Perfusion Culture Process Optimization

As a continuous cell culture technique, perfusion was developed back in the 1980s to increase protein titers. Today, perfusion technology is considered promising for constant biopharmaceutical production, increasing efficiency and productivity while reducing costs. As a specialist in fermentation process development and microbial strains breeding, BOC Sciences offers perfusion culture process optimization and GMP manufacturing services to clients in various fields. Our advanced automation facilities and extensive experience in process optimization offer a comprehensive solution to microbial fermentation R&D and production.

Introduction of Perfusion Culture

The demand for biologics has proliferated in recent years, and the cell culture process with perfusion mode has become increasingly popular for its high productivity, quality and efficiency.

Perfusion culture is a process that involves the constant addition of fresh medium, and removal of products as well as spent medium while retaining the viable cells. Generally, advantages of typical batch culture include longer durations, fewer turnaround operations, higher cell densities and productivities, healthier and more uniform culture, as well as potentially more consistent product quality.

Application of Perfusion Culture

• The perfusion culture has been proved to be capable of producing a variety of therapeutic proteins, including enzymes and monoclonal antibodies, which brings additional benefits such as allowing smaller size bioreactors and replacing reusable consumables and equipment.
• The perfusion culture has been used as an effective method to enhance the yield of unstable recombinant products due to the reduced product residence time in the reactor during perfusion culture and the reduced product contact with degradation enzymes found in the culture.

Our Advantages for Perfusion Culture Process Optimization

• Over 20 years of ongoing experience in strain development.
• Extensive knowledge is used to discover the most suitable solution for our customers and promote business success.
• GMP production facilities with a total reaction capacity of hundreds of tons support large-scale fermentation.
• Advanced cell culture technologies and optimum media selections.
• State-of-the-art bioreactors and process control systems to equip your upstream processing
• Flexible and customizable fermentation process optimization.
• Perfusion culture process optimization can streamline bioreactor processes and media formulation development.

Our Methods for Perfusion Culture Process Optimization

Removing spent media while keeping cells in culture can be done using alternating tangential flow (ATF) and standard tangential flow filtration (TFF).

• Tangential flow filtration (TFF) is combined with permeable membrane filtration and flow. The major difference between TFF and other filtration systems revealed that fluid in the TFF passed parallel to the filter, avoiding possible clogging caused by a direct vertical push through the filter membrane, and allowing continuous filtration and reproducible performance. Moreover, particles that pass through membrane are put off to the side, while retentate is recycled back to the feed.
• Alternating tangential flow (ATF) system is used for cells retention, and its major features include self-cleaning and back-flushing, attributed to the action of the diaphragm pump. The repeated and rapid flow by a diaphragm pump inhibits filter membrane blockage. Also, the back-flushing flow generated by varying the transmembrane pressure protects filters from biofilm formation on surfaces. These two features allow high cell density culture and extend the perfusion time in ATF perfusion culture.

Project Workflow of Perfusion Culture Process Optimization

• Customer advisory
• Project discussion
• Selection of microbial host
• Microbial strains culture and perfusion culture process optimization
• Project delivery