RESUMO
The development of human cell therapy and gene therapy products has progressed internationally. Efforts have been made to address regulatory challenges in the evaluation of quality, efficacy, and safety of the products. In this forum, updates on the specific challenges in quality, efficacy, and safety of products in the view of international development were shared through the exchange of information and opinions among experts from regulatory authorities, academic institutions, and industry practitioners. Sessions identified specific/critical points to consider for the evaluation of human cell therapy and gene therapy products that are different from conventional biological products; common approaches and practices among regulatory regions were also shared. Certain elements of current international guidelines might not be appropriate to be applied to these products. Further, international discussion on the concept of potency and in vivo tumorigenicity studies, among others, is needed. This forum concluded that the continued collective actions are expected to promote international convergence of regulatory approaches of the products. The Pharmaceuticals and Medical Devices Agency and Japanese Society for Regenerative Medicine jointly convened the forum with support from the National Institutes of Biomedical Innovation, Health and Nutrition. Participants at the forum include 300 experts in and outside of Japan.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Terapia Baseada em Transplante de Células e Tecidos/instrumentação , Congressos como Assunto , Terapia Genética/instrumentação , HumanosRESUMO
The regulatory environment for cell- and tissue-based therapeutic products and gene therapy products is rapidly evolving and drug regulatory agencies are working towards establishing a risk-based system in the regulatory framework. Similarly in Singapore, a risk-based tiered approach has been applied whereby clinical trials and product licence of high-risk cell- and tissue-based therapeutic products (substantially manipulated products, products intended for nonhomologous use or combined products) and gene therapy products are regulated as medicinal products under the Medicines Act. There is no legal definition for cell- and tissue-based therapeutic and gene therapy products. The current working definition for a cell- and tissue-based therapeutic product is an article containing or consisting of an autologous or allogeneic human cell or tissue that are used for or administered to, or intended to be used for or administered to, human beings for the diagnosis, treatment, or prevention of human diseases or conditions. Gene therapy products are included under the current biological medicinal product definition.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/ética , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Terapia Genética/legislação & jurisprudência , Aplicação de Novas Drogas em Teste/legislação & jurisprudência , Pesquisa Translacional Biomédica/legislação & jurisprudência , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos/métodos , Terapia Genética/ética , Humanos , Segurança do Paciente/legislação & jurisprudência , Guias de Prática Clínica como Assunto , Controle de Qualidade , Projetos de Pesquisa , Singapura , Pesquisa Translacional Biomédica/éticaRESUMO
Rapid developments in scientific and technological aspects in stem cell biology and tissue engineering have led to the increased use of human cells and tissues for the treatment of various diseases and injuries. The regulatory environment for CTT products is rapidly evolving and drug regulatory agencies are working towards establishment of a risk-based system with some common features. Various drug regulatory agencies in many countries/regions have implemented regulatory controls in the last few years. This article will highlight some of works done till date to regulate CTT products in Australia, Canada, Europe, Japan, Korea, Singapore and United States of America.
Assuntos
Pesquisa Biomédica/normas , Terapia Baseada em Transplante de Células e Tecidos/normas , Austrália , Pesquisa Biomédica/legislação & jurisprudência , Pesquisa Biomédica/métodos , Canadá , Terapia Baseada em Transplante de Células e Tecidos/métodos , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/métodos , União Europeia , Regulamentação Governamental , Humanos , Japão , Coreia (Geográfico) , Medição de Risco/legislação & jurisprudência , Medição de Risco/métodos , Singapura , Estados UnidosRESUMO
The regulatory environment for cell- and tissue-based therapeutic (CTT) products is rapidly evolving and drug regulatory agencies are working toward establishing a risk-based system in their regulatory approach. In Singapore, CTT products such as cell therapy products, stem cell products, and tissue-engineered products in regenerative medicine are regulated as medicinal products. CTT products are defined as articles containing or consisting of autologous or allogeneic human or xenogeneic cells or tissues that are used for or administered to, or intended to be used for or administered to human beings for the diagnosis, treatment, or prevention of human diseases or conditions. Currently, we have applied a risk-based tiered approach whereby high-risk CTT products (substantially manipulated products, products intended for nonhomologous use or combined/used in conjunction with a drug, biologic, or device) are regulated under the Medicines Act. A new standalone regulation for CTT products is being proposed under the Health Products Act where we propose to regulate the entire spectrum (high and low risk) of CTT products.
Assuntos
Produtos Biológicos/normas , Terapia Baseada em Transplante de Células e Tecidos/normas , Células-Tronco , Engenharia Tecidual , Animais , Produtos Biológicos/uso terapêutico , Humanos , Singapura , Engenharia Tecidual/legislação & jurisprudência , Engenharia Tecidual/normasRESUMO
Immunomics research uses in silico epitope prediction, as well as in vivo and in vitro approaches. We inoculated BALB/c (H2d) mice with 17DD yellow fever vaccine to investigate the correlations between approaches used for epitope discovery: ELISPOT assays, binding assays, and prediction software. Our results showed a good agreement between ELISPOT and binding assays, which seemed to correlate with the protein immunogenicity. PREDBALB/c prediction software partially agreed with the ELISPOT and binding assay results, but presented low specificity. The use of prediction software to exclude peptides containing no epitopes, followed by high throughput screening of the remaining peptides by ELISPOT, and the use of MHC-biding assays to characterize the MHC restrictions demonstrated to be an efficient strategy. The results allowed the characterization of 2 MHC class I and 17 class II epitopes in the envelope protein of the YF virus in BALB/c (H2d) mice.
Assuntos
Modelos Animais de Doenças , Mapeamento de Epitopos , Epitopos de Linfócito T/imunologia , Proteínas Estruturais Virais/metabolismo , Febre Amarela/imunologia , Vírus da Febre Amarela/imunologia , Sequência de Aminoácidos , Animais , Biologia Computacional , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Software , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/imunologia , Febre Amarela/prevenção & controle , Febre Amarela/virologia , Vacina contra Febre Amarela/administração & dosagem , Vacina contra Febre Amarela/imunologiaRESUMO
Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-gamma and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-gamma responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N76-114, each of which contained nonameric H2d binding domains with high binding scores for both class I and, except for N76-93, class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-gamma and IL-4 responses and strong memory CTL responses to the LAMP-N chimera.