The Bioprocessing Summit

Cambridge Healthtech Institute’s 4th Annual
Bioproduction: Scale, Bioreactors & Disposables
Making It Work
Part of CHI’s 6th Annual The Bioprocessing Summit

August 20-21, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts


This meeting explores production and process issues faced when manufacturing biological drugs, including representative scale-down models, optimizing bioprocess development, issues of scaling up bioproduction, and bioreactor design & engineering.  In addition, issues that surround the integration of disposable/single-use systems into bioprocesses, and how to keep delicate cells alive, will also be addressed, as will monitoring and analyzing processes in order to reach optimal conditions and productivity.


Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 

Suggested Short Course*:

Extractables & Leachables: Study Design for Disposables and Qualification Consideration 

Tuesday, August 19, 6:00-8:30 pm


*Separate registration required


Wednesday, August 20

7:00 am Registration and Morning Coffee


BIOPRODUCTION STRATEGIES

8:05 Chairperson’s Remarks

Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology

 

8:15 KEYNOTE PRESENTATION

The Future of Biologics Development and Manufacturing

 Nuno Fontes, Ph.D., Director, Protein Science, Boehringer Ingelheim, Inc.

With monoclonal antibodies dominating today’s biologics pipelines, and cost of goods that represent only a very small fraction of drug prices, biologics development and manufacturing is typically focused on fully leveraging and continuously improving a relatively mature “consensus” industry platform. However, the staggering cost of overall drug development in today’s pharma business model, as well as, strong pressures to reduce overall healthcare cost will fuel new models such as Biosimilars, Biobetters and personalized or precision medicines. Flexible and innovative development and manufacturing concepts will support these new models.


9:00 Bioreactor Design Considerations for Bioprocess Pilot Plants

William Brazier, Principal Engineer, Amgen

Process performance offsets from commercial scale equipment can be observed when the same process is executed at pilot scale if the process is not scaled appropriately or if there are specific design constraints at pilot scale. This talk will cover the key design features of a bioreactor that can impact the ability to accurately create a scale-down model in a pilot plant setting. The use of analytical tools such as computational fluid dynamics (CFD) and normalized gassing rates are examples of approaches used for assessing the contributing factors to performance offsets as well as aid in the model development. This presentation will include case studies on key design and process considerations in pilot plant bioreactors. This presentation will also include tools used to understand the interactions with typical cell culture processes.

9:30 Fed-Batch Process for the Production of Recombinant Hemagglutinins, Components of Influenza Vaccine Flublok

Nikolai KhramtsovNikolai Khramtsov, Ph.D., Associate Director, Upstream Development, Protein Sciences Corporation

We developed a universal process for the expression and purification of influenza recombinant hemagglutinins (rHA) at different scales without re-developing the process for new rHAs. We have optimized the process to manufacture drug substance in less than two months from cloning the gene to the production of drug substance. The fed-batch process yielded at least a two fold increase for all seasonal and pandemic rHAs. The quality of purified rHAs produced by the fed-batch process is similar to rHA proteins produced in batch process.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


DISPOSABLES

10:45 DSP Single-Use Technologies to Move to a Fully-Closed Process

Steven StrubbeSteven Strubbe, DSP Specialist, Merck

Single-use biomanufacturing systems promise to reduce the risk of cross-contamination, make clinical development faster, technology transfer easier with a lower process cost, minimal validation and cleaning issues. Thus future process designs will require downstream device innovation to move open phases to fully closed ones. New technologies, such as precipitation in single-use bags or disposable CEX devices for Mab purification were assessed. Performance results as well as process cost, scale-up considerations and facility designs will be discussed.

11:15 Opportunities and Limits of Disposables in Non-Platform Processes

Stefan SchmidtStefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology

Single-use systems are an industry standard in platform processes. But current pipelines contain many novel fusion proteins. These molecules are difficult to manufacture due to low titer, lack of an affinity matrix, or tendency to aggregate. In selected case studies, we demonstrate when it is economically and technically reasonable to rely on single use, when a hybrid model is advantageous, or when conventional approaches are preferable. Advice will be given on successful process design, optimization strategies, and critical manufacturing parameters.

11:45 Innovative Simulation Technologies to Optimize Cell Culture

Marc Horner PhDMarc Horner, Ph.D., Lead Technical Services Engineer, ANSYS, Inc.

Cell culture is a delicate process in which cell growth and occasionally cell damage are influenced by flow conditions. Engineering simulation and CFD are used to investigate the transient flow behavior in bioreactors. ANSYS experts discuss how influential parameters affect the flow pattern and hence the evolution of cell culture. This insight opens the door to simulation based process optimization.

12:00 pm Cleaning and Compliance: Considerations for Today’s Bioprocessing

Brady_MikeMichael Brady, Ph.D., Director, Microbiology Services, Toxikon Corporation

Bioprocessing equipment requires a validated cleaning procedure for efficient bioproduction, product safety, and regulatory compliance. This brief presentation will review critical process parameters, analytical and sampling methods, as well as acceptance criteria for cleaning processes. Maintenance of a validated state and inspection considerations will be presented. 


12:15  LUNCHEON PRESENTATION:
Scale-Up Evaluation of Mobius CellReady Disposable Bioreactor Operation from 3L to 50L Scale: Best Practices for a Perfusion Application

Michael CunninghamMichael Cunningham, Ph.D., Senior Applications Scientist, Biomanufacturing Sciences Network, EMD Millipore

The Mobius CellReady bioreactor portfolio provides disposable bioproduction capabilities important for the optimal performance of mammalian cell cultures in suspension. This presentation will review the utilization of EMD Millipore’s 3L and 50L CellReady single-use bioreactors for a perfusion-based CHO cell bioproduction application, where hollow fiber connection and operation points to consider will be reviewed. In addition, results of the evaluation of scalability from bench to engineering scale will be presented.

12:45 Session Break


BIOREACTOR OPTIMIZATION

1:55 Chairperson’s Remarks

Michael Brady, Ph.D., Director, Microbiology Services, Toxikon Corporation

2:00 Scale-Up by Design: How to Design a Production Scale Bioreactor

Yogesh WaghmareYogesh Waghmare, Ph.D., Process Engineer III, Global Manufacturing Science and Technology, Genzyme, a Sanofi Company

This presentation will describe a methodology of how a production scale bioreactor was re-engineered and re-designed in order to reduce the risk of scaling-up a microcarrier-based mammalian cell culture. The approach taken here involved synergistic use of engineering tools including computational fluid dynamics models, empirical analysis and pilot scale wet testing. Three dimensional printing of the pilot scale reactor and its components was chosen as the method to facilitate meeting tight marketing timelines.

2:30 The Application of Advanced Process Control and Model-Based Strategies for Improved Bioprocess Performance

Jessica Whelan, Ph.D., Director, Life Sciences, APC, Ltd.

The development of robust, consistent and reliable bioprocess performance can be greatly enhanced through the application of model-based strategies which mirror equivalent process development approaches in other manufacturing industries. The integration of such models into process control strategies can further enhance process optimization performance. In this talk, we will present the experimental and theoretical framework for such strategies. In addition, we will discuss some results from specific studies with cell culture processes in PAT-enabled pilot-scale bioreactor batches.

3:00 Using Lactate Dehydrogenase Measurements to Quantify, Understand and Predict Cell Growth in a High-Density Perfusion Bioreactor

Cheng ChengCheng Cheng, Process Engineer, Late Stage Cell Culture Development, Genzyme, a Sanofi company

We developed a model for lactate dehydrogenase (LDH) release kinetics that uses intracellular and extracellular LDH concentration measurements to estimate cell lysis rates as well as intrinsic growth and death rates for high-density CHO cell culture in long-duration perfusion bioreactors. Using this model, we demonstrate that intrinsic cell growth rate remains stable throughout a 60-day bioreactor run despite differences in cell culture performance. We also show that our model for cell death and growth is a useful tool for appropriately calculating generation number across different bioreactor scales.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing


SCALE-UP / SCALE-DOWN

4:15 Case Studies for Utilization of Conventional and CFD Approaches for Successful Scale-Up and Scale-Down of Bioreactor Processes for Monoclonal Antibodies

MichelleLaFondMichelle LaFond, Director, Bioreactor Scale-Up and Development, Regeneron Pharmaceuticals

Conventional approaches to scale-up of bioreactor process parameters to new facilities have historically been successful, but not all monoclonal antibody processes are created equal. For some programs, these methods can result in suboptimal process performance and require optimization to be performed at manufacturing scale. 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.

 

4:45 High-Throughput System for Cell Culture (HTS-CC) Comparability: Generating Data to Guide 2L Small-Scale Experiments

Kristen DouglasKristen Douglas, Ph.D., Scientist and Group Leader, Late Stage Cell Culture, Genentech, A Member of the Roche Group





5:15 Networking Reception in the Exhibit Hall with Poster Viewing   


6:30 End of Day





Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios