Cambridge Healthtech Institute’s 5th Annual
Advances in Purification & Recovery
Intensifying and Optimizing Downstream Process
August 14-15, 2019
New and emerging molecules coming down the pipeline brings a new set of challenges to the downstream team. Downstream scientists are thus increasingly looking to process intensification and optimization methods, automation, mechanistic modeling and high
throughput processes to meet the challenges of higher upstream titers and complex molecules while improving products and reducing cost.
CHI’s 5th Annual Advances in Purification & Recovery invites scientists to share their pursuit of new materials such as nanomembranes, or new technologies including process intensification, high throughput
purification and enhanced chromatography approaches.
Final Agenda
TUESDAY, AUGUST 13
Beacon Hill
6:00-8:30 Recommended Dinner Short Course*
SC6: Integrated Continuous Biomanufacturing – An Implementation Approach
Instructor:
Robert Dream, Managing Director, HDR Company Ltd.
The importance and value of continuous processing’s economic and sustainability advantages due to the modular nature of continuous processes means that the industry is able to adapt more rapidly to changing market demands. Factors other than scientific
ones, are the barriers to change from batch to continuous production. The (bio)pharmaceutical industry has reached a stage that requires a change in the production paradigm. Continuous manufacturing is as productive and has a much smaller footprint
of the manufacturing plant, avoiding multiple non-value added unit operations. This course will cover strategies to transition from batch to continuous, areas to implement continuous manufacturing (from upstream to fill-finish), step-wise approach
to implementation, new technologies and impact of big data, and more.
Wednesday, August 14
6:00 - 6:45 am Seaport Fun Run/Walk (Seaport Hotel Plaza Lobby)
7:00 Registration Open and Morning Coffee
8:05 Chairperson’s Remarks
Alois Jungbauer, PhD, Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna and Austrian Centre of Industrial Biotechnology
8:15 KEYNOTE PRESENTATION: Challenges and Innovations in Downstream Processing of Gene Therapy Products
Juan
Hernandez Bort, PhD, Head, Gene Therapy Technologies, Takeda
In the areas of gene and cell therapy more than 450 substances are currently in clinical trials and the number of approved products is expected to grow rapidly over the next years. Those products are very complex and require innovative approaches to meet
safety requirements, clinical and market demands and cost of goods targets. Smart combinations of traditional downstream approaches and novel technologies are needed to develop scalable and robust purification processes for cell and gene therapy products.
9:00 Development of a Robust Purification and Separation Strategy for a Novel ADC Platform
Engin Ayturk, PhD,
Director, CMC Process Engineering & Conjugation, Mersana Therapeutics
Mersana Therapeutics is a clinical-stage biopharmaceutical company with an innovative and differentiated antibody drug conjugates (ADCs) pipeline built upon novel linker platforms such as Dolaflexin® and Dolasynthen that deliver proprietary auristatin-based
payloads via the state-of-the-art bioconjugation strategies that enable an enhanced therapeutic window for the treatment of multiple cancers. This presentation will provide an overview of Mersana’s novel ADC platform and discuss the QbD-based
process development and scale-up strategies via relevant case studies.
9:30 Purification of Antibody Fragments: From Enzyme Digestion to rFab Purification, and from Manual to Automation Chromatographic Cyclic Approach
Wan-Ching Lai,
PhD, Principal Scientist, Abbott Diagnostic Division, Abbott Laboratories
Manufacturing operation site discards chromatographic resins including expensive affinity matrix after every batch production. The goal of this study is to develop a robust, transferrable, and cost effective affinity chromatography process for rFab
manufacturing.DOE is used to evaluate and further optimize process parameter ranges of CH1-XL affinity chromatography. The final manufacturing chromatography process consists of sixteen cycles, reducing resin cost up to 93% (i.e. 16 cycles vs.
1 cycle).
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Purification Considerations for Plasmid DNA to Enable Gene Therapies
Karolina Les, PhD,
Scientist II, Biopharmaceuticals Development, AstraZeneca
Development of next generation medicines to treat or even cure some of the most common and serious of human diseases is on the near horizon. Recombinant proteins remain the most prevalent biotherapeutics in the Biotech industry; however this landscape
is now changing. There is an increased focus on new strategies based around oligonucleotide and viral delivery technologies. This presentation will focus on the critical considerations around the development of a scalable manufacturing process
to produce therapeutic grade plasmid DNA.
11:15 Implementing 'Manufacturing by Design' (MbD) Strategy for Accelerated Commercial Biologics Manufacturing
Hemant Kumar, PhD, CPM, Senior Vice President & Head, Technical Development & Manufacturing Operations, AnaptysBio, Inc.
11:45 Future of Non-Platformable Downstream Processes: A Roadmap to Improved Process Design and Manufacturability
Karol Lacki, PhD,
Vice President,Technology Development, Avitide, Inc.
Proportion and complexity of non-mAb bio-therapeutics among approved biologics is increasing. From the bioprocessing perspective, this fact translates into challenges and specific needs that ought to be addressed for those molecules to be safely and
economically manufactured. This presentation will address those challenges and provide examples of already existing technical solutions that simplify downstream processes for non-platformable protein therapeutics. Specific emphasis will be given
to the primary and secondary purifications steps using affinity chromatography.
12:15 pm Enjoy Lunch on Your Own
1:00 Dessert Break in the Exhibit Hall with Poster Viewing
1:45 Chairperson’s Remarks
Ronald Bates, PhD, Director, MS&T, Bristol-Myers Squibb
1:50 Perforated Nanomembrances for Separation of Proteins
Alois Jungbauer, PhD, Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna and Austrian Centre of Industrial Biotechnology
Ultrathin perforated nanomembranes with a thickness below 100 nm can be freely suspended on the cm scale, exhibit high mechanical strength, low surface energies and a sharp permeability cutoff at a hydrodynamic diameter of 10 nm suitable for protein
separations. They preserve their robustness in organic solvents and show resistance to high pH values which is ideal for implementation in biotechnological applications. Examples are shown as to how such membranes could be used for downstream
processing.
2:20 New Strategies for Magnetic Nanoparticles in Industrial Biotechnology
Sonja
Berensmeier, PhD, Professor, Bioseparation Engineering, Technical University of Munich
Magnetic particles are playing an increasingly important role in the field of biotechnology. They have particularly become popular in the field of molecular biology or drug-delivery, where their easy handling has a significant advantage for the user.
We show that biocompatible magnetic nanoparticles can also serve as resin for downstream processing. In addition to simple processing even on larger scales, they can be obtained cost-effectively by iron salts and have very large specific surfaces
areas.
2:50 Functionalized Protein Nanoparticle Crosslinking for Enhanced Affinity Precipitation of Monoclonal Antibodies
Wilfred Chen, PhD,
Gore Professor, Chemical and Biomolecular Engineering, University of Delaware
Affinity precipitation using environmentally responsive, Z-domain-elastin-like polypeptide (Z-ELP) fusion proteins has been shown to be a promising alternative. However, elevated temperature and salt concentrations necessary for precipitation resulted
in decreased antibody monomer content and reduced purification capacity. To improve upon the existing technology, we have demonstrated the benefit of conjugating Z-ELP to a 25 nm diameter, self-assembled E2 protein nanocage (Z-ELP-E2), which significantly
outperformed traditional Z-ELP-based methods.
3:20 Revolutionising Chromatography: 3D Printed Monoliths for Protein Chromatography
Ursula Simon, Senior
PhD Student, School of Engineering, University of Edinburgh
- 3D printing in the field of protein chromatography
- Fabrication of highly ordered chromatography beds in contrast to traditional randomly packed beds
- Development of novel materials for the direct printing of fully functional ion exchange monoliths
- Application of 3D printed monolith for protein separation
3:50 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Plenary Keynote Session View details
6:00 A Taste of New England Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
Thursday, August 15
6:00 - 6:45 am Namaste@#BPSMT (Seaport Hotel Plaza Lobby)
8:00 Registration Open and Morning Coffee
8:25 Chairperson’s Remarks
Engin Ayturk, PhD, Director, CMC Process Engineering & Conjugation, Mersana Therapeutics
8:30 Learning Opportunities during Commercial Manufacturing
Ronald Bates,
PhD, Director, MS&T, Bristol-Myers Squibb
A biotherapeutic product’s lifetime involves thousands of lots encompassing scales from microscale during high-through screening to laboratory and then pilot/early clinical and eventually commercial scale. The vast majority of these lots
most likely will occur during commercial manufacturing.This presentation will explore, through case studies and thought-provoking situations, the numerous opportunities available to increase process knowledge after a product is commercialized.
9:00 KEYNOTE PRESENTATION II: The Search for Process Intensification and Simplification: Alternative Approaches versus Current Platform Processes for Monoclonal Antibodies
Robert Gronke, PhD,
Senior Principal Scientist, ASO Process Development & Manufacturing, Biogen, Inc.
A platform process approach to production and purification of monoclonal antibodies has been developed and utilized across the Biopharmaceutical industry since the mid 1990s. How a company chooses to maintain vs. evolve their platform will depend
on a number of factors. This talk will highlight how best to address changes to the mAb platform, focusing on process intensification and simplification.
9:30 SELECTED POSTER PRESENTATION: Evaluation of a Multimodal Chromatography Capability for Host Cell Protein Clearance
Haiying Bao, Scientist
II, Bristol-Myers Squibb
Host cell protein (HCP) impurities clearance is a key concern during downstream process development for biological drug substance. The HCP impurities need to be effectively cleared using chromatographic steps in the downstream purification process
to produce safe and effective biological drug substance. In this study, we explored the potential of a multimodal chromatography as a polishing step to clear the host cell protein impurities in a recombinant protein downstream purification
scheme. A systematic DoE study was designed and performed to define an optimized operating space for this multimodal chromatography in terms of impurity clearance and yield. Here we defined this multimodal chromatography operating space that
clears the HCP impurities to levels well within targeted specification levels acceptable for drug substance at 50 - 100 fold HCP reduction. The robustness of the HCP impurity clearance is further confirmed and successfully applied in the manufacturing
scale process.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Leveraging Displacement to Enhance Ion-Exchange Chromatography of Product-Related Variants
Abraham M. Lenhoff, PhD, Allan P. Colburn Professor, Chemical and Biomolecular Engineering, University of Delaware
The combination of protein A chromatography and subsequent polishing steps is routinely effective at removing impurities in mAb bioprocessing. However, for product-related species such as charge variants, the customary use of cation-exchange chromatography
may not achieve the needed levels of performance. This presentation will discuss the use of self-displacement to enhance chromatographic performance, specifically for charge variants but also as a more powerful tool for impurity clearance
more generally.
11:15 Enhancing the Discovery of Challenging Therapeutic Molecules Using Cutting-Edge Processes, Automation, and Informatics Tools
Daniel Yoo, Scientist, Biologics, Amgen, Inc.
With the increasing challenges of identifying promising therapeutic biologics that produce significant and durable responses for unmet medical needs, the drug discovery landscape has evolved beyond monotherapies to multi-specific and multi-valent
formats. However, many of these formats can be difficult to produce efficiently due to byproducts of expression such as aggregation, chain mispairing, disulfide crossed domains, and non-covalently paired species. These molecules require extensive
screening efforts to identify the most promising candidates for development. To address this, we developed enhancements to our discovery processes that accelerate and improve screening, increase throughput with automation, and integrate high
quality informatics to enable quality decision making.
11:45 Enhancing Virus Filter Throughput for Hydrophobic Proteins
Lu Wang, PhD, Assoc Director,
CMC Process Development, Teva Pharmaceuticals
Viral safety is one of the major aspects considered by the agency during IND and BLA applications. Downstream manufacturing process has to demonstrate sufficient virus clearance capability to fulfill the regulatory requirements. Virus reduction
filtration (VRF) is considered as one of the robust and effective virus clearance steps used in the manufacture of biologics. However, for hydrophobic proteins, VRF process development can be challenging due to filter fouling, which results
in low throughput. This presentation is a case study that compares the VRF performance based on protein hydrophobicity, and demonstrate a strategy to improve the viral filter throughput from 100 L/m2 to >600 L/m2 for a product to enable
GMP manufacturing facility fit. The aspects considered during VRF development and the proposed mechanisms of improvement will be discussed.
12:15 pm Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing
1:55 End of Conference