influenza vaccine - who · sÃo paulo - brazil 1901: vital brazil creates instituto butantan and...
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INFLUENZA VACCINE
Belgrade, Serbia
March 27-29th, 2012
Instituto Butantan | 1
INSTITUTO / FUNDAÇÃO BUTANTAN
SÃO PAULO - BRAZIL
1901: Vital Brazil creates Instituto Butantan and starts to produce
anti-pest serum.
Main producer of vaccines and sera in South America
Production: ~ 160 million doses of vaccine (51 %)
~ 410,000 ampoules of serum (56 %)
( in 2010)
Instituto Butantan | 2
INDUSTRIAL PRODUCTION
SEASONAL INFLUENZA VACCINE
1999: Technology transfer signed with Butantan and Sanofi-
Pasteur (Pasteur-Merieux)
Quality control tests → Filled Vaccine → Formulated
bulk → Blending, filling and packing → Production
Technology
2009: Water Batches (11 lots)
2010: H3N2 production tests (59 lots)
Seasonal vaccine
2010-11: ~ 5 millions doses (45 lots)
2011-12: ~ 20 millions doses (146 lots)
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INFLUENZA LABORATORY
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INFLUENZA PILOT PLANT
Pilot Plant (renovated building): ~ 300 m2, BSL 3
Grantees: WHO, CDC, MoH
Instituto Butantan |
• 2007: testing production line - A/Panama/2007/99 (H3N2)
• 2007- 08: Production
- A/Vietnam/1194/2005- NIBRG-14 (H5N1): master and
working seed and production (split and whole virus)
• 2008: Installation of Quality Control Laboratory for Influenza
• 2009-10: Production
- A/California/210/2009 (A/H1N1): master and working
seed and production (split and whole virus)
• 2011: Production
- A/Victoria/120/2009 (H3N2) and B/Brisbane/60/2008:
master and working seed for seasonal vaccine
5
PILOT SCALE PRODUCTION
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INFLUENZA PILOT PLANT
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INFLUENZA VACCINE
SPLIT X WHOLE VIRUS
BUTANTAN INSTITUTE
BUTANTAN FOUNDATION
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SPLIT X WHOLE
Clarification X X X X
Concentration X X X
1st purification X X X
2nd purification X
Diafiltration/concentration X X
Chromatograph* X X
Spliting X
Inactivation X X X X
Final filtration X X X X
* Size exclusion (sheparose 4 FF)
WHOLE VIRUSSTEP SPLIT
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Fig.1. Flow diagram for the production of split and whole vaccine
Alantoic fluid
Clarification
Concentration Clarification
Purification Inactivation and diafiltration/concentration
Split, diafiltration and inactivation Gel filtration chromatography
Final filtration Final filtration
SPLIT VACCINE WHOLE VACCINE
C. Miyaki et al. / Vaccine 28 (2010) 2505–2509
SPLIT X WHOLE
Instituto Butantan |
WHOLE VIRUS VACCINE
• Clarification: 7000 rpm/20 min or continuous flow
• Inactivation: 0.2 % formaldehyde
• Clarification: 7000 rpm/10 min or continuous flow
• Concentration: 20 times
• Ultrafiltration/Diafiltration: 20 times (PBS)
• SEC: Sepharose 4FF
High ~ 60 cm
• Load 6 – 10 % CV
• Final filtration: 0.65 + 0.45 + 0.22 µm
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INFLUENZA WHOLE VIRUS VACCINE
97
66
45
30
20
14
AF W W S MW S W H3 H3
SDS-Page
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H1N1 Split 1.5 20.8 41.0 2.0
H1N1 Whole 6.9 25.4 5.2 0.2
H3N2 Split 2.0 - - -
H3N2 Whole 3.0 - - -
B Split 1.3 - - -
B Whole 1.5 - - -
SPLIT X WHOLE
- On analysis
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SPLIT X WHOLE
Instituto Butantan |
PHASE I CLINICAL TRIAL – A/H1N1
Instituto Butantan | 15
Av. Vital Brasil, 1500 - Butantã
São Paulo – SP
Zip Code - 05503-900
(+ 55 11) 2627-9372
www.butantan.gov.br
Muito Obrigada!
Cosue Miyaki
Mauricio Meros de Oliveira