Optimizing Bioproduction Media to Improve Protein Production – A Discussion
We recently finished our Ask the Expert discussion on Optimizing Media and Improving Protein Production with Defined Supplements. Enhancing protein production is a common goal in the biomanufacturing industry. During this Ask the Expert session, we discussed the challenges associated with animal origin free media optimization and how defined supplements can provide an increase in productivity and yield. Essential Pharmaceuticals is addressing the challenge of animal origin free media optimization with their Cell-Ess supplement. Use of this product at 1% concentration resulted in a 37% increase in productivity. When using the supplement as a feed it resulted in in a 25% increase in yield and an extension of peak protein production with functional protein increase and desired glycosylation achieved. Results suggest that an increase in protein production may not necessarily require a change in the metabolic state of the cells.
In this discussion, specific culture related questions included cell types tried, media tested, benefits to already high titer cultures, impact to metabolic profile, peak protein yield, effect on downstream purification, and use in vaccine manufacturing. There were also manufacturing focused questions related to cost analysis, specific productivity, glycosylation profile, and regulatory considerations.
This Ask the Expert session was sponsored by Essential Pharmaceuticals and hosted by Dr. Adam Elhofy, Ph.D., CSO. Dr. Elhofy developed the core technology for the Ess line of products and aided in creating patents around novel uses of materials. Dr. Elhofy has over 14 years of scientific research experience in the areas of immunology, neuroscience, and oncology. He was funded by both the National Institutes of Health and the Multiple Sclerosis society as an investigator at Northwestern University Medical School. His doctoral research won him the award of the Top 5 trainee scientists by the American Association of Immunologists. Dr. Elhofy has 14 scientific publications in peer reviewed journals. He has played a variety of roles with start-up biotech companies ranging from Principal Investigator to Director of Corporate Development.
Below is a sneak peek of the discussion, for a full transcript, please see – Ask the Expert – Optimizing Media and Improving Protein Production with Defined Supplements.
With titers at 3g/l or in most cases even better, we aren’t necessarily looking for improved titer. Are there other benefits to be gained?
This is great question. I will try to address this from 2 different perspectives.
The first way to think about a benefit is through logistics. When we have used Cell-Ess as a feed, we found the increased output occurred early. We reached the max yield of the control group 2 days earlier than in the control. In this case you could have the benefit of ending a run 2 days earlier.
The other half to consider is protein quality. Quality is measured through many assays. The quality of a protein is driven by the endoplasmic reticulum and Golgi apparatus. Cell-Ess may support better health of both of these organelles. We are currently running assays to access what, if any, are the effects of Cell Ess on protein quality.
What cell types have you used your Cell Ess with?
Cell Ess has been used with a variety of cell types. Cell Ess has been used in cell lines and primary cells. In cell lines Cell Ess has been used a549, HEK 293, VERO, CHOk1, and many other cancer cell lines both adherent and suspension type of cells. For cell lines there is a adaptation that is required and possible optimization required. For example there are some cancer models using cell lines that are hormonally dependent in those cases it may require the addition of the needed hormone like estrogen.
Cell Ess also works with primary cells. In the case of primary cells there is no need for adaption but there may still be the need for optimization based on the goals of the research. For example there are some cells that require the presence of TGF-b for their function. In those cases you would have to add exogenous TGF-b.
We designed Cell Ess to be used across many cell types for that reason there may be cell specific or lab specific optimization. Once the optimization is determined the results have been consistent and reproducible.
When you talk about improving bioproduction, are you adding this supplement to classic or chemically defined production media?
This is an interesting question. We have tried both methods. The most common media used for bioproduction is chemically defined media. In many cased there are internal proprietary formulations. We tested Cell Ess in a chemically defined system as part of an optimization strategy to see if we could improve performance of the system. We found a benefit if we added Cell Ess as either an initial supplement or as feed.
In serum containing systems we adopted the system to serum free and then were able to see similar performance as was in the serum containing media.