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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
• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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
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)
• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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
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
• PER.C6® cell line
• PER.C6® & PIN process
• PER.C6 ®, PIN process & IPV
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
Poliovirus production in PER.C6® cells constant at different production scale
High yields of all 3 poliovirus independently of the scale
Polio Virus produced on PER.C6 & PIN process Successfully purified
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VP1
VP2
VP3
SAUKETT
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
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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