Cambridge Healthtech Institute’s 3rd Annual
Advances in Purification Technologies
Economics and Efficiencies for Next-Generation Biomanufacturing
Part of CHI's 8th Annual The Bioprocessing Summit
August 17-18, 2016 | Westin Boston Waterfront | Boston, Massachusetts
When asked what are the key themes being discussed at their internal meetings, the downstream scientists unanimously stated "process integration" and "process intensification". How can we integrate the processes to eliminate bottlenecks and downtime?
How can we intensify the process to reduce purification steps, achieve higher productivity and lower COGS?
The 3rd Annual Advances in Purification Technologies conference delivers new trends in downstream processing, new strategies and approaches to purification of novel and complex molecules, as well as new advances and updates in technologies
and equipment.
Final Agenda
TUESDAY, August 16
6:00 – 8:30 Recommended Dinner Short Course*
SC7: Purification of Advanced Medicine Therapy Products
* Separate registration required
Wednesday, August 17
7:00 am Registration Opens and Morning Coffee
8:05 Chairperson’s Opening Remarks
Christoph Brandenbusch, Ph.D., Group Leader, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund University
8:15 From Purification to Vaccine Development: A Challenging but Rewarding Journey
Yan-Ping Yang, Ph.D., Head, Bioprocess R&D North America, Sanofi Pasteur
The vaccine industry has high risk, long cycle time, and requires approximately 12 years bringing a product from pre-clinical to licensure at a cost of ~$1 billion. Purification of vaccine candidates to achieve consistent product purity and quality
in a timely manner is an integral part of vaccine product development process. This presentation focuses on the applications of cutting edge purification technologies to facilitate vaccine process development and move faster to clinical evaluations.
9:00 Positioning Downstream Processing to Successfully Conquer Future Challenges
John Pieracci, Ph.D., Director, Purification Development, Biogen
The biotechnology industry will be
facing considerable challenges in the future to provide wider access to
treatments or cures to diseases affecting millions of people. The
solution to supplying these large patient populations will come from new
classes of therapeutic drugs possessing greater specificity, higher potency or
better manufacturability and by driving up the productivity of the
manufacturing process for existing drugs. This presentation will review
the impact that these potential options could have on the development of
downstream processes. Substantial pressure will be on downstream
scientists to support more productive batch processes in order to leverage the
full potential of existing manufacturing infrastructure, as well as develop
continuous downstream processes for alternative manufacturing plant designs.
New downstream process platforms will be needed to enable new classes of drugs
or to support the application of more productive expression systems to current
modalities. Identifying existing downstream technologies that can be
readily implemented or investing in breakthrough technologies that could take
time to mature, but could represent significant leaps, will be key.
9:30 Defining Process Design Space for a Multimodal Chromatography Purification Step by Custom Design
Jie Chen, Ph.D., Senior Scientist, Process Development, Bristol-Myers Squibb
A process characterization study was performed to gain understanding of the multimodal chromatography (MMC) purification process and to map the design space. Seven factors out of thirty-eight process parameters were identified to be important. Custom
design was employed to study multi-dimensional combination of operational variables for mapping of the process design space. A robust operating window was identified for this multimodal chromatography process that enabled sufficient impurity removal
while ensuring acceptable process yield.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Continuous Aqueous Two-Phase Extraction of Proteins Part I – Estimating Process Windows and Industrial Applicability
Christoph Brandenbusch, Ph.D., Group Leader, Department of Biochemical and
Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund University
Increasing product titers in pharmaceutical protein production lead to a demand for novel workup strategies (eg: protein extraction by Aqueous 2-Phase System). However the effort and costs required in selecting appropriate ATPS and the determination of
process windows hinders the industrial applicability. To enable estimations on the applicability of this workup strategy, hybrid ShortCut models to calculate partition coefficients have to be available.
11:15 Continuous Aqueous Two-Phase Extraction of Proteins Part II – Separation Principle and Novel Techniques
Gerhard Schembecker, Ph.D., Professor, Biochemical and Chemical Engineering, TU Dortmund
University
Aqueous Two Phase Extraction (ATPE) offers a gentle and biocompatible environment to separate industrially interesting enzymes from complex mixtures. The presentation will introduce the separation principle and existing and novel techniques will be discussed
particularly in the light of continuous operation. Besides single and multi-stage mixer settler setups innovative processes immobilizing one of the two aqueous phases either in the pores of particles or by use of a centrifugal force fields will be
investigated.
11:45
Amsphere A3: Considerations of Bead and Pore structure, Surface Chemistries, and Ligand Design for Affinity Resins
Masayoshi Nagaya, Business Strategy Manager, Bioprocess, JSR Life Sciences
Industry needs, patent expirations of ligand design and market dynamics have accelerated the development and availability of many protein affinity resins. Technology providers must consider a range of design parameters such as resin backbone, bead size,
pore size, surface chemistry, ligand construct and how they relate to performance criteria such as DBC, life time, caustic stability, and column packing among others. The balance between resin design and performance will be illustrated through a case
study.
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:00 Session Break
1:45 Chairperson’s Remarks
Yan-Ping Yang, Ph.D., Head, Bioprocess R&D North America, Sanofi Pasteur
1:50 Creating an Efficient Biopharmaceutical Factory: Protein Purification Using a Self-Cleaving Split Intein
Merideth Cooper, MSc, Chemical and Biomolecular Engineering, Ohio State University
Although affinity tags are commonly used in laboratory settings, tagged proteins cannot be used as therapeutics because of the potential immunogenicity of the tag. In this work, we describe a novel self-cleaving tag technology, based on a highly modified
split-intein cleaving element. This approach is convenient and effective for the purification of traceless target glycoproteins from mammalian cell culture, and is currently being applied in a BioMOD platform device for on-demand biologics production.
2:20 The PA Tag Toolbox Offers a System for Easy Affinity Isolation, Robust Detection, and Recyclable Immobilization of High-Value Target Proteins
Junichi Takagi, Ph.D., Professor, Institute for Protein Research, Osaka University
We recently developed a novel and versatile epitope tag system dubbed “PA tag”. It is a dodecapeptide tag recognized by an antibody NZ-1, with a characteristic slow dissociation kinetics. PA tag enables purification, detection, and stable
and reversible capturing of high value target proteins produced in mammalian cells. We also find that the PA tag can be “inserted” into a protein domain, which adds unique advantage over the existing tagging systems.
2:50 Application of Negative Mode Expanded Bed Chromatography to Improve Filtration-Based Washing Strategies of Human Mesenchymal Stem Cells
Barbara Cunha, MSc, Animal Cell Technology, iBET – Instituto de Biologia Experimental e Tecnologica
The use of human mesenchymal stem cells (hMSC) in autologous and allogeneic therapies has been increasing over the last decade. To be applied in a clinical setting, hMSC need to comply with specific requirements in terms of identity, potency and purity.
This talk will focus on the improvement of established tangential flow filtration-based washing strategies, by increasing hMSC purity, using negative mode expanded bed adsorption (EBA) chromatography with a new multimodal prototype matrix based
on core-shell bead technology.
3:20 Accelerating Bispecific Drug Discovery Using Enhanced Purification and Analytical Techniques
Daniel Yoo, Scientist, Biologics, Amgen
Isolating high quality proteins from other undesired byproducts of expression, including aggregates, half antibodies, homodimer molecules, and mispaired species, poses significant purification challenges due to the similarities in physical properties
of these molecules. Here, I present strategies we have explored to accelerate bispecific drug discovery using a combination of higher throughput screening, automated sample handling, and enhanced purification and analytical techniques to identify
higher quality therapeutic candidates.
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Plenary Keynote Session
6:00 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
Thursday, August 18
8:00 am Registration Opens and Morning Coffee
8:25 Chairperson’s Remarks
Guy de Roo, Ph.D., Project Leader, Downstream Processing, Synthon BV
8:30 KEYNOTE PRESENTATION:
Development and Manufacturing of MCLA-128 and MCLA-117 Biclonics® Common Light Chain Bispecific Antibodies
Lex Bakker, Ph.D., Senior Vice President & CDO, Merus Biopharmaceuticals
MCLA-128 is an ADCC-enhanced bispecific IgG1 antibody targeting HER2 and HER3. MCLA-117 is a T cell engaging bispecific antibody targeting CD3 and CLEC12A, a novel AML-associated antigen. MCLA-128 and MCLA-117 are produced using Merus’ proprietary
CH3 heterodimerization technology. Both Biclonics® product leads are manufactured using IgG1 platform approaches.
9:00 Poster Highlight I:
A Split Intein Based Platform for the Purification
of ANY Biological Therapeutic Protein
Ashwin Lahiry, Ph.D. Candidate, Wood
Lab, The Ohio State University
Currently, there is no
simple, low cost platform for the purification of non-antibody therapeutic
proteins. Our lab has developed an affinity tag-based platform for purification of ANY
recombinant protein. This platform utilizes an engineered self-cleaving
split-intein tag that enables tagless and traceless purification of recombinant
proteins. We have successfully demonstrated the utility of this split-intein platform
in E. coli, Mammalian and CHO IVT
expression systems.
9:15 Poster Highlight II: To be Announced
9:30
Inline Protein Concentration for Downstream Processing
Ramsey Shanbaky, Product Manager, Sales, C Technologies, Inc
Accurate concentration measurement is critical during downstream processes. Providing real-time concentration during protein purification processes expedites process development and reduces risk in manufacturing processes. The FlowVPE is a new tool
to provide real-time concentration during downstream processes. This talk will discuss applications in chromatography and UF/DF.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Process Development of the Antibody-Drug Conjugate (ADC) SYD985 - A Case Study
Guy de Roo, Ph.D., Project Leader, Downstream Processing, Synthon BV
SYD985 is an antibody-drug conjugate (ADC) based on trastuzumab and a cleavable linker-duocarmycin payload. A case study will be presented in which a hydrophobic interaction chromatography (HIC) purification process was developed allowing removal
of the undesired antibody species together with unbound linker-drug. It was possible to elute the product (SYD985) using mild conditions without requirement for any organic solvent. The HIC purification step was scaled up, demonstrating consistency
and robustness.
11:15 Preparative Separation of VLP and Extra Cellular Particles (Exosomes)
Alois Jungbauer, Ph.D., Professor, Laboratory of Protein Technology and Downstream Processing,
Austrian Center of Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences
Enveloped VLPs are interesting candidates for vaccines and cancer
immunotherapy. They have a size of about 100 -200 nm which is similar to
exosomes and other extra cellular particles. The surface properties are very
similar because VLPs and extra cellular particles are budded from the host
cell. A strategy is shown who solve this
extremely challenging purification task using HIV-gag VLP expressed in CHO
cells as model.
11:45 Navigating the Downstream Processing Challenges for Novel Monoclonal and Bispecific Antibodies
Chen Wang, Ph.D., Principal Scientist, Process Sciences, Abbvie Bioresearch Center
As we expand our biotherapeutic product portfolio, significant processing limitations have arisen with the existing platform for some of the novel monoclonal and bi-specific antibodies such as dual variable domain immunoglobulins (DVD-IgsTM). Through
exploring unconventional chromatographic methods, adopting state-of-the-art purification technologies and understanding protein-protein interaction mechanism, we were able to develop effective strategy and toolbox to overcome processing challenges
for molecules with platform fit concern.
12:15 Lunch Available for Purchase in the Exhibit Hall
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 End of Conference