Achieving high cell densities in long-term cultures is often a challenge facing bioprocessing manufacturers, and one that requires the support of optimal media. FUJIFILM Irvine Scientific recently sat down with Luis Rodriguez, PhD, R&D Manager, Bioproduction, to discuss the new Perfusion Media Survey Panel (PMSP) that enables bioprocessing manufacturers to identify the best media options for their applications.
What is the Perfusion Media Survey Panel (PMSP) comprised of?
The Perfusion Media Survey Panel, or PMSP, is a survey panel of media specifically designed for a continuous, long-term culturing process. Widely used in bioprocessing, perfusion cultures can be used as a seed train, or to concentrate the product in a bioreactor as a long-term or short-term process. Both types perfusion processes have their advantages and disadvantages, but what they have in common is the goal of achieving high cell densities and an increase in production. The PMSP comprises perfusion media capable of achieving and maintaining high cell densities for a continuous, long-term process, and customers can evaluate these media in their own lab using their specific processes.
Why does FUJIFILM Irvine Scientific call PMSP a media survey?
FUJIFILM Irvine Scientific has an active R&D Department that continually strives to improve our products and provide customers with the best media options. Media surveys are used to gather information about media performance, and help us provide customers with the best media for their process. This is in contrast to a “screening” process, as it is more usually called, that randomly selects media to test with cells. Media surveys comprise a more targeted, individualized approach to media selection, where we encourage our customers to provide feedback. Working together with our customers allows us to provide the best medium for their process.
How do I evaluate the PMSP? What parameters in a perfusion process should I assess when testing the PMSP?
The success of a perfusion culture is measured by its ability to attain and sustain high cell densities, while achieving maximum productivity for prolonged culture periods. The first step in assessing a perfusion medium is to determine if it is capable of attaining and sustaining high cell densities with your cell lines.
Additionally, measuring viable cells and yield alone cannot determine whether a perfusion media is suitable for a cell culture process. Other key perfusion metrics must be considered, including cell-specific productivity (qP), volumetric productivity (VP), and cell specific perfusion rate (CSPR). These metrics allow you to compare media on the basis of how productive each cell in the culture is. qP is a measure of the productivity per cell per day. The VP of a culture is a measure of the grams per liter per day that a bioreactor is capable of producing. It is derived from the qP and the cell density of the culture.
The final key parameter to consider is CSPR—a measure of the performance of the cell culture media. CSPR measures the exchange rate in picoliters per cell per day, which is derived from the perfusion rate normalized to the cell density. A high qP and VP with a low CSPR suggests you are maximizing the medium for the production of your therapeutic.
What makes a perfusion media survey event successful and what can I expect to gain in terms of knowledge or tangible benefits?
A successful media survey brings customers closer to optimal, chemically defined media that will increase cell line productivity. FUJIFILM Irvine Scientific PMSP media are designed to sustain high cell densities over a long-term process. By surveying our PMSP, customers can identify a medium with more optimal components that may outperform their current selection.
What components of a medium can be adjusted to achieve improvement?
As part of the FUJIFILM Irvine Scientific Media Development and Optimization program, we work with customers to optimize any medium component to maximize growth, productivity, or protein quality attributes. Customers may use a medium from the PMSP as a starting point for improving their custom chemically defined formulation. Any component can be adjusted or modified to achieve the desired performance required by the customer.
What are the differences between the various media in the PMSP?
The PMSP is comprised of various media capable of achieving and maintaining high cell densities and promoting increases in productivity. The differences in the media are variations of components that we have tested to support growth of both CHO-GS and CHO-DG44 cells.
What kind of support does FUJIFILM Irvine Scientific provide while I am evaluating the PMSP?
Our goal in offering the PMSP is to provide targeted, collaborative support for our customers as they evaluate media and processes for cell culture media needs. To ensure customers successfully complete their evaluation, we provide protocols and know-how to support them, as well as offer screening and analytical services for the evaluation process.
How can the media in the PMSP help maximize the productivity of my cells and improve protein expression?
We have more than 50 years of extensive research history in cell culture media development and understand that one medium may not fit all cells. For example, studies have shown the heterogeneity of CHO cell genomes between the various CHO cell line lineages currently being used in manufacturing. In fact, heterogeneity is also seen between clones expressing the same product. By evaluating our PMSP, a medium formulation can be identified that promotes increased productivity and expression in a specific clonal cell line. To maximize the value of the PMSP, further media optimization can be pursued in a Media Development and Optimization project, with the goal of maximizing productivity and protein expression.
If I identify a medium or media combination that works well for my cells, what is the next step? Are the media available from GMP?
All of our PMSP media are ready to manufacture in our GMP facility. Once a customer has identified a medium that works well for their cells, a custom made-to-order purchase can be placed by the customer through their sales representative.
What are my options for scaling up my cell culture all the way to XL bioreactors?
FUJIFILM Irvine Scientific is a manufacturer of cell culture media, with three locations in California, Japan, and Europe that distribute our products globally. Our Express Media Service (EMS) can produce up to 18 kg of powder and 200 L of liquid for any process development as you scale-up to larger bioreactors. EMS uses the same raw material and processes as our GMP manufacturing facility, which is capable of manufacturing and delivering the amounts required for your largest bioreactors.
Contact a Media Specialist today to learn more about the Perfusion Media Survey Panel and our Media Development and Optimization services.
Dr. Luis Rodriguez received his BS degree in Cell and Molecular Biology from California State University, Northridge and his PhD degree in Biochemistry, Molecular and Cellular Biology from Cornell University. With many years of research experience in academia, government, and industry, Luis leads a FUJIFILM Irvine Scientific team that drives media development projects for the production of biotherapeutics, encompassing Luis' knowledge in cell growth, protein expression, and cell culture media.