Transcript Slide 1
BRINGING THE BEST TO HEALTHCARE THROUGH PARTNERSHIP AND INNOVATION Driving innovation through constructive partnership
Prof. Ian Marison
18th IPHA Annual Meeting 2011
Contents • General Introduction • Introduction to NIBRT • NIBRT Facility:
an Irish asset
• NIBRT Training:
transforming performance
• NIBRT Services:
A support to industry
• NIBRT Research:
creating a competitive advantage
• Next steps
General Introduction
Driving innovation through constructive partnership
My talk will deal with Healthcare and Innovation by looking specifically at the following: • The need to coordinate activities in Ireland in the
Healthcare/ pharma
sectors • The need to coordinate activities in Ireland in the
Education
sector • The need to coordinate
innovation
activities in applied research • The need to coordinate
innovation
activities in basic research
What do we mean by innovation and partnership?
In this context means: • The development of new solutions for overcoming existing problems/ shortfalls in the Irish medical/ pharma and education sectors • The creation of structures which allow the interaction of groups of individuals from academia, research, medicine and industry to create new solutions to scientific/ health/ social problems • The creation of structures which allow original research • Identification of ways to stimulate young people to take an interest in studying and training in key areas essential for Irelands future.
Introduction to NIBRT
An Innovative Partnership • National Institute for Bioprocessing Research and Training • Created for industry – in partnership with industry • Initially four leading academic institutions- expanding to become a truly National facility e.g. incorporation of all 7 universities and Institutes of Technology • Funded (€57 million) by the Irish Government (IDA Ireland) • Operated as a non-profit making company
Our Mission
To support the growth of the Irish (bio)pharma industry by providing: • Training • Education • Applied research • Research services • Services We listen to industry needs We bring together groups of people from the national institutions, HEIs, research centres We solve problems and provide services We stimulate the economy We form partnerships between academia and industry
Our Clients…
to name but a few
and many more……
Ireland
• The number 1 location in Europe for Life Sciences • 44,000 direct employees • Exports €44bn in 2008 (51% of national total) • 33 FDA approved pharma and biopharma plants • 8 out of the top 10 Pharma companies • 15 out of the top 25 top med tech companies • 6 out of the top 10 top blockbusters manufactured in Ireland • Excellent regulatory record, since mid 1960’s
NIBRT facility:
an Irish asset
NIBRT Facility
• • • • • • Inauguration (by Sean Sherlock) 9 th June 2011 NIBRT training and education programmes Research and development programmes Test bed for new technologies and processes Showcase for latest technologies and products Conference, meeting, events
Upstream Pilot Plant
• • • • • • • Inoculum preparation laboratory Shake flasks and 2 wave reactor trains (up to 30L) 15L, 30L, 2 x 150L bioreactors with support vessels (media hold and harvest) Vessels capable of batch and fed-batch operation with 30L capable of perfusion Utilities for disposable bioreactor up to 1000L Harvest MF and centrifuge system Culture clarification skid
Downstream pilot plant
• 2 UF/DF skids • 2 Chromatography skids • Column packing skid • Vessels for pH viral inactivation • Integrity testing stations • Instrumentation rig
Fill finish suite
• Media fill of vials under LAF and RABS using clinical trial skid • Clean room classification and operation • Rapid microbial analysis and objectionable organism typing • Environmental monitoring • Viable and non viable cell counters
Training for Industry:
transforming performance
Training and Education
• Competency based learning • Certified programmes • Customised to client’s requirements • Cost effective
Training and Education
Open schedule
Training paths:
Operator Training Programme
Training Path Key topics covered Duration Who should attend Learning outcomes Certification Location NIBRT Biopharma Operator Training Programme Introduction to Bioprocessing:
Principles of cell biology, Principles of microbiology.
Introduction to Upstream Processing:
Bioreactor operations theory, bioreactor operations –practicals and assessments, cell growth, cell counting techniques, aseptic transfer, bioreactor inoculation, Vi-cell operation, bioanalyser operation and analysis.
Introduction to Downstream Processing :
Weigh and dispense / media-buffer preparation / WFI usage, downstream filtration practical incl. filter design and filter integrity testing. Protein purification /separation techniques , column design / packing /chromatography systems. Sterilisation techniques . Cleaning andSsanitisation / autoclaving.
Aseptic manufacturing:
Clean room operations /HVAC systems.cleanroom environmental monitoring. Formulation and fill finish systems. Lyophilisation Systems.
Facilities, utlilities, regulatory affairs, business skills as applicable.
5 weeks Start up technicians and operatives working in drug substance or drug product requiring a comprehensive overview of the biopharma production process Staff will be exposed to all theoretical and practical hands on aspects of biopharmaceutical production in upstream, downstream and fill finish and safety in a quasi GMP environment using cutting edge industrial type equipment and processes.
Accredited prior learning / recognised prior learning In accordance with Bologna classification (level 6 equivalent) All practical content is delivered in NIBRT facility.
Theoretical content can be delivered at any location including at the client site and also by distance learning.
Masters Programme
Masters in Bioprocessing Engineering
Dublin City University (DCU) in association with NIBRT
Course description
The M.Sc. is an interactive and dynamic programme that will develop your knowledge and appreciation of the conceptual and factual basis for bioprocess design and operation. It also develops your understanding of bioprocessing, particularly the structures, roles and experimental methods associated with biopharmaceuticals, their analysis, production methods and technology for monitoring and control of bioprocesses.
Key topics covered Duration
Fundamentals of Bioreaction Pocesses Bioseparations Recombinant DNA Technology Bioprocessing Laboratory Introduction to Biopharmaceutical Engineering Bioprocess Scale Up & Technology Transfer Animal Cell Culture Technology Biopharmaceutical Industry Regulation and Mgt Bioreactor Design, Modelling and Monitoring Regulatory Affairs Science for Biotech Products Formulation and Delivery of Biopharmaceuticals Biopharmaceutical Facility Design and Operation 1 year full-time/ 2-4 years part-time
Specialisation
Separation processes/ unit operations Process analytical technologies (PAT) Process modelling Regulatory affairs Fill-Finish Drug delivery cGMP facilities design and operation Glycobiology Bioanalytics QA/QC
Who should attend Accreditation
The programme is open to graduates and those currently working in industry with an honours degree (minimum second class honours grade 2) in Science or Engineering. Mature student entry, deferred entry and entry by students participating in European Union exchange programmes and the transfer of students from other relevant courses within DCU with be in accordance with the current regulations of those universities.
M.Sc (Level 9)
Location
DCU and NIBRT
Awards
Winners in the Continuous Professional Development Company of the Year Awards 2009
Large-sized company category Pfizer Biotechnology Ireland • • In May 2008, Pfizer announced the establishment of a new biologics facility in Shanbally, Cork, Ireland. This facility was to manufacture monoclonal antibodies for clinical trial purposes.The facility requires an 190 € million investment with an anticipated headcount of approximately 100 highly skilled personnel.
NIBRT partnered with Pfizer to design, develop and deliver appropriate training solutions and received an award from Engineers Ireland for: “…
a learning and development programme for operating personnel was developed and implemented during plant construction by colleagues from Pfizer Global Manufacturing, Pfizer Global R&D, and NIBRT
….” http://www.iei.ie/media/engineersireland/services/engineersjournal/2009/nov-dec2009issue9/CPD%20Category%20Winners.pdf
Autumn Series of Training 2011
NIBRT Certified Training
Introduction to Biopharmaceutical Operations Upstream Processing: principles and practice Downstream Processing: principles and practice Fill Finish and Aseptic Processing Biopharma Analytical Techniques Sept 19-20 Oct 17-19 Oct 3-5 Oct 24-27 Nov 7-9
Training in association with Honeyman Group Limited
Sterilisation: Principles in Practice Applied Sterilisation Technology Microbiology for Non Microbiologists Water: Principles in Practice GAMP Environmental monitoring Applied Sterilisation Technology Sept 13-16 Sept 20-23 Sept 27-29 Oct 4-6 Oct 11-13 Oct 11-13 Oct 18-21 Find out further information and register today at www.nibrt.ie
Bioanalytical training 2012
New series in Complete Process and Product Characterisation\\; Product characterisation:
Basic protein analysis Intermediate level protein analysis- from gels to HPLC/MS Advanced level protein analysis- UPLC-MS Advanced level protein analysis- glycan profiling
Process characterisation:
Basic Quality Control Intermediate Quality Control Advanced Quality Control PAT- spectroscopic methods Chemometrics and multivariate analysis Find out further information and register today at www.nibrt.ie
Return on Investment for NIBRT training
Process measurement technology 2012
Example of an Innovative Partnership with
Endress +Hauser Contract signed 28/11/2011 in Reinach Switzerland; Training rig delivered 14/11/2011
Process measurement technology 2012
Example of an Innovative Partnership with Waters
Contract due this week, agreed delivery of €1.6 million high level analytical equipment for training in bioanalytics.
This lab forms basis of
Complete Process and Product Characterisation Facility
This will be the world’s only such analytical facility and used to supply industries with contract services, training and new analytical method development.
NIBRT research:
creating a competitive advantage
Research
• Applied research covering all aspects of bioprocessing manufacturing • Consultancy, contract and collaborative research programmes • World class Principal Investigators and facilities • Industry focused contracts and project management
Process Analytical Technologies
Raw Materials Analysis Spectroscopy Microscopy FCS Mass Spectrometry Glycan Analysis Intermolecular Interactions Static and Dynamic Light Scattering Small angle X-ray Scattering Phase Diagrams Process Analytical Techniques (PAT) Size Analysis Dynamic Light Scattering HPLC Analytical Ultracentrifugation Transmission Electron Microscopy Cell Culture Design Protein Solution Stability Static and Dynamic Light Scattering Differential Scanning Calorimetry HPLC, Analytical Ultracentrifugation Phase Diagram Structural Characterisation X-ray crystallography IR/CD spectroscopy Small Angle X-ray scattering NMR Cell Medium Design
Objectives:
• Provide a complete range of analytical methods required to fully characterize a recombinant protein and to define whether it meets requirements.
• Understand each stage of a bioprocess and identifying the conditions which may affect product stability/ aggregation.
• Design systems to monitor and control the process at each stage, in order to maintain product stability/aggregation.
Process optimisation and aggregation
Raw Materials Analysis
PI: Alan Ryder
Structural Aspects of Aggregation
PI: Peter Crowley
Cell Culture and Medium Design
PI: Nigel Jenkins
Protein Aggregation Research Workflow Biophysical Characterization (Down-stream Processing)
PI: Jennifer McManus
Bioprocess development, monitoring/ control (PAT)
PI: Ian Marison
Glycan Analysis
PI: Pauline Rudd
Objectives:
Protein aggregation is a dynamic process which also occurs after the protein is packaged. The aim of this research programme is not only to define what is necessary to meet regulatory requirements during production, but also to understand the aggregation process for each new therapeutic protein product to ensure that what is passed from production to market is a known entity, ensuring that the product has consistent quality and safety.
Process optimisation and glycosylation
Cell line selection Ensuring appropriate glycosylation QbD
Full product characterisation
Initial analysis
Effect of glycosylation on product activity/function
Glycosylation in Bioproduction Fill finish analysis
Effect of product excipient composition on glycosylation
Bioproduction
Role of glycosylation in cellular processes
Purification/formulation
Glycan analysis of fractions
Objectives:
Determining bioprocessing conditions for optimal glycosylation.
Development of robust glycotechnology for quantitative, detailed structural N- and O-glycan analysis. Quality assurance of glycosylated biologicals and batch-to-batch consistence Building customised databases including human, CHO, plant, yeast and insect glycans. Glycosylation changes in disease
Quantitative analysis of complex media
Spectroscopy Raman, fluorescence, NIR, FTIR Technology transfer Quantitative analysis of complex media Chemometrics
•
Experimental design
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Spectral analysis
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Data preprocessing
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Calibration/validation
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Innovative method development
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Data integration
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Hyphenating data
Integrated solution Objectives:
Development of rapid, inexpensive analytical methods for cell culture media and bioprocess broths: a chemometrics and spectroscopic approach.
Fc Receptor Platform
Objective:
Development of an Fc receptor platform to evaluate IgG biological activity.
SUBs and Product Integrity
WP 1: Analysis of leachables WP4: Product quality analysis WP2: Adsorption of components WP3: Cell culture
Objectives:
• The use of single use bioreactors (SUBs) is becoming increasingly popular for mammalian cell-based biopharmaceutical production, especially in the manufacture of biosimilars and material for clinical trials. This research programme assesses the impact of SUBs on product integrity. •The programme will study leachable and extractable profiles of different types of SUB under various conditions and also detect any adsorption of recombinant proteins or key media components to SUB surfaces. Another major strand of the programme will be measuring key performance criteria (cell growth, cell viability, productivity, product quality) in different types of SUB. •Scaled-down models will developed to increase experimental throughput, and a small number of runs in conventional steel bioreactors will be performed for benchmarking purposes.
Process optimisation
Objectives:
Analysis of existing processes Identification of key bottlenecks Innovative methods to optimise process to increase yield, productivity and product quality- gives competitive advantage by increasing efficiency, reduces costs, improves product safety Development of novel analytical methods
From: viruses to microbial to animal cells
Microbial Bioprocessing
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Production of bioethanol from a range of substrates
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Production of recombinant proteins using bacterial systems like E.coli e.g. alpha interferon, tPA
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Production of recombinant proteins using yeast expression systems e.g.
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Pichia pastoris
• • •
Yarrowia lipolytica Saccharomyces cerevesiae Candida utilis
etc.
•
Production of small molecules using bacterial and yeast systems e.g.
• amino acids, astaxanthin (carotenoids) etc •
Process analytical technologies
• Monitoring and control of batch, fed-batch and continuous/ perfusion cultures • In-situ product recovery e.g. continuous removal of toxic product, labile product (e.g. antibiotics like penicilllin, geldanamycin •
Aerobes, obligate anaerobes, facultative anaerobes
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Mass and heat transfer in microbial systems
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Effect of process conditions on protein expression and activity e.g. growth rate, aggregation, raw materials
Research case studies: some examples
Co-development of glycan analytical technologies to enable the monitoring of cell culture conditions.
Technology transfer of NIBRT’s high throughput N-glycan analysis process.
3 year project, 2 NIBRT Post Docs “embedded” in Lilly.
Cell culture media charcterisation and optimisation.
2 year project, 2 NIBRT Post Docs and 1 Research Assistant “embedded” in BD.
Combination of systems biology modelling and experimental validation in vitro, to advance the understanding of glycosylation-related enzyme expression, regulation and action in production systems. 4 year, 2 Post Docs and 2 PhD students Effects of raw materials on productivity and product quality Process optimisation 3 year, 2 Post Docs and 1 PhD student
Further information
Key contacts
Prof Ian Marison Ian Nelligan Killian O’Driscoll Executive Director Training Director Director of Projects Prof Pauline Rudd Principal Investigator Visits can be arranged at any time.