Experiências Nacionais e Desafios no Desenvolvimento de Novas
Tecnologias Preventivas e Terapêuticas
Pesquisa em Vacina Anti-HIV: Questões Éticas e Regulatórias
Celio L Silva
Brasília, 04 -05 Outubro 2006
Modern vaccines
Antigens
Delivery systems
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up Quality Control
Immune potentiators or immune regulators
(Adjuvants)
Modern vaccines
Antigens
Delivery systems
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up Quality Control
Immune potentiators or immune regulators
(Adjuvants)
NBR ISO IEC 17025
Platforms for R&D&I
Infrastructure Human resources
Technological capabilities
Academy
(REDE TB and CPT)
Company
(Farmacore)
Regulation
Technological platform for R&D&I
NBR ISO IEC 17025
Institutional organization
Modern vaccines
Antigens
Delivery systems
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
y
Immune potentiators or immune regulators
(Adjuvants)
Scalle up Quality Control
NBR ISO IEC 17025
Th2
Humoral I.R.
Th1
Cellular I.R.
Immuno modulators or imuno potentiators
ADJUVANTS
•Heat Shock Proteins (HSPs)•CpGs ODN•TDM•KLK•Liposomes•Water-in-oil emulsion
NBR ISO IEC 17025
HSPs-Peptide complexHSPs-Peptide complex
PEPTIDE
Tumoral
Viral
Bacterial
Fúngal
Protection against
Cancer
Infectious diseases
HSP
Nature Reviews Immunology 2002
NBR ISO IEC 17025
Viral peptides chaperoned by Heat Shock Proteins (HSPs)
DNAhsp65
1. Phase I/II clinical trial of DNAhsp65 in patients coinfected with HIV/TB, especially those in advanced immunodeficiency status and non-responsive to antiretroviral regimens
2. Evaluate the ability of DCs pulsated with inactivated virus and stimulated with DNAhsp65 to enhance specific and unspecific anti-HIV immune response.
Therapeutical vaccine
Immunological mediators
NBR ISO IEC 17025
Modern vaccines
Antigens
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up
Delivery systems
Immune potentiators or immune regulators
(Adjuvants)
Quality Control
NBR ISO IEC 17025
Delivery systems
NBR ISO IEC 17025
LiposomesLiposomes
SUV
LUV
MLV
SUV
LUV
MLV
SUV 25 – 100 nm
20 nm – 3m
•DNA vaccine: gD-p24(Gag)•DNA vaccine: p24(Gag)-hsp65
•Mucosal administration
NBR ISO IEC 17025
0 30 60 90 days
100%
75%
50%
25%
DNA
Protein
Prime Booster
Single dose vaccines using “prime – boost” concept
Fast release - days Slow release – weeks to months
PRIME BOOSTER
DNAgD-p24(Gag) recombinant Protein p24
DNAgD-p24(Gag)
rp24(Gag)
NBR ISO IEC 17025
Modern vaccines
Antigens
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up
Delivery systems
Immune potentiators or immune regulators
(Adjuvants)
Quality Control
NBR ISO IEC 17025
Production of pilot lots in GMP conditions
Upstream Downstream
NBR ISO IEC 17025
DNAhsp65 and rhsp65 produced in GMP
Production of Delivery Systems in GLP conditions
PLGA microspheres
Liposomes
NBR ISO IEC 17025
Modern vaccines
Antigens
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up
Delivery systems
Immune potentiators or immune regulators
(Adjuvants)
Quality Control
NBR ISO IEC 17025
Quality Control
NBR ISO IEC 17025
Modern vaccines
Antigens
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up
Delivery systems
Immune potentiators or immune regulators
(Adjuvants)
Quality Control
NBR ISO IEC 17025
NBR ISO IEC 17025
Guidelines for Nonclinical Safety Assessment
Nonclinical Toxicity Studies
NBR ISO IEC 17025
Types of Nonclinical Toxicity Studies
NBR ISO IEC 17025
Modern vaccines
Antigens
Delivery systems
Pre-clinical and clinical studies
Profilactic or therapeutic vaccine efficacy
Reg
ula
tion
Acad
em
y
Com
pan
yScalle up Quality Control
Immune potentiators or immune regulators
(Adjuvants)
Certification
BPL
NRB ISO/IEC 17025:2005
Boas Práticas de Laboratório
Organização dos processos e das condiçõessob as quais os ensaios serão:•Planejados;•Executados;•Monitorados;•Registrados, •Relatados
Exigências Regulatórias
Nacionais e Internacionais:•ANVISA•INMETRO•FDA (USA)•CE (EUROPA)
NBR ISO IEC 17025
Boas Práticas de Laboratório
Certificações
CERTIFICAÇÕES
• Eficácia e Segurança
• Facilidades para registro de Produtos
• Diferencial competitivo
• Adequação ao mercado internacional
NBR ISO IEC 17025
Agradecimentos