Progress Toward A Low COGs PER.C6 based IPV · Progress Toward A Low COGs PER.C6® based IPV 11th WHO/UNICEF Consultation with OPV/IPV Manufacturers and NRAs Geneva, Switzerland 25

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

10

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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