NEPIC Innovation Day, November 15th 2011
Centre of Excellence in Biopharmaceuticals
(CoEBP)
Alan Dickson
The University of Manchester
Background: Science Need
CoEBP
CoEBP:
What can we do
Success to date
Future plans
Contacting us
Source Evaluate Pharma 2010
Science Need
Predicted Top Ten Therapeutics for 2016
Rank Product
Company(s)
Technology
2009
($bn)
2016
($bn)
1
Humira
Abbott Laboratories/Eisai
5.6
10.1
2
Avastin
Roche
5.7
8.9
3
Enbrel
Amgen/Pfizer/Takeda
6.5
7.3
4
Rituxan
Roche/Biogen Idec
5.6
6.8
5
Crestor
AstraZeneca Shionogi Chiesi
4.8
6.3
6
Herceptin
Roche
4.9
6.2
7
Remicade
Johnson & Johnson Merck & Co Mitsubishi Tanabe
5.9
5.7
8
Lantus
Sanofi-Aventis
4.3
5.3
9
Advair/Sereti GlaxoSmithKline/Almirall/Others
de
Prolia
Amgen/Daiichi Sankyo/
GlaxoSmithKline
Monoclonal
antibody
Monoclonal
antibody
Recombinant
Product
Monoclonal
antibody
Small molecule
chemistry
Monoclonal
antibody
Monoclonal
antibody
Recombinant
product
Small molecule
chemistry
Monoclonal
antibody
8.0
5.2
0
5.2
10
Source Evaluate Pharma 2010
Science Need
Transcription
RNA processing
Translation
Secretion
Amount
Quality
Purity
Properties
Bioprocessing
Science Need
Bioprocess – biopharmaceuticals, biologics
Bioprocess - activities that enable design, development
and production of biological medicines both
in bulk and final dosage form
Includes
• Cell line development and cell banking,
• Fermentation processes,
• Recovery and purification processes,
• Chemical modification,
• Formulation process and dosage form,
• Storage and stability,
• Analytical methods,
• Final product and stability testing
Science Need
Biopharmaceuticals: Current commercial reality
58 new biopharms products approved 2006-2010
32 – Chinese hamster ovary (CHO) cell
17 – E.coli
4 - S. cerevisiae
2 - Transgenic animals
2 - Insect cells
1 - Pichia pastoris (GlycoFi)
Walsh, G [2010] Nature Biotechnology 28: 917-924
Science Need
Immunoglobulin structure
Commercially valuable
Complex –
IgG
150,000Da
Aspirin
180Da
Possible modifications
100 Billion combinations
Functional quality
R. Jefferis (2006) Nature Biotech. 24: 1230-1231
Structure generated by Peter Artymiuk (University of Sheffield,
Sheffield, UK) using PyMOL (http://pymol.sourceforge.net/).
Science Need
The challenge of
“improved” products
-The complexity of
the biological system
Antibody
(mAb)
Fab
scFv
scAb
Science Need
The Biopharmaceuticals “pipeline”/system
Required product (vs target)
Expression system
Helping with
industrial
challenges
Scale-up and quantity
Downstream processing/purification
Formulation/storage
Patient delivery
The CoEBP
Centre of Excellence in Biopharmaceuticals (COEBP)
A short history
• BIGT Report 2003 – maintaining UK position/investment
• bioProcess UK (KTN) 2005 – industry/BRIC funding (£13M)
• bioProcess UK 2006 – call for new Centres (especially training)
• BRIC funding 2006/7– 19 companies/24 academic projects
• Potential new Centres “anointed” 2007 – support (non-financial)
• COEBP and NWDA 2007 onwards – application(s) from UoM
• COEBP and ERDF/NWDA 2009 – application funded Oct 2009
• BRIC2 2010 – evolving industry funding route (£10M)
• COEBP 2010 - staff appointments May 2009
• COEBP 2010 – robotics facility complete December 2010
The CoEBP
Discovery
Target identification
Lead identification
Lead optimisation
Development
Manufacturing
Pharmaceutics
Formulation/delivery
Pre-clinical
Clinical
Toxicology
Commercial
Marketing/sales
Manufacturing
Supply chain
Pharmaco-vigilance
Discovery
Bioprocessing*
Formulation*
Delivery*
Toxicology*
Clinical Research
Diagnostics
The CoEBP
Centre of Excellence in Biopharmaceuticals (COEBP)
Key activities:
• Direct Business Support
• Academic/industrial research collaborations
• Exchange placements – industry/academia
• Work-based Training
• Establishment of Robotics capability
TAP
Thermo
“New academic involvement”
- engagement of “naïve” academics
with the biopharms sector
-application of new technologies
and approaches to the sector
What can we do?
Pharmacy/
formulation,
delivery
Systems
biology
Structural
biology
Cell and
molecular
biology
CoEBP
Computational
biology
Physical sciences/
mathematics
Toxicology/
immunogenicity
Chemical
engineering
Analytical
scientists
What can we do?
Knowledge transfer/
training activities
Advisory services
to the sector
CoEBP
Direct industry
funded research
(project/PhD)
Industry advisory
consultancies
Contract
services
Research Funding
(underpinning)
Collaborative industry
research (project/PhD)
What can we do?
Sonata – Protein Expression Automation
Accelerating development
of Biopharmaceuticals
Mammalian Suspension Cell Culture
Biologics Process Development
− Culture Optimisation
− Stability Studies
− Scale-up
Research & Drug Discovery
− Protein Reagent Supply
What can we do?
Thermo Fisher Momentum F5
Accelerating development
of Biopharmaceuticals
Complete processing microtitre plates
- High throughput capability
- High content capability
- Automated cell/reagent dispensing
Assay and screening automation
- Cellomics Arrayscan
- Imaging of individual cells
- Automated data handling and storage
Success to date
17 Internal research programmes undertaken – 12 completed and
some form grant applications, 5 on-going)
5 Research Council Project grants (£2.1M)
7 externally-funded PhD studentships
21 “Core” Academics
40+ 2° Academics
Grant applications >£12M under consideration
6 Industrial group PhDs under discussion
External Engagement
30 UK-based companies (14SMEs, 16 LOs)
5 EU/USA-based (1 SME, 4 Los)
3 directly-funded research contracts
5 programmes under discussion
(2 technology evaluations)
(3 research collaborations)
Seminars and training modules (Aggregation, Systems Biology, Analytics)
Advisory roles in consultancies and advisory committees
Success to date
Best?
Growth rate, IVC,Qp,
PTM and secretion,
selective product
handling, feed response
Find the best cell (clone)?
Success to date
CHO clone
selection –
GFP cherry
picking
ThermoFisher
System
Success to date
CHO Cell line (in)stability
Specific productivity
Cell growth
Generation time
Sonata TAP System
Success to date
Primary
Neurone
Screening
ThermoFisher
System
Future plans
Knowledge-based BioEconomy Research Vision
Industrial Biotechnology - Bioprocessing
- Funding bodies priorities
- Strategic challenge UoM
Long-term academic research funding – recruitment
Short-/medium term industrial exchange/training
Increased SME networking
Increased generic training
Contacting us
http://www.coebp.ls.manchester.ac.uk
University of Manchester
Centre of Excellence in Biopharmaceuticals
Professor David Clarke
Dr Simon Merrywest
Dr Joanne Flannelly
Dr Annes Lambert
Professor Ian Kimber
Professor Pedro Mendes
Dr Aline Miller
Ms Rachel Ashworth
Dr Malcolm Rhodes
Professor Mike Sutcliffe
Dr Egor Zindy
COEBP Scientific Advisory
Board
Dr Kevin Cox
Dr Geoff Davison
Prof Douglas Kell
Dr Mark Douglas
Dr Ian Madley
Dr Linda Magee
Dr Daniel Smith
The Dickson lab group and funders
BBSRC
BRIC (BBSRC/EPSRC/Industry)
GlaxoSmithKline
Life Technologies
Lonza Biologics
MedImmune (CAT)
Pall
Pfizer
RecipharmCobraBiologics
UCB Celltech