1. No category

Better Lives. Better Planet.SM
Pall is Upstream…
Our solutions for viral
vaccine platforms
Dr Chidananda Chandrashekaraiah
India 201503
This presentation is the confidential work product of Pall Corporation and no portion
of this presentation may be copied, published, performed, or redistributed without
the express written authority of a Pall corporate officer
© 2014 Pall Corporation
Proprietary and Confidential ©2009 ATMI, Inc. All Rights Reserved.
Viral Vaccine Manufacturing Imperatives
Potency
- antigen (live
attenuated, inactivated)
- formulation
Regulatory
requirements
Safety
- stability
- sterility
- manufacturing
robustness
- Purity
- Validation
-Process control
Highest
Quality
2
COST
…Enable Quality + Speed + Economics
Robust processes
• Reduced failure rate
• Increased safety
Reduced development time
• High throughput and scalable tools
• Flexible facilities
Process economics
• Yield increase
• Reduced unit operations
3
What is available to grow adherent cells?
What is available to increase number of doses...
What are the options????
Or go for another one?
4
Carriers + stirred tank option
 This is the most classical approach...
 Pall has a unique combination of carriers and stirred
tank
5
Innovative Microcarriers – SOLOHILL
The translation of cell/virus process for novel bioreactor designs
SolohillTM
Need

Capacity increase for static
technology-based
manufacturing is challenging
with dextran-based µcarriers

Polystyrene µbeads that
offer comparable surface
when compared to static
flasks
Polystyrene beads with
multitude of surface
treatments for specific
cells needs
Polystyrene beads can be
gamma irradiated

Design
Solution



Benefit
Value

Vero cells on Hillex® II
Same surface offers easier
technical transfer
Scale-up to >1,000L
bioreactors
Gamma sterilization makes
easy the use in combination
with single-use bioreactors
6
Allegro® PadReactor® - Characteristics
 Square-shaped vessel: efficient
mixing
 From development to industrial
scale
13L 25L
 Re-usable or single-use
sensors
 Low shear mixing
– No carriers degradation
– Good cells attachment
 Microcarrier perfect suspension
– no gradient, no settling
 Efficient gas transfer/Dynamic
sparging
– Excellent O2 supply and CO2 stripping
7
50L
125L 250L
600L
1200L
Solohill carriers + Pad reactor: unique
combination
 Polystyrene carriers (same surface as classical static
systems)
 Gamma irradiable carriers
 Low shear stress bioreactor with highly efficient
mixing
 Winning combination
8
High Cell Density Growth of VERO in
PadReactor
11.2 x106 cells/ml
Vero cells grown on Pall SoloHill
Collagen microcarriers (30 g/L) (5%
FBS) in a 25 L Integrity PadReactor.
Glucose concentration (blue) was
maintained with media perfusion
through Day 6.
Day 7 Vero cells
9
Different approach : Fixed bed option
 iCELLis technology is a single use reactor
 Its heart is a macro carriers fixed bed
 Single use reactor is part of a cGMP compliant
controller
 Design to simplify and significantly decrease costs
10
iCELLis™ carriers
iCELLis™ is a fixed-bed bioreactor filled with proprietary macrocarriers.
• PALL has developed its own carriers
• Microfibers of polyethylene terephthalate
(PET)
• Medical-grade, non woven
• PET fiber carriers are compressed into a
doughnut shaped basket offering the
cells a total cell friendly surface of up to
500m²
• Carriers for adherent and suspension
cell culture
11
iCELLis® scale-down unit: iCELLis® Nano
iCELLis™ nano is a system for: feasibility studies and small-scale virus and protein
production.
Cap
Cross section view and top view of the
iCELLis nano
NaOH
Media in T probe
Vent
DO &
pH
probes
Sampling
Media in
Impeller
Sampling
Air/CO2/O2
Fixed-bed
12
Media out
iCELLis® 500 – Manufacturing
iCELLis® is the next generation disposable bioreactor.
•
•
•
•
•
•
•
•
•
Fully integrated process control system
Integrated perfusion module
Five pumps: Perf IN/OUT, NaOH addition,
cells/sampling
Integrated biomass transmitter
PLC-Scada process control system
GAMP & 21cfr part11 compliant
Production sequences Mode
Data recording/trending: SQL database
(option) or local acquisition
Alarm Management System
13
From Nano to iCELLis 500: linear scalability
Bed height remains constant as scale increases.
, 4 & 10cm
6 cm / 2.4”)
14
iCELLis® platform – Features
Equivalence between fixed-bed volumes and number of Roller Bottles or Cell Factories or
micro beads quantities
Equipment
Fixed-Bed
volume (L)
Culture
surface area
(m²)
Equivalent
CS-10
(6300cm²)
Equivalent
CS-40
(25200cm²)
Equivalent
RB (850cm²)
Equivalent
Micro beads
(0.44m²/g)
iCELLis™ nano
0,04
0,53
NA
NA
6
1,2g
iCELLis™ nano
0.04
0,8
1
NA
9
1.8g
iCELLis™ nano
0.2
1,6
2
NA
19
3,6g
iCELLis™ nano
0.2
4
6
1-2
47
9g
iCELLis™ 500/100
5
100
159
40
1176
227g
iCELLis™ 500/200
10
200
317
79
2353
455g
iCELLis™ 500/500
25
500
794
198
5882
1136g
Fixed-bed height 2 cm
Fixed-bed height 2 cm
Fixed-bed height 4 cm
Fixed-bed height 10 cm
Fixed-bed height 2 cm
Fixed-bed height 4 cm
Fixed-bed height 10 cm
15
iCELLis® fixed-bed bioreactors offers an alternative to
increase capacity
4RB
4RB
4RB
16
20RB
20RB
100RB
40L
600RB
3000RB
200L
20RB
1000L
iCELLis 500
16
iCELLis answers customer needs
iCELLis answer
Customer needs
 Robust processes
 iCELLis is robust
– No failure (or reduced risk)
– Fully controlled process
– Reproducibility batch to batch
– cGMP compliant controller integrated
– Virus containment
– Fully close system
 Reduced development times
 iCELLis reduces development time and T2M
– Short process development/easy
validation
– No need to do beads to beads transfers, to
validate use of small, middle and large scale
– Scalability
– Strictly linear scalability between Nano and large
 Process economics
– Cost control
– Yield Increase
 iCELLis dramatically decreases costs
– 1 operator (2) only for a run equivalent to 3,000
RB
– High cell density achieved from a low seed
– Reduced unit operations
– Standalone equipment, no other reactors, no
perfusion equipment needed
– Capacity increase
– Dramatically reduced footprint/cleanrooms
Single Use. Multiple Solutions.
17
iCELLis® - Vet Vaccine US company Case Study
& Value Proposition
Case study: US veterinary vaccine company. Need: increasing number of batches (same product & size, use existing facility)
Roller Bottles
Bioreactors w/
µbeads
iCELLis™
570 RB/batch
200L bioreactor
1,2kg µbeads
1 iCELLis™ 200
Huge number of
manual operations
Development of
bioreactors at
10, 50, 200
Simplified seed train
Standard process
6RB, 1 iCELLis™ 200
No need to move to µbeads
OR
High labor costs
Development of
bead-to-bead
transfers
Carriers inside
Reduce manual operations –
labor costs
High
contamination risks
Development of
Perfusion techniques
(ATF, spin filter)
Integrated
perfusion
Reduced contamination risk
Re-use existing facility
Not adapted
18
3 years
development
<1 year to
commercial scale
18
How does iCELLis work?
Click on the picture to run the video
19
iCELLis Unique benefits – take home message
 Unique single use technology
 Small footprint
 Scalability between Nano and large iCELLis
 Perfusion included
 Decrease COG’s and PD
 High cell density/productivity
20
Viral vaccine production is not just equipment...
 Customers need complete platforms/solutions
 From media preparation to fill and finish
 Pall has all of this...
21
21
On-line: Pall’s Viral Vaccine Facility
http://www.pall.com/main/biopharmaceuticals/viral-vaccines-andviral-vaccines-48569.page
22
Media prep – Cell culture in iCELLis
2000 L
tank
Pump
23
Virus harvest / Clarification / Purification
Automated Tangential
Flow Filtration
Allegro SU TFF with
Cadence™ SUTFF
Chromatography
Mustang® Q XT
Sterile filtration and
integrity testing
24
Formulation and Filling
25
Pall Life Sciences R&D centers
“Customer Problem Solving”
 Pall approach combines both Product Development and
Process Development / Optimization.
 Pall has 4 Cell Culture Application & Development centers:
– PD Services / Technology implementation
– Tech transfer to customer facility or CMO
– Ph.D., Bioengineers, Scientists in cell & molecular
biology
 On site application support and bioprocess consulting
services
Europe
Brussels, Belgium – 500m² - PD, Application support, R&D
Portsmouth, UK – 500m² - R&D, PD
USA
• Westborough, MA – 500m² - R&D, Application support, PD
• Ann Arbor, MI – 400m² - R&D, PD
26
Thank you for your attention
27