Cell Culture & Upstream Processing - IBC Life Sciences

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Friday, September 26, 2008 • Main Conference (continued)
Cell Culture & Upstream Processing
1:30 Chairperson’s Remarks
Thomas Seewoester, Ph.D., Director, Process Development, Amgen Inc.
Impact of Upstream Advances on Downstream
Processing and Product Quality –
Act Locally but Think Globally
1:45 Achieving 10+ Grams per Liter – Challenges in
Process Development
Effective development of a high-titer process 'platform' is greatly facilitated by an
integrated, multifaceted approach. Technological advances beginning as early as
molecular selection, and encompassing all aspects of cell culture and purification
process design afford tremendous opportunity to both enhance performance
and to assist in ready transfer, scale-up and implementation. Examples will be
provided to illustrate the benefits of having a comprehensive toolkit of cuttingedge
process options in achieving transformational production performance.
Timothy S. Charlebois, Ph.D., Senior Director, Drug Substance Development,
Wyeth BioPharma
2:15 Different Development Paths to Higher Productivity and
Improved Quality
Cell culture improvements may be obtained through multiple paths. A strategic
improvement plan could include the examination of expression technologies,
host cell selection, cell line development, media development and bioreactor
operations. Most organizations must prioritize cell culture improvement activities
to achieve a balance of both short-term and long-term benefits. This presentation
examines the different aspects of cell culture improvement, providing a high level
understanding of the complexity and benefits of the various initiatives.
Gary Welch, Director, Process Development, Abbott Bioresearch Center
2:45 The Impact of Sequence on Product Attributes and
Process Outcome
Similarities among monoclonal antibodies have enabled the implementation
of efficient platform process development procedures leading to dramatically
shortened process development timelines. Our diversified portfolio at Wyeth
includes antibodies, Fc-fusion proteins and smaller, simpler, non glycosylated
molecules. This talk will illustrate how the choice of product type and sequence
can significantly impact the process development options and outcome.
Martin Allen, Ph.D., Principal Research Scientist, Cell and Molecular Sciences,
Wyeth BioPharma
3:15 Networking Refreshment Break
Overcoming Manufacturing Issues
3:30 Avoiding Pitfalls in Quality by Design CASE
Quality by Design (QbD) techniques have proven effective in evaluation
STUDY
and understanding of biologics manufacturing processes including identification
of CQA’s and COP’s. However, there are pitfalls in the application of QbD
techniques that can mislead the identification of “Design Space” with
consequences for manufacturing control and consistency. In this presentation,
examples will be used to illustrate best practices to avoid pitfalls in QbD.
Graham McCreath, Ph.D., Senior Scientist, Avecia Biologics Limited, United Kingdom
Mahesh Shivhare, Statistician, R&D, Avecia Biologics Limited, United Kingdom
4:00 Towards More Modular, Compact, and Cost Effective
Manufacturing Facilities: Combining the Latest Advances in
Process Development with Bioreactor Technology Development
We have successfully completed implementation of a fully disposable cell culture
platform, both in development and in cGMP clinical manufacturing suites. This
disposable platform encompasses media and harvest storage, cell expansion in
preculture and seed bioreactors, and production bioreactors. This disposable platform
is capable of making clinical and commercial supplies. We will share our experience
with the disposable systems, discuss the design and implementation challenges, and
elaborate on how disposable platforms can change the future of cell culture processes.
Sadettin Ozturk, Ph.D., Head, Bioprocess Technology, Centocor R&D
4:30 Impact of Impeller Design on Antibody Production
CASE
by Chinese Hamster Ovary Cells
STUDY
Large scale production of monoclonal antibodies has been accomplished using
bioreactors with different length to diameter ratios, and diverse impeller and sparger
designs. The differences in these physical attributes could result in dissimilar mass
transfer, shear dynamics and mixing inside the bioreactor, which could lead to disparities
in cell growth, antibody production and final product quality. The purpose of this study is
to understand the impact of impeller designs on process and culture parameters.
Sandeepa Sandadi, Scientist II, Biological & Sterile Product Development,
Schering-Plough Research Institute
5:00 Close of BPI 2008
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Recovery & Purification
1:30 Chairperson’s Remarks
Adam Goldstein, M.S., Senior Manager, Oceanside Clinical Operations,
Genentech, Inc.
Protein A and Beyond
1:45 Considerations for the Optimization of the Protein A
Capture Step in Antibody Processes
Abstract not available at press date.
Please visit www.IBCLifeSciences.com/BPI/US for updates.
Sanchayita Ghose, Ph.D., Manager, Process Sciences Downstream,
Bristol-Myers Squibb
2:15 Development and Scale Up of Q Membrane
CASE
Chromatography in Non-Affinity Purification
STUDY
Processes of HuMAbs
Disposable membrane chromatography has been successful in replacing resin
flowthrough chromatography and provides an efficient viral removal strategy
for non-affinity purification processes of HuMAbs. Scaleability of membrane
application has been tested up to 350 and 200L bioreactors to process harvests
for different molecules. Loading capabilities on this single use chromatography
were increased up to 10g/L to positively impact process economics without
compromising viral clearance capability. HuMAbs case studies will be described.
Gisela M. Ferreira, Ph.D., Senior Process Engineer, Purification Process
Development, Medarex Inc.
2:45 Reduction of Host Cell DNA Using Charged Filters at
Protein A Capture for Monoclonal Antibody Production
One of the products generated by perfusion cell culture at Centocor had higher
than usual host cell DNA (~20 ug/mL) in the harvest. Bench-scale studies (~ 10
liters) were performed using various positively charged depth filters to reduce the
host cell DNA level. These filters were placed in-line during loading harvest onto
the Protein A column. The CUNO charged filter 120ZA10A EXT was found to
reduce the DNA by greater than 1 log when processing at 220 L of harvest/m2.
John Wesner, Associate Scientist, Development Pilot Plant, Centocor R&D
3:15 Networking Refreshment Break
Improving Downstream Economies and Efficiencies
Using Disposables in Chromatography
3:30 Disposable Applications in Antibody Purification
New advances in disposable technologies are creating a wider range for single-use systems
in the upstream and downstream processing arenas, including cell-culture bioreactors,
formulation and filling applications, new mixing technology, and disposable depth
filters used in harvesting equipment. This talk will examine the development of recent
improvements in the production of bulk antibodies. The benefits and limitations of these
applications will be presented including the application of a new design for frozen bulk.
Adam Goldstein, M.S., Senior Manager, Oceanside Clinical Operations, Genentech, Inc.
4:00 Effective Incorporation of Disposables into mAb Drug
Substance Production
In this presentation, the incorporation or implementation of three disposable
systems such as depth filtration, membrane chromatography, and nanometer
filtration technology in first-in-human and commercial processes will be introduced.
Integration of disposable systems into an existing process will be examined and
an excellent data set of impurity removal and viral clearance will be presented.
Advantages and disadvantages including cost analysis, validation and facility usage will
be discussed. Possible future disposable systems such as mix mode membranes and
monoliths in 2-column downstream purification will be further discussed.
Joe Zhou, Ph.D., Scientific Director, Process Development, Amgen Inc.
4:30 Minimizing Buffer Storage Requirements for Antibody
Purification in High Titer Processes: Integration of
Inline Dilution, Disposable Technology and Optimized
Buffer Preparation
A case study will be presented that illustrates how inline dilution of buffer concentrates
and large volume disposable bag technology can be integrated, to effectively eliminate
buffer capacity bottlenecks, significantly reduce the required tankage volume and
introduce flexibility. Approaches to further reducing total volume requirements in
buffer preparation and optimizing solids handling will also be discussed, together with
select examples of challenges encountered as a 25,000 L mammalian cell culture facility
employing these new technologies was brought online.
Mark Smith, Ph.D., Process Support Engineer, Genentech, Inc.
5:00 Close of BPI 2008
Visit www.IBCLifeSciences.com/BPI/US for up-to-date information on this event 17