Informa Life Sciences is part of the Knowledge and Networking Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 3099067.

Informa
Key Sessions

Thomas Leitch

Adapting biomanufacturing strategies and technologies for next generation therapies

bluebird bio

Oct 10
Show Filter
Showing of Streams
10:30 - 11:10

Morning Coffee

More
Showing of Streams
12:55 - 13:10

Lunch

More
13:10 - 14:00

Poster Tour

More
Showing of Streams
15:30 - 16:00

Afternoon Coffee

More
Showing of Streams
17:30 - 17:35
End of BioProduction 2018

End of BioProduction 2018

More
08:50 - 09:00 10 mins
Cell Culture & Upstream Process Development
Chairperson's Opening Remarks
  • Ron Bates - Director, Bristol-Myers Squibb
08:50 - 09:00 10 mins
Downstream Processing
Chairperson's Opening Remarks
  • Ron Bates - Director, Bristol-Myers Squibb
08:50 - 09:00 10 mins
Manufacturing Strategy & Technology
Chairperson's Opening Remarks
  • Ron Bates - Director, Bristol-Myers Squibb
08:50 - 09:00 10 mins
Smart Factories
Chairperson's Opening Remarks
  • Ron Bates - Director, Bristol-Myers Squibb
08:50 - 09:00 10 mins
Microbial Manufacturing
Chairperson's Opening Remarks
  • Ron Bates - Director, Bristol-Myers Squibb
08:50 - 09:00 10 mins
Bioanalytical Congress
Chairperson's Opening Remarks
  • Patrick Sheehy - Scientific Director, Janssen
09:00 - 09:30 30 mins
Cell Culture & Upstream Process Development
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Thomas Leitch - Vice President, Vector Manufacturing, bluebird bio
09:00 - 09:30 30 mins
Downstream Processing
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Thomas Leitch - Vice President, Vector Manufacturing, bluebird bio
09:00 - 09:30 30 mins
Manufacturing Strategy & Technology
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Thomas Leitch - Vice President, Vector Manufacturing, bluebird bio
09:00 - 09:30 30 mins
Smart Factories
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Thomas Leitch - Vice President, Vector Manufacturing, bluebird bio
09:00 - 09:30 30 mins
Microbial Manufacturing
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Thomas Leitch - Vice President, Vector Manufacturing, bluebird bio
09:00 - 09:30 30 mins
Bioanalytical Congress
Bispecific antibodies – key process and analytical challenges
  • Patrick Sheehy - Scientific Director, Janssen
09:30 - 10:00 30 mins
Info
Cell Culture & Upstream Process Development
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Aad Van De Leur - COO, Synthon Biopharmaceuticals BV

With the introduction of new innovative high potent biopharmaceuticals like Antibody Drug Conjugates (ADCs) the industry had to adapt and move to complete different strategies to produce these products. Next to the standard cGMP requirements additional safety aspects need to be taken into account. In addition, the volumes of these products would be limited resulting in smaller facilities and options to utilize single use materials but also the need to adapt certain equipment. In this talk I will present how Synthon Biopharmaceuticals approached these challenges resulting in in-house manufacturing capabilities.

09:30 - 10:00 30 mins
Info
Downstream Processing
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Aad Van De Leur - COO, Synthon Biopharmaceuticals BV

With the introduction of new innovative high potent biopharmaceuticals like Antibody Drug Conjugates (ADCs) the industry had to adapt and move to complete different strategies to produce these products. Next to the standard cGMP requirements additional safety aspects need to be taken into account. In addition, the volumes of these products would be limited resulting in smaller facilities and options to utilize single use materials but also the need to adapt certain equipment. In this talk I will present how Synthon Biopharmaceuticals approached these challenges resulting in in-house manufacturing capabilities.

09:30 - 10:00 30 mins
Info
Manufacturing Strategy & Technology
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Aad Van De Leur - COO, Synthon Biopharmaceuticals BV

With the introduction of new innovative high potent biopharmaceuticals like Antibody Drug Conjugates (ADCs) the industry had to adapt and move to complete different strategies to produce these products. Next to the standard cGMP requirements additional safety aspects need to be taken into account. In addition, the volumes of these products would be limited resulting in smaller facilities and options to utilize single use materials but also the need to adapt certain equipment. In this talk I will present how Synthon Biopharmaceuticals approached these challenges resulting in in-house manufacturing capabilities.

09:30 - 10:00 30 mins
Info
Smart Factories
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Aad Van De Leur - COO, Synthon Biopharmaceuticals BV

With the introduction of new innovative high potent biopharmaceuticals like Antibody Drug Conjugates (ADCs) the industry had to adapt and move to complete different strategies to produce these products. Next to the standard cGMP requirements additional safety aspects need to be taken into account. In addition, the volumes of these products would be limited resulting in smaller facilities and options to utilize single use materials but also the need to adapt certain equipment. In this talk I will present how Synthon Biopharmaceuticals approached these challenges resulting in in-house manufacturing capabilities.

09:30 - 10:00 30 mins
Info
Microbial Manufacturing
Adapting biomanufacturing strategies and technologies for next generation therapies
  • Aad Van De Leur - COO, Synthon Biopharmaceuticals BV

With the introduction of new innovative high potent biopharmaceuticals like Antibody Drug Conjugates (ADCs) the industry had to adapt and move to complete different strategies to produce these products. Next to the standard cGMP requirements additional safety aspects need to be taken into account. In addition, the volumes of these products would be limited resulting in smaller facilities and options to utilize single use materials but also the need to adapt certain equipment. In this talk I will present how Synthon Biopharmaceuticals approached these challenges resulting in in-house manufacturing capabilities.

09:30 - 10:00 30 mins
Info
Bioanalytical Congress
How innovation of drugs shapes modern bioanalysis and potency assessment – The rise of ATMPs and the challenge of appropriate assays
  • Melody Sauerborn - Trainer and Independent Consultant, Scientia Potentia Consultancy

Innovation is a pivotal process in drug development to address unmet medical needs. Advanced therapy medicinal products (ATMPs) are amongst these innovations and the number of ATMPs entering clinical stages has been substantially increasing over the last few years. Bioanalysis and potency assessment has proven to be a challenge, as the mode of action for cellular therapeutics is often not fully characterized. Currently most companies apply a multi-assay approach, often consisting of cellular surface analysis, cytokine release and one form of functional cell-based assay. The challenge arises when these assays need to be validated. While walking you through some case studies, we will address these assay and regulatory challenges and how they can be handled.

10:00 - 10:30 30 mins
Cell Culture & Upstream Process Development
Smart biomanufacturing facilities of the future- A Representative from IDBS
10:00 - 10:30 30 mins
Downstream Processing
Smart biomanufacturing facilities of the future- A Representative from IDBS
10:00 - 10:30 30 mins
Manufacturing Strategy & Technology
Smart biomanufacturing facilities of the future- A Representative from IDBS
10:00 - 10:30 30 mins
Smart Factories
Smart biomanufacturing facilities of the future- A Representative from IDBS
10:00 - 10:30 30 mins
Microbial Manufacturing
Smart biomanufacturing facilities of the future- A Representative from IDBS
10:00 - 10:30 30 mins
Info
Bioanalytical Congress
Accelerating the timeline to GMP through high-throughput bio-analytical tools
  • Bernardo Estupiñán-Gaisbauer - Vice President Business Development, KBI Biopharma, Inc.


  • Accelerated FIH Development requires knowledge of mAbs, bispecifics, fc-fusion proteins, recombinant enzymes, and other glycoproteins, and a good understanding of the analytical tools to drive development from cell line development through manufacturing is critical.
  • KBI will be providing a roadmap to accelerated FIH Development and also an overview of KBI’s vast capabilities to support development and manufacturing of biomolecules.
10:30 - 11:10 40 mins
Morning Coffee
11:10 - 11:40 30 mins
Info
Cell Culture & Upstream Process Development
Process robustness using Quality by Design driven approaches
  • Christoph Herwig - Professor for Bioprocess Engineering, Vienna University of Technology

Cell culture processes seem to be established but still lack of thorough understanding in reaching higher titers and process robustness using process technological means. This contribution show different aspects of Quality by Design driven approaches for

  • identification of the limiting amino acid using PAT and automated modelling approaches
  • model based experimental designs for targeting maximum information content of the experiment for a given objective, such as media titer optimization or lactate uptake
  • scale down model establishment to analyze the effect of large scale in homogeneities.

 We want to provide a methodological toolset which should be used as a development for established but also novel products.

11:10 - 11:40 30 mins
Info
Downstream Processing
Late stage development and control strategy for monoclonals
  • Bas Kokke - Principal Scientist, Synthon

The control strategy is in the biopharmaceutical industry an integral part of the QbD paradigm used within Upstream and Downstream Processing. In Downstream Processing control can be achieved in multiple ways. At Synthon advanced automation is combined with a disposable materials approach. Selective testing is used to further exercise control. In this presentation two Downstream Processing examples will be given, describing control strategies for both monoclonal antibody and antibody drug conjugates, which both have their specific demands.

11:10 - 11:40 30 mins
Info
Manufacturing Strategy & Technology
Thought Leaders Discussion: Steps towards standardisation and interchangeability to ensure single use systems supply chain security
  • Ron Bates - Director, Bristol-Myers Squibb
  • Thomas Hilfer - Senior Scientist, Biologics Engineering, MSD, USA
  • Steps towards the standardisation of single use technologies e.g. standardised geometrics and connectors
  • Interchangeability and improving connectivity of single use systems
  • Ensuring supply chain security for critical equipment and single use components in commercial manufacturing
  • How to improve company internal organisation to ensue supply chain security
  • Interactions between vendors and pharma companies
  • Addressing the future challenges and equipment demands in the industry today
11:10 - 11:40 30 mins
Info
Smart Factories
Hybrid modelling: Beyond purely data driven approaches for efficient knowledge management in industry 4.0
  • Moritz von Stosch - Senior Manager Fermentation, GlaxoSmithKline

At the moment, the (bio)pharmaceutical industry is adopting high-throughput technologies to investigate process conditions, recording the data in dedicated data-bases. Artificial Intelligence (AI), data science and big data approaches are being promoted to exploit the data and describe the complex systems. While for some cases this might proof possible, even with high-throughput experimentation it will be infeasible to study the impact of the combinations of all possible changes in the process and/or organisms experimentally (referred to as the curse of dimensionality), wherefore the application of the data-driven approaches is overall only of limited use. To overcome this problem knowledge from first-principles, biology, physics, which is freely available and generally valid, can be integrated along with data-driven approaches, reducing the complexity of the modeling problem at hand. The application of such an approach, referred to as hybrid modeling, to a controlled drug release case is presented and the learnings from the development of this model are shared.

11:10 - 11:40 30 mins
Info
Microbial Manufacturing
Continuous harvesting of secreted products from high cell density perfusion bioreactor of Pichia Pastoris
  • Dhinakar Kompala - Founder & CEO, Sudhin Biopharma Company

We have developed a novel harvesting device, BioSettler, to settle the microbial yeast cells from the harvest stream and return the settled cells to high cell density perfusion bioreactor. We demonstrate this continuous harvesting application for BioSettler on a 1.5 liter high cell density perfusion bioreactor of yeast Pichia pastoris cells, overexpressing and secreting a natural sweetener protein Brazzein.

11:10 - 11:40 30 mins
Bioanalytical Congress
Analytical assay development for CAR T cell characterization
  • Eric Alonzo - Scientist, Cellular Analytics, Bluebird Bio
11:40 - 12:10 30 mins
Info
Cell Culture & Upstream Process Development
On-line and Off-line monitoring of CHO cell health in a bioreactor to allow for early identification of cell death
  • Adam Bergin - PhD Student, NIBRT

Monitoring and maintenance of cell health in a bioprocess is crucial with regards to both the productivity of the cells and to the overall quality of the final product.

Traditional approaches involve sampling and off-line testing of cell viability using dye exclusion at fixed points throughout the process. By utilising the novel methods of on-line digital holography and impedance flow cytometry we can provide a more complete picture of cell health during a bioreactor run, allowing for informed intervention at potential critical points in the process.   Such methods compare well with off-line methods of conventional flow cytometry and dye exclusion.

These methods not only provide a more in depth look at the stage of cell death but also analyse the population on a single cell basis thus providing an insight into the cell population dynamics, which might otherwise be masked in the bulk population.  Such methods can lead to potentially greater yields of the desired product.  

11:40 - 12:10 30 mins
Info
Downstream Processing
Online Monitoring of product quantity, purity and potency during chromatographic purification
  • Dominik Sauer - PhD Student, University of Natural Resources and Life Sciences, Vienna

Currently, regulatory agencies encourage pharmaceutical industry to implement QbD approaches into manufacturing processes. We integrated additional online sensors for monitoring of loading and elution during into a conventional chromatography workstation. By mathematical correlation of offline data on quantity, purity and potency to the obtained online data predictive models have been established. These generated models enable controlled loading and peak cutting based on defined quality settings. Time and labour intense offline analytics are only needed for the model set-up not during the process. Batch to batch variations are detected in real time and batch failure can be reduced by real time process control.

11:40 - 12:10 30 mins
Info
Manufacturing Strategy & Technology
Data driven approaches for performance optimisation of commercial DS manufacturing
  • Francisca Gouveia - Senior Process Expert, Novartis

In this presentation, we demonstrate how scientific and data-driven approaches were used to improve process performance and consistency of a commercial mAb within established/registered manufacturing process ranges. For the cell culture process, a multivariate data investigation identified an interaction effect between two manually-driven parameters contributing to variability in USP titre and quality attributes For protein purification, value stream/process flow mapping identified numerous opportunities to reduce wastes (non-processed material) at various unit operations. Realisation of these opportunities was approached in a non-regulatory impactful way (working within existing ranges) to reduce post-approval change management to a minimum.

The combined effect of these changes has resulted in an increase in 10% final DS quantity at minimal additional manufacturing cost and disruption (to implement the changes) to manufacturing operations. The key role of creating and maintaining good process databases and the application of appropriate analytics tools as key enablers for process changes (and the need for further investment here) will be discussed

11:40 - 12:10 30 mins
Info
Smart Factories
Data driven approaches for performance optimisation of commercial DS manufacturing
  • Francisca Gouveia - Senior Process Expert, Novartis

In this presentation, we demonstrate how scientific and data-driven approaches were used to improve process performance and consistency of a commercial mAb within established/registered manufacturing process ranges. For the cell culture process, a multivariate data investigation identified an interaction effect between two manually-driven parameters contributing to variability in USP titre and quality attributes For protein purification, value stream/process flow mapping identified numerous opportunities to reduce wastes (non-processed material) at various unit operations. Realisation of these opportunities was approached in a non-regulatory impactful way (working within existing ranges) to reduce post-approval change management to a minimum.

The combined effect of these changes has resulted in an increase in 10% final DS quantity at minimal additional manufacturing cost and disruption (to implement the changes) to manufacturing operations. The key role of creating and maintaining good process databases and the application of appropriate analytics tools as key enablers for process changes (and the need for further investment here) will be discussed

11:40 - 12:10 30 mins
Info
Microbial Manufacturing
Application of Computational Fluid Dynamics: Increasing scale-up insight and directing optimisation of equipment
  • Christian Sam - Process Science, Boehringer Ingelheim RCV GmbH & Co KG

The demand for complex therapeutic proteins, plasmids and antibodies for treatment of various diseases has increased continuously in the last decades, prompting the continuous development of new production processes. These complex molecules can only be produced via cell cultivation of under controlled parameters in a reactor. These fermentation processes are performed in small scale during development and early clinical phases (e.g. 5 - 200 L). Only in later clinical phases and during market supply the full production scale is utilized (e.g. 4000L). These processes are also transferred between sites in order to cope with additional market demand. So all production processes undergo scale-up and transfer steps that have the potential to significantly impact quality parameters or business performance. In microbial fermentation the main transfer and scaling parameters are volumetric, however there are some significant differences if equipment is scaled up only volumetrically. The experience of the many successfully performed process scale-ups and transfers shows that procedures are well understood. Still the additional usage of computational fluid dynamics (CFD) is advisable, and it can assist in risk mitigation upfront and reduce time during root cause analysis. Calculating the reactor specific energy demand of our equipment, looking at shear rates and turbulence parameters, can identify anomalies or local extremes that can be addressed. This makes CFD a powerful tool in optimizing geometries as well as in finding suitable operating conditions in pharmaceutical production processes. In this case CFD simulations with ANSYS Fluent were generated for a 20L Pilot-scale fermenter in the development area and a 4000L Large Scale Manufacturing fermenter. Both simulations were verified via mixing times in situ, and subsequently several output parameters were compared. Differences can be identified, that have a potential to impact the production process. With the aim to continuously reduce the gap between development and production scale, several equipment setups were designed. CFD with ANSYS Fluent was used to evaluate agitator set ups in terms of physical and functional properties. Interestingly, no solution approximates to the production scale in all studied aspects. Based on a wide experience of process scale-up, the parameters were ranked according to the relevance for process performance and we propose a path forward toward a more robust scale up.

11:40 - 12:10 30 mins
Info
Bioanalytical Congress
Immunogenicity - and what about the targets?
  • Clara Albani - Research Associate, Covagen

A short introduction about T-cell independent ADA response and multimeric targets (TNFα and IL-17) followed by a case study based on COVA322, a dual TNFα and IL-17A inhibitor that went into a FIH SAD Psoriasis Study stopped due to the observed safety profile

12:10 - 12:40 30 mins
Info
Cell Culture & Upstream Process Development
Multi-Product, Multi-Platform, Multi-Scale: Why Settle for Less?
  • Eric Rudolph - Vice President, Single-Use Custom Single Run (CSR®), ABEC

Standard equipment designs with limited flexibility for process, operational and facility needs… and suppliers who are unwilling to be flexible? Flexible design and configurable solutions can meet process requirements, increase capital productivity and reduce cost. Learn how innovative design concepts, new technologies and unique agile, flexible, efficient and effective solutions will generate bigger volumes, in less space, improving cost of goods sold and return on investment.

12:10 - 12:25 15 mins
Info
Downstream Processing
FlowVPE: Accurate inline concentration measurements for downstream processes
  • Ramsey Shanbaky - Sr. Product Engineer, C Technologies, inc.

Utilizing proven variable path length spectroscopy, the FlowVPE can speed development and increase efficiencies and quality by reading concentration inline during downstream processes. This presentation will go through various applications of the device including protein A capture, HMW detection during CEX/IEX, SPTFF and UF/DF.

12:10 - 12:40 30 mins
Info
Manufacturing Strategy & Technology
Managing raw materials and auxiliary components supply with in-time delivery and release to enable continuous manufacturing
  • Nandu Deorkar - VicePresident R&D Biopharma, Avantor

Various market drivers such as increase range of therapeutic molecules beyond monoclonal antibodies, personalized medicine, making therapy options available to broader affected population and improving patient outcome while managing cost to patients, forcing biopharmaceutical industry to look beyond traditional discovery to development to manufacturing options.  The manufacturing process innovation that lead to increase in flexibility while  decreasing overall drug product cost can help meeting some of the market challenges. A lot of progress has been made to improve upstream to downstream unit operations. However, many challenges need to overcome to implement well-functioning fully integrated continuous manufacturing. Typical biologic manufacturing consumes hundreds of raw materials including media, supplements, process chemicals, filters, resins, and excipients.  Managing of flow of these components and releasing them on a timely basis is a daunting task without either increasing inventory levels or implementing non-traditional approach to receive release and use these materials while meeting all quality requirements. In this presentation we will present available technologies and discuss various options with risk and benefit analysis to overcome some of these challenges.

12:10 - 12:40 30 mins
Info
Smart Factories
Enhanced control of glucose concentration in high-yielding mammalian cell cultures through development of novel soft-sensor.
  • Stephen Goldrick - Post-doctoral Researcher, University College London

This study outlines the development of a novel control strategy for glucose concentration utilising readily available process measurements. The method generates a correlation between the cumulative oxygen transfer rate and the cumulative glucose consumed. The proposed method is highly robust and flexible and was verified at multiple scales and across multiple cell lines with significantly varied glucose uptake rates. Authors: Stephen Goldrick, Kenneth Lee, Christopher Spencer, Richard Turner, and Suzanne S. Farid

12:10 - 12:40 30 mins
Info
Microbial Manufacturing
New online biomass monitoring in ambr® high throughput bioreactors for microbial applications
  • Alison Rees-Manley - ambr 15 Product Manager, Sartorius Stedim Biotech

ambr® 15 fermentation and ambr® 250 (modular and high throughput) systems offer an alternative approach for microbial cultivation to plates, shake flasks and conventional benchtop fermenters in an automated, multi-parallel, high throughput format.  These systems are implemented within the upstream workflow as a screening platform, for generating process development data and as scale-down models of larger pilot / production fermenters.  At the small scale they can be run parallel with very low demands on operator time, set-up and turn-around time due to automation and single-use components.  Optical density monitoring however has previously been possible only with offline analysis requiring manual operations and removal of sample from the bioreactors.  Through the integration of online biomass measurement capability it is now possible to continuously monitor and control process events based on real-time cell biomass data.  Furthermore these operations are completely automated and translatable up to the larger scale.  Online measurement is achieved using a multiplexed optical scattering method which, coupled with high-frequency signal processing, provides high dynamic range monitoring with high robustness to culture conditions, without the need for an invasive probe. Comparisons of online data with conventional OD600 absorbance measurements have demonstrated high accuracy of measurement for E. coli, S. cerevisiae and P. pastoris for a range of culture conditions.

12:10 - 12:40 30 mins
Info
Bioanalytical Congress
A Smart Microfluidic Technology for Early Discovery and Analytics
  • Anubhav Tripathi, Ph.D., - Professor, Bioengineering and Medical Science, Brown University, USA

Protein purity analysis by microfluidic separation offers distinct advantages over traditional capillary electrophoresis in sample consumption, ease of use, and speed of analysis. Using a smart microfluidic platform for high throughput quantitation and quality screening of proteins. The method utilizes a microchip which utilizes real-time electro-hydrodynamic optimization to eliminate variability in reported results, i.e. run-to-run and day-to-day variability, which may be caused by micro-scale fluctuations in the physical properties of chips, reagents, or instrument components.

12:25 - 12:55 30 mins
Info
Downstream Processing
What are the main features required for a virus filter in a continuous process?
  • Mathithas Kandasamy - Product Manager and Cellufine Specialist, Asahi Kasei Bioprocess

Today Biopharmaceutical industry is actively exploring possible ways to move from batch to continuous manufacturing process. Virus filtration is one of the vital steps into a fully integrated continuous downstream process which needs to be explored further. Three main conditions are present in a continuous nanofiltration step: a constant flow-rate operation, fluctuating feed solution characteristics (concentration, pH, conductivity) and it can be run for long times. These conditions require several important features for the nanofilter, such as a good resistance to fouling, a robust virus removal, an excellent scalability, etc...

This presentation will address these features through concreate case studies and technical data.

12:55 - 13:10 15 mins
Lunch
13:10 - 14:00 50 mins
Poster Tour
14:00 - 14:30 30 mins
Info
Cell Culture & Upstream Process Development
Innovative Dynamic Control of Upstream Processes using Soft sensors and Predictive Metabolic Modeling Approaches
  • Dr Wolfgang Paul, Ph.D. - Senior Scientist, Group leader Cell Culture Research, Large Molecule Research, Roche Diagnostics GmbH

Therapeutic proteins development becomes more challenging due to the complexity of the diverse molecule formats. In-depth characterization of high producer cell lines and bioprocesses is essential to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. Controlling the environmental stress present during the cultivation of cells is a key for the successful production of an intended bio-therapeutic protein. Process development and in particular the use of high throughput systems required sampling for controlling. One of the most important parameter is the cell growth, but sampling, sample dilution and analyzing is time consuming and generates high efforts in the case of high throughput fermentation systems. Sampling allows also only a look in the culture status at a certain time point, the information between two sample points is missing. Therefore we develop a new soft sensor, which takes online signals of the bioreactor, which are correlated to cell growth to estimate the cell growth. 

The new approach based on multiple linear regression and on artificial neural network processed the common online signals of the bioreactors to estimate the cell growth as online signal during cultivation time. The captured data is applied in a metabolic network model for the analysis of intracellular metabolic fluxes of Roche’s working horse of therapeutic protein production - the Chinese Hamster Ovary cell. The generated metabolic information and prediction has the potential to set a new standard for efficient and innovative process development and process control bridging from research to market. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic traits characteristic of high-performance clones and empowers the scientists to develop efficient processes. New approach in metabolic/process modeling/controlling and results will be presented.

14:00 - 14:30 30 mins
Info
Downstream Processing
Productivity opportunities in downstream commercial processes
  • Albin Simoni - Senior Process Engineer Global MSAT, Roche

Two case studies will be presented to show productivity opportunities undergone at Roche to standardize processes and reduce waste. Improvement of the endotoxin control process validation strategy and global alignment on vent filter integrity testing. Both projects were implemented to the Drug Substance manufacturing network, reducing resources and costs.


14:00 - 14:30 30 mins
Manufacturing Strategy & Technology
Regulatory Feedback: GMP inspections
  • Dearbhla Cullen - Inspector, Health Products Regulatory Authority (HPRA)
14:00 - 14:30 30 mins
Info
Smart Factories
Innovative Dynamic Control of Upstream Processes using Soft sensors and Predictive Metabolic Modeling Approaches
  • Dr Wolfgang Paul, Ph.D. - Senior Scientist, Group leader Cell Culture Research, Large Molecule Research, Roche Diagnostics GmbH

Therapeutic proteins development becomes more challenging due to the complexity of the diverse molecule formats. In-depth characterization of high producer cell lines and bioprocesses is essential to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. Controlling the environmental stress present during the cultivation of cells is a key for the successful production of an intended bio-therapeutic protein. Process development and in particular the use of high throughput systems required sampling for controlling. One of the most important parameter is the cell growth, but sampling, sample dilution and analyzing is time consuming and generates high efforts in the case of high throughput fermentation systems. Sampling allows also only a look in the culture status at a certain time point, the information between two sample points is missing. Therefore we develop a new soft sensor, which takes online signals of the bioreactor, which are correlated to cell growth to estimate the cell growth. 

The new approach based on multiple linear regression and on artificial neural network processed the common online signals of the bioreactors to estimate the cell growth as online signal during cultivation time. The captured data is applied in a metabolic network model for the analysis of intracellular metabolic fluxes of Roche’s working horse of therapeutic protein production - the Chinese Hamster Ovary cell. The generated metabolic information and prediction has the potential to set a new standard for efficient and innovative process development and process control bridging from research to market. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic traits characteristic of high-performance clones and empowers the scientists to develop efficient processes. New approach in metabolic/process modeling/controlling and results will be presented.

14:00 - 14:30 30 mins
Info
Microbial Manufacturing
Production of fabs in E. Coli – A comparison of expression systems
  • Oliver Spadiut - Assoc. Prof.; Integrated Bioprocess Development, TU Wien

In my talk, I will compare different E. coli expression platforms for the production of Fabs and discuss their advantages and challenges to be tackled.

14:00 - 14:30 30 mins
Info
Bioanalytical Congress
The analytical toolbox for viral vector characterisation: progress and challenges
  • Clare Trippett - Senior Bioanalytical Scientist, Centre for Process Innovation

The field of gene therapy through the use of viral vectors has advanced rapidly in recent years with an increasing number of clinical programs moving towards market approval. As advances are made in this area there is the need for an analytical toolbox to enable rigorous characterisation of viral vectors to demonstrate purity, potency, stability and safety. In addition, the analytics to support process development for manufacture of viral vectors must be in place to ensure clinical demands can be met for different products and higher vector quantities per product.

Current analytical methods for viral vector characterisation will be discussed as well as some of the challenges faced in process development and characterisation of the expanding potential commercial product pipeline.

14:30 - 15:00 30 mins
Cell Culture & Upstream Process Development
Case study on upstream processing from Allergan
  • Helene Trottin - Senior Technical Specialist (Process Sciences), Allergan Biologics Ltd., an affiliate of Allergan plc
14:30 - 15:00 30 mins
Info
Downstream Processing
Supporting the Biopharmaceutical Industry through Innovations in Downstream Purification
  • Stuart Jamieson - Senior Downstream Scientist, Centre for Process Innovation

CPI supports the UK biopharmaceutical industry by engaging in a variety of collaborative work programmes to support process innovation and facilitate the development and adoption of new manufacturing and analytical technologies. Case studies will be presented from a number of collaborative projects looking to improve downstream operation through formulation innovation, the development of automated continuous purification, the development of a platform for virus production and prediction of performance characteristics to improve the efficiency of manufacturing systems for future targets.

14:30 - 15:00 30 mins
Info
Manufacturing Strategy & Technology
Optimising process fit to enhance annualised productivity
  • Cillian McCabe - Team Leader, Technical Services/Manufacturing Sciences, Eli Lilly and Company

Tech Transfer between facilities presents a business opportunity to enhance productivity and optimise facility fit whilst minimising impact on process performance and reliable supply. This presentation presents a case study of an intra-site tech transfer of a commercially approved platform biologics process. An overview of the productivity opportunities evaluated, the risk based approach to implementation and tech transfer outcomes are provided.

14:30 - 15:00 30 mins
Info
Smart Factories
Mastering the digitalization challenge in bioprocessing through smart data analytics and modeling
  • Michael Sokolov - Postdoctoral Fellow and Lecturer, ETH Zurich

Throughout the past years, we elaborated several digital solutions based on advanced engineering statistics, machine learning and deterministic approaches for the analysis, modeling and interpretation of bioprocesses. Furthermore, we integrated them into the process development workflow in several collaboration projects with the biopharmaceutical industry. This presentation will show the possibilities to accelerate development and reduce risks in bioprocessing through digital engineering solutions, and will outline key technology and business drivers to master the digital transformation challenge in bioprocessing.

14:30 - 15:00 30 mins
Microbial Manufacturing
Development of a high yielding E. coli periplasmic Fab production platform
  • Mark Ellis - Principal Scientist, UCB
14:30 - 15:00 30 mins
Info
Bioanalytical Congress
Anisotropy Resolved Multi-dimensional Emission Spectroscopy (ARMES) for the analysis of proteins in solution
  • Alan Ryder - Principal Investigator, NUI Galway

The use of intrinsic fluorescence spectroscopy for the analysis of protein structure, stability, and aggregation has significant benefits in terms of sensitivity and minimal unwanted perturbation.  However, most fluorescence-based assays use either single point measurements or two-dimensional spectra both of which have poor information content.  The situation is further complicated by the presence of multiple-fluorophores in most therapeutic proteins (e.g. IgG > 100 fluorophores…) which makes spectral interpretation difficult because of extensive spectral overlap.  To facilitate detailed structural analysis of multi-fluorophore proteins, Anisotropy Resolved Multi-Dimensional Emission Spectroscopy (ARMES) can be used to extract more information from a single fast measurement.  ARMES is a 4D measurement (λex×λem×If×r) in which the anisotropy (r) measurement can provide information about both structural and physicochemical changes and aggregation of proteins.  This novel method also involves the use and development of multivariate analysis tools to extract the most useful information from the 4D measurements which can be implemented using standard benchtop spectrometers.  Here we present some of the latest ARMES developments for the characterisation of proteins with case studies involving Insulin, IgG, and albumin type proteins.

15:00 - 15:30 30 mins
Info
Cell Culture & Upstream Process Development
Accelerated media and feed development through use of media and feed library screening
  • Noemi Moroni - Upstream Scientist, Menarini Biotech, Italy

Simplifying and accelerating upstream process development is a must for biotech firms. We found that effective collaborations with specialized media development companies is paramount. Menarini Biotech and BD developed a medium/feed platform for particularly challenging CHO DG44 cell lines. Through this program, we evaluated 20 proprietary chemically defined media and six feeds. The best combination resulted in four-fold performance increase in less than three months.

15:00 - 15:30 30 mins
Info
Downstream Processing
Chromassette®: A stackable, single-use chromatography cassette enabling next-generation bioprocessing
  • Gerald Platteau - Senior Application Engineer, JSR Life Sciences

A stackable, single-use and pre-packed chromatography cassette with a supported bed, Chromassette® is a novel product concept in DSP, addressing the current key challenges in manufacturing. Chromassette combines the separation capabilities of chromatography resins with the convenience of a pre-packed, modular cassette as shown in a range of application examples.

15:00 - 15:30 30 mins
Info
Manufacturing Strategy & Technology
Applications of handheld Raman Truscan RM in biopharmaceutical manufacturing
  • Shailesh Karavadra - Technical Sales Manager, ThermoScientific

Raman spectroscopy, a vibrational spectroscopy with a number of useful properties (non-destructive, non-contact, robustness) has significant potential benefits in biopharmaceutical manufacturing. Raman spectroscopy offers intrinsically high molecular selectivity, the ability to measure in water, no (or minimal) sample preparation, and flexible sampling options. From its inception, our handheld Raman spectrometer, TruScan RM, has provided small molecule manufacturing 100% raw materials inspection without prohibitive financial or staffing investments. Now TruScan RM has evolved with the addition of TruTools, an on-board chemometric software package which expands raw material identification applications to complex material analysis problems such as materials with similar chemical compound structures, at-line process checks, and final product identification. Here we present a few examples of how Truscan RM and TruTools can be used in biopharmaceutical manufacturing for raw material analysis (Amino acids, Cell Culture media and buffers), at-line monitoring of fermentation, and final product identification of therapeutic proteins.

15:00 - 15:30 30 mins
Info
Microbial Manufacturing
Reinventing a legacy process for the 21st century: A case study on implementing a single-use bioreactor in an anthrax vaccine fermentation
  • Williams Olughu - Senior Scientist, Porton Biopharma Limited

This talk presents the factors considered in the development of a modern but comparable anthrax vaccine fermentation process to a legacy counterpart. It highlights the approach of using data gathered from a legacy process to design a new operating space. Also, the role of how a single-use rocked bioreactor was used to achieve this transformation will be discussed.

15:00 - 15:30 30 mins
Info
Bioanalytical Congress
Measuring Protein Assembly at High Concentration
  • Jennifer McManus - Head of Department of Chemistry, Maynooth University

The self-assembly and aggregation of proteins can lead to the formation of protein assemblies with sizes ranging from nanometres to micrometres. For several biologic formulations, protein concentrations in excess of 150mg/ml are required. Analysis of size heterogeneity at high protein concentrations presents an analytical challenge. I will discuss methods we use for aggregation analysis at protein concentrations up to 200mg/ml.

15:30 - 16:00 30 mins
Afternoon Coffee
16:00 - 16:30 30 mins
Info
Cell Culture & Upstream Process Development
Assessing the potential of a 24-well miniature bioreactor system as scale-down model for mammalian cell culture processes
  • Frank Baganz - Senior Lecturer, University College London

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. The robustness of the MBR will be demonstrated with regard to the reproducibility of 24 parallel fed-batch CHO cultivations. Examples will be given for the application of this MBR to characterise and rationally scale cell culture processes.

16:00 - 16:30 30 mins
Downstream Processing
Development and validation of high throughput scale down purification models
  • Andrea Rayat - Senior Enterprise Fellow in Bioprocessing, University College London
16:00 - 16:30 30 mins
Info
Manufacturing Strategy & Technology
Control of antibody glycosylation during the upstream or downstream stages of a bioprocess
  • Michael Butler - Chief Scientific Officer (CSO), National Institute of Bioprocessing Research & Training (NIBRT), Ireland

Glycan profiles of monoclonal antibodies produced in cellular bioprocesses are dependent upon the enzymic activities present in the host cell line as well as the growth conditions during the bioprocess.  The glycosylation profile can be controlled during upstream processing by cell engineering or media manipulation during cell growth.  An alternative approach is by enzymic remodelling during downstream processing.  The relative value of each of these possible strategies will be evaluated for the production of an antibody.

16:00 - 16:30 30 mins
Info
Smart Factories
Control of antibody glycosylation during the upstream or downstream stages of a bioprocess
  • Michael Butler - Chief Scientific Officer (CSO), National Institute of Bioprocessing Research & Training (NIBRT), Ireland

Glycan profiles of monoclonal antibodies produced in cellular bioprocesses are dependent upon the enzymic activities present in the host cell line as well as the growth conditions during the bioprocess.  The glycosylation profile can be controlled during upstream processing by cell engineering or media manipulation during cell growth.  An alternative approach is by enzymic remodelling during downstream processing.  The relative value of each of these possible strategies will be evaluated for the production of an antibody.

16:00 - 16:30 30 mins
Info
Microbial Manufacturing
Rational design for further advancement of E. Coli expression systems and production processes
  • Gerald Striedner - Assoc. Prof., Univ. of Nat. Resources and Life Sciences

In view of a continuously growing number of hosts used for production of recombinant proteins E. coli is still one of the most frequently used microbial expression systems. The rapidly growing knowledge on E. coli´s cell physiology and new molecular technologies represent the basis for rational and efficient molecular modification. Consequently we see increasing product yields, improved quality and a steadily expanding range of proteins which can economically be produced with E. coli. However, there is still potential for further improvements especially in context with the synchronization/harmonization of host cells capabilities, recombinant protein production and fermentation process design. Our approach in this context aims at a reduction of the recombinant system to the absolute required minimum in order to avoid nonessential burden in expression systems and to follow a “minimal invasive” host cell design approach. We have also established alternative E. coli system that is based on decoupling recombinant protein production and cell growth. The system can be used to produce toxic proteins that would otherwise interfere with cell growth. However, we also observed higher specific protein yields even for proteins that can be efficiently produced with conventional E. coli systems. With respect to production and scale-up the system is fully scalable and high specific protein concentrations also supports down-stream processing.

16:00 - 16:30 30 mins
Info
Bioanalytical Congress
Biophysical characterization of HexaBody®-based IgG antibodies: The impact of formulation
  • Muriel van Kampen - Senior Scientist, Genmab

The HexaBody® format is a novel platform for the potentiation of therapeutic antibodies by enhancement of antigen-dependent hexamer formation at the cell surface, which may drive subsequent target receptor activation or complement activation. The biophysical characteristics and stability of HexaBody-based model compounds in different formulations will be discussed, probed by a variety of analytical techniques.

16:30 - 17:00 30 mins
Info
Cell Culture & Upstream Process Development
Faster process development via hybrid modeling and intensified Design of Experiments
  • Moritz von Stosch - Senior Manager Fermentation, GlaxoSmithKline

In this contribution, an intensified Design of Experiment (iDoE) methodology will be introduced. The iDoE approach is based on the idea that the values of certain factors do not need to be kept constant throughout the experiments. Instead the value of the factors can be changed during the experiments, e.g. after a specified time a step-change from 23 to 30 (°C) can be applied in temperature. In this way a classical Design of Experiment plan can in principle be executed using less experiments. The iDoE method is applied to industrial and simulated E.coli fed-batch fermentations. A dynamic hybrid modeling method is adopted for the analysis of the data, since the analysis cannot be accomplished with the traditional static statistical methods. The process understanding gathered from the iDoE is compared to DoE results. The results suggest that the number of experiments can be reduced by a factor of three to two, meaning less than half of the experiments of a classical DoE are required with the iDoE method. In addition, the understanding of the process dynamics is much improved, which is of particular importance to assess the impact of temporal deviations in the factors on the process response. It also seems possible to integrate the process development activities better with the development of the process control strategy.

16:30 - 17:00 30 mins
Info
Downstream Processing
Evaluating the impact of mixing during viral inactivation and neutralization post protein A chromatography using small scale mixing models
  • Maike Juergens - Purification Scientist, Bristol-Myers Squibb

In a typical downstream purification process, mAbs and Fc-fusion proteins are exposed to acidic conditions during elution from affinity resins and during viral inactivation. It is well known that acidic pH and high ionic strength can promote formation of non-native protein structures, thereby resulting in aggregation. pH adjustments of the solution generally require a mixing process that can have a potential impact on formation of aggregates and necessitates the requirement of a scale down model to study its impact. However, developing scale down models for mixing during viral inactivation poses a number of challenges due to the number of factors impacting the process. Mixing models need to account for the engineering principles governing mixing scale down, as well as shear parameters. In addition, mixing models should account for the addition rates of acid/base during the process and location of the addition ports and pH electrodes within the vessel. The above parameters can impact the product through generation of high molecular weight species as well as process related impurities through precipitation of host cell proteins. This case study looks into the impact of mixing speed and acid/base addition rates on process performance and generation/reduction of process related impurities.

16:30 - 17:00 30 mins
Info
Manufacturing Strategy & Technology
Strategies towards the development of holistic manufacturing control strategy
  • Julian Morris - Technical Director, University of Strathcylde
  • Industry integration of diagnostics metrics and systems to track process behaviour and process capability: Understanding how well your processes are doing?
  • How IT links to Pharma 4.0 and enables smarter project and operational execution
  • Development of preventive measures as well as detection methods
  • Steps towards the development of a holistic approach for biomanufacturing control
  • Best practices from other industries
16:30 - 17:00 30 mins
Info
Smart Factories
Strategies towards the development of holistic manufacturing control strategy
  • Julian Morris - Technical Director, University of Strathcylde
  • Industry integration of diagnostics metrics and systems to track process behaviour and process capability: Understanding how well your processes are doing?
  • How IT links to Pharma 4.0 and enables smarter project and operational execution
  • Development of preventive measures as well as detection methods
  • Steps towards the development of a holistic approach for biomanufacturing control
  • Best practices from other industries
16:30 - 17:00 30 mins
Info
Microbial Manufacturing
Faster process development via hybrid modeling and intensified Design of Experiments
  • Moritz von Stosch - Senior Manager Fermentation, GlaxoSmithKline

In this contribution, an intensified Design of Experiment (iDoE) methodology will be introduced. The iDoE approach is based on the idea that the values of certain factors do not need to be kept constant throughout the experiments. Instead the value of the factors can be changed during the experiments, e.g. after a specified time a step-change from 23 to 30 (°C) can be applied in temperature. In this way a classical Design of Experiment plan can in principle be executed using less experiments. The iDoE method is applied to industrial and simulated E.coli fed-batch fermentations. A dynamic hybrid modeling method is adopted for the analysis of the data, since the analysis cannot be accomplished with the traditional static statistical methods. The process understanding gathered from the iDoE is compared to DoE results. The results suggest that the number of experiments can be reduced by a factor of three to two, meaning less than half of the experiments of a classical DoE are required with the iDoE method. In addition, the understanding of the process dynamics is much improved, which is of particular importance to assess the impact of temporal deviations in the factors on the process response. It also seems possible to integrate the process development activities better with the development of the process control strategy.

16:30 - 17:00 30 mins
Info
Bioanalytical Congress
Computational approaches to study biopharmaceutical stability and formulation
  • Jim Warwicker - Reader, Manchester University

As software tools become available for aiding in the design and formulation of biopharmaceuticals, it is necessary to evaluate their usefulness. Such an effort requires collaboration between groups, exchange of data, and ultimately the establishment of benchmark datasets. This presentation will discuss the available predictive tools, their molecular bases, and the scope for providing benchmark evaluations to the wider community of researchers.

17:00 - 17:30 30 mins
Info
Downstream Processing
In-Line Buffer Conditioning for use in column chromatography processing steps
  • James Murphy - Technical Specialist, MSD, Ireland
  • Tibor Nagy - Subject Matter Expert Bioinformatics, Protein Refolding, FUJIFILM Diosynth Biotechnologies

Large scale manufacture of biologics typically requires large volumes of process solutions. The conventional approach for the supply of these buffers has been to utilise multiple preparation and storage vessels. This tank farm approach requires a large area footprint and high capital investment as well as associated validation, cleaning and maintenance of the buffer preparation and storage equipment. To circumvent this challenge we have introduced an innovative combined In-line Conditioning and Chromatography (ILC-Chrom) system. ILC skids generate buffers in-line from concentrated stocks of acid, base, water and salt allowing formulation of buffers for downstream on-demand. The ILC skid has multiple modes of operation including, recipe/flow feedback, pH feedback and pH & conductivity feedback which can be applied for the generation of buffers. Through a series of pH and conductivity Instruments the ILC can both monitor and control the formulation of buffers to the desired specification. Along with buffer preparation capabilities the ILC-Chrom system allows for integrated chromatography with the prepared buffer delivered directly to the process. The ILC-Chrom system incorporates all the capabilities of a standard production scale chromatography skid. Here, we will outline the pros and cons of the system with respect to the traditional solution preparation approaches in biologics manufacturing. Furthermore, we will discuss the technical aspects of this novel technology and outline some results and learnings generated from Proof of Concept studies and Factory Acceptance Tests of the new equipment. Given the advantages this system provides, ILC technology has the potential to become the new standard to which manufacturing facilities are constructed and how downstream processing is operated

17:00 - 17:30 30 mins
Info
Bioanalytical Congress
Using Chemical Denaturants to Improve Predictions of Biopharmaceutical Aggregation during Storage
  • Robin Curtis - Senior Lecturer, The University of Manchester

A key obstacle to predicting aggregation is difficulties in isolating the partially folded states believed to be key intermediates in the aggregation pathways. One approach not yet fully explored is to study the self association behaviour of partially or unfolded states under chemically denaturing conditions when they occur at much larger populations. Typically, these measurements are carried out using static or dynamic light scattering in terms of an osmotic second virial coefficient or a diffusion interaction parameter kD. Here we show how to account for the high concentration of denaturants in the data analysis, which if unaccounted for, could lead to data mis-interpretation. We then correlate light scattering measurements of five monoclonal antibodies at high denaturant concentration with their shelf stability. The results indicate there is a window of denaturant concentration over which the self association behaviour provides an indicator for the aggregation propensity upon storage.

17:30 - 17:35 5 mins
End of BioProduction 2018