New Tools for Optimizing Custom Media Design

Presented by Michael Gillmeister

Michael Gillmeister is a senior scientist at Lonza Biologics, United States

Gillmeister presented independent case studies of a media optimization program offered jointly by Lonza and Sartorius Stedim Biotech. The program uses an ambr® 15 microbioreactor system to generate custom media that are chemically defined and contain no products of animal origin. The CHOptimizer™ service comes into play when commercially available media fall short of expectations and optimized custom media must be developed as rapidly as possible for high-producing cell lines.
Through a collaborative partnership, Lonza and Sartorius offer media optimization services for their customers, noting that different genetic constructs, clone-to-clone variation, host-to-host variation, and even molecule-to-molecule variation among candidate cell lines require customization of media formulations. The approach recognizes that many different techniques of platform manipulation exist, from minor correction of “off the shelf” media to their full-blown redesign. However, “in house” knowledge of media constituency and development expertise are essential. Time and resources are required to adjust and fine-tune different components.
Gillmeister described how Lonza takes media optimization information and assembles it in a single, integrative process running in an ambr15 system to yield a formulation optimization strategy. This protocol partners clients with Lonza and Sartorius media and bioreactor experts.

Lonza has organized the systems for completing the entire media optimization process into a single program. For companies that do not have the instrumentation, Lonza supplies a “traveling” ambr® 15 unit. An applications specialist expert also travels to customer sites, making it unnecessary to ship cells.
<r> By using predefined software protocols that can be run on the ambr® 15 system, long development times can be prevented. Experiments are run using a design of experiments (DoE) approach for both inputs and outputs in an integrated, streamlined solution, carried out at a customer’s site. With the ambr® 15 system, automated samples can be taken and analyzed to generate models based on culture parameters such as cell proliferation and titer. Samples also are retained to use in spent media analysis for component consumption and feed design.
The flexibility of the ambr15 technology offers a range of possibilities for clients. If cells fail to perform optimally under a particular process parameter such as temperature shift, or if they absolutely require a temperature shift, Lonza can formulate the factorial design of experiments for feed development to reflect those requirements. That allows addition or removal of parameters for optimized performance. Availability of such data and appropriate analytical tools allows researchers to compare combinations of growth and productivity to provide the best total outcome for a program.
Gillmeister stressed that taking advantage of the ambr15 system’s ability to rapidly collect data on many features of cellular growth in a controlled microbioreactor environment, a fully optimized program required only six months for completion. Thus, productivity, titer, and rate of proliferation can be efficiently balanced to provide clients with custom built, optimal fed-batch media solutions.</r>