Scaling up production for biologics requires finesse and engineering know-how. Delicate cells must be understood and coaxed into greater productivity through optimizing conditions and mastering myriad parameters. Representative small-scale models are increasingly relied on to predict success when large amounts of product are at risk of contamination or simply not working.
This meeting will explore strategies for scaling up production, including representative scale-down models used to predict process parameters and ultimate success. Single-use/disposable technologies will also be discussed, along with bioreactor design and engineering. Examining how bioreactors process cells will be addressed, from small operational details to large-scale bioproduction. The in-depth discussions will include monitoring and analyzing processes in order to reach optimal conditions for productivity, with the goal of ensuring quality and efficiency.
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MONDAY, MAY 5
7:00 am Registration and Morning Coffee
Plenary Keynote Session
8:30 Chairperson’s Opening Plenary Remarks
Kristi Sarno, Chair, Greater Boston Chapter, Women in Bio; Director, Business Development, Pfenex, Inc.
8:40 Harnessing the Patient’s Immune System to Combat Cancer
Bahija Jallal, Ph.D., Executive Vice President, MedImmune
With recent FDA approvals, modulation of the immune system is now a clinically validated approach in the treatment of some cancers. At MedImmune, the Oncology Department is developing assets and expertise in Immune Mediated Therapy of Cancer (IMT-C). The challenges from a drug development perspective are multi-fold. The talk will focus on the relevance of preclinical models and translational science to address key issues, including dose selection and rationale combinations.
9:25 Building Regeneron’s Pipeline: From Trap Technology to the VelocImmune Platform to Veloci-Next
George D. Yancopoulos, M.D., Ph.D., President, Regeneron Laboratories; CSO, Regeneron Pharmaceuticals, Inc.
George D. Yancopoulos, M.D., Ph.D., who is the Founding Scientist, President, Research Laboratories and Chief Scientific Officer of Regeneron Pharmaceuticals, one of the world’s top biotechnology companies, will discuss how he and his colleagues exploited a commitment to science and technology to start the company, withstand years of challenges and failures, and emerge with a pipeline of promising technologies and novel/biologics that are beginning to bring hope to countless patients and their families.
10:10 Opening Coffee Break in the Exhibit Hall with Poster Viewing
11:05 Chairperson's Remarks
Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology
11:10 Opening Keynote Presentation: Bioprocess Scale-Up Strategies for Rapid Process Development – A QbD Perspective
Kumar Dhanasekharan, Ph.D., Director, Process Development, Cook Pharmica LLC
The talk will discuss the different scale-up approaches for both upstream and downstream development such as high-throughput approaches, platform based methods and traditional approaches to optimize a particular output or set of outputs, such as productivity/yield while maintaining product quality. Scale-dependent and scale-independent parameter considerations and selection will also be discussed. Case study examples will be used to illustrate key points.
11:40 CHO Small-Scale Model Development and Scale-Up Strategies for Glycoprotein Production
Siguang Sui, Ph.D., Development Scientist I, Upstream Development, Alexion Pharmaceuticals, Inc.
When a cell culture process was scaled from 2L to a 200L bioreactor, significantly lower productivity was observed at the larger scale. With CFD modeling, engineering approaches were implemented to develop and characterize the small-scale model to meet the requirement for both productivity and product quality attributes including purity, sialylation, and glycosylation. Strategies for scaling-up this process at 10,000L scale are proposed.
12:10 pm Protein Aggregate and Contaminant Removal by Mixed Mode Chromatography
Yamuna Dasarathy, Ph.D., Director, Marketing, Pall Life Sciences
Aggregation has been found to be a cause of immunogenicity and it reduces productivity of a process by impacting purity, recovery and yield. Additionally, host cell proteins that are inherent to all production processes can reduce efficacy. Some biopharmaceuticals show a penchant for aggregating in solution and once formed they must be removed during process development resulting in maximum degree of purity. Mixed mode chromatography can be used to remove aggregates and other trace contaminants including host cell proteins and we will present a case study to elucidate how mixed mode chromatography can be used in high throughput process development mode in designing a robust purification process.
12:25 Sponsored Presentation (Opportunity Available)
12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own
1:40 Session Break
2:00 Chairperson's Remarks
Mark R. Nagel, Senior Research Associate, GE Service Manager, Protein Chemistry, Genentech, Inc.
2:05 Case Studies for Utilization of Conventional and CFD Approaches for Successful Scale-Up and Scale-Down of Bioreactor Processes for Monoclonal Antibodies
Michelle LaFond, Director, Bioreactor Scale-Up and Development, Regeneron Pharmaceuticals
More recently, use of both conventional and computational fluid dynamic approaches to develop scale-down, pilot-scale models of production bioreactors have resulted in improved process understanding and more successful transfer for late stage processes. The new scale-down models are more predictive of manufacturing and are used to map out impact of scale-up parameters to process performance. Case studies of both approaches will be discussed.
2:35 A Universal Manufacturing Platform for Vaccine and Protein Therapeutic Production
Elena Feshchenko, Ph.D., Associate Director, GeneXpress, Protein Sciences Corporation
Protein Sciences’ proprietary baculovirus expression technology (BEVS) is used to produce high quality recombinant proteins quickly, reliably and at a low cost. The key advantage of this recombinant protein manufacturing platform is that a universal “plug and play” process is used for producing a broad range of protein based therapeutic vaccines for both human and veterinary use.
3:05 Strategies and Considerations for Scaling a CHO Fed-Batch Process
Yun Jiang, Ph.D., Senior Scientist Project Team Leader Upstream, Drug Design & Development, Swedish Orphan Biovitrum AB
From process development to commercial manufacturing, scale-up and scale-down are critical to developing a robust process and maintaining product quality. Here we share our experience with a CHO fed-batch process. The process has been scaled up to 3000L at two CMOs for production of clinical materials. The process has also been characterized with a 2L scale-down model and is now successfully validated for commercial production.
3:35 Scale-Up and Scale-Down Strategies for CHO Cell Clarification and Monoclonal Antibody Purification
Rachel Behan Wollacott, Ph.D, R&D Scientist II, MassBiologics
With the universal adoption of “platform” technologies in the biopharmaceutical industry, it is important to have scale-down process models to quickly demonstrate that a new molecule will fit the platform process. We will present our work concerning small-scale cell clarification with microfiltration. We will also present our strategies for high-throughput purification development and discuss scalability of MAb purification conditions from 96-well plates to chromatography columns.
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Problem-Solving Breakout Discussions
Solving Manufacturing Issues of Fusion Proteins
Moderator: Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology
- Feed strategies for optimized glycoprofiles
- Strategies for higher titers
- Aggregate removal
- Lack of affinity resins
Transient Plasmid Purification Revisited
Moderator: Mark R. Nagel, Senior Research Associate, GE Service Manager, Protein Chemistry, Genentech, Inc.
- Trouble shooting purification systems and design
- Evaluation of pDNA purity
Practical Issues for Scaling a Cell Culture Process
Moderator: Yun Jiang, Ph.D., Senior Scientist Project Team Leader Upstream, Drug Design & Development, Swedish Orphan Biovitrum AB
Agitation: best practice for choosing the agitation rate (mixing time, power input, kLa)
pCO2: overcoming the issue with low pCO2 for scale-down model
pH: impact of sampling and measurement devices at different scales
DO: impact of altitude, tank pressure and liquid height
5:45 Welcome Reception in the Exhibit Hall with Poster Viewing
6:45 End of Day
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