Cambridge Healthtech Institute’s Inaugural
Bioproduction: Scaling Up and Down

Modeling to Manufacturing

5-6 November 2015

The inaugural “Bioproduction: Scaling Up & Down” conference looks at the bigger picture of bioprocessing while exploring the details of optimizing processes. Creating models for scaling down and developing strategies for scaling up production will also be discussed, as will monitoring and analyzing processes in order to reach optimal conditions and productivity. Disposable and Single-Use Technologies will also be addressed, as will examining how bioreactors process cells, from small operational details to large-scale bioproduction.

Final Agenda

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

: Unpublished Data | : Case Study

Thursday, 5 November

12:30 Registration

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

INNOVATING BIOPRODUCTION

13:30 Chairperson’s Opening Remarks

Mark Smales, Ph.D., Professor, Biotechnology, Biosciences, University of Kent

FEATURED PRESENTATION

14:20 Manufacture of Therapeutic Proteins at the Point-of-Care

Antonio Moreira, Ph.D., Vice Provost for Academic Affairs, Provost’s Office and Center for Advanced Sensor Technology; Professor, Chemical and Biochemical Engineering, University of Maryland

Our team has been developing a compact, agile platform designed to produce therapeutic proteins at the point-of-care. In this presentation, we will describe our progress towards making a briefcase sized device that will serve as the factory of the future, and enable biologics production on-demand at the point-of-care. Our core technology uses a novel CHO cell extract for in vitro expression of virtually any protein and couples it with a simple, single step intein-based purification system that has the potential of producing a therapeutic ready for delivery to the patient.

14:50 SELECTED POSTER PRESENTATION:
Optimization of 2G UNicT Technology for Enhanced Protein Production Under GS Selection in CHO-S and CHO GS -/- Cells
Bart Engels, Ph.D., Scientist, ProteoNic B.V.

15:20 Refreshment Break in the Exhibit Hall with Poster Viewing

STRATEGIES FOR ANTIBODY PROCESSING

16:05 From Bench to GMP, Develop Quick and Clean ADC Processes

Eric Lacoste, Ph.D., ADC Team Leader, Chemistry & Biotechnology Development, Sanofi-Aventis Research & Development

How to go Quick and Clean from bench to GMP? How to deal with project constraints? The Sanofi’s ADC team develops processes in QbD-oriented strategies to rapidly deliver a scaleable process contributing to process and product knowledge. Selected examples on conjugation reaction and purification development will be presented.
September 2015 Speaker Interview  

16:35 Bispecific Antibodies from Engineering to Optimized In-House Phase I Manufacturing

Stanislas Blein, Ph.D., Senior Director and Head, Antibody Engineering, Biologics Research, Glenmark Pharmaceuticals S.A.

Glenmark Pharmaceutical`s BEAT® platform is a novel bispecific heavy chain hetero-dimerization platform based on a unique concept of bio-mimicry. We have produced several T cell recruiting bispecific antibodies against different cancers. Our most advanced program GBR 1302 potently re-directs T cells to HER2 positive cancer cells demonstrating strong tumour cell lysis activity with an excellent safety-efficacy window. Preclinical data and manufacturing process will be presented.

17:05 End of Day

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

Friday, 6 November

07:30 Morning Coffee

SCALING UP & DOWN

08:30 Chairperson’s Remarks

Alan G. Ryder, Ph.D., Senior Lecturer, Nanoscale Biophotonics Laboratory, School of Chemistry, National University of Ireland, Galway

08:35 Scale-Down Models Enable Identification of microRNAs to Enhance Cellular Performance of Mammalian Cell Factories

Kerstin Otte, Ph.D., Professor, Molecular Biology and Gene Technology, Pharmaceutical Biotechnology, University of Applied Sciences Biberach

Mammalian expression systems still exhibit bottlenecks during protein production invoking efforts to improve production capacity of host cells. The development of novel engineering strategies is usually performed in small scale formats. We will present a small scale, high-throughput functional screen using microRNAs to optimize production in CHO cells revealing vast numbers of microRNAs to improve production performance. An entire miRNA family is shown to exhibit pro-productive properties transferable from small scale to larger scale formats.

09:05 Challenges in Scale-Up of Cell Culture Processes from Lab Scale to Full Commercial

Christian Sieblist, Ph.D., Manager, Science and Engineering Lab, Roche Pharma Biotech Production, Roche Diagnostics GmbH

10:35 Coffee Break with Poster Viewing

ENHANCING PRODUCTIVITY

11:00 Impact of Large-Scale Bioreactor Heterogeneities on Transcriptional and Metabolic Regulation in Industrial Producers

Ralf Takors, Ph.D., Director, Biochemical Engineering, University of Stuttgart

E. coli is commonly used for recombinant protein production in lab and in production scale. When cells are exposed to large scale production conditions, they face frequently varying micro-environmental conditions due to insufficient mixing and spatial heterogeneities. This contribution shows impacts of large scale heterogeneities mirrored on the metabolic and transcriptional levels of E. coli that finally serve to optimize bioreactor design and the genomic platform of the producer cell.

11:30 CHO Cell Line Engineering – Protein Quantification on the Octet RED96

Stefan Kol, Ph.D., Protein Biochemist, CHO Cell Line Engineering Core Facility, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

Erythropoietin (EPO) quantification during cell line selection and bioreactor cultivation has traditionally been performed with ELISA or HPLC. As these techniques suffer from several drawbacks, we developed a novel EPO quantification assay. A camelid single-domain antibody fragment (VHH) directed against human EPO was evaluated as a capturing antibody in a label-free biolayer interferometry-based quantification assay. Human recombinant EPO can be specifically detected in Chinese hamster ovary cell supernatants in a sensitive and pH-dependent manner. This method enables rapid and robust quantification of EPO in a high-throughput setting.

12:00 Determination of Recombinant Mammalian Cell Line Phenotypes in the Bioreactor at the 96-Deep Well Plate Scale during Cell Line Development Using Intact MALDI-ToF Mass Spectrometry and PLS-DA Modeling

Mark Smales, Ph.D., Professor, Biotechnology, Biosciences, University of Kent

Here we described the application of an intact cell MALDI-ToF mass spectrometry fingerprinting method coupled with mathematical modeling to the cell line construction process for the prediction and isolation of high producing cell lines. We show how MALDI-ToF mass spectrometry data of cell lines gathered at the 96 deep well plate stage of cell line construction can be used to predict the phenotype of mammalian cell lines at the 10 L fermenter scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. The modeling approach provides the basis for the early prediction of cell line performance in cGMP manufacturing-scale bioreactors. We will discuss the possibility of extending the application to product quality attributes.

12:30 Enjoy Lunch on Your Own

SINGLE-USE, MONITORING QUALITY & PROCESS EXCELLENCE STRATEGIES

14:00 Chairperson’s Remarks
Ravinder Bhatia, MSc, Scientific Director, PDMS/API-LM, Janssen Research & Development

14:05 Case Study: Scale-Up of an Allogeneic Cell Therapy Product Using Single-Use Systems

Ravinder Bhatia, MSc, Scientific Director, PDMS/API-LM, Janssen Research & Development

One of the major challenges with cell therapy products is the development of a robust and scalable process to produce the product for clinical trials and commercialization. Currently, numerous technologies are available for the scale-up of an allogeneic cell therapy product in static (e.g. T-flasks and cell factories) or suspension (e.g. microcarriers, bioreactor type) cultures. In this presentation, a case study will be presented on process development and scale-up of an allogeneic human somatic cell therapy product using single-use technologies.

14:35 Combining Multi-Dimensional Fluorescence Spectroscopy and Chemometric Analysis for Quantitative Bioprocess Monitoring

Alan G. Ryder, Ph.D., Senior Lecturer, Nanoscale Biophotonics Laboratory, School of Chemistry, National University of Ireland, Galway

Multi-dimensional fluorescence spectroscopy (MDFS) was used for quantitative predictive analysis of glycoprotein production and content in CHO cell fed-batch process. MDFS spectra of complex solutions were sensitive to compositional change and as cultivation progressed, amino acid, and glycoprotein product emission varied as the chemical composition changed and culture progress could be monitored quantitatively using a variety of multivariate analysis techniques. In one case, unique dityrosine emission from product glycoprotein could be used to follow product formation. The MDFS variance could also be used to generate quantitative predictive models of process performance based on glycoprotein yield.

15:05 Using Different QbD Tools to Support Scale-Down and Scale-Up of Bioprocesses: Examples from Small and Large Molecules

Jose C. Menezes, Ph.D., Professor, Bioengineering and Biosciences, Technical University of Lisbon

The use of disciplines from the QbD (Quality by Design) tool box will be demonstrated to support science-based bioprocess industrialization and manufacturing (e.g., design-spaces, multivariate end-point and batch trajectory control). Scale-up with PAT tools and/or validated scale-down models for DoE and troubleshooting will be highlighted for small and large molecules. Process performance and product quality will be considered in these approaches.

15:35 Monoliths as PAT Tools for Bioprocess Improvement

Oliver Spadiut, Ph.D., Group Leader, Integrated Bioprocess Development, Biochemical Engineering, Vienna University of Technology

Monolithic columns are a special type of chromatography column which can be used for the purification of different biomolecules. They have become popular due to their high mass transfer properties and short purification times. However, they also describe powerful PAT tools for bioprocess monitoring and development. I will show how monoliths can be used as efficient impurity monitoring tools during bioreactor cultivations but also across unit operations for recombinant protein production processes with yeast.
September 2015 Speaker Interview  

16:05 Hybrid Modeling as a QbD Tool for PAT in Biopharma

Moritz von Stosch, Ph.D., Lecturer, Chemical Engineering and Advanced Materials, Science, Agriculture and Engineering, Newcastle University; CEO, HybPAT Technologies

Process understanding is at the heart of the PAT initiative and QbD paradigm. The integration of Risk Analysis, Design of Experiments and Multivariate Data Analysis (MVDA) is the predominantly applied approach in biopharma to understand processes, nowadays. In this talk, it will be shown that the integration of fundamental process knowledge along with MVDA into hybrid models has the potential to improve the prediction performance, reduce the experimental effort and support the knowledge exchange between scales.

16:35 End of Conference

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

: Unpublished Data | : Case Study

Conference Programs

• Display of Biologics
• Engineering Antibodies
• Machine Learning - Part 2

• Antibody-Based Therapies
• Emerging Targets & Approaches
• Membrane Protein Targets

• Safety & Efficacy
• Advancing Bispecifics
• Engineering Bispecifics

• Modulating the TME
• Innovative CAR T Therapy
• Next-Gen Immunotherapies

• Optimisation & Developability
• Analytical Characterisation
• Protein Stability & Formulation

• Data Science & Engineering
• Optimising Expression
• Process Development

• Intro to Machine Learning
• Machine Learning - Part 1
• Machine Learning - Part 2

• Antibody-based Therapies
• Engineering Conjugates
• Next-Gen Immunotherapies