To maximize performance of cell lines, biopharma manufacturers must find the right media, relevant to their production mode. For instance, perfused seed trains and production bioreactors require new media formulations for optimal performance.
Feed strategies must be based on empirical data from media screening and optimization, as well as nutrient testing. Feed volumes and timing of feed administration should be determined for each specific process and cell line via high throughput (HTP) and design of experiment (DOE) approaches. These can be conducted internally or by partnering with experts to expedite simultaneous screenings.
Tech Brief: Lay the Proper Foundation for Upstream Success
White Paper: Turnkey Solutions to Improve Cell Culture Performance
Application Note: Improving Fed-batch Yields by Combining EX-CELL® Advanced and Cellvento® Cell Culture Media Portfolios
Flyer: Media Selection Guide
White Paper: Optimizing Media Feed Strategies for Cellvento® CHO Media Platform
Flyer: Cellvento® and EX-CELL Feed Mixing Protocol
Webinar: The Importance of Media Selection and Scale-down Models for High-titer Expression in CHO Cells
Application note: Process guidance Cellvento® 4CHO Fed-batch Medium
Webinar: Turnkey Solutions for Upstream Cell Culture Processes
White paper: Strategies for Upstream Intensification
White Paper: A Cost Analysis and Evaluation of Perfused Seed Train Scenarios Through Process Modeling
White Paper: Seed Train Intensification Using High Cell Density Cryopreservation and Specially-designed Expansion Medium
White Paper: Upstream Intensification – Enabling Perfusion Processes with Cell Retention Technologies
White Paper: Guidelines for Developing a High Cell Density Cryopreservation Process
Application Note: Preparing CHO Cells for Higher Productivity by Optimizing a Perfused Seed Train
Article: Innovative Strategies for Cell Culture Media Preparation
White Paper: Mitigating Risks Associated with Cell Culture Media Preparation and Handling
Webinar: Compacted Cell Culture Media – Improving Solubility and Stability
Article: Using Modified Amino Acids to Simplify Fed-batch Bioprocessing
Webinar: Simplification of Fed-batch Processes Using Modified Amino Acids
Article: Innovative Chemicals for Process Intensification in Cell Culture Media
Dry powder cell culture media formulations provide many advantages for shipping and storage. To leverage these benefits, dry powder media formulations need to be highly soluble and homogeneous. These properties can be achieved by the combination of optimized milling procedures and suitable formulation technologies. Additionally, media should arrive in a format that is convenient to handle, such as pre-weighed dry powder bags that connect directly to hydration tanks. This minimizes product contamination risks, safeguarding employees and facilities. When mixing, especially at high volume, good dispersion and dissolution of particles can be managed with specially designed single-use mixing systems.
From thawing a single vial of cells, to expanding cells for a GMP manufacturing batch run is time-consuming, labor intensive, and requires open cell culture operations. Use of a High Cell Density Cryopreservation (HCDC) method, which feeds into the first seed train bioreactor, can streamline the overall process. As the frozen volume is relatively high, single-use bags are more appropriate than vials. This allows HCDC to be used in closed processing, thus reducing contamination risks.
Perfusing the seed train is a solution for achieving higher cell densities, and it is recommended to use specially designed expansion media for an optimal result. It enables high seed inoculation of your production bioreactor through higher cell biomass or reduces your upstream footprint by decreasing the number of bioreactors in the seed train. In addition, it saves time by eliminating adaptation during transfers from the vial thaw to expansion and production.
Contamination often originates from raw materials and animal-derived components such as bovine serum or trypsin. Wherever possible, raw materials and animal-derived components at high risk of virus contamination should be replaced with low(er)-risk alternatives, such as chemically defined cell culture media and non-animal origin recombinant supplements. They also simplify regulatory processes.
The essential amino acids tyrosine and cysteine present a challenge when used in upstream processing, due to low solubility (tyrosine) and low stability (cysteine) at neutral pH. To simplify fed-batch processes and enable high available concentrations of both amino acids, chemically modified tyrosine and cysteine enable a single feed strategy at neutral pH. Other benefits of this approach include reduction of feed volume and increased volumetric productivity.
Lack of consistency in raw materials can create significant variation in upstream processes, causing unexpected loss of cell density and viability – and ultimately, reduced yield. A better understanding of raw materials increases ability to control process variabilities. This can be achieved by tracing the supply chain back to raw materials and characterizing them.
Current regulatory and industry guidelines do not define clear standards for chemicals used in upstream bioprocessing. In the absence of standards, drug manufacturers rely heavily on their suppliers for efficient sourcing and qualification of raw materials; however, typical timelines to collect raw material information via questionnaires and separate statements can be unacceptably long, often taking several weeks. Consequently, manufacturers are seeking supply partners who can provide raw materials that are stringently qualified to industry-leading standards and are supported by comprehensive documentation packages that meet pharmaceutical manufacturers’ information needs when qualifying raw materials, completing a risk assessment or optimizing a manufacturing process.
Monoclonal antibody manufacturing is a highly templated approach used to produce mAb-based immunotherapies. Robust, scalable process solutions are required at every step to ensure high therapeutic concentration and process safety, while meeting speed-to-market and cost containment concerns.