About the Biomanufacturing Summit 2017 Training

Module 1: Upstream Bioprocessing

Carl Lawton, Ph.D., Associate Professor, Department of Chemical Engineering, UMass Lowell

This module will cover fundamental principles underlying cell growth, protein expression, and upstream bioprocesses. The module will provide basic knowledge for the following modules so that all participants are competent in fundamental principles for engineers and scientist working in biopharmaceutical process development, particularly those new to the field. In the module, participants will learn about:  

  1. Properties of proteins relevant in process development: Physical properties, in process analytical techniques 
  2. Choice of cell type for expression: Chinese Hamster Ovary (CHO), NSO, Spodoptera frugiperda, Pichia, E. coli 
  3. Expression systems: Promoters, enhancers, chromatin modifiers, etc. 
  4. Media development: Selection, experimental design 
  5. Cell cultivation: Batch, fed batch, continuous 
Carl Lawton, Ph.D., is the director of the Massachusetts BioManufacturing Center (MBMC) and an associate professor in the Department of Chemical Engineering at UMass Lowell. Lawton is responsible for overseeing the coordination and completion of process development client services including expression development, fermentation and cell-culture development, downstream processing, process optimization and characterization. Lawton is developing and maintaining an applied research program which focuses on technological advances to improve the quality, cost and productivity of large-scale biomanufacturing production. Before joining UMass Lowell and creating the MBMC, Lawton was a bioengineering process consultant to companies in the US, Canada, and Europe. He holds a BS degree in Microbiology from Purdue University and a MS degree in Microbiology and a Ph.D. in Chemical Engineering from the University of Connecticut.

Module 2: Downstream Bioprocessing

Christopher Gillespie, Ph.D., Manager & Head of Downstream, Next Gen Biopro, MilliporeSigma
Melissa Holstein, Ph.D., Sr. Scientist, Next Generation Bioprocessing, MilliporeSigma 
Akshat Gupta, Ph.D., Sr Bioprocess Engineer, Mfg Sciences and Technology, MilliporeSigma 
Downstream bioprocessing strategies are evolving to meet the growing demands of industry and regulatory expectations. Increasing bioreactor titers, increased competition, and growing portfolios of molecules are some of the driving forces that have led to improvements in traditional downstream unit operations (process intensification), new unit operations, and enhanced overall productivity in the downstream processing train. In an effort to optimize process efficiency, unit operations are being connected together and, in some cases, fully continuous biomanufacturing processes are being developed. While connected and continuous processing strategies can greatly enhance productivity, there are many challenges to be addressed for seamless integration of the various processing steps. 
This module will cover current state-of-the-art downstream processing operations, practical considerations for moving towards continuous processing, and ways to overcome typical obstacles in implementing these processes. Major topics will include the shifts from batch capture chromatography to continuous capture chromatography, from tangential flow filtration (TFF) to single pass TFF, and from bind/elute to flow through technologies. Resin and filter selection, equipment options, scale-up options, and experimental design will be discussed. An overview of the many enabling technologies behind these process advancements will also be provided, including single use materials such as sterile connectors. Case studies quantifying the potential productivity improvements resulting from continuous processing will be examined. The case studies will highlight the possible advantages of continuous processing in terms of product throughput, shorter processing time, reduced buffer consumption, and overall cost savings. This module is designed to provide in-depth fundamental understanding of current and future downstream processing strategies as well as practical considerations and best practices for effective implementation of these strategies.
Christopher Gillespie, Ph.D. is a R&D Manager and Head of Downstream, Next Generation Bioprocessing at MilliporeSigma, with a focus on advanced applications and technology development for the factory of the future and holistic process development for therapeutics ranging from mAbs to vaccines. Gillespie has been with the company for eight years, focusing primarily on novel technology development for the production of biotherapeutics. His prior experience includes time at Cambrex Bioscience, where he developed downstream processes for recombinant proteins. While at WR Grace his focus was on the characterization and performance evaluations of new silica-based protein A chromatography media. He holds a BS in Chemical Engineering from the University of Maryland Baltimore County (UMBC) and a Ph.D. in Chemical Engineering from the University of Delaware.
Melissa Holstein, Ph.D., is a Senior Scientist at MilliporeSigma in the Next Generation BioProcessing R&D group. She has extensive experience in chromatography resin development and downstream processing applications. Prior to joining MilliporeSigma, Holstein graduated from Rensselaer Polytechnic Institute with B.S. and Ph.D. degrees in chemical engineering. Melissa is also an Adjunct Professor in the Department of Chemical Engineering at UMass Lowell. 
Akshat Gupta, Ph.D., is a Senior Bioprocess Engineer at MilliporeSigma in Applications Engineering, Manufacturing Sciences and Technology (MSAT) group. He has extensive experience in cell culture clarification and tangential flow Filtration. Prior to starting at MilliporeSigma Akshat was a process engineer at Shire in Manufacturing Sciences & Technology group. Akshat holds a B.Tech degree in Chemical Engineering from Vellore Institute of Technology and a Ph.D. from University of Massachusetts Lowell. 

Module 3: Analytical Technology in Bioprocessing

Jason A. Starkey Ph.D., Senior Director, Pfizer Inc.
This module will cover analytical strategies and technologies used to support the Chemistry, Manufacturing, and Controls (CMC) development of protein biologics. Basic and advanced concepts will be reviewed with an emphasis on their application as current industry practices supporting the manufacture and characterization of monoclonal antibodies and antibody drug conjugates. The content of this module is tailored around the application of analytics to enable clinical bioprocessing and content that typically is provided in regulatory submissions. 
A review of quality attributes, degradation pathways, and product characterization using compendial, potency assays, chromatography, electrophoresis, spectroscopy, and mass spectrometry will be provided.

Jason Starkey, Ph.D., is senior director of Analytical Research and Development in Pfizer’s Biotherapeutics Pharmaceutical Sciences division. He is responsible for method validations/transfers, and analytical technology transfers from clinical development into commercial testing laboratories for biological and vaccine programs. Prior to this role, Starkey supported the early clinical development and analytical strategy for vaccine and antibody conjugates. He has been at Pfizer, Inc since 2007. He received his Ph.D. in Analytical Chemistry from Indiana University and undergraduate degree from Wabash College. 

Module 4: Gene therapy bioprocessing

Guangping Gao, Ph.D., Professor and Director, Horae Gene Therapy Center and Vector Core, University of Massachusetts Medical School 
This module will cover basics in gene therapy, and differences from other traditional biological therapeutics. The following contents will be addressed in detail.
  • Different Gene therapy vectors, their unique biology and applications 
  • How to manufacture different types of vectors and specific challenges for each of them in principle
  • Vector of choice for in vivo gene therapy, how to produce in large scale and challenges in production -  
  • Vector of choice for ex vivo gene therapy, how to scale up in production and challenges. 
Research in the Gao Lab primarily involves the discovery, development and use of adeno-associated virus vectors for gene replacement, addition, silencing and editing for in vivo somatic gene therapy of genetic diseases. The lab works on isolation, characterization and vectorology of novel AAV vectors from primate tissues, molecular mechanisms of AAV evolution and diversity, and molecular interactions between endogenous AAV, AAV vector, and host genomes. His research group also develops next generation of recombinant AAV (rAAV) manufacturing and Quality Control testing pipelines. In addition, the group devotes research effort to preclinical, translational and clinical development of rAAV gene therapy for rare diseases such as Canavan disease, an inherited lethal white matter degenerative disorder by using novel AAVs that can cross the blood-brain-barrier for efficient CNS gene delivery and endogenous miRNA-mediated posttranscriptional de-targeting. Another area of research interest in the lab is to explore AAV vectors for delivery of de novo synthesized biological miRNA antagonists or over expression of microRNAs to elucidate micro RNA functions in adult mammals as well as vectored ImmunoProphylaxis and secreted anti-cancer factors.

Guangping Gao has Ph.D. degree from Florida International University, and had post-doctoral training at University of Pennsylvania, School of Medicine.

Module 5: Cell Therapy Bioprocessing

Tiffany Hood, Engineer, Cell Therapy Bioprocessing, MilliporeSigma
Mark Lalli, Ph.D., Engineer, Cell Therapy Bioprocessing, MilliporeSigma 
Kara Levine, Ph.D.,Head of Systems and Tools, Cell Therapy Bioprocessing, MilliporeSigma 
Julie Murrell, Ph.D., Head of Cell Therapy Bioprocessing, MilliporeSigma 
As regenerative medicine grows in prominence, the demand for reliable expansion of therapeutic cells at large-scale increases. Notably, the limited number of downstream steps associated with cell therapy bioprocessing compared to biomanufacturing of recombinant proteins places extra constraints on the scalability of processing. Whereas planar culture methods are standard for small-scale expansion of anchorage-dependent human mesenchymal stromal cells (hMSCs), the cost of production per dose remains higher than that associated with stirred tank bioreactor culture. However, optimization of bioreactor culture of anchorage -dependent cell types is nontrivial and, furthermore, the downstream processing is complicated by the requirement to separate therapeutic cells from microcarriers. Upstream considerations include investigation of the interaction between media formulation and substrate, the choice of the cell substrate itself, and the determination of culture conditions resulting in maintenance of stem cell phenotype. 
This module will cover the current landscape of relevant technologies, upstream considerations for practical bioreactor culture, process optimization strategies, and an overview of the limited downstream processing in cell therapy manufacturing. Media optimization and sourcing of xeno-free reagents as well as microcarrier selection and performance will be covered in the upstream portion of this module. Reactor process control and agitation strategies as well as a case study of process development for hMSC production within a 50L bioreactor system will be presented. Finally, cell harvest will be examined as the limited relevant downstream portion of cell therapy bioprocessing. This module is intended to provide a framework of understanding for scale-up of bioprocessing in which the downstream product is cell-based rather than protein or viral. 
Tiffany Hood is an engineer in the Cell Therapy Bioprocessing group at MilliporeSigma, providing cell culture process expertise to advance cell therapy manufacturing strategies in stirred tank bioreactors. During her time at MilliporeSigma, she has been the technical lead for bioreactor process development efforts and contributed to the development of cell therapy downstream products. Additionally, she has worked with multiple external collaborators to optimize bioreactor processes for specific cell therapies. Hood earned her degree in Biological Engineering from Massachusetts Institute of Technology. 
Mark Lalli, Ph.D., is an engineer within the Cell Therapy Bioprocessing group at MilliporeSigma. At MilliporeSigma, Lalli primarily develops methods of improving bioreactor efficiency in production of stem cells. Lalli earned a Ph.D. at Northeastern University in chemical engineering with research focusing on the cell biology associated with collective cell migration and its role in cancer progression. He also holds a B.S.E. in chemical engineering from the University of Massachusetts Lowell with a nanomaterials engineering focus. His cross-functional background has led him to pursue research and development into chemical sensors, microfluidics, and medical devices prior to applying his efforts to the reaction engineering of stem cell bioreactors.
Kara Levine, Ph.D., has been part of MilliporeSigma’s Life Science business for more than 7 years. She currently manages product development, process development, and application projects for cell therapy manufacturing, providing expertise in cell culture, media formulation, and single use technologies. Levine’s previous roles have included R&D scientist supporting chromatography product development, technical team leader driving optimization of cell culture media products for monoclonal antibody production and more recently, project manager overseeing single use device development. She earned her Ph.D. from the University of Massachusetts Medical School in the fields of biochemistry and cell biology, with a focus on understanding the protein structure function relationship amongst membrane uniporters.
Julie Murrell, Ph.D., is the Head of Cell Therapy Bioprocessing and leads a team of scientists and engineers at MilliporeSigma, a leader in Life Science products. Murrell has led multiple technology groups at the company for over 10 years. Through that time, she has driven the efforts to establish robust analytics and develop manufacturing strategies for stem cell industrialization, with a focus on hMSCs, T cells and iPSCs. The group also works with collaborators to complete process development activities. Murrell’s background is in Cell and Developmental Biology. She earned her Ph.D. at Tufts University School of Medicine in the field of Developmental Neuroscience, completed a Post-Doctoral Fellowship in Translational Medicine at Harvard Medical School and a Fellowship in Stem Cell Biology at the University of Massachusetts. Her multi-disciplinary background has led to innovative team-driven solutions in the field of stem cell production. 

Module 6: Process Analytics in Bioprocessing

Seongkyu Yoon, Ph.D., Associate Professor, University of Massachusetts Lowell 
Process Analytics provides convenient and useful tools for analyzing improving continuous processes. These tools can be very well utilized for improving productivity and product quality consistency. However, since current biopharmaceutical processes are based on batch operations, these benefits have not been fully exercised in the industry. By introducing the continuous paradigm in biopharmaceutical industry, these tools can be implemented for continuous bioprocesses. This module is designed to introduce the basic concepts and potential applications of the systems engineering technologies. In this module, participants will learn about Advanced control algorithm – feedforward, cascase, and predictor; Multiloop and Multivariable control; Model Predictive Control Process; Optimization Planning and Scheduling; Experimental Design; Multivariate Data Analysis – Summary; Regression and Classification 
Seongkyu Yoon, Ph.D., is co-director of the Massachusetts BioManufacturing Center (MBMC), process system engineering and an assosiate professor in the department of Chemical Engineering of the University of Massachusetts Lowell. His research area is Life Sciences Systems Engineering. Research covers Process Analytical Technology (PAT) and Quality by Design (QbD), Application of Design of Experiment (DoE) and MultiVariate Data Analysis (MVDA), supply chain management in biologics, and chemometrics in life sciences. His research aims at developing innovative systems technology with which one can improve drug development efficiency.