactors which often results in modular facility designs. This results in a smaller footprint, lower upfront capex investment and reduced changeover times due to single-use technology implementation.

  • Biostat STR® and Biostat® RM bioreactors, supported with optimal media handling solutions, are suited for different intensified processes and enable small, modular single-use facilities.

Explore Dynamic Perfusion     Consult Our Experts

Reducing Facility Footprint with Process Intensification

Reducing your bioprocess footprint can help you maximize efficiency and conserve valuable resources. Find out how to save space at your site with process intensification.

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Shorten Timelines

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Reducing the Time Demands of Process Development

Speed-to-market is often what determines a product’s competitive position and pricing. Selecting the right process development tools that can reduce your development timelines and establish scalable flexible processes becomes very critical.

Reach IND Submission Sooner With the Right Tools

Sartorius offers several solutions to accelerate IND submission by reducing time spent on process development while integrating PAT for faster process optimization. Easy scale-up to any of the different upstream intensification schemes makes this approach very flexible.

  • Sartorius´ CHO Platform Service Package delivers DNA to RCB within 14 weeks and RCB to MCB in five months. With no media or process optimization required from small to large scale for cell line, media and scalable upstream processes, manufacturers can save up to two months in development.
  • Sartorius’ high throughput Ambr® systems along with PAT integration allow faster process optimization. The Ambr® 15 Cell culture system is the smallest single-use bioreactor which can mimic perfusion culture at 15 mL volume to optimize the selection of cell line and media. While Ambr® 250 perfusion system is an ideal scale-down process development/characterization system.

Explore PD & Pilot Scale     Consult Our Experts

Shortening Timelines with Process Intensification

Biopharmaceutical organizations are always up against time pressures, and their biomanufacturing is often a major limiting factor, learn how process intensification can help.

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Process Intensification Workflow

Media & Buffer Preparation

Managing the media and buffer requirements for an intensified process is a crucial and demanding step that may pose further filtration challenges due to increased volumes and storage times. Optimal delivery of media and buffers is required to manage these volumes and processing.

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Your Need:

To overcome media and buffer related challenges, you will need optimized and automated single-use solutions, that can prepare, mix, and store them for various intensified processes. In addition, high-throughput filters are required for optimal sterile filtration and risk mitigation. Thus, you will need:

  • Mixing and storage capacities to handle large volumes
  • High flux/throughput filtration for media and buffers
  • Flexible automated single-use solutions
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Our Unique Solutions:

To help you manage your media and buffer preparation, Sartorius´ portfolio of  bioprocessing applications includes the following solutions:

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Seed Train & Production

With increased demands, cost pressures and a multitude of products, facilities must be flexible, agile, and highly productive. Process intensification can help meet these demands, but implementation can be challenging. An effective solution is to intensify either the seed train or the production bioreactor with easily implemented and cost-effective solutions that enhance flexibility and productivity. For increased process understanding, in-line Process Analytical Technology (PAT) solutions are necessary, along with optimum clarification schemes, especially for high cell density perfusion processes.

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Your Need:

To realize process intensification, you will need single-use, cost-effective solutions. Thus, for an intensified seed train or production bioreactor you will need:   

  • Tested and proven single-use scalable perfusion-enabled rocking motion and STR bioreactors
  • In-line process control technologies for increased understanding of process parameters
  • Robust and scalable clarification solutions
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Our Unique Solutions:

If you are considering a shift from fed-batch to intensified process, Sartorius offers the following flexible perfusion-enabled solutions for both seed train and production  

  • Biostat® RM systems with state-of-the-art Flexsafe® RM bags featuring an integrated perfusion membrane
  • Biostat STR® single-use stirred tank bioreactors with integrated XCell ATF® technology
  • SIMCA® and SIMCA®-online for multivariate data analysis for increased process understanding and mitigation of risk due to deviations
  • PAT Toolbox with integrated, scalable single-use sensors, such as BioPAT® Trace, BioPAT® Viamass and BioPAT® Spectro, for real-time data measurement and automated process control

 
We offer the following single-use clarification solutions for high cell density cultures to remove cell debris and other product-related impurities:  

  • Ksep® systems are scalable, fully automated, single-use centrifugation solutions that are completely closed. They are optimized to handle very high cell densities while providing high recoveries and product quality in a continuous manner
  • Sartoclear® systems are scalable, single|dual layer high-capacity depth filters with varying pore sizes to accommodate different feed streams

Consult Our Experts

Capture Chromatography

Capture chromatography is usually the first purification step and requires optimal reduction of both product- and process-related impurities while maintaining high yields. Chromatography media can be very expensive, and its capacity can be reduced in a single column operation. Packing large columns leads to very labor- and time-intensive procedures that need additional space for processing and storage. It is desirable to have a semi-continuous mode of operation that is rarely satisfied by a single-column system with upstream perfusion processes.

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Your Need:

For integration with high-titer, intensified upstream processes, you will need semi-continuous capture capabilities and technologies to:

  • Use resins (especially Protein A) efficiently to decrease costs
  • Implement multi-column capture
  • Increase flexibility and automation
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Our Unique Solutions:

To increase your productivity over batch chromatography and to reduce spending on chromatography resin, Sartorius offers the following flexible and scalable single-use solution for affinity chromatography:

  • BioSMB Process System, which is a single-use, high-productivity multi-column chromatography (MCC) solution with efficient resin utilization for fed-batch and perfusion processes 

Consult Our Experts

Polishing

Varying feed streams, concentrations and impurity profiles lengthen development and the optimization cycle of polishing chromatography steps. One needs to adjust the downstream suite rapidly to cater to changes in molecules coming in the pipeline. All these factors lead to low yields, ineffective impurity removal and thus a sub-optimal downstream process.

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Your Need:

To intensify your polishing step effectively, you will need scalable chromatography solutions that enable efficient impurity removal and support flexibility, automation, and low footprint. You will need:

  • Scalable chromatography media
  • Single-use and flexible chromatography systems for your unique process requirements
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Our Unique Solutions:

To help you achieve efficient impurity removal and increased yield while reducing footprint and buffer consumption, Sartorius provides the following single-use chromatography systems, along with high-capacity chromatography media and|or plug-and-play membrane adsorbers :

 Consult Our Experts

Virus Clearance

Viral clearance, including viral inactivation and removal, is crucial for patient safety. Inefficient virus inactivation due to lack of adequate hold times or pH control remains a challenge. Moreover, inefficient removal of different virus types, virus breakthrough due to pressure drops, low capacity and low flux filters result in increased filtration times and costs due to larger filter area required.

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Your Need:

Your virus clearance approach requires reliable, scalable, and cost-efficient strategies that also deliver high product yields. You will need:

  • High-capacity virus filtration
  • Effective bioburden reduction
  • Flexible and automated solutions
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Our Unique Solutions:

To support you in achieving robust virus inactivation, bioburden reduction and virus removal from various feed streams, Sartorius supplies the following scalable, high-capacity filters and single-use, modular automation platforms:  

  • Virosart® Max for optimum prefiltration, resulting in increased filter capacity  
  • Virosart® HF high-capacity filters for robust and efficient virus removal
  • Sartoclear® single-use, single|dual layer depth filters for high-capacity clarification after low pH inactivation
  • Sartopore® 2 single-use sterilizing grade filters for efficient bioburden reduction
  • FlexAct® VI and VR configurable and modular platform solutions for virus inactivation (VI) and virus retention (VR), respectively, including bag assemblies with integrated prefilters, filters, and transfer sets

 Consult Our Experts

TFF & Final Filtration

Tangential flow filtration (TFF) and sterile filtration are the last downstream steps to obtain the desired product concentration, buffer formulation, and final filtration of the drug substance. Low filter flux and capacity resulting from a very concentrated, potentially viscous feed stream lead to large filtration times and filter areas, thereby increasing overall costs. Furthermore, variation in feed streams and concentration leads to low throughputs over final filtration, resulting in a low yield of the drug substance.

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Your Need:

To achieve formulated, sterile filtered bulk drug substance, you will need a high-capacity, high-throughput and fully scalable hardware system and consumable solutions for final formulation and filtration that include:

  • Low-adsorptive, high-flux filters   
  • TFF cassettes ideal for highly concentrated, viscous solutions
  • Flexible, single-use and automated system
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Our Unique Solutions:

To boost your final product concentration, buffer formulation and sterile filtration, Sartorius offers the following high-flux, high-capacity, flexible and single-use TFF and final filtration solutions:

  • Sartoflow®1000 and 4500 single-use TFF systems that are fully automated for UF|DF needs and are also suitable for molecules sensitive to shear  
  • Hydrosart® cassettes, which consist of highly hydrophilic, low-adsorptive and high-flux regenerated cellulose membranes for TFF
  • Sartopore® Platinum single-use sterile filters with low adsorption, made with unique and patented surface-modified membranes for bulk drug substance filtration

Consult Our Experts

Learn More About Process Intensification

Featured Assets

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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.
Download eBook

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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Related Assets

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The Medicine Maker Webinar: Downstream Process Intensification

Join Sartorius as we explore solutions for downstream process intensification. Our experts will discuss key technologies such as chromatography.

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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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Process Intensification Webinar Series

Sartorius' experts sharing best practices and addressing critical questions.

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Article

(Re)Defining Process Intensification

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Mind the Gap - Managing Relationships Between Upstream and Downstream Intensification

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A Strategic Approach To Selecting the Optimal Process Intensification Scenario

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Simplifying the Bioprocessing 4.0 Journey

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Enabling Broader Adoption of Process Intensification in Biopharma

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

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Sartorius Takes a Single-Use Approach to Derive Value from Biomanufacturing

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Article

Intensified Seed Train Strategy for Faster, Cost-Effective Scale-Up of Biologics Manufacturing

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eBook

Process Intensification - Key Considerations and Expert Insights

PDF | 6.0 MB
White Paper

Intensifying Upstream Processing and the Implications for Media Management

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Application Note

Maximizing Scale and Speed with Intensified Single-Use Tangential Flow Filtration (SUTFF) 

PDF | 1.1 MB
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Fed-Batch to Semi-Perfusion Using Automated Small Scale Bioreactors

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Poster

Simplify Upstream Process Intensification From PD to Manufacturing

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PI Videos

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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.

Why is the Biomanufacturing Industry Moving Towards Process Intensification?

Miriam Monge talks about the significance of intensified and continuous processing, the importance of the arrival of biosimilars on the market, and exciting Sartorius developments in the commercial biomanufacturing industry.

The Changing Landscape of Single-Use Technologies and Process Intensification

The industry is redefining regulatory and industry standards due to the implementation of single-use technologies. How does this affect the benefits of process intensification? Watch Miriam Monge in discussion with Dan Stanton, Editor of Bioprocess Insider.

Single-Use and Process Intensification in Commercial Biomanufacturing

How do single-use facilities influence cost of goods, flexibility, and reduced footprint in biopharmaceutical manufacturing and how does process intensification play a role? Watch Gerben Zijlstra in discussion with Dan Stanton, Editor of Bioprocess Insider.

Consult Our Experts

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