August 21-22, 2013
Cambridge Healthtech Institute’s 3rd Annual
Scaling Up & Down with Optimized Bioreactors + Disposables
Making It Work
Day 1 | Day 2 | Short Courses | Download Brochure
Wednesday, August 21
7:45 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Michael Butler, Ph.D., Professor, Microbiology, University of Manitoba
8:30 Opening Keynote Presentation:
Scale-Up of an Allogeneic Cell Therapy Product Using Single-Use Systems
Ravinder Bhatia, Associate Director, Pharmaceutical Development and Manufacturing Sciences, Janssen Research & Development - Biography
One of the major challenges with cell therapy products is the development of a robust and scalable process to produce the product for clinical trials and commercialization. Currently, numerous technologies are available for the scale-up of an allogenic cell therapy product in static (e.g., T-flasks and cell factories) and/or suspension (e.g., microcarriers, bioreactor type) cultures. The selection of a platform to expand cells (upstream process) should be made based on criteria such as clinical and commercialization requirements of the product, product stability, process scalability and implementation in manufacturing. In this presentation, a case study will be presented on process development and scale-up of an allogeneic human somatic cell therapy product using single-use technologies.
9:00 Scale-Dependent and Scale-Independent Parameter Considerations for Scale-Up / Scale-Down of Bioreactors
Kumar Dhanasekharan, Ph.D., Associate Director, Process Sciences & Technology (Biologics), Genzyme – A Sanofi Company - Biography
In this presentation, general principles and considerations of how to scale up and scale down scale-independent parameters such as bioreactor pH, pCO2, and scale-dependent parameters such as power per unit volume, impeller speed, etc. are discussed along with examples to illustrate key points. The benefits of the outlined approach include less trial and error, leading to rapid development of small-scale models. Scale-down model qualification using statistical approaches including multivariate methods are also discussed.
9:30 Solving Scale-Up and Manufacturing Issues of Fusion Proteins
Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology - Biography
Strategies in the context of fusion proteins are summarized, highlighting approaches such as perfusion vs. fed batch processes and utilization of disposable equipment or DoE to accelerate process development and production for clinical applications. Here selected case studies are presented that demonstrate how to overcome the typical difficulties such as absence of a traditional platform technology, low titer, lack of an affinity matrix, tendency to aggregate, etc. Additionally, practical advice will be given regarding what parameters to consider when optimizing the “manufacturability” of a novel molecule.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Strategies in Bioreactor Scale-Down Model Development and Characterization
LiYing Yang, Ph.D., Scientist, Manufacturing Sciences & Technology, MedImmune - Biography
Bioreactor scale-down model development and characterization becomes an essential element in process development and commercialization in the QbD paradigm. In this presentation, key strategies in bioreactor scale-down model development and characterization will be discussed. A 4-Liter bioreactor scale-down model was developed for the 15,000-Liter commercial scale bioreactor. Mass transfer characterization studies were conducted, from which the results were summarized and utilized to guide scale-down model development / characterization. Case studies will be presented to demonstrate the suitability of the 4-L scale down model for multiple mammalian cell culture processes.
11:15 Using Small-Scale Studies to Optimize Process Operational Parameters for Scaling to Commercial Scale in a Cost- and Time-Efficient Manner
Tim Lee, Ph.D., Senior Biopharm Consultant, Biomanufacturing, Latham Biopharm Group - Biography
This presentation focuses on using microbioreactor technology to determine fermentation conditions without having to perform multiple bioreactor experiments at the 2L to 200 L scale. The purpose is to optimize and finalize culture conditions at a small scale while keeping large-scale manufacturing facility and equipment constraints in mind for smoother process transfer. Small-scale studies include optimizing and finalizing key process parameters like oxygen transfer coefficient, temperature, pH, biomass production during production.
11:45 Impact of Disposable Technology on Bio-Manufacturing Landscape
Richard Eglen, Ph.D., Vice President & General Manager, Corning Life Sciences
One of the key trends in bio-manufacturing is the move from the production of small molecule drugs to biologics and cellular therapies. In this environment, single-use technology platforms are a key enabler for increasing productivity and reducing costs. Here we discuss the benefits of disposable solutions.
12:00 pm Sponsored Luncheon Presentation (Opportunity Available)
1:55 Chairperson’s Remarks
Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology
2:00 Process Development of High Cell Density Fermentations using a Miniature Bioreactor in Conjunction with Ultra Scale-Down Cell Recovery Tools
Frank Baganz, Ph.D., AMIChemE, Senior Lecturer, The Advanced Centre for Biochemical Engineering, University College London
The use of miniature bioreactors that are scalable is highly desirable to accelerate bioprocess development. This presentation will focus on a prototype 25 mL miniaturised stirred tank bioreactor (MSBR) that has been characterized to assess its potential to grow high cell density cultures. Results from fed-batch fermentations using Fab’ producing E. coli at matched power inputs demonstrated that the MSBR can accurately scale-down the performance of 20L and 75L STRs in terms of growth and Fab’ production as well as shear sensitivity and centrifugation performance of the harvest material. The conjoint use of the MSBR with ultra scale-down mimics to rapidly develop bioprocesses will be discussed.
2:30 Applications of Imaged Capillary Isoelectric Focussing Technique in Development of Biopharmaceutical Glycoprotein-Based Products
Richard Rustandi, Ph.D., Principal Scientist, Vaccine Analytical Development, Merck & Co.
CE-based methods have increasingly been applied to the analysis of a variety of different types of proteins. One of those techniques is imaged capillary isoelectric focusing (icIEF), a method that has been used extensively in the field of protein-based drug development as a tool for product identification, stability monitoring, and characterization. It offers many advantages over the traditional labor intensive IEF slab gel method and even standard cIEF with on-line detection technologies with regard to method development, reproducibility, robustness, and speed. Here, specific examples are provided for biopharmaceutical glycoprotein products such as mAbs, erythropoietin (EPO), and recombinant Fc-fusion proteins, though the technique can be adapted to many other therapeutic proteins.
3:00 POSTER HIGHLIGHT
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 A Novel Dielectrophoretic (DEP) Cytometer to Monitor CHO Cultures
Michael Butler, Ph.D., Professor, Microbiology, University of Manitoba - Biography
A prototype dielectrophoretic (DEP) cytometer has been developed to analyze individual CHO cells subjected to a radiofrequency actuator in a narrow bore capillary. Cell samples during the course of a bioreactor run show distinct shifts in the dielectric properties corresponding to loss of cell viability. Early apoptotic events can be identified followed by discrete sub-populations of cells that progress through apoptosis. The sub-populations can be correlated with alternative measurements by fluorescent markers and a cell population-based capacitance probe.
4:45 Extractable Protocol and Vendor Expectation Document Standardization Efforts from BPOG Working Group
Ken M. Wong, Senior Scientist, Specialty Analytical, Center for Extractables and Leachables, Merck & Co., Inc.
The extractable protocol standardization was designed to ensure all Single-Use (SU) vendors will perform their extractable studies in a consistent manner (hence, shorten decision-making processes with the resulted relevant extractable data by end users). Rationales will be provided to support the proposed extractable parameters based on surveys of biopharma BPOG member companies and shared knowledge. Update on possible adaption of this standard extractable protocol with BPSA supplier members will be provided.
5:15 Networking Reception with Exhibit & Poster Viewing
6:45 End of Day
Day 1 | Day 2 | Short Courses | Download Brochure