Progress Toward A Low COGs PER.C6 based IPV · Progress Toward A Low COGs PER.C6® based IPV 11th...
Transcript of Progress Toward A Low COGs PER.C6 based IPV · Progress Toward A Low COGs PER.C6® based IPV 11th...
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Progress Toward A Low COGs PER.C6® based IPV 11th WHO/UNICEF Consultation with OPV/IPV Manufacturers and NRAs Geneva, Switzerland 25 October, 2012
Gabriella Rolli Program Director, Crucell
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A new chapter in the story of IPV?
• Janssen/Crucell aims to develop and deliver an affordable IPV vaccine
• Using an innovative technology platform based on
– PER.C6 cell line
– PIN Process (Crucell Process INtensification)
• Targeting
– High Production Capacity
– Low Cost of Goods
– Adjuvant-free
– Intramuscular administration
– Comparable Immunogenic & Safety profile to current marketed IPV
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• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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Development of PER.C6® The remarkable science of A.J. van der Eb
Transformed Clones
1o Human Retinal Cells
MCB
P29 1996 A068-016
E1
PER.C6®
CaPO4
Adherent PER.C6® cells
Suspension PER.C6® cells
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PER.C6® Cell Line
• Human cell line immortalized by adenovirus E1
• Growth Serum Free in suspension
• Stable without antibiotic selection pressure
• Compliant with regulatory guidelines
– Extensively tested Cell banks in place
– Extensive documentation on origin & history
– Strong safety record based on comprehensive bacterial/viral testing,
tumorigenicity & oncogenicity, PrP
• Endorsed as cell substrate for vaccine manufacture VRBPAC, (FDA Advisory committee, 2001)
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• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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Cell culture attributes of PER.C6® Serum Free: high density growth in suspension
PER.C6® : SF growth as single cell suspensions
PER.C6® : SF growth with perfusion to cell densities > 100 Million cells/mL
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PER.C6 in PERMEXCIX100L intensified process
0 1 2 3 4 5 6 7 8 9 100
25
50
75
0
20
40
60
80
100
TCD
Viability
Time(days)
Ce
ll d
en
sit
y
(x10
6 c
ells/m
L)
Via
bility
(%)
PER.C6® & Intensified Process (PIN process)
PER.C6® grow in suspension
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PIN process – Crucell Intensified Technology Increase production while decreasing production volume
PIN Process: Increase the number of active ingredients (= PER.C6® cells)
in the bioreactor to increase the output per bioreactor
27 g/L
Cell growth to >100 Millions cells/mL
Sanofi and Lonza
Cell growth to ≥5 Millions cells/mL
Non-Intensified process 20.000 L scale
PIN Process 500 L scale
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• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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Sanders et al., 2012. Manuscript submitted & accepted, Vaccine
Polio Virus productivity in PER.C6® >10 fold higher compared to VERO cells
Poliovirus production on PER.C6® cells (PIN) vs. VERO cells (micro-carriers)
expressed in titers/mL
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Comparison of PER.C6 and VERO derived Specific D-Antigen Content (DU/cell)
MOI=2 MOI=0.1 MOI=2 MOI=0.1 MOI=2 MOI=0.1 MOI=2 MOI=0.10.00001
0.0001
0.001
VERO grown
PER.C6
Grown
PV1 Brunenders PV2 MEF1 PV1 Mahoney PV3 Saukett
D-A
ntigen (
DU
/cell)
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Poliovirus productivity per cell in PER.C6® 2.5 fold higher compared to VERO cell
Polio Virus in PER.C6 cells compared to VERO cells,
expressed in DU/cell D
-an
tig
en
(D
U/c
ell
)
PV1 Brunenders PV2 MEF-1 PV1 Mahoney PV3 Saukett
MOI=2 MOI=0.1
PV1 Brunenders
MOI=2 MOI=0.1 MOI=2 MOI=0.1 MOI=2 MOI=0.1
0.001
0.0001
0.00001
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MOI= Multiplicity of infection
Sanders et al., 2012. Manuscript submitted & accepted, Vaccine
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PER.C6® & PIN Poliovirus productivity significantly increased
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Poliovirus Cell specific productivity at 1x107 cell,
similar to unit productivities at 1x106 cells
VERO : Bakker et al; 2011
PER.C6 ® data from 10L scale
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Poliovirus production in PER.C6® cells constant at different production scale
High yields of all 3 poliovirus independently of the scale
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Polio Virus produced on PER.C6 & PIN process Successfully purified
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VP1
VP2
VP3
SAUKETT
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Summary
IPV manufactured with PER.C6® & PIN Technology, compared to IPV produced
with current process based on VERO cells, results in:
- Number of cells per bioreactor
- Polio virus productivity/cell
- Overall Poliovirus productivity (DU/L)
- To produce 200 Million doses/year
14
12 fold
increase
2,5 fold
increase
30 fold
increase
1 x 500L
bioreactor
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To support the WHO Polio Eradication Program by filling current worldwide gap in capacity for affordable IPV
To develop an affordable IPV that can be used in hexavalent combination vaccines
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