PD and Pilot Scale Process Intensification
Efficient process development (PD) including a high-titer cell line, clone selection and optimization, and process characterization is critical to develop a scalable upstream process. Now, with technology scalable to fit different intensified process types, PD also enables opportunities to optimize.
Sartorius offers PD solutions for high productivity, flexible upstream intensification processes and increased speed to IND.
High throughput screening tools allow for faster selection of optimized clone, media and upstream process.
Be “right first time” by integrating PAT and data analytic tools for enhanced molecule characterization and process understanding.
Bioprocessing 4.0 starts from PD. Data management, trend monitoring and recipe transfer tools ensure reliable scale-up and tech transfer.
For the development of a new therapeutic, early identification of robust, stable and highly productive cell line, media and cell culture conditions suitable for intensified processes are very important. However, the multitude of time- and labor-intensive experiments required to generate a viable cell line result in longer development times and higher cost.
Early identification of a productive cell line depends on a robust and efficient screening platform or a reliable partner that can develop a perfusion process in less time. In particular, you need:
Sartorius supplies state-of-the-art, industry-leading solutions and services for cell line development, as well as clone and media screening. Our solutions include:
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Accelerating upstream process development and time to IND requires a reliable, scalable and optimized process. However, manual and time-intensive development processes, lack of in-line process sensors and high-capacity clarification solutions extend development timelines.
To realize the benefits of intensified upstream process development, you need reliable and efficient scale-down models that predict performance at large scales, with the following capabilities:
Sartorius provides scalable and perfusion-enabled solutions for upstream process optimization and clarification from 250 mL to 2000 L, including:
Affinity chromatography captures the target molecule by binding it to a ligand while most of the bulk impurities flow through from the clarified feed stream. However, higher product titers obtained using perfusion processes and the labor-and time-intensive chromatography process development lead to high costs, low productivity and low product yields.
Your affinity capture program requires semi-continuous capture capabilities that can be easily integrated with upstream perfusion technology and that supports:
Sartorius offers the following flexible and cost-effective solution for affinity chromatography, providing 3-5x productivity along with significant savings on resin costs:
Polishing chromatography occurs post-capture to remove remaining impurities, such as HCP, DNA and potential viruses, from the product stream. However, the low capacity of chromatography media combined with highly manual and long development processes increase overall costs and extend timelines.
For effective polishing, you need scalable chromatography media that enable efficient impurity removal and that feature:
Sartorius provides flexible choices between membrane adsorbers and resins that reduce footprint and buffer usage, driving cost-effectiveness while increasing flexibility in operations:
Viral clearance strategies include virus inactivation and removal. pH adjustment after low pH virus inactivation can lead to a lot of aggregate formation that requires efficient filtration. Robust removal of all potential viruses is also critical. However, low depth filter flux and capacity, low virus filter throughput and early virus breakthrough lead to long filtration times and large filter areas.
Your virus clearance strategy requires robust and scalable viral clearance and bioburden reduction solutions that deliver:
Sartorius provides efficient, reliable and cost-effective solutions for viral clearance, aggregate removal and bioburden reduction:
Final steps of downstream processing call for tangential flow filtration (TFF) to obtain the desired product concentration and buffer formulation, as well as sterile filtration to ensure sterility and safety. However, multiple experiments for optimized formulation buffer, variation in feed streams and low flux filters result in long filtration times and large filter areas.
To produce a final drug substance, you need robust and efficient solutions for formulation screening, crossflow process development and sterile filtration of the drug substance, including:
Sartorius provides robust, scalable, efficient TFF and final filtration solutions that accelerate process development and enable high product yield:
Critical steps that determine future success
Support rapid growth to high densities
Real-time, scalable data at your fingertips
Cell Line Development (CLD) includes gene cloning, cell line selection and characterization, media selection and Master Cell and Working Cell banking. Many regard the selection of the appropriate production clone as the most critical step in CLD. If the PD team starts with one clone and then decides to switch to another, it would require major process changes . These changes would bring both significant delays and additional costs.
This is why development and characterization of the cell line for identity, purity and stability are crucial. Sartorius is a reliable partner for these critical steps, offering a Cell Line Development Service, a high-titer cell line with CellcaCHO Expression Platform, and perfusion enabled media.
The CellcaCHO Expression Platform is a scalable cell line and fed-batch process development system. It delivers stable research clones from DNA to research cell bank in 14 weeks and a fully characterized master cell bank in 10 months.
The CellcaCHO supports the potential of optimization:
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The 4Cell® XtraCHO-Media system is chemically defined and optimized for CHO DG44 cell lines:
The 4Cell® XtraCHO-Media system is cost-efficient, compliant with regulatory guidelines, and provides reliable batch-to-batch consistency.
Reducing COGS has become mission critical
Smaller footprint and initial investment, greater efficiency
Achieve the highest productivity possible
Cell culture media optimization is a crucial point of focus when exploring perfusion processes to achieve higher productivity. The medium should support rapid growth to high densities, achieve high cell growth rates with maximum viable cell concentration and provide batch-to-batch consistency.
Many cell lines were identified in a standard fed-batch process performed in Ambr® 15 microbioreactors. These cell lines show high intensification potential, but the best clone from standard fed-batch selection might not be the best in perfusion.
Mimicking the perfusion process for clone selection will not only save time, it can also enable a three-fold increase in productivity. Sartorius‘ Process Development Service makes this possible by offering a combined solution that includes cell line, media, process development and the technology to deliver optimal results.
The Ambr® 15 is the smallest single-use bioreactor on the market with system automation and parallel operation, and can be a starting point for process intensification:
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MODDE® is an easy-to-use solution for Design of Experiments (DOE). It offers design space functionality, multiple automated workflows, and improved process understanding through visualization and graph interaction. With an efficient DOE approach to problem-solving, you can:
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iQue3 is an advanced flow cytometry platform for high throughput clone screening.
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Characterizing an established perfusion-based process in scale-down models helps identify the economy of the process while mimicking the performance of large-scale bioreactors. Process parameters such as cell density and viability, titer and lactate level must be monitored in real-time to get the most benefit from the data.
Sartorius offers single-use and scalable technology solutions to supports perfusion-based process development.
The Biostat® B-DCU benchtop bioreactor with advanced PAT and MFCS perfusion recipes can be used from screening to characterization of intensified processes.
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Ambr® 250 HT perfusion supports the rapid development of scalable perfusion processes:
Only Sartorius offers a fully integrated solution for perfusion at the PD scale. Processes developed in Ambr® systems can be easily scaled from RM 20/50 to RM 200 and up to STR 2000 L.
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Octet is a low maintenance, label-free biomolecular interactions analysis platform. It monitors binding of proteins from solution to a biosensor surface in real time. Using Octet during process characterization effectively:
Key applications for process intensification are functional characterization and protein quantification, as well as glycan screening and contaminant testing. Octet can also be used for residual host cell protein detection.
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Join Sartorius as we explore solutions for downstream process intensification. Our experts will discuss key technologies such as chromatography.
Explore the implications of media management in an intensification strategy in this webinar featuring Sartorius experts.
Sartorius' experts sharing best practices and addressing critical questions.
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