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