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Efficient and Cost-Effective Monoclonal Antibody Scale-Up
DAVID SOLBACH 실험실 아카데미
- 제약
- Cell Culture
- 효율성
- Mixer 및 Shaker
- BioNews article
Propelled by the COVID-19 pandemic, the pressure increases to develop more products for treating unexpected viral diseases. Products must be available in a timely manner while ensuring that manufacturing is cost-effective and under safe conditions. Monoclonal antibodies (mAb) may hold great promise here as an addition to vaccines and anti-viral drugs. However, satisfying market needs with competitive products entails several hurdles and risks. How can manufacturers tackle the challenges?
This article appeared first in BioNews, Eppendorf’s application-oriented customer magazine since 1993.
When it comes to a fast time to market or staying ahead in the market, time is money. The early stages of cell line development and scale-up are key to the overall success of the process. Establishing a highly robust, efficient, and cost-effective mAb workflow requires an early process characterization. Reliable and stable processes must be developed, featured by reproducible cell growth, consistent high viability of cells, and maximized yield. Highest efficiency with reduced manual handling steps is paramount. Single-use technologies and process-intensification help addressing these goals. Employing continuous manufacturing strategies results in higher yields and can help to reduce the costs, compared to classical batch and fed-batch approaches. A reproducible transfer from small scale to larger volumes is the prerequisite for a fast time to market and for mitigating risks with respect to supply chain and market access.
Process development – maximizing yields and process stability
Challenge and goal is always to maximize the yield, which depends on the viability and productivity of the cells. Each cell line and even each clone performs differently. To ensure stable cell growth profiles and antibody yields from small- and bench-scale to production-scale requires a strategy based on a detailed process understanding and optimized bioreactor conditions.
Media optimization, designing a better expression system, or studying the metabolic pathways can increase productivity. Precise equipment such as pumps, sensors, and gas control is the prerequisite to ensure stable and consistent process runs. Proper instrumentation allows to monitor metabolic pathways, assessing productivity consequences of, for example, carbon source depletions and optimize conditions in the bioreactor.
Analytical equipment with sensor integration in parallel systems is superior for process insights. Different settings, parameters and cell lines can be tested at early stage at the same time. The parallel control of multiple bioreactors and simultaneous monitoring of various process parameter speeds up process characterization and increases time and cost efficiency. Software-supported process control with sensor-driven feedback loops enables automation, reduces manual handling steps and the risk of human errors, thereby increasing safety, reproducibility, and efficiency.
Scale-up – maintaining cell growth profiles and antibody yields
One of the major mAb production challenges is cell culture scale-up. Studying the reactor conditions help cells to grow effectively and to produce a proper amount of product.
Essential for efficient mixing and mass transfer throughout the different bioreactor sizes is an optimal vessel geometry based on the ratio of impeller diameter to vessel diameter. Popular scale-up strategies enable a reproducible transfer from small scale to larger volumes. However, calculations are complex and require expert knowledge.
Software-guided calculations of important process parameters save time, considerably ease process setups, and mitigate the risk of failures. Combined with new open-concept controllers, similar cell growth profiles can be produced in a variety of bioreactors, regardless of supplier, from bench to production scale.
Device management – preventing downtimes and failures
Cutting corners in selecting equipment could have a big and potentially negative impact on the process. The worst-case scenario leads to batch failures that cause supply shortages of critical medication.
A system should support industry standards, give insights about its status, and send reminder if service is required. Industries with a large base of installed equipment will particularly benefit from that. Digital sensors that provide information about their lifetime allow to replace a sensor that is close to end of life. This can lead to significant cost savings as risks of process failures due to defect sensors are avoided.
Instrumentation suppliers should provide any data on the suitability of the equipment for a specific process. Being familiar with problems manufacturers face, they can provide expert support based on a common understanding.
Conclusion
Development of a robust, efficient, and cost-effective monoclonal antibody research and development process is accompanied by many hurdles and risks. With the right and reliable equipment, process development and optimization at bench, pilot and production scale will lead to success.
When it comes to a fast time to market or staying ahead in the market, time is money. The early stages of cell line development and scale-up are key to the overall success of the process. Establishing a highly robust, efficient, and cost-effective mAb workflow requires an early process characterization. Reliable and stable processes must be developed, featured by reproducible cell growth, consistent high viability of cells, and maximized yield. Highest efficiency with reduced manual handling steps is paramount. Single-use technologies and process-intensification help addressing these goals. Employing continuous manufacturing strategies results in higher yields and can help to reduce the costs, compared to classical batch and fed-batch approaches. A reproducible transfer from small scale to larger volumes is the prerequisite for a fast time to market and for mitigating risks with respect to supply chain and market access.
Process development – maximizing yields and process stability
Challenge and goal is always to maximize the yield, which depends on the viability and productivity of the cells. Each cell line and even each clone performs differently. To ensure stable cell growth profiles and antibody yields from small- and bench-scale to production-scale requires a strategy based on a detailed process understanding and optimized bioreactor conditions.
Media optimization, designing a better expression system, or studying the metabolic pathways can increase productivity. Precise equipment such as pumps, sensors, and gas control is the prerequisite to ensure stable and consistent process runs. Proper instrumentation allows to monitor metabolic pathways, assessing productivity consequences of, for example, carbon source depletions and optimize conditions in the bioreactor.
Analytical equipment with sensor integration in parallel systems is superior for process insights. Different settings, parameters and cell lines can be tested at early stage at the same time. The parallel control of multiple bioreactors and simultaneous monitoring of various process parameter speeds up process characterization and increases time and cost efficiency. Software-supported process control with sensor-driven feedback loops enables automation, reduces manual handling steps and the risk of human errors, thereby increasing safety, reproducibility, and efficiency.
Scale-up – maintaining cell growth profiles and antibody yields
One of the major mAb production challenges is cell culture scale-up. Studying the reactor conditions help cells to grow effectively and to produce a proper amount of product.
Essential for efficient mixing and mass transfer throughout the different bioreactor sizes is an optimal vessel geometry based on the ratio of impeller diameter to vessel diameter. Popular scale-up strategies enable a reproducible transfer from small scale to larger volumes. However, calculations are complex and require expert knowledge.
Software-guided calculations of important process parameters save time, considerably ease process setups, and mitigate the risk of failures. Combined with new open-concept controllers, similar cell growth profiles can be produced in a variety of bioreactors, regardless of supplier, from bench to production scale.
Device management – preventing downtimes and failures
Cutting corners in selecting equipment could have a big and potentially negative impact on the process. The worst-case scenario leads to batch failures that cause supply shortages of critical medication.
A system should support industry standards, give insights about its status, and send reminder if service is required. Industries with a large base of installed equipment will particularly benefit from that. Digital sensors that provide information about their lifetime allow to replace a sensor that is close to end of life. This can lead to significant cost savings as risks of process failures due to defect sensors are avoided.
Instrumentation suppliers should provide any data on the suitability of the equipment for a specific process. Being familiar with problems manufacturers face, they can provide expert support based on a common understanding.
Conclusion
Development of a robust, efficient, and cost-effective monoclonal antibody research and development process is accompanied by many hurdles and risks. With the right and reliable equipment, process development and optimization at bench, pilot and production scale will lead to success.
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