"Technologies for Point of Care Manufacturing of CAR-T Therapies"
ABSTRACT Here we present an instrument capable of supporting automated microscale continuous culture experiments. The instrument has a 2 mL working volume, high oxygen transfer rate, fast mixing, accurate flow control and closed loop control over temperature, cell density, dissolved oxygen, and pH. Integrated peristaltic pumps and valves provide control over input concentrations and allow the system to perform different types of cell culture on a single device, such as batch, chemostat, and turbidostat continuous cultures. This microbioreactor platform is used to demonstrate anti-CD19 CAR T cell culture-on-a-chip. We show that T cells can be activated, transduced, and expanded to densities exceeding 150 million cells/mL in a two-milliliter perfusion-capable microfluidic bioreactor, thus enabling the production of CAR T cells at clinical dose levels in a small footprint. The process intensification and online analytics offered by the microbioreactor could facilitate high-throughput process optimization studies, as well as enable efficient scale-out of cell therapy manufacturing, while providing insights into the growth and metabolic state of the CAR T cells during ex vivo culture.
BIO Rajeev J. Ram is Professor of Electrical Engineering and Computer Science at MIT. His group works on optical biosensing and microfluidic control of cellular processes. During the last decade, his focus has been on developing microbioreactors for bacterial, yeast, and mammalian cell lines. His group has developed batch, fed-batch, perfusion, and continuous culture microbioreactors. Most recently they have worked on the precise control of synthetic gene circuits in Pichia pastoris and process intensification for anti-CD19 CAR T cells using this platform. In addition to his work on microfluidics, his group has worked on rapid optical analysis techniques. They demonstrated the first quantitative Raman analysis in situ within a bioreactor. Their group has developed Raman for the quantification of metabolites in microbial and mammalian cell culture as well as for medical applications. He has served on the Defense Sciences Research Council advising DARPA on new areas for investment and served as a Program Director at the newly founded Advanced Research Project Agency-Energy. He co-founded AyarLabs and erbi Biosystems. He is a MacVicar Faculty Fellow, a Bose Research Fellow at MIT, and a Fellow of Optica and IEEE Fellow.
Heng Liang TAN Merck Life Sciences
"Cell Therapy: From Lab to Manufacturing – Considerations, Requirements, and Insights for Allogenic Therapies"
ABSTRACT The discussion focuses on the considerations and emerging best practices to bring allogenic CT drugs from research to GMP manufacturing. Here we have highlighted 2 main areas that one needs to pay attention, namely, (1) Process Considerations and (2) Contamination Control Strategy Considerations.
BIO Heng Liang has many years of experience in the cell therapy industry. He holds a PhD in Medicine from the National University of Singapore. He spent 17 years as a researcher and scientist at the Bioprocessing Technology Institute (BTI), ASTAR. His research focused on the bioprocessing of pluripotent stem cells (PSCs) whereby the team was the first to report of an antibody that kills PSCs. The antibody could be used as a purification method to eliminate residual teratoma-forming PSCs. He was also the first to demonstrate the use of an antibody drug conjugate (ADC) to eliminate teratoma-forming PSCs circulating in in vivo mouse models. At BTI, he also helped to establish the antibody development platform. Heng Liang also spent 2 years in Lonza Singapore as the MSAT Manager for the Cell and Gene Therapy (CGT) Division. Besides overseeing the technology transfer from customers and the manufacturing of CGT products, he also established the facility fit protocol and technology transfer protocol. Now, Heng Liang is a Value Management Consultant in Merck and at the same time, assisting the company to establish the CGT portfolio.