SC1A: Optimizing Cell Culture Media
Monday, August 13 2018 9:00 – 11:30 AM

9:00 Improved Antibody Product Quality through Custom Media Development and Analytics

Kevin Tan, PhD, Senior Scientist, Irvine Scientific, Inc.

The production of therapeutic antibodies requires high titers and excellent product quality to ensure efficient manufacturing and potent drug efficacy. The N-glycan profile is a critical quality aspect that can alter antibody binding and function. Irvine Scientific is capable of maximizing a cell line’s potential and improving antibody product quality through our custom Media Development and Optimization program. Media development begins with a Media Survey Panel to improve cell growth and titer and then focuses on improving product quality through our analytics and optimization processes.

9:30 Streamlining High Throughput Cell Culture Media Optimization with Templated Data Capture, Visualization and Data Analysis

Ronan O’Kennedy, PhD, Director and Principal Consultant, ROK Bioconsulting

In this workshop, we will look at bottlenecks and solutions to processing data from high throughput (HTP) media optimization platforms. Equipment such as Ambr15, Vicell/Cedex, Octet, metabolite analysers typically used for HTP media optimisation result in manual experimental data flows that can be time consuming, prone to errors and dependent on the user ability. The speed of merging from each data source and subsequent analysis can be improved using a templated capture and analysis approach. Data sets need to be efficiently merged & parsed, checked for errors, visualized & analysed. A templated spreadsheet approach will be shown to automate these data flows after data entry. Automated plots allow rapid at-line assessment of each culture and identification of outlier measurements so that repeat measurements or sampling can be carried out. After outlier detection, data analysis flows evaluate experimental replication. Experimental responses are automatically extracted and calculated from the raw data. These responses are formatted to be transferred directly to user analysis program of choice. Analysis flows and outputs are considered depending on the nature of the experiment (media optimisation, cell line selection, shake -flask or multi-parallel bioreactor). Three automated analysis outputs are considered in the talk DOE in MODDE / DX10, SIMCA batch analysis and cluster analysis which rapidly delivers different views of their experiments. This approach improves data analysis flows and reduces analysis bottlenecks leading to more rapid decision making.

10:00 Refreshment Break

10:30 Comprehensive Manipulation of Glycosylation Profiles across Development Scales

Sven Loebrich, PhD, Senior Development Scientist, Upstream Process Engineering, ImmunoGen, Inc.

The glycosylation profile of mAbs can profoundly affect drug efficacy and patient safety. Unforeseen changes to product quality, including the glycosylation profile, can occur upon scale-up or transfer of an upstream process. Numerous media additives have been described in the literature as glyco-tuning excipients. Understanding the causal relationships of media composition and product quality is central to an effective, adaptable development platform. Here, we tested ten additives in univariate and in combination (DOE), and built a model that allows for fine-tuning of glycosylation profiles. We show commonalities between different CHO cell lineages expressing different IgG molecules, and demonstrate good control over the glycosylation profile across development scales.

11:00 Adapting Late Stage Cell Culture Media to High-Temperature Short-Time Pasteurization Technology - Challenges and Mitigations

Chentian Zhang, PhD, Engineer I, Manufacturing Science and Technology (MST), Bristol-Myers Squibb Co.

Viral contamination in cell culture media can cause serious consequences on productivity, product quality and safety for biopharmaceutical manufacturing plants. High-temperature short-time (HTST) treatment is an effective and economical technology to prevent viral contamination of cell culture media. Adapting cell culture media for late-stage clinical or commercial processes to be HTST-compatible poses certain challenges due to the constraints on changing media composition, limitations in the media preparation facility, and disruption of established manufacturing workflows. In this talk, we will cover the journey of adapting two of BMS’s commercial cell culture media to be HTST-compatible through optimization of media preparation procedures while minimizing impact to manufacturing workflow. pH-shift and media-component-addback methods were explored to mitigate precipitation during HTST. The media-component-addback method was preferred as worked for each of the tested media formulations and should be independent of the process.

Specifically, we have come up with an approach that
1) Maintained HTST treated media quality without changing final media formulation
2) Fit the media preparation procedures with the existing manufacturing facility and workflows
3) Demonstrated universality of this approach in the current late stage pipeline

11:30 Close of Optimizing Media Course

 

Instructor Biographies:

 

Kevin-TanKevin Tan, PhD, Senior Scientist, Irvine Scientific, Inc.

Kevin Tan is a senior scientist at Irvine Scientific and currently works on developing and optimizing cell culture media for improvements in cell growth, titer, and glycan profile. He received his Ph.D. from the University of Washington and his B.S. from the University of California, Los Angeles.


Ronan_O'KennedyRonan O’Kennedy, PhD, Director and Principal Consultant, ROK Bioconsulting

Dr. O’Kennedy is the director and principal consultant at ROK Bioconsulting. ROK Bioconsulting provides technical and strategic support for biopharmaceutical development throughout the product development lifecycle. He has over twenty years of experience in the biopharmaceutical industry and academia working within process development and CMO organizations. Research focus include linking upstream process performance to downstream product quality and data driven process modelling in support of PAT and QbD objectives maximizing the value of process data and data re-use throughout the product lifecycle.

Sven_LoebrichSven Loebrich, PhD, Senior Development Scientist, Upstream Process Engineering, ImmunoGen, Inc.

Sven is the Leader of the media development group where he optimizes chemically defined media to support internal development programs. He designed basal media and feed formulations and built platform processes; and has comprehensive experience with glycosylation profile tuning through media additives. Sven has also designed and executed bioreactor studies using glass 4L vessels, as well as disposable 2L and 50L models. And he’s discovered and characterized media additives for improved harvest robustness. Sven is also the Leader of a cross-functional team for an internal development program with experience as a project manager in the CMC space, closely coordinating internal and CMO teams.

Sven received his Ph.D. in Biology from the Center for Molecular Neurobiology at the Hamburg University in Germany.
Ph.D. Hamburg University, Germany (summa cum laude) 2002 – 2006
(Biology) Department of Biology, Center for Molecular Neurobiology

Chentian_ZhangChentian Zhang, PhD, Engineer I, Manufacturing Science and Technology (MST), Bristol-Myers Squibb Co.

Chentian Zhang is an upstream engineer from manufacturing science and technology (MST) group at Bristol-Myers Squibb (BMS). During his tenure, he has contributed significantly to the commercial biologics programs through scale-down-model development, depending process understanding as well as process improvement. He also led successful technology transfer of commercial programs through lab study to close gap, Person in Plant (PIP) support and investigation support. More recently, his work focused on adapting BMS’s commercial and late stage cell culture processes to become high temperature short time (HTST) treatment for viral contamination mitigation, which have a great impact on the robustness and quality of these processes. Prior to joining BMS, Chentian was a PhD student in biomedical engineering from Boston University. His research investigates cancer metastasis and specifically why certain primary tumor prefer certain organ/tissue as the target for metastasis. He designed and implemented various microfluidics devices to pattern cells and observe cell migration. Chentian also hold a BS in biomedical engineering from University of Michigan, Ann Arbor.