Introduction to Cell Culture
Supplements & Expression
Technology

We know the pressure is on and we’re here to help.

“Today, we estimate that there are over 425 biotechnology drugs in the pipeline, including 210 for cancer, 50 for infectious disease, 44 for autoimmune disorders and 22 for AIDS/HIV. By product category, there are 160 monoclonal antibodies, 62 vaccines, 43 recombinant hormones/proteins, 26 interferons and interleukins and 16 growth factors…”
- J. P. Morgan report. “Biomanufacturing: A Closer Look at the Biomanufacturing Landscape,” July 9, 2007

With the significant growth in the number and breadth of biotherapeutic products, the cell culture market is being required to do more than ever before. Researchers and manufacturers alike face regulatory concerns including traceability and sourcing of materials, while seeking the most appropriate and economically sound strategies for cell culture supplementation. At the same time there is an increasing demand for research into new biotherapeutic products and production methodologies, as well as the need to scale these into an efficient, robust manufacturing process.

Biopharmaceutical scientists, manufacturing engineers, and executives’ end goal is optimal yields, generated from consistent results. The objective is to control protein characteristics while enhancing cell growth rate and protein production. This can be done through several key steps:

Engineering stable, high-expressing cell lines
Optimizing feeding strategies
Improving characterization and standardization of supplements
Promoting efficient screening

The evolution is towards more serum-free and chemically-defined supplements and media. Typically, a stepwise progression is recommended to continue normal production while evaluating and validating substitute or second-sourced supplements.

Even with existing supplements, whether animal-derived to animal-free, there are several actions that can be taken to reduce process variability and improve both process quality and consistency.

Tighten the specifications and improve the characterization of existing supplements to provide a consistent, reliable source of supplements

Partner with suppliers to characterize potential additives and/or contaminants as much as possible
Confirm appropriate sourcing and traceability of raw materials whether the raw materials are animal-derived supplements from GBR-1 countries such as New Zealand, to GMO-free sources for hydrolysates

Reduce the risk of contaminating biological processes and products

Review process flow for manufacturing to lower the risk of external contaminants
Confirm appropriate sourcing and traceability of raw materials
Leverage appropriate quality control testing such as ELISA, HPLC Protein A, and other tests to set acceptance criteria for consistency, microbial content, clearance of bovine viruses for animal-derived supplements (9 CFR 113), and endotoxins
Develop appropriate metrics (e.g. EU/g, CFU/g, etc.) and testing methodologies for contamination levels

Ensure compliance with existing guidelines

Ensure supplements are manufactured in fully validated (via ISO 9001:2000) manufacturing plants built to cGMP compliance
Verify EP and USP compliant processes

Support the commitment to research

Promote the development of new cell culture expression technologies to increase recombinant protein product yield from both pools and clones
Partner with companies to drive next-generation updates, whether to improve consistency for a specific cell line, or to help reduce overall cost of consumables for commercial biomanufacturing