Cambridge Healthtech Institute’s 6th Annual
Bioproduction: Scale, Bioreactors & Disposables
Making It Work
Part of CHI's 8th Annual The Bioprocessing Summit
August 17-18, 2016 | Westin Boston Waterfront | Boston, Massachusetts

This 6th annual “Bioproduction” conference will examine the elements of producing biologics, including creating scale-down models, scaling up production, engineering bioreactors, single-use systems, and ensuring quality within the context of increasing productivity. A holistic examination of bioprocessing will be explored, as well as practical details such as monitoring and analyzing processes, and looking in depth into how bioreactors process cells. The meeting will again feature a session exploring the design and use of scale-down models, as well as a session addressing the challenges of scaling up production.

Final Agenda

Wednesday, August 17

7:00 am Registration Opens and Morning Coffee

8:05 Chairperson’s Opening Remarks

Stefan Junne, Ph.D., Group Leader and Chair, Bioprocess Engineering, Biotechnology, Technische Universität Berlin

8:15 KEYNOTE PRESENTATION:
Innovation in Bioprocessing and Manufacturing Facility Design – Current Trends

Berthold_Boedeker Berthold Bödeker, Ph.D., Chief Scientist, Global Drug Discovery - Global Biologics, Biotech Development, Bayer AG

Disposables, closed system operation, and continuous processing, as well as less segregated simplified plant design, have made significant advances in the past years. This talk will summarize several aspects of these innovative elements on modern bioprocessing and plant design as well as some risks associated with these technologies particularly in the area of continuous processing and ball room concept plant design.

9:00 FEATURED PRESENTATION:
Developing and Adapting Manufacturing Processes for More Complex Products

Lada_Laenen-Horvat Lada Laenen-Horvat, Ph.D., Senior Director & Head, Allston Manufacturing Science & Technology, Genzyme Corp., A Sanofi Company

9:30 Multivariate Data Analysis for Glycoprotein Manufacturing Process Improvement: A Case Study of Raw Material Control Impact on Process Performance and Product Quality

Siguang_Sui Siguang Sui, Ph.D., Development Scientist II, Late Stage Upstream Development, Alexion Pharmaceuticals, Inc.

A glycoprotein manufacturing process exhibited out-of-trend lower sialylation in the bulk drug substance. Multivariate statistical analysis revealed sialylation was correlated to many process parameters and attributes, among which the daily viabilities from N-1 and production bioreactor, though only differed by a few percent, had the strongest correlation observed. Small-scale experiments were conducted to evaluate the correlation of Pluronic lot on the process performance and product quality.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Single-Use Versus Stainless Steel Bioreactors: Quality Factors for Consideration when Selecting a Suitable System

Trevor_Deeks Trevor Deeks, Ph.D., QA and QC Consultant, Teva Biopharmaceuticals USA, Inc.

The relative merits of single-use as compared to stainless steel bioreactors has been widely covered in the literature and in conference presentations. Relative cost, convenience and capabilities have been the main areas for discussion, but there has been relatively little debate about Quality considerations. Quality considerations are not often part of the decision-making process to determine the type of system to select. This presentation discusses these Quality factors and the relevance to the process, and how these factors might influence the decision to use single-use or stainless steel systems.

11:15 The Decision Process for the Utilization of Disposables in Bioprocessing

Stefan_Schmidt Stefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnology

The competition between stainless steel and single-use equipment has increased over the last decade. We have systematically assessed the rationale when it makes sense to implement disposable equipment and where a conventional approach is favorable. Here we discuss the main decision points regarding cost, scale and safety and illustrate our reasoning by a number of case studies and examples.

11:45 Expansion of Human Stem Cells in BioBLU® Single-Use Vessels from Eppendorf

Willard_Stacey Stacey Willard, Ph.D., Senior Technical Applications Specialist, Bioprocess, Eppendorf

Experimentation involving human stem cells (HSCs) is one of the fastest growing fields in research and development due, in large part, to its potential for revolutionizing human disease treatment. There are multiple HSC platforms being investigated, including human mesenchymal stem cells (hMSCs) and human induced pluripotent stem cells (hiPSCs).

12:15 Luncheon Presentation: Optimize Continuous Processing with Smarter Tools

Paldus_Barbara Barbara Paldus, Ph.D., CEO, Finesse Solutions

The current biopharma development and manufacturing models create challenges for the enterprise to meet their goals for high success rates, lower cost and faster time to market. With the paradigm shifting from titer to process optimization and analytics, the biopharma business model can be improved using continuous processing to manage complexity. Smart technology exists today which can increase flexibility, decrease cost, and improve production.

1:00 Session Break

1:45 Chairperson’s Remarks

Trevor Deeks, Ph.D., QA and QC Consultant, Teva Biopharmaceuticals USA, Inc.

1:50 Bioreactor Concepts and Soft Sensor Tools for Scale-Up and Down

Stefan_Junne Stefan Junne, Ph.D., Group Leader and Chair, Bioprocess Engineering, Biotechnology, Technische Universität Berlin

For scale-down experiments, several designs of multi- and single-use bioreactors are applied. Scalability is of basic importance to mimic industrial scale conditions properly. Aside from stirred reactors, rocking and orbitally shaken single-use bioreactors exhibit a very good scalability. Application of process analytical technologies support the identification of suitable scale down conditions: whenever lack of knowledge restrict a classical engineering approach, physiological and morphological features of cells should be considered.

2:20 Scaling-Down Local Mixing Effects for Biotechnology Applications

Marcio_Machado Marcio B. Machado, Ph.D., Research Associate, Chemical and Materials Engineering, University of Alberta

One of the most critical steps for a process scale-down or scale-up is to have a fully turbulent flow regime in the bench scale mixing vessel. We compare scale-down methods for the conventional stirred tank, the confined impeller stirred tank (CIST), and shaker flasks. These results have implications both for scale-up and for many industrial applications. Consideration of meso-mixing effects and local concentration and turbulence effects are important considerations.

2:50 Establishing a Single-Use Benchtop Bioreator Model to Support Flexible Manufacturing Strategies

Seth_Kitchener Seth Kitchener, Associate Director, Upstream Process Development, ImmunoGen, Inc.

Representative bioreactor scale-down models are essential for successful development, transfer, and scale up of cell culture processes. These needs are coupled with increasing demand for speed and flexibility as programs and manufacturing strategies evolve. This case study will describe the implementation of a new single-use benchtop bioreactor scale-down model to support late-phase process characterization studies and future, flexible manufacturing strategies. Collaboration with CMO and comparability of process performance and product quality relative to existing models is discussed.

3:20 Development and Process Verification of Novel Scale-Down Tools for Periplasmic Fab Extraction

Asma_Ahmad Asma Ahmad, Eng.D., Researcher, Biochemical Engineering, University College London

A 20ml miniature vessel was designed and used as a scale-down model to successfully mimic the periplasmic Fab extraction process 10,000 fold from the 200L scale, using constant power per unit volume (P/V). The process has been scaled down a further 10 fold into disposable 24 micro-well plates and recent data comparing 20L and 2L extractions to 2ml is promising and indicates feasibility of using plates to increase throughput.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing

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

Stefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnology

8:30 Expression Tuning for Enhanced Recombinant Protein Production in E.coli

David_Wurm David J. Wurm, Project Assistant, Biochemical Engineering, Vienna University of Technology

Strong induction of recombinant protein production in E. coli can lead to agglomeration of inactive product. We developed a feeding strategy to tune recombinant protein expression on a cellular level which leads to higher yields of soluble and active product. We successfully applied this system to the production of 1) GFP, 2) a pharmaceutically highly relevant enzyme and 3) an antibody fragment.

9:00 Increasing Protein Production with Novel Cell Ess Supplement

Adam_Elhofy Adam Elhofy, Ph.D., CSO, Essential Pharmaceuticals

Enhancing protein production is a common goal in the biomanufacturing industry. At a concentration of 1% Cell Ess supplement resulted in a 37% increase in productivity. When using the supplement as a feed it resulted in in a 25% increase in yield and an extension of peak protein production. Functional protein increase and desired glycosylation achieved. Our results suggest that an increase in protein production may not necessarily require a change in the metabolic state of the cells.

Munholand_Luke 9:30 Using Simulation to Boost Bioreactor and Process Equipment's Productivity

Luke Munholand, Ph.D., Lead Engineer, ANSYS, Inc.

Living entities play a central role in bioreactors. A subtle balance of operating conditions is necessary to ensure an optimum productivity rate. Engineering simulation can offer insight into chemical reactions, mixing, and multiphase flows commonly found in bioreactors and other process equipment. ANSYS simulation tools enable designers and the operators to boost the process line productivity.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Overcoming the Quality Challenges in Transferring a CHO Fed-Batch Process for Large-Scale Manufacturing

Yun_Jiang Yun Jiang, Ph.D., Principal Scientist, Project Team Leader Upstream, Drug Design & Development, Swedish Orphan Biovitrum AB

A CHO fed-batch process has been transferred to two CMO facilities. The comparability study showed that drug substance produced at the two manufacturing sites had different patterns in the second product main peak in the RP-HPLC chromatography. It was found that the difference was due to an increased level of product variants at the second site. A risk assessment of the product variants was performed and a process change was implemented to secure a robust production process over time.

11:15 Harnessing Exosome Biology to Develop the Biotherapeutics of the Future

Kathryn_Golden Kathryn Golden, M.Eng., Associate Director, Upstream Development and Manufacturing, Codiak Biosciences
Codiak Biosciences is currently developing exosomes, natural vesicles that mediate inter-cellular communication, as both a powerful therapeutic modality and an advanced diagnostic system. An introduction to the biology and therapeutic benefits of exosome technology will be discussed. The philosophy and methodology of transforming a traditionally academic production approach into an optimized full-scale manufacturing process will also be outlined, including updating historically nonscalable upstream and downstream methods, improving limited analytical capability, and working with CMOs.