Progress since EPSRC
Centre feasibility
April, 2015
Purification Solutions for
Biotherapeutic Manufacturing
Find out more: www.puridify.com
Puridify’s anatomy of innovation
Unmet
need
O. Hardick
starts
doctoral
research
program
Project idea
conceived
at BBRSC
BRIC
workshop
2008
First patent
application
for the
technology
O. Hardick
starts
enterprise
fellowship
to consider
next steps
Puridify
founded
and wins 1st
OneStart
competition
Puridify
begins
operations
at
Stevenage
Biocatalyst
Further
capital
raised key
employees
appointed
Venture Capital
raised for
commercialisation
2015
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Chromatography: Critical purification step
A critical tool in part of the $153bn biotechnology market
Chromatography reagent market: $5bn (18% CAGR)1
1. Global Markets for Reagents for Chromatography, BCC Research, September 2012
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Technology: Bead resin is outdated
Porous Bead Resin
Old vs New
•
Expensive – costs $10m
•
Economical – uses 10x less reagent
•
Slow – relies on diffusion
•
Fast – can use convective flow
•
Variable – column packing issues
•
Robust – fixed structure & screening
•
Outdated - next gen drugs too large
•
Flexible – suitable for next gen drugs
•
Large – takes up lots of space
•
Small – small clean room footprint
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FibroSelect: Advantage of nanofibres in bind-elute
Bead Resin
FibroSelect
Membrane
Monolith
Pore diffusion = limiting
High porosity
Limited surface area
High porosity
Prone to fouling :
deadend channels
Optimal surface areapore size
Deadend structure
Focus is
marcomolecular
Pore size: 15-40nm
Pore size: 0.2-2.0µm
Pore size: 0.2-0.5µm
Pore size: 2µm
Capture area: 40m2/g
Capture area: 10m2/g
Capture area: 2m2/g
Capture area:1-200m2/g
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FibroSelect: Allows low pressure operations
∇ Membrane A;  Membrane B; ⊙ Membrane C; ◊ FibroSelect
Low pressure at high flowrate maximises productivity
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Binding capacity (mg/ml)
FibroSelect: Strong performance at all flowrates
Cation Exchange
o
Anion Exchange
□
Flowrate (cm/hr)
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Recent Progress
10mL DEAE cartridge
400mL/min, BSA load until 10% BT
1400
90
80
1200
UV absorbance
60
800
UV absorbance
50
600
Conductivity
40
400
30
200
Conductivity (mS/cm)
70
1000
20
0
10
-200
0
0
100
200
300
400
500
600
700
800
Volume (ml)
High throughput screening
Research optimisation
Pilot purification
Solid structure also allows uniform performance over scales
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Recent growth in recombinant vaccines
• Move away from egg vaccine production
• Growth of focus on preventative strategies for non-infectious
diseases such as Parkinson’s disease and therapeutic use such as
cancer
• Requirement to shorten time to market with outbreaks like Ebola,
Flu variants, SARS and other sources of potential epidemics
• Cost of goods and scalability for global populations
• Veterinary vaccines: foot & mouth, avian influenza
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Desirable adsorption surface properties
•
Surface area - Capture capacity
•
Porosity - Pressure drop and access to surface area
•
Stability - chemical, biological & physical
•
Hydrophilicity - (can be introduced)
•
Functional groups for modification
•
ROBUSTNESS - reproducible in fabrication and operation
Developed for mAb purification, applied to viral vectors
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Desirable adsorption surface properties
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Macromolecular Biomolecule Purification
100 nm
Size and labile nature of AV make them difficult to purify
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Infectivity of the product
Filled
Empty
•
Adenovirus has a complex maturation cycle, with mixed subtype batches
leading to lower therapeutic efficacy
•
Much is yet to be understood about the positive or negative adjuvant effect
caused due to the ratio of infective vs non-infective viral capsids
•
Utilisation of diverse ligand library and buffer conditions will be required in IEX
setting to separate adeno subtypes
Future potential to control infectivity of viral particles
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FibroSelect: Simple plug and play technology
1. Truly disposable operation:
Lifetime of FibroSelect unit (number of cycles) used in a single sitting makes
disposable operation economic
2. Increased throughput:
Rapid cycling increases grams of therapeutic purified, per hour, per litre of
adsorbent
3. Flexible operation
Smaller, disposable FibroSelect units are better suited to the new generation of
smaller, geographically local, multi product, manufacturing facilities
4. Robustness of operation
No column packing, easier to predict performance, using well trusted materials
and purification chemistries
Enabling new process operations without changing underlying
purification principals with the support of the bioindustry
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Thank you
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.com
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