The NanoAssemblr™ Platform : Microfluidics-Based ...ppt • Low energy input • Readily scalable...
Transcript of The NanoAssemblr™ Platform : Microfluidics-Based ...ppt • Low energy input • Readily scalable...
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The NanoAssemblr™ Platform : Microfluidics-Based Manufacture of
siRNA Nanoparticles Colin Walsh, Ph.D.
University of British Columbia
Controlled Release Society 2013 Annual Meeting
July 23, 2013
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Conceptual Drug
Product Scale-up Formulation Process Manufacturability Final
Drug Product
Nanoparticle Drug Development Process
Current nanoparticle manufacturing techniques limit innovation
• Poorly controlled processes • Limited application for biologics (nucleic acids,
proteins, peptides)
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Microfluidics Enables Exquisite Process Control
Molecular Self-Assembly
• Control: laminar flow
• Nanoliter reaction volumes
• Rapid mixing: Timemix < Timeppt
• Low energy input
• Readily scalable
Solvent + Nanoparticle Components
Aqueous + Drug
Rapid & Controlled Mixing
Mixer design by: Stroock et al., Science 2002
Channel Dimensions: ~100 µm
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The NanoAssemblr™: Microfluidics Enables Smarter Nanoparticles
ü Enable rapid nanoparticle
prototyping
ü Remove process variability
ü Robustly manipulate single
variables
ü Remove operator variability
ü Enable seamless scale-up
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NanoAssemblr™
Microfluidic Cartridge
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The NanoAssemblr™ : Rapidly Screen Formulation and Process
Parameters
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Simple Technology Transfer Between Users and Sites
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siRNA-LNP (Cationic Lipid:DSPC:Cholesterol:PEG)
Automated instrumentation removes operator variability
Dia
me
ter
(nm
)
Sample
20
40
1 40
60
2 3 5 6
PD
I
0.04
0.12
0.00
0.16
0.08
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Nanoparticle Drug Development Using the NanoAssemblr™
Rapid formulation and process development
Conceptual Drug
Product Scale-up Formulation Process Manufacturability Final
Drug Product
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Small Scale Formulation Development
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• Removal of process variability allows for rational formulation optimization • Robustly manipulate single variables in nanoparticle composition
Changing Composition siRNA-LNP (Cationic Lipid:DSPC:Cholesterol:PEG)
Dia
me
ter
(nm
)
PEG-Lipid Content (mol %)
10
20
30
1.0 2.5 5.00
40
50
60
PD
I
0.02
0.04
0.08
0.00
0.10
0.06
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• Removal of process variability allows for rational process optimization • Robustly manipulate single variables in process
Small Scale Process Development Changing Process
siRNA-LNP (Cationic Lipid:DSPC:Cholesterol:PEG) D
iam
ete
r (n
m)
Flow Rate (mL / min)
20
40
0 120
60
80
100
4 8 16 20 24
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Formulation & Process Manufacturability Assessment
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Stable Results = Robust Process = Scalable Process
Design of Experiment (DoE) variables
– Lipid Concentration – Flow Rate – Mixing Conditions – Lipid:siRNA Ratio
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Nanoparticle Drug Development Using the NanoAssemblr™
Seamless process scalability makes small scale results more relevant
Conceptual Drug
Product Scale-up Formulation Process Manufacturability Final
Drug Product
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Continuous Flow NanoAssemblr™ Enables Seamless Scale-Up
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Continuous flow system: ü Rapidly achieves steady state ü Maintains particle quality with scale ü siRNA encapsulation efficiency > 94% in all fractions
PD
ID
iam
ete
r (n
m)
NanoAssemblrTM Scale-upCumulative Fraction (mL)
NanoAssemblr
TM
10
20
30
15
Primin
g (5m
L) 2535
4555
6575
8595
1000
40
50
60
0.020.04
0.08
0.00
0.10
0.12
0.06
0.14
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Microfluidics as a Scalable Manufacturing Platform
Parallelization facilitates large volume production with identical reactor conditions
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6x Mixer
1x Mixer
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Processing Final Drug Product
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Final RNA Concentration = 0.96 mg/mL siRNA Encapsulation Efficiency = 96%
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Nanoparticle Drug Development Using the NanoAssemblr Platform
Conceptual Drug
Product Scale-up Formulation Process Manufacturability Final
Drug Product
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Acknowledgements
University of British Columbia
Prof. Pieter Cullis Prof. Carl Hansen Igor Zhigaltzev Chris Tam Genc Basha Paulo Lin
Chen Wan Alex Leung Justin Lee Sam Chen Ismail Hafez
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Precision NanoSystems
Euan Ramsay James Taylor
Nathan Belliveau Andre Wild Tim Leaver
Kevin Ou Aysha Ansari
David Zwaenepoel
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The NanoAssemblr™ Platform ü Microfluidics-based nanoparticle manufacturing process ü Rationally engineered nanoparticle systems ü Automated instrumentation, precise process control, rapid prototyping ü Seamless scale-up
Come see the NanoAssemblr™ at BOOTH # 307 WE’RE HIRING Contact James Taylor Colin Walsh [email protected] [email protected]
www.nanoassemblr.com
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Microfluidics Enables Manufacture of Potent LNP siRNA Systems
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