Cambridge Healthtech Institute ’s 2nd Annual

Bioproduction: Scale, Bioreactors & Disposables

Making It Work

20-21 March 2019

 

Cambridge Healthtech Institute’s “Bioproduction” conference reviews the finesse required to manufacture biologics including scale-down models, scaling up production, engineering bioreactors, single-use systems, and ensuring quality, within the context of increasing productivity; while ensuring safety and achieving reduced costs. A holistic review of bioprocessing will be explored, as well as practical details, such as monitoring and analyzing processes, and examining in detail how bioreactors process cells and how to keep those cells happy. The conference will address robust production processes and next-generation technologies, while improving manufacturing platforms and ensuring product quality.

Final Agenda

Wednesday, 20 March

10:00 Registration Open

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

Plenary Session: NEXT-GENERATION PROCESSES AND PRODUCTS

11:15 Chairperson’s Remarks

Manuel Carrondo imageManuel 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 imageStefanos 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

HARNESSING DATA AND MODELING TO IMPROVE BIOPROCESSES

13:40 Chairperson’s Opening Remarks

Ronan O’Kennedy, PhD, Consulting Bioprocess Specialist, ROK Bioconsulting

13:45 KEYNOTE PRESENTATION:
Big Data and Bioengineering: The Perfect Marriage

Arlindo Oliveira, PhD, Professor, Computer Science & Engineering, Instituto Superior Técnico

Modern artificial intelligence techniques, heavily based on machine learning approaches, have created the possibility to analyse large volumes of data in many domains in ways that were inaccessible until now. Modern bioengineering depends heavily, if not totally, on data-based approaches that are able to uncover the knowledge hidden in the large amounts of data generated by genomics, proteomics, metabolomics and other “omics”. This talk will describe some methodologies that can be used to extract knowledge from biological data and to direct bioengineering research.

14:15 Mathematical Modelling Across Reactor Scales

Gernaey_KristKrist Gernaey, PhD, Professor, Head, Process and Systems Engineering Center (PROSYS), Chemical and Biochemical Engineering, Technical University of Denmark

Modelling plays an increasingly important role in bioprocess development. Computational Fluid Dynamics (CFD) is now generally used as a tool for the description of bioreactor hydrodynamics, also at large scale. CFD will be presented as a modelling framework forming the basis for development of compartment and scale-down models. Furthermore, challenges related to model validation and potential solutions are highlighted, and future perspectives related to advanced modelling frameworks are presented.

14:45 Individual-Based Models for Bioprocesses

Rebeca González-Cabaleiro, PhD, Lecturer, Infrastructure & Environment, Engineering, University of Glasgow

Microbial communities are complex. Our lack of knowledge makes our capacity to engineer them limited and biosystems are in many cases unpredictable. This reduces the interest of bio-based industrial processes and therefore the full versatility and potential of these systems remains unexploited. Mathematical models at the micro-scale level are a perfect tool to describe the heterogeneity of microbial communities, explore their capacities and predict their behavior.

15:15 Presentation to be Announced

15:30 Sponsored Presentation (Opportunity Available)

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

MONITORING QUALITY

16:25 Online Monitoring in Microfluidics and Micro(bio)reactors with Integrated Optical Chemical Sensor

Mayr_TorstenTorsten Mayr, PhD, Associate Professor, Analytical Chemistry, Graz University of Technology (TU Graz)

We present the miniaturization and integration of optical chemical sensors for oxygen, pH and glucose in microfluidic and micro-bioreactors. Miniaturized sensor layers and spots in sizes down to 100 micrometers are read out with miniaturized instruments. In addition, luminescent nanobeads are demonstrated as an attractive alternative to integrated sensor layers since they can be easily injected into the flow, do not interfere with the sample, and have fast response times.

16:55 High Resolution Native LC-MS for Product CQA Assessment and Process Monitoring

Bones_JonathanJonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)

 

 

17:25 Risk Management in ICH Q12: Supporting Quality, Compliance & Culture Excellence Over Lifecycle of Biologic Products

Menezes_JoseJosé Monteiro Cardoso de Menezes, PhD, Associate Professor, Pharmaceutical Engineering, Institute for Biotechnology & Bioengineering, Instituto Superior Técnico, University of Lisboa, and CEO, 4Tune Engineering

RM is to KM what PAT is to QbD! Although presently the industry may lack better ways to manage knowledge (KM) through sophisticated tools and platforms, risk-management (RM) tools can provide very effective capabilities to capture, retain, and support knowledge-driven lifecycle activities. There is a recent regulatory expectation (ICH Q12) that companies can retrospectively use key QbD elements (e.g., RM) to address and justify improvements in their current legacy control strategies, supporting post-approval changes using risk- and knowledge-based approaches.

17:55 End of Day

18:00 Dinner Short Course Registration

18:30 - 21:00 Suggested Dinner Short Course*

SC5: Saving Time in Process Development with Next-Generation Methods: iDoE, Hybrid Modeling and PAT

Instructors:

Moritz von Stosch, PhD, Senior Manager, Drug Substance, Technical R&D, GSK Vaccines

Gerald Striedner, PhD, Associate Professor, Biotechnology, University of Natural Resources and Life Sciences (BOKU)

Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences (BOKU)

In this short course, we show how a more accurate design space can be defined that provides increased flexibility for process operation based on the iDoE-hybrid modeling strategy. We also show how advanced monitoring strategies support the tracking of the deviations and how these methods can readily be developed from the iDoE data. It will be illustrated how the combination of the hybrid model with monitoring can directly be exploited for process control, thus naturally evolving the last step of the QbD roadmap.

*Separate registration required.

Thursday, 21 March

8:00 Registration and Morning Coffee

NEXT-GENERATION STRATEGIES

8:25 Chairperson’s Opening Remarks

Jonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)

8:30 FEATURED PRESENTATION:
Next-Generation Processes, Technologies and Operations

Pohlscheidt_MichaelMichael Pohlscheidt, PhD, Site Head & Head of Operations, Solothurn Manufacturing Facility, Biogen

A critical step in meeting the demand of biologic production worldwide involves implementing disruptive manufacturing technologies, processes and capabilities. This talk will evaluate Biogen’s new manufacturing site in Switzerland, due to go online in 2019, including the new processes, operational models and technologies being adopted to drive value through innovation and deliver new medicines in areas such as Alzheimer’s.

9:00 Characterisation and Application of a Miniature Bioreactor System for Cell Culture Process Development

Baganz_FrankFrank Baganz, PhD, Associate Professor, Biochemical Engineering, University College London (UCL)

The need to bring new biopharmaceutical products to market more quickly and to reduce final manufacturing costs is driving early-stage, small-scale bioprocess development. This presentation will cover the engineering characterisation of a single-use 24-well parallel miniature bioreactor (MBR) in terms of power input, liquid phase mixing and oxygen mass transfer. Examples will be given for the application of this MBR to optimize and scale cell culture processes.

9:30 Sponsored Presentation (Opportunity Available)

10:00 Improving the Yields of Complex Monoclonal Antibodies and Fusion Proteins for Cancer Therapy

Peter Blas, PhD, Lecturer, Biochemical Engineering, University College London (UCL)

The bioprocessing of a fusion protein is characterised by low yields, and through recovery and purification, an overall 90% loss. However, there is evidence of the protection of degradation products which occurs in the presence of shear plus air/liquid interfaces. This study seeks to characterise the loss and use of ultra‐scale‐down studies to predict its occurrence; and shows loss may be diminished by the use of protective reagents, such as Pluronic F68.

10:30 Coffee Break in the Exhibit Hall. Last chance for poster viewing.

SINGLE-USE SYSTEMS

11:15 Scaling Up and Down of Single-Use Bioreactor Cultivations

Junne__StefanStefan Junne, PhD, Group Leader & Chair, Bioprocess Engineering, Technische Universität Berlin

Process scalability has been an issue for over 50 years in the area of stainless steel bioreactors. Methods for the characterization of industrial-scale bioreactors and scale-down systems have been established; however, this subject gained new relevance by the various designs of single-use bioreactors. Therefore, the current state of scaling up and down single-use bioprocesses are presented and discussed based on examples from typical cell culture to niche applications, which offer new possibilities for single-use based bioprocessing.

11:45 A DOE Approach to Oxygen Transfer Modelling in Single-Use Bioreactors

Ronan_O_KennedyRonan O’Kennedy, PhD, Consulting Bioprocess Specialist, ROK Bioconsulting

A DOE approach was used to characterize the effects of total gas flow-rate, % inlet O2 conc, agitation, and % fill volume on KLa in three single use bioreactor scales commonly used for process development and scale up. The relative effects of operating parameters and interactions at each scale were evaluated. We show that the combined model can be used to make accurate predictions of KLa across the 2 – 200 L bioreactor range, thereby simplifying the scale up of the upstream processes.

12:15 De-Intensifying Protein Production with Pichia pastoris

Mattanovich_DiethardDiethard Mattanovich, PhD, Professor, Microbial Strain Design, Biotechnology, University of Natural Resources and Life Sciences (BOKU)

The major benefit of Pichia pastoris, i.e., high expression levels on methanol, driven by methanol inducible promoters, is also the source of a major drawback: methanol utilization leads to high oxygen consumption and metabolic off-heat. Here, we present a strategy to produce protein in a strain deleted in the alcohol oxidase genes, which reduces maximum oxygen transfer rates to 11% and maximum heat production to 16%. This strategy can save installation and operation costs, and make P. pastoris amenable for single-use bioreactors.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Session Break

PROCESS IMPROVEMENTS

13:45 Chairperson’s Remarks

Stefan Junne, PhD, Group Leader & Chair, Bioprocess Engineering, Technische Universität Berlin

13:50 Bioprocess Engineering of Insect Cells for Enhanced Gag-VLPs Production

Roldao_AntonioAntónio Roldão, PhD, Senior Scientist, Health & Pharma Division, Animal Cell Technology Unit, Cell-Based Vaccines Development Lab, iBET - Instituto de Biologia Experimental e Tecnológica

In this work, the production of Gag-VLPs was achieved and further optimized by (i) generating stable insect cell lines using site-specific gene integration based on flipase-mediated cassette exchange technology, and (ii) adaptive laboratory evolution of insect cells to hypothermic culture conditions and supplementation with productivity enhancers. Overall, the insect cell platform and bioprocess engineering strategy herein assembled has the potential to assist and accelerate vaccine development.

14:20 Bioprocessing of Cell Culture Derived Vaccines in Bioreactors

Leeann Naicker, PhD, Researcher, Research and Development, OBP Vaccines

Currently, we are evaluating various Bioreactors for the production of vaccines. These processes will be adopted into our GMP facility. Various parameters are being assessed, including pH, glucose consumption, online monitoring, dissolved oxygen, cell production, virus production, scaling up, and effects of shear stress. Bioreactors such as the Tide cell, Bello cell, Icellis, Biostat stirrer tanks have been evaluated, and currently the Biostat Cultibag is being evaluated for cell and vaccine production.

14:50 A Scalable Cost-Effective Alternative to ATF Filters for N-1 Perfusion: Wavebags with Lillypad

Ruchika Bandekar, MSc, Associate Scientist II, Cell Culture and Fermentation Sciences, MedImmune LLC

Implementation of perfusion at seed stage has increased output by 30% by boosting productivity and decreasing the duration, with no impact on product quality. This has the potential to be considered at-scale as the seed phase is usually shorter, so the media requirements will not be very demanding compared to production reactors, and there will be no downstream processing required. The evaluation was successfully performed on two different CHO cell lines expressing monoclonal antibodies.

15:20 Close of Conference