Cambridge Healthtech Institute ’s 2nd Annual

Advances in Recovery and Purification

20-21 March 2019

 

Cambridge Healthtech Institute’s Advances in Recovery and Purification meeting brings together industry and academia to discuss the latest developments in the capture, recovery and purification of biotherapeutics, with data driven case studies on next-generation technologies and strategies in affinity chromatography, clarification, depth filtration, new membranes, flocculation, as well as DSP strategies for emerging modalities such as gene therapies, ADCs, bispecifics, fusion proteins and antibody fragments. How do your strategies compare?

Final Agenda

Wednesday, 20 March

10:00 Registration Open

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

Plenary Session: NEXT-GENERATION PROCESSES AND PRODUCTS

11:15 Chairperson’s Remarks

Manuel Carrondo, PhD, Professor of Chemical and Biochemical Engineering, FCT-UNL; Vice President, IBET

 

11:20 Bioprocessing Innovations in the Era of Clinical Acceleration and Process Intensification

Stefanos Grammatikos, PhD, Vice President, Head, Biotech Sciences, UCB Pharma

Current trends in clinical development acceleration and bioprocess intensification impose an unprecedented compression of CMC development timelines and new bioprocessing challenges downstream of the cell culture bioreactor. In this talk I will present a series of innovations we have introduced, some incremental and some potentially disruptive, in an effort to avoid further complications while rising to the latest challenges of bio CMC development and bioprocessing.

11:50 Opportunities and Challenges in CAR T Manufacturing

Markwin Velders, PhD, Vice President, Operations, Managing Director, Kite Pharma EU B.V.

Update on the status of CAR-T development for use in the treatment of cancer. The success story of this paradigm shift and the challenges and opportunities that lay ahead for this therapy will be presented and discussed.

 

12:20 Session Break

12:30 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:00 Session Break

OPTIMIZING DSP

13:40 Chairperson’s Opening Remarks

David_O_ConnellDavid O’Connell, PhD, Lecturer in Biotherapeutics, School of Biomolecular & Biomedical Science, University College Dublin

 

 

13:45 FEATURED PRESENTATION: Challenges in Developing a Scale-Down Model for Primary Recovery in mAb Processes

Richard_ShahRichard Shah, PhD, Downstream Manager, Manufacturing Sciences and Technology, Bristol-Myers Squibb

Continuous flow disk-stack centrifugation is often used to harvest commercial-scale cell culture processes. However, a major limitation is its ability to remove particulates below a certain size and so requires additional filtration to remove the remaining particulates. In this presentation, an approach to characterizing primary recovery (i.e. centrifugation, depth and membrane filtration) will be discussed. Particular attention will be paid to scaling centrifuges using sigma theory, some of the challenges encountered and the impact to filtration throughput.

14:15 Validation of Next-Generation Depth Filter Technology in a Commercial Downstream Process

Kim_HermansKim Hermans, PhD, Team Lead, MSAT Purification, Sanofi

 

 

 

14:45 Centrifugation Scale-Up Modelling

Daniel_KronbergerDaniel Kronberger, PhD, Head, Downstream Pilot, Process Science, Boehringer Ingelheim

In bioprocess development centrifugation steps continue to be a major element of uncertainty during scale up. Varying centrifugation performance causes differences in product recovery and purity and may interfere with subsequent unit operations such as depth filtration or inclusion body solubilization. The main cause for performance variance lies in the different types of centrifuges and separators that are in use at different scales. Current scale up strategies are only effective if both devices are functionally identical. However, most construction types are either principally not suitable or not obtainable for all scales.

15:15 Raman Monitoring of Downstream Bioprocesses: Opportunities to Fix Analytical Bottleneck

Christophe Bonneville, President, RESOLUTION Spectra Systems

In-line Raman spectroscopy demonstrates strong capabilities to monitor key parameters, such as structure and conformation of proteins, titer, purity, enabling to monitor some downstream processes. From a QC perspective, this technique is also efficient to quickly control product CQA. However, in order to widely implement this technology, some issues need to be carefully taken care of: validity, robustness and transferability of models over time, process evolution and devices. We will present opportunities based on examples.

15:45 Refreshment Break in the Exhibit Hall with Poster Viewing

16:25 Removal of High-Molecular-Weight Species by Protein A Chromatography

Daniëlle_van_WijkDaniëlle van Wijk, PhD, Lead Scientist, Downstream Processing, Synthon Biopharmaceuticals

In this study, the potential of Protein A chromatography to separate antibody monomer from HMW species was investigated. A design-of-experiments approach was used and shows that HMW species can potentially be separated from antibody monomer by Protein A chromatography to the desired levels while maintaining an acceptable monomer recovery. This would result in the use of a more efficient Protein A step and allow for reduction of DSP economics.

16:55 Affinity Chromatography for the Next Generation of Biotherapeutics, Empirical Approaches to Engineering a Universal Process

David_O_ConnellDavid O’Connell, PhD, Lecturer in Biotherapeutics, School of Biomolecular & Biomedical Science, University College Dublin

Developing novel affinity methods for the separation of biomolecules requires the integration of biochemical and biophysical parameters that ensure the protein is delivered in an active, native conformation that will greatly depend on how it is captured and how it is released. This talk will focus on engineering protein sequences that facilitate specificity and stability without compromising the integrity of the protein product with some recent examples of successful biotherapeutic candidates.

17:25 Modeling and Simulation of Ion-Exchange in Bio-Processes – Illustrations from Industrial Biotech to Biopharma

Roger_Marc_NicoudRoger-Marc Nicoud, CEO, Ypso-Facto

In industrial biotech (citric acid separation, amino-acids purification), complexity of ion exchange phenomena has been modeled and fairly predicted. However, as molecules in biopharma represent a higher degree of complexity, they challenge the rigorous description of ion exchange phenomena involved in their isolation. We will show how to deal with complexity of molecules and ion exchange to bring on hand modeling and consequently a rigorous and competitive design of industrial biopharma processes.

17:55 End of Day

18:00 Dinner Short Course Registration

18:30 - 21:00 Recommended Short Course*

SC6: Flocculation, Precipitation and Crystallization for DSP of Biopharmaceuticals

Instructor:

Alois Jungbauer, PhD, Professor, Department of Biotechnology, University of Natural Resources Life Science, Vienna, Austria and Austrian Centre of Industrial Biotechnology

Flocculation, precipitation and crystallization are alternative methods to chromatography and membrane filtration for downstream processing of biopharmaceuticals. With the advent of integrated and/or continuous processing and feed stocks with much higher titers as in the past precipitation, flocculation, and crystallization again became very attractive. These techniques are and will be integrated into existing processes to intensify them. These methods are progressively integrated to new ones to establish simpler processes. In this workshop we will address the principles and methods for developing methods, scale up and large scale operation.

*Separate registration required.

Thursday, 21 March

8:00 Registration and Morning Coffee

New DSP Technologies and Modalities

8:25 Chairperson’s Opening Remarks

David O’Connell, PhD, Lecturer in Biotherapeutics, School of Biomolecular & Biomedical Science, University College Dublin

8:30 KEYNOTE PRESENTATION: Developing and Processing of Low-Cost Magnetic Particles for Protein Separation in the Technical Scale

Sonja Berensmeier, PhD, Professor, Bioseparation Engineering Group, Department of Mechanical Engineering, TechnicalUniversity of Munich

We were able to create new peptide tags that bind an inexpensive non-functionalized, bare surface. As adsorber material, we used biocompatible magnetic nanoparticles, a promising material that has shown applicability in a wide range of areas. This work paves the way for a new, economical purification process of biotechnologically produced proteins and contributes to a deeper understanding of bio-nano interactions.

9:00 Generic Buffer System: A Smart Tool for Efficient Next-Generation Downstream Processes

Anja_TrappAnja Trapp, Scientist, Bioprocessing Technology & Innovation, Rentschler-Biopharma

New strategies improving protein purification are an inevitable prerequisite for next-generation processes. Our generic buffer system enables a smart development of a simple and economic production process. On this basis, a modular toolbox of separation techniques is used to achieve the desired product quality and purity. The talk will give insights into our flexible approach in form of different case studies.

9:30 A Novel Alkaline Stable Protein A Resin Based on Monodisperse Agarose Beads

Hans J. Johansson, Global Applications Director – Agarose, Purolite Life Sciences

In contrast to batch emulsification, by utilising a scalable continuous emulsification technology termed ‘jetting’ - beads with a very narrow particle distribution have been manufactured, omitting the need for sieving, and resulting in almost quantitative yield. The performance data of a new range of chromatography resins will be presented.

9:45 Sponsored Presentation (opportunity available)

10:00 Multi-Component Adsorption as a Challenge for Process Chromatography

Rainer_HahnRainer Hahn, PhD, Associate Professor, Department of Biotechnology, BOKU

Chromatography is the most effective method when it comes to preparative protein separation, as it provides the highest selectivity and resolution power. However, with complex feed stocks many adsorption systems are not in equilibrium or even far away from it, even if the chromatographic separation is performed at low velocity. Several examples of such systems will be shown and methods to overcome limitations in chromatographic processing will be discussed.

10:30 Coffee Break in the Exhibit Hall. Last Chance for Poster Viewing.

11:15 Continuous Chromatographic Purification of Exosomes

Ricardo_Jorge_Sousa_da_SilvaRicardo Jorge Sousa da Silva, PhD, Researcher, iBET

Extracellular vesicles, more particularly exosomes, are nanostructures of great medical interest. Similar to other complex biopharmaceuticals such as viruses, the purification of these nanovesicles is still a considerable challenge. Here we describe an efficient and scalable purification strategy based in multi-column chromatography.

11:45 Improving Oncolytic Virus Biomanufacturing to GMP Compatible Bioprocess

Cristina_PeixotoCristina Peixoto, PhD, Head, Downstream Processing Laboratory, IBET

Oncolytic virotherapy represents a new class of cancer drugs. The rise of the number of clinical trials using this virus generates the demand to develop an improved purification platform to lower costs of treatments. Herein we will present and discuss the challenges on the purification of oncolytic adenovirus for clinical trials, the strategies and novel technologies to be adopted in order to enable a faster development of novel vectored vaccine candidates focusing on several case studies, supported by process technology innovation.

12:15 A New Developed Chromatographic Platform Based on a Single-Column

Abimaelle_ChiberioAbimaelle Chiberio, PhD Student, Universidade Nova de Lisboa

Downstream processing represents up to 80% of the costs of biopharmaceuticals. However, the biopharmaceutical economy started to demand an evolution in the downstream part, in order to reduce the costs of the biopharmaceutical production process. A newly developed chromatographic platform based on a single-column device mimics the operation and performance of recent multicolumn capture and polish processes designed for the efficient separation and purification of monoclonal antibodies and biosimilars.

12:45 Luncheon Presentation to be Announced

13:15 Session Break

IMPROVING DSP KNOWLEDGE AND CONTROL

13:45 Chairperson’s Remarks

Cristina Peixoto, PhD, Head, Downstream Processing Laboratory, IBET

13:50 DuoBody Technology: A Versatile Platform for Bispecific Antibody Discovery and Development

Rick_HibbertRick Hibbert, PhD, Assistant Director, Genmab

 

 

 

14:20 The Time Has Come – More Control in Inclusion Body Processing

Oliver_SpadiutOliver Spadiut, PhD, Associate Professor, Integrated Bioprocess Development, TU Wien

Inclusion body processing is still based on empiricism rather than sound process knowledge. State-of-the-art refolding processes mostly happen in unmonitored dilution approaches giving a lot of misfolded product and low space-time-yields. I will present how we tackle this challenge by introducing more monitoring and control in these processes. I will present case studies for three different proteins.

14:50 Process Development Considerations for Novel Highly Potent Recombinant Proteins

David_GruberDavid Gruber, PhD, Head, Downstream Processing, Ipsen Biopharm

Botulinum neurotoxin is effective in the treatment of several movement disorders. Native BoNT/A is comprised of a family of highly related neurotoxins produced by Clostridium botulinum bacteria and BoNT/A (subtype A1) is notable as the strain used to produce the commercial products such as abobotulinumtoxinA (Dysport). An increased understanding of the structure-function relationship of BoNT provides an opportunity to engineer recombinant (r) BoNTs with unique pharmacologic properties and therapeutic applications. This presentation will describe the challenges and opportunities associated with process development and GMP manufacture for rBoNT products.

15:20 Close of Conference