Validação dos processos envolvidos na obtenção do polissacarídeo capsular de Haemophilus influenzae tipo b conjugado com toxóide tetânico utilizado para produção de vacina

• Autor(a) principal: Barreira, Aline Louzada Santos
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12020
• topic: validation; conjugate vaccine; haemophilus influenzae type b; validação; vacina conjugada; haemophilus influenzae tipo b; CNPQ::ENGENHARIAS::ENGENHARIA QUIMICA::TECNOLOGIA QUIMICA

Haemophilus influenzae type b (Hib) is a primary cause of bacterial pneumonia and meningitis in children under 5 years of age. The disease can be prevented by immunization with a population of polysaccharide-protein conjugate vaccine, once the polysaccharide vaccine is not effective. Since 1999, the Ministry of Health included the Hib conjugate vaccine in the routine immunization schedule children routinely. Since this is a production process of importance to people and significant demand for the Brazilian government, it is required under rules that national and international regulatory processes of this kind should be validated. An operation validated ensures the production of uniform batches that attend the required specifications, consequently generating to the manufacturer charge of providing a quality product. The work proposes the development of a methodology that provides evidence that the process and ensures the production of a polysaccharide-protein conjugate by chemical conjugation method will be produced consistently and according to its predefined specifications. The quality attributes, guaranteeing, not the lack of Haemophilus influenzae type b by process deviations, which would cause increased value added to the product in question. Therefore, the validation methodology was applied to the validation study. The study was based on three stages. The first one was based on examination of chemical conjugation process parameters for mapping and establishing critical control ranges for these parameters; the second phase was carried out with the production of three consecutive batches on an industrial scale with regular monitoring of critical parameters mapped previously. The final stage consisted in collected samples, at predetermined time, during the process management and control of the final product in a lot 50% higher than in the routine production. These samples were analyzed using research methods that they have been validated before to ensure reproducibility of the results. The robustness of the process was ensured since all process parameters evaluated showed results within the compliance standard determined with results of in-process control and final product for the population sampled within specifications defined by analytical methodologies validated ensuring the results. The proposed work secured status validated process for polysaccharide-protein conjugate with exceptional yields obtained and combined with well-defined chemical characteristics