Fed-Batch Culture Process Optimization

Fed-Batch Culture Process Optimization

BOC Sciences specializes in upstream process (USP) optimization for fermentation to accelerate clients’ biological products development. Recently, the increasing competition of biopharmaceutical industries requires product scale-up to ensure sufficient supply. As the core of USP for most biotherapeutics, cell culture improvement is a top priority to achieve overall bioprocess flow enhancement. Among all optimization processes, the fed-batch process is the mainstay of industries. With our extensive fermentation R&D experience, BOC Sciences offers fed-batch culture optimization services to meet the needs of commercial-scale fermentation production for all industries.

Introduction

Fed-batch culture refers to the feed medium added to bioreactors during cell culture, thus preventing the base medium’s nutrient depletion, as well as retaining all products until the final bioreactor run. In addition to improvements in cell lines, media formulation and bioreactor engineering design, further modifications can be made to the culture methods. In particular, fed-batch culture has been widely used to achieve enhanced upstream culture by combining different operational or process designs. Commonly intensifying fed-batch cell culture processes include high cell-density culture, concentrated fed-batch (CFB), N-1 perfusion high inoculum fed-batch, high productivity harvesting (HPH), etc.

Application of Fed-Batch Culture Process Optimization

The fed-batch process optimization is considered an optimum strategy for cell culture to increase fermentation production capacity while lowering costs. The fed-batch process optimization can be used to:

  • Improve volumetric product efficiency
  • Increase living cell density
  • Increase seeding density
  • Improve cell-specific productivity
  • Enhance production bioreactor’s utilization

Our Advantages

  • Our extensive knowledge is applied to finding the most suitable solution for our customers and promoting business success.
  • Our GMP manufacturing facilities retain a total reaction capacity of hundreds of tons to support large-scale as well as commercial-scale fermentation.
  • Our upstream processing is equipped with state-of-the-art bioreactors and process control systems.
  • Our fermentation process optimization services are flexible and comprehensively tailored to our customers.

Our Methods

  • Concentrated fed-batch (CFB): CFB cell culture allows for flexible throughput but limited volume capacity, enhancing cell culture titers and allowing smaller facilities to match the throughput. Evidence has supported that CFB improved culture process and product quality, as well as cell line output and heterogeneity of products, including antibodies.
  • High-density cell culture: The fed-batch strategy has been used in bio-industrial processes to high cell density in the bioreactor. High-density cell banks can simplify growth steps required in the seed amplification process, as traditional approaches typically start with freezing and require longer thawing and amplification times.
  • N-1 perfusion high inoculum fed-batch: Upstream optimization can often accelerate the timeline by simplifying growth steps or reducing production days required to produce bioreactors in the N stage. A desirable hybrid option is to implement perfusion in the N-1 bioreactor stage while maintaining a fed-batch process for the production reactor. Moreover, increasing production bioreactor capacity is often costly and time-consuming, so switching to N-1 perfusion can reduce the potential for upstream bottlenecks when scaling up a process. N-1 perfusion combined with high-density inoculation can facilitate production bioreactor run times.

Project Workflow

  • Customer advisory
  • Project discussion
  • Selection of microbial host
  • Cells culture and fed-batch culture process optimization
  • Project delivery

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