Cambridge Healthtech Institute ’s 3rd Annual

Advances in Recovery and Purification

Optimizing DSP, Reducing Costs

25-26 March 2020

 

As product pipelines diversify away from traditional mAbs, downstream processing teams are under increasing pressure to develop new recovery and purification platforms for more complex products, such as bispecifics, ADCs, viral vectors, while at the same time reducing timelines, costs and bottlenecks for traditional mAbs therapies.

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

Final Agenda

Wednesday, 25 March

10:30 Registration

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

PLENARY SESSION:

NEXT-GENERATION PROCESSES AND PRODUCTS

11:15 Chairperson’s Remarks

Jarka Glassey, PhD, Professor, Chemical Engineering, Engineering, Newcastle University

11:20 Current Opportunities and Challenges in Biotherapeutic CMC

Schumacher_RalfRalf Schumacher, PhD, Global Head, Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG

As biologic pipelines continue to grow and diversify, there is an increasing need to standardize, automate and find efficiencies along the entire value chain. This presentation will discuss the current challenges and opportunities in biotherapeutic CMC and the impact new modalities are having on upstream and downstream processing, analytics and formulation. The advantages of predictive process parameters in early stage development and digital development concepts to speed up the CMC development will also be discussed.

11:50 Gene Therapy Manufacturing and Technical Development

Diane_BlumenthaDiane Blumenthal, PhD, Head, Technical Development, Spark Therapeutics

In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU with many more in the pipeline. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This presentation will focus on the key technical development challenges facing the industry as product development programs move the into the later stages of process development and scale-up, process performance qualification and ultimately commercialization.

12:20 Session Break

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

13:00 Session Break

MACHINE LEARNING, HTPD AND NOVEL DSP APPROACHES

13:45 Chairperson’s Opening Remarks

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

13:50 How to Kill Your Complex Protein during Cell Removal and Strategies to Solve the Issue: Alternatives to Classical Depth Filtration

Fleischanderl_DanielDaniel Fleischanderl, Head, Upstream Process Development Austria, R&D Pharmaceutical Sciences, Takeda

During the scale-up of a 2nd-gen process for a complex non-mAb-like protein, an unexpected, almost complete loss of activity was observed. Increased proteolytic activity due to cell disruption during depth filtration inactivated the protein. Successful alternatives to traditional depth filtration like low shear single-use centrifugation and (single-use) settlers to solve this issue will be explained. In addition, the talk will elaborate on the potential of these alternatives for continuous applications.

14:20 KEYNOTE PRESENTATION: Application of Integrated Process Modelling and Machine Learning Techniques in High-Throughput Process Development

Anne Tscheließnig, PhD, Head, Downstream Development II, Biopharma Process Science Austria, Boehringer Ingelheim

The development of a complete production process usually occurs by sequential optimization of each individual unit operation. This strategy does not consider potential interactions between different process steps and does not guarantee optimal overall process performance. We established a platform for holistic process development utilizing integrated process models using machine learning techniques. We show the successful application of this strategy in a case study.

14:50 Optimization and Utilization of an IgG-Binding, Protein A-Based Purification Matrix

Hober_SophiaSophia Hober, PhD, Professor, School of Biotechnology, KTH Royal Institute of Technology

The most common tool used for purification of antibodies is protein A affinity chromatography, a method that offers high productivity and pure protein product. However, elution of captured antibodies requires low pH and that might be deleterious. We have addressed this issue by developing a protein domain displaying calcium-dependent binding to IgG. To evaluate the domain in affinity chromatography, a matrix based on a tetrameric version of this domain was produced. From this column, elution in physiological pH was possible and IgG recovery was shown to be comparable to commercial matrices.

15:20 Presentation to be Announced

15:50 Refreshment Break in the Exhibit Hall with Poster Viewing

16:25 New Process Development for Purification of Novel D9k-Loop and D9k-Side Protein Scaffold Therapeutic Candidate

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

This presentation will focus on the development of high-affinity, highly-specific diagnostic and therapeutic binding molecules based on the creation of two novel phage displayed libraries of a uniquely stable and hydrophilic protein scaffold characterized in our previous studies of calcium-binding proteins. This novel scaffold has molecular properties designed to achieve significant impact as a new generation of powerful tools in areas of clinical need, both as diagnostic and therapeutic entities. Processing of specific candidates will be described.

16:55 Astonishing Features of Protein A Affinity Chromatography Resins

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

Protein A affinity chromatography is the workhorse for antibody purification. Novel media exhibit some amazing features, like extreme pH transitions, which can be triggered by specific buffer selection leading to process conditions that can benefit the respective antibody to be purified. Furthermore, protein A ligand properties can change significantly upon alkaline treatment and eventually lead to enhanced mass transfer.

17:25 Critical Factors for the Precipitation of Monoclonal Antibodies

Dutra_GregGregory Dutra, PhD Student, Department of Biotechnology, BOKU

Continuous antibody precipitation combined with tangential flow filtration allows a constant mass flow process. Fine-tuning the conditions is imperative for achieving acceptable recovery and purity rates. Using a cross-linking agent as the main precipitant, we describe the critical factors and its effects on the precipitation of different recombinant monoclonal antibodies.

17:40 In-Line Buffer and Media Reconstitution from Solids

Komuczki_DanielDaniel Komuczki, PhD Candidate, Institute of Bioprocessing Science and Engineering, Working Group Jungbauer, BOKU

Integrated continuous biomanufacturing requires big hold tanks for buffer and media preparation. The current trend to reconstitute from stock solutions is especially problematic for fermentation media. We show a proof-of-concept for a continuous reconstitution of media and buffers from solids in lab scale. This opens a new playground for development of strategies in upstream and downstream and several applications of this concept will be demonstrated.

17:55 End of Day

18:00 Dinner Short Course Registration


Recommended Dinner Short Course*

18:30 - 21:00 SC6: Understanding Chromatography to Design Efficient Bioprocesses with a Predictive Approach

Instructors:Hector Osuna, PhD, Head of Biotech Modeling, Ypso-Facto

Lucrèce Nicoud, PhD, Project Manager, Ypso-Facto

*Separate registration required

Thursday, 26 March

8:00 Registration and Morning Coffee

PURIFICATION OF NOVEL THERAPIES

8:25 Chairperson’s Remarks

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

8:30 Strategies and Advances in Purification of New Therapeutic Modalities

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

The last few decades have witnessed a huge development in the design of new virus-based biopharmaceuticals. They have been used for cancer treatment, neurodegenerative and genetic diseases, as well as in immunotherapies. However, their purification still presents challenges related to the high dosages and high purity required. New insights on how the additive manufacturing and new affinity matrices improve the global recoveries are presented and discussed.

9:00 Purification Considerations for Plasmid DNA to Enable Gene Therapies

Les_KarolinaKarolina Les, PhD, Scientist II, R&D Biopharmaceuticals, Purification Process Scientist, AstraZeneca

Development of next-generation medicines to treat or cure some of the most serious of human diseases is on the near horizon. Majority of treatments rely on recombinant proteins, however this landscape is now changing to include oligonucleotides and viral delivery technologies. This presentation will focus on the critical considerations around the development of a scalable manufacturing process to produce plasmid DNA as final product or intermediate to gene therapies.

9:30 Continuous Bioprocess Development or Therapeutic Bioparticles

Ricardo_Jorge_Sousa_da_SilvaRicardo Jorge Sousa da Silva, PhD, Senior Scientist, Animal Cell Technology Group, iBET

Novel therapeutic modalities, such as virus-based biologics or exosomes, are hailed as potential game-changers for healthcare. However, these complex entities may require complex approaches regarding manufacturing. The present talk will highlight some of the challenges faced in the development of continuous bioprocesses for this new class of therapeutics.

10:00 Enhancing Continuous Processing: Implementation of Chromatographic Clarification Advantages and Approaches3M

El-Sabbahy_HaniHani El-Sabbahy, PhD, Biopharmaceutical Application Engineering Specialist, Separation and Purification Sciences Division, 3M United Kingdom PLC, 3M

A number of commercial and academic entities are exploring continuous processing for recombinant protein manufacturing. It has the potential to bring many advantages to the production of biotherapeutics such as; lower capital costs, higher productivity, smaller equipment footprint, lower buffer consumption, and, in some circumstances, steady state operation. However, one of the key barriers to implementation, particularly with respect to the continuous capture step, is system complexity. 

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

NOVEL PURIFICATION AND DIGITAL PLATFORMS

11:15 Application of Ion-Exchange to the Purification of an Active Pharmaceutical Ingredient with Multivalent Isomers: Modeling and Simulation

Osuna_HectorHector Osuna, Head of Biotech Modeling, Ypso-Facto

In biopharmaceutical applications, ion-exchange is generally described with classical adsorption isotherms, an approximation which often proves limiting. Based on an industrial process example, we illustrate how to deal with a mixture of complex multivalent enantiomers containing an active pharmaceutical ingredient. With a rational and methodological approach based on appropriate ion-exchange modeling and simulation, the process has been better understood, optimized and adapted to changes, resulting in major process performance improvements.

11:45 Developing a Continuous Non-Chromatographic Purification Stage for Monoclonal Antibodies

Philip Cormer, PhD, Scientist, Technical Lead, CPI Biologics

12:15 A Microfluidic Platform for Biopharmaceuticals Manufacturing Optimization

Raquel Aires-Barros, PhD, Professor, Bioengineering, Instituto Superior Técnico

The number of biotechnology-based pharmaceuticals in the late-stage pipeline has been increasing more than ever; in particular monoclonal antibodies (mAbs) represent a quarter of all biopharmaceuticals in clinical trials. As a result, there is an enhanced demand for more efficient and cost-effective processes. Here, the potential of miniaturization as a high-throughput screening tool to speed up process optimization is explored, considering optimization of antibody extraction conditions with ATPS and chromatographic conditions optimization using a multimodal ligand.

GORE12:45 Luncheon Presentation to be Announced

 

 

13:30 Session Break

13:45 Chairperson’s Remarks

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

13:50 CO-PRESENTATION: Inclusion Body Processing – A REAL Black Box Case Study

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

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

In this shared talk, we will present an exciting industry-academia challenge. At the Bioprocessing Summit 2019, the Downstream Process experts from Boehringer Ingelheim RCV (BI RCV) and the group of “Integrated Bioprocess Development” of TU Wien both presented their strategies in inclusion body processing. Based thereon, the workflows developed at TU Wien were put to the ultimate test: BI RCV provided washed inclusion bodies and only some key information on the industrially-relevant product and left the inclusion body process development totally to the academic partner. In this extraordinary talk, you will learn the outcome of this great challenge!

14:20 A Digital Platform Concept Based on Hybrid Modeling for Biologics Development

Rui_OliveiraRui Oliveira, PhD, Associate Professor, Faculty of Science and Engineering, Universidade Nova Lisboa

This project seeks for ultra-fast process development to increase yield and productivity before completion of Phase II clinical trials using integrative digitalization across the different development stages, namely cell line development, clone selection, culture media optimization, process control and scale-up to commercial phase. For this purpose, we propose a toolbox of hybrid machine learning/mechanistic in silico tools that integrate the heterogeneity of data/knowledge across the different process development states.

14:50 CO-PRESENTATION: A Digital Downstream Process – Specification-Driven Intermediate Acceptance Criteria Using a Digital Twin

Herwig_ChristophChristoph Herwig, TU WIEN


Marschall_LukeLukas Marschall, Exputec GmbH

The most commonly applied approach for intermediate acceptance range definition, a 3-sigma range, leads to higher out-of-specification probabilities and a restrained manufacturing flexibility. Using a digital twin – with the same amount of data – we derive specification-driven acceptance criteria that ensure a predefined out-of-specification probability. These specification-driven ranges enable us to set up a control strategy that prevents failed batches while maintaining the highest possible manufacturing flexibility.

15:20 Close of Summit