Cambridge Healthtech Institute’s Kent Simmons recently spoke with Dr. Min Zhang, Director of Manufacturing Sciences and Technology for AstraZeneca, about his upcoming presentation “Cell Culture Media Characterization Strategy and Related Challenges in Commercial Manufacturing,” to be delivered in the Process Characterization and Control conference at the 2018 Bioprocessing Summit.

PRESENTATION: Thursday, August 16 at 3:15 pm

Cell Culture Media Characterization Strategy and Related Challenges in Commercial Manufacturing

In overall upstream process characterization strategy, a well-defined cell culture media characterization plan is deemed crucial and highly desirable to ensure a robust commercial manufacturing process. The media characterization strategy generally considers raw material variability (lot-to-lot, vendor-to-vendor), the optimal media preparation process, acceptable ranges for key scaling parameters, and related media preparation operational variability. This presentation outlines the media characterization strategy at AZ and how it impacts commercial manufacturing.

Q. What is the general scope of cell culture media characterization?

The media characterization strategy generally consists of the variability assessment (lot-to-lot, vendor-to-vendor) of key cell culture media raw materials (RMs) and/or components, optimal media preparation methodology including acceptable ranges for key scaling parameters during media preparation, and related media preparation operational variability.

Q. Is the variability a high risk of the key cell culture media raw materials/components in commercial manufacturing?

Yes or no. The occurrence of the manufacturing process failure due to the cell culture RMs variability is marginal. However, the impact to commercial manufacturing business could be significant. This is particularly crucial to complex, undefined cell culture RMs (e.g. hydrolysates).

Q. What is the general strategy for media lot-to-lot variability assessment?

Typically, multiple batches of cGMP-grade media components (minimal 3 lots with significant RMs lot difference) are either included in early clinical phases development and/or manufacturing OR included in the process characterization studies by using qualified scale-down bioreactor model to build process control strategy.

Q. What does a robust media preparation process look like to deliver reliable and consistent commercial manufacturing performance?

Generally speaking, for commercial manufacturing, the characteristics of a robust media preparation process include good scalability, accurate predictability including acceptable media preparation time for bioburden control, and less variability between the batches. Establishing a good media preparation scale-down model with proper indicators would significant help.

SPEAKER BIOGRAPHY:

Min Zhang, PhD, Director, Manufacturing Sciences and Technology, AstraZeneca

Dr. Min Zhang is Director of Upstream Department, Manufacturing Sciences & Technology (MS&T) at AstraZeneca/Medimmune, where he leads an upstream team to support AZ biologics process transfer, scale-up, and large-scale manufacturing. Prior to joining AZ, he was a Senior Principal Scientist and Group Leader at FUJIFILM Diosynth Biotechnologies U.S.A., Inc. (FDBU) where he led a cell culture team to support upstream process development and cGMP manufacturing for cell culture programs at various development and clinical phases. Along with the tenures in Cell Culture Process Development at Eli Lilly and SAFC (Sigma-Aldrich), Min has achieved significant experience in mammalian cell culture, including Tech Transfer, process characterization, process scaling, process development, cGMP manufacturing, cell line engineering, Quality-by-Design (QbD), and therapeutic protein commercialization. Min was a Staff Scientist and did his postdoc research at University of California at Berkeley after he received his doctorate in Molecular Cell Biology from Institute of Genetics at Fudan University.