By Lalit Saxena, Senior Director of MSAT, and Sungkeum Seo, Director of MSAT Labs Upstream Processing at Samsung Biologics
Introduction
The biopharmaceutical industry is expanding rapidly, driven by an increasing demand for complex biomedicines. Today, manufacturing biomolecules presents unique challenges, like cost pressure and market uncertainty. The need to develop proprietary processes to differentiate from competitors is higher than ever before. Furthermore, companies need to ensure product consistency across scalable production processes and meet regulatory standards, all while trying to maintain a low cost of goods sold (COGS) (Lee & Lee, 2023).
To remain competitive and meet the growing demand for biomedicines that meet specific therapy targets, companies are turning to innovative production methods. One of the most promising technologies for improving efficiency and scalability is N-1 perfusion (Lee & Lee, 2023).
Advantages of Continuous Biomedicine Manufacturing Using N-1 Perfusion
During the last two decades, suspension culture technologies have improved. Yields of traditional batch processes doubled every 2-3 years, due to improved expression systems, media development for high cell density cultures and precise process control.
Continuous biomanufacturing using N-1 perfusion offers several benefits as well. These benefits comprise higher cell densities, shorter cell culture duration, increased productivity, reduced process time and cost, a lower number of control strategies required, improved COGS and greater flexibility compared with traditional fed-batch production (Lee & Lee, 2023).
Today, the biopharmaceutical industry is moving towards a hybrid approach to take advantage of the high seed densities obtained with N-1 perfusion and greater yields obtained with batch technologies.
Key Considerations for Continuous Biomedicine Manufacturing Using N-1 Perfusion
Successfully implementing N-1 perfusion is challenging and may be slow because companies have focused on implementing and optimizing fed-batch processes only during the last decade. Companies are often stuck with scale-down models, decision tools, equipment and procedures in place for traditional processes. For perfusion to be successful, vendors and manufacturers have to adapt their platforms and capabilities to achieve similar robustness as the current standards.
Additionally, N-1 perfusion comes with specific operational challenges. For example, maintaining optimal flow rates is essential to prevent issues such as filter clogging and shear stress, the process must be integrated with the bioreactor’s control logic to ensure that volume, temperature, dissolved oxygen and pH remain stable throughout the process and the process development must be optimized effectively to keep costs and required time low (Lee & Lee, 2023).
Samsung Biologics’ advanced capabilities for innovative biomedicine production
Samsung Biologics, a global Contract Development and Manufacturing Organization (CDMO), has optimized commercialization-scale biomolecule production. As a pioneer in N-1 perfusion technology, Samsung Biologics has the instrumentation and expert operators to help companies achieve their production goals (Lee & Lee, 2023).
The expertise of Samsung Biologics’ technical team is the main advantage for our clients. As we are growing fast, the teams gain extensive experience for fast-track technology transfer, process design, process scale-up, manufacturing and troubleshooting, which is a valuable and unique advantage the client has when working with Samsung Biologics.
Even though perfusion technology is already applied on a small scale, few companies have optimized this technology to produce biomolecules commercially. Samsung Biologics has successfully performed a 3000 L N-1 perfusion to supply its 15,000 L commercial production process (Samsung Biologics, 2024). By cultivating cell densities of more than 70-80∙106 cells/mL and seeding fed-batch cultures with a higher initial cell count, Samsung Biologics can increase the manufacturing capacity and thereby reduce the production time for its clients by up to 30%, without experiencing filter or oxygen transfer limitations (Samsung Biologics, 2024).
To reach stable operations, media feed, harvest and bleed flow rates must be properly controlled and monitored in real-time to maintain the desired perfusion rate and cell density. Samsung Biologics has the necessary expertise and instruments, such as capacitance sensors, spectrometers and Raman technology to estimate the oxygen uptake rate and carbon dioxide evolution rate.
Finally, scale-down tools are needed to support process development, operation of the production process and troubleshooting. Usually, lab-scale bioreactors of 2 L to 10 L are used as scale-down models for manufacturing. Samsung Biologics has experts who help clients develop perfusion-based processes. Its MSAT team is experienced in assessing the techno-commercial benefit and comparing Tangential Flow Filtration (TFF) with Alternating Tangential Flow (ATF) technologies for best performance, facility fit and scale-up to manufacturing.
Conclusion
Samsung Biologics is a trusted CDMO partner and has a track record of success (BPI Staff, 2019). Innovation, high quality, speed to market and technical expertise are what best describe the values Samsung Biologics provides to our clients.
References
BPI Staff. (2019). CDMO Samsung BioLogics has used an Alternating Tangential Flow (ATF) system to perform N-1 perfusion at its 180,000 L facility in South Korea. BioProcess International. Retrieved October 1st from https://www.bioprocessintl.com/upstream-downstream-processing/commercial-n-1-perfusion-carried-out-by-samsung-biologics
Lee, S., & Lee, C. (2023). Large-Scale Continuous Biomanufacturing: Utilizing N-1 Technology for Higher Productivity and Quality. Samsung Biologics.
Samsung Biologics. (2024). Samsung Biologics Implements Large Scale N-1 Perfusion for Commercial Application https://samsungbiologics.com/front/en/mediaCenter/pressReleasesView.do?boardSeq=468