OIWEEK 2017
Nov2016
© 2016 Butantan Institute - Reproduction forbidden without prior authorization
1901
2016
Established
to produce
against
the bubonic
One
of the main
public serum
producers
of vaccines
and plague
Vital Brazil, first
investigated antivenoms against snake bites
antivenoms
in director,
Latin America
mission
To contribute to public health through research, innovation, production and
development of biological products, sharing knowledge with the society
vision
To be a world-class public institution dedicated to research, development,
dissemination, education and the manufacturing of biological products for public
health demands
organizational structure
Instituto Butantan
Vaccine and Sera
Production
Scientific
Research &
Development
1.948 direct employees
35% public employees
65% Foundation workers
~100 outsourced employees
Source: Instituto Butantan (Jun2016)
Butantan
Foundation
Cultural Center
Other areas
~750,000 sq m
in the heart of
the urban area
Butantan campus
USP
300,000
visitors/year
60%
preserved
green area
4
museums
Butantan campus
history museum
microbiology museum
biology museum
Emílio Ribas museum
scientific research & development labs
•
Research units
- Scientific Development Division [19 labs]
- Center of Biotechnology [8 labs]
•
•
Hospital Vital Brazil [10 beds]
•
•
180 PhD researchers
Central Animal Facility
500 graduate students
scientific research & development labs
4
major areas
Labs
animal
biology
toxinology
vaccinology
development
Arthropods
Bacteriology
Biochemistry
Biotechnology Center
Cell Cycle
Cellular Biology
Ecology and Evolution
Genetic
Herpetology
Immunochemistry
Immunogenetics
Immunopathology
Pain and Signaling
Parasitology
Pathophysiology
Pharmacology
Special Lab of Applied Toxinology
Viral Immunology
Virology
Zoological Collections
educational programs
•
scientific knowledge courses
•
more than 20 graduate extension courses
•
Graduate Studies in Toxinology
•
Inter-institutional Graduate Studies in Biotechnology
•
MBA in Health Innovation Management
•
Scientific Initiation
•
PAP - Professional Advancement
Program
venomous animals; sera and vaccines; pharmacovigilance; amphibian biology etc.
approved by CAPES in August 2010, with a grade of 5 (out of 7 points), for Masters and PhDs
[University of São Paulo, Institute for Technological Research - IPT, Instituto Butantan]
Trains professionals for the management of
critical functions of the innovation process,
promoting the creation of mechanisms to
facilitate technology transfers.
Health sector professional training
horse immunization
São Joaquim Farm
50 km from São Paulo
antivenom production
~ 800 horses
22,000 liters of plasma/year
snake facility
~1,000 animals
venon for antivenom production
- Bothrops - 5 species
- Crotalus - 2 subspecies
- Lachesis - 1 species
- Micrurus - 2 species
spider / scorpion facility
~ 15,000 animals
- Loxosceles spider (brown spider)
- Phoneutria spider (banana spider)
- Tityus scorpion (yellow scorpion)
caterpillar lab
~ 600 animals
- Lonomia caterpillar
industrial complex - production
•
•
•
•
•
•
•
7 plants
Anaerobic vaccines
- Tetanus and Botulism
Bacterial Purification Center
Aerobic Vaccines
- Diphtheria and Pertussis
Hepatitis B
Influenza
Rabies
Sera
1 Formulation and Filling Center
5 multifunctional pilot plants
o Dengue
o Rotavirus
o Monoclonal antibodies
o Influenza - H5N1
o Blood products
13
immunoglobulins
portfolio of serum products
5 snake antivenoms
2016 capacity
500,000 vials/ year
Ministry of Health demand
900,000 vials/ year
diphtheria antitoxin
tetanus antitoxin
spider antivenom
botulism AB antitoxin
scorpion antivenom
botulism E antitoxin
caterpillar antivenom
rabies antiviral
9 vaccines of the national calendar
88 million doses (2015)
Programa Nacional de Imunizações - PNI
[National Immunization Program]
free of charge vaccination
5.570 cities - 27 states (all Brazilian states)
7 official vaccine manufacturers
DTP
Diphtheria-Tetanus-Pertussis
rabies
DTP
Diphtheria-Tetanus-Pertussis
hepatitis B
portfolio of vaccines
(celular)
(acelular)
dT
Diphtheria-Tetanus
(for adults)
DT
Diphtheria-Tetanus
(for children)
hepatitis A
influenza
HPV
tetravalent
Hepatitis B
- 1st recombinant vaccine produced
in Brazil
- 100% produced by Instituto Butantan
- target audience (2013):150 million people
under the age of 49 years
(75,6% of the population)
- 800.000 carriers in Brazil
HPV
- 685,400 infected people/year
- 95% of the cases of cervical cancer
- second most common cancer in women
Influenza
- TT concluded
- 50 million doses produced in 2016
Instituto Butantan: complete biological production lines certified with Anvisa GMP
Sources: SINAN; website Portal da Saúde - SUS; Ministry of Health (2013)
120%
328 m
306 m
452 m
311 m
211 m
230 m
235 m
244 m
doses
100%
11%
80%
% of acquired doses
Programa Nacional de Imunizações - PNI
Ministry of Health acquisitions
34%
8%
5%
6%
13%
7%
12%
6%
4%
27%
4%
4%
24%
11%
Opas
PAHO
6%
Tecpar
5%
2%
4%
3%
4%
60%
22%
5%
4%
5%
6%
Funed
40%
34%
39%
15%
35%
32%
5%
34%
40%
FAP
21%
Butantan
48%
42%
20%
36%
40%
40%
40%
29%
28%
0%
2008
2009
2010
2011
2012
2013
2014
2015
BioManguinhos /
Fiocruz
study of bioactive components of poisonous animals
poisonous animals
pharmacological activities
•
•
•
•
•
•
analgesic
anti-inflammatory
anticoagulant
antitumor
nervous system related action
anti-hypertensive
patents
vaccine
serum
immunotherapy
haemostasis
analgesic
peptide
tissue regeneration
anti cancer
antibody
others*
total
quantity
12
3
3
2
2
2
2
1
2
11
40
* others include: propolis extract, protein from
Leptospira, spider proteins, recombinant protein for
AIDS diagnosis, etc.
Silica (SBA-15) – 1 patent
Cristália / Fapesp
Lopap – 4 patents
Biolab / Fapesp
Amblyomin-X – 2 patents
União Química / Fapesp
patents
Immunosuppressor – 1 patent
Cristália / Fundação Butantan
Pertussis low – 1 patent
Crotalphine – 2 patents
Biolab / Fapesp
pipeline
nr Products
description
1
Dengue Vaccine
Attenuated tetravalent vaccine (serotypes DEN1, DEN2, DEN3, DEN4) –
Phase 3 of clinical trials
Inactivated, DNA, attenuated
2
Zika vaccine
3
Rotavirus vaccine
4
Pertussis low vaccine
Attenuated pentavalent vaccine (serotypes G1, G2, G3, G4, G9) –
Phase 2 of clinical trials
B. pertussis whole cell with lower content of LPS for adults and combinations
5
Pneumococcal vaccine
Inactivated non-encapsulated pneumococcal whole cell
6
Hepatitis B + MPLA vaccine
For > 50 years old and immunocompromised persons
7
rBCG - Hep B vaccine
For neonates
8
Onco rBCG vaccine
For bladder cancer treatment
9
Adjuvant BpMPLA
BpMPLA derived from LPS of B.pertussis to be combined to different vaccines
10
Bee’s antivenom
Treatment against multiple bee stings
11
Sílica (SBA-15)
Adjuvant for orally administrated vaccines
12
Amblyomin-X
Anticancer medicine, obtained from tick saliva
13
Crotalphine
Potent analgesic drug from snake venom. Long-lasting analgesic (2-5 days)
14
Crotamin
15
Lopap
Cell penetrating peptide - Introduction of genetic materials into the cells, such as DNA and
RNA
Prothrombin Activator, anti-apoptotic activity and other pharmaceutical formulations
16
Monoclonal antibodies
Anti-CD3 for transplantion rejection and other monoclonals for other uses
17
Hemoderivatives
Production of IgG, factor VIII, IX, Albumin and other products
18
Diagnostic kits
For Dengue, zika and leptospirosis diagnostic
dengue – Butantan-NIH vaccine
•
phase II clinical trials
- 2 clinical sites (Hospital das Clínicas da
Faculdade de Medicina - Universidade
de São Paulo
- 300 volunteers, 18-59 yo
step a
50 dengue-naïve participants
step b
50 dengue-naïve participants
200 dengue experienced participants
Boa Vista
Manaus
•
Recife
phase III clinical trials
started on Jan 2016
- 14 clinical research centers
- 17,000 volunteers, 2-59 yo
- safety, immunogenicity and efficacy
objective: vaccine license by Anvisa
Fortaleza
Porto Velho
Cuiabá
00
Campo Grande
Aracaju
Brasília
Belo Horizonte
São José do Rio Preto
São Paulo
Porto Alegre
zika virus program – Instituto Butantan
1. Diagnostic tests
serology test
- Butantan and Medical School of the University of São Paulo
(Grant Horizon 2020: infrastructure for the Butantan dengue vaccine phase III clinical trials)
- Instituto Butantan and Los Alamos National Laboratory (USA)
2. Therapy
- horse immunization – Butantan R&D program
- neutralizing human anti-zika monoclonal antibodies
Butantan and Rockfeller University (USA)
- small molecules with antiviral action
3. Vaccine development
- inactivated zika vaccine: Butantan R&D program – Barda / WHO support
- live attenuated pentavelent dengue-zika vaccine – Butantan / NIH
- live attenuated zika vaccine – Butantan R&D program
- subunity zika vaccine – Butantan / USP
INCTtox
Instituto Nacional de Ciência e Tecnologia em Toxinas
[National Institute of Science and Technology for Toxins]
centres of excellence
Financial support: CNPq
Centro de Toxinas,
Resposta-Imune e
Sinalização Celular
[Center of Toxins, Immune-Response and Cellular Signaling]
10 projects – biochemical, molecular and cellular mechanisms of toxins with therapeutic potential
Financial support: Fapesp
discovery and validation of therapeutic targets
for the development of new drugs for
inflammatory based diseases
Financial support: GSK-Fapesp
international collaboration
Instituto
Butantan
Steering
Committee
3-4 Nov 16
Zika Summit
Butantan - Myanmar
Dengue vaccine
Zika vaccine
Mar 2017
Workshop Butantan
- United Kingdom
Oct 2017
Workshop Butantan CEA/France
Science
dissemination,
animal biology and
neuroscience
Vaccines –
Immunology; Toxin
analysis by in vivo
Imaging; Therapeutic
toxins and Expression
of toxic proteins
Agência Brasileira de
Cooperação - MRE
national and international partnerships
Harvard
‘
masterplan
current
occupation
considering
- public and restricted circulation
- preserved areas
labs
education
production
Institut for Innovation in
Biotechnology Butantan - IIBB
cultural
administration areas
Butantan
fase 2
grupo de ação rápida para
doenças emergentes
GARDE
fase 1
USP
total area : 30,000 sq m
Institut for Innovation
in Biotechnology Butantan - IIBB
• center dedicated to research, innovation and generation of
innovative enterprises
• renovated building (30,000 sq m)
• promotion of
- Group of prompt action for emergent diseases (Garde)
- joint ventures with private institutions
- Butantan and partners development projects
IIBB
conceptual
project
Geraldo Alckmin
Governor of the State of São Paulo
David Uip
State Secretary of Health
Sergio Swain Muller
Coordinator of Science, Technology
and Strategical Health Products
Jorge Kalil
Director
Marcelo De Franco
Deputy diretor
Board of Directors
Jorge Kalil (presidente)
Erney F. Plessmann de Camargo
Fernando de Souza Meirelles
Gonzalo Vecina Neto
Luiz R. Raja Gabaglia Travassos
Luiz Vicente Rizzo
Moisés Goldbaum
Paulo Lee Ho
Yara Cury
Erney F. P. De Camargo
President
Board of Curators
Jorge Kalil (president)
Fernando de Souza Meirelles
Gonzalo Vecina Neto
João Fernando Gomes da Oliveira
Luiz R. Raja Gabaglia Travassos
Luiz Vicente Rizzo
Marcelo De Franco
Moisés Goldbaum
Paulo Lee Ho
Yara Cury
Finance Council
Carlos Alberto Marsal
Joaquim José C. Engler
Hélio Nogueira da Cruz