Aplicación del análisis de riesgo en la preparación de soluciones para producción de Quimi-Hib® / Risk assessment tools in the preparation of the solutions used in the production of Quimi-Hib®

Entre las técnicas avanzadas de administración de riesgo se encuentran las herramientas de soporte estadístico, así como los histogramas y gráficos de frecuencia acumulada, los cuales sirven de base para la acumulación de datos. Se realizó un análisis de los mismos y se evaluó la influencia de diferentes parámetros sobre un proceso determinado para la toma de decisiones. Los resultados obtenidos demostraron que existe riesgo de contaminación de las soluciones en una cabina de flujo laminar. Todos los tampones evaluados cumplieron satisfactoriamente con los límites establecidos para el contenido de endotoxinas y límite microbiano. Los valores de carga microbiana, determinados por diferentes métodos en el ambiente de trabajo, estuvieron dentro de los límites, acorde con la clasificación de las áreas. La higienización de los tanques de preparación demostró que los procedimientos empleados garantizaron una adecuada remoción de los contaminantes. Se concluyó que los riesgos y escenarios evaluados fueron aceptables para alcanzar la calidad del producto(AU)

Among the advanced techniques of risk management are the tools of statistical support, such as histograms and cumulative frequency plots, which are the basis for the accumulation of data. An analysis of these and evaluated the influe.nce of different parameters on a particular process for making decisions. The results showed that a risk contamination of the solutions named in a laminar flow cabinet in which filtered. All buffers tested satisfactorily complied with the limits for the content of endotoxin and microbial limit. The microbial load values determined by different methods in the workplace gave values within the limits, according to the classification of areas. The sanitizing preparation tanks showed that the procedures ensured adequate removal of contaminants. It was concluded that the risks and scenarios evaluated to achieve acceptable product quality(AU)

Cromatografía de adsorción para purificar el disacárido espaciador del ingrediente farmacéutico activo de la vacuna QuimiHib® / Adsorption chromatography to purify Spacer disaccharide of Active Pharmaceutical Ingredient of QuimiHib® vaccine

En este trabajo se estudiaron las condiciones de la cromatografía de adsorción en Silicagel 60 para la purificación del disacárido espaciador (DSE), componente del ingrediente farmacéutico activo de la vacuna QuimiHib®. Para ello se realizó un desescalado a una escala analítica que representó el 1,8% del proceso industrial. Se logró reproducibilidad en términos de calidad de empaque, pureza y recobrado entre ambas escalas. Se determinó que la capacidad dinámica de carga de la resina Silicagel 60 por el DSE fuera de aproximadamente 125±0,2 mg/mL de resina empacada; 3,4 veces superior al proceso base. El perfil de elución que se obtuvo indicó la posibilidad de colectar una fracción única en el rango 195±2 y 260±2 min. Si se mantiene un correcto empaque de la resina cromatográfica, determinado por un factor de asimetría entre 0,8 y 1,2 se garantiza un recobrado de 58,9±4,5 por ciento y una pureza equivalente a la del patrón de referencia en el análisis por cromatografía de capa delgada. El ajuste de la condición de adsorción incrementa la productividad de la operación en 3,5 veces, indicando que la propuesta es económicamente factible(AU)

In this paper we study the conditions of adsorption chromatography on Silica gel 60 for purification of Spacer disaccharide a component of Active Pharmaceutical Ingredient (API) of QuimiHib® vaccine. For that, we made a scale down on an analytical scale that represented at 1.8% of industrial process, indicating reproducibility between two procedures in terms of packing efficiency, purity and recovery. Dynamic binding capacity of the resin Silicagel 60 by the DSE was roughly 125±0.2 mg /mL, 3.4 times the base process. The elution profile obtained, showed the possibility of collecting a unique fraction at range 195±2 and 260±2 minutes, if it is maintained a proper packing of the chromatography resin determined by asymmetry factor from 0.8 to 1.2, which ensures a recovery of 58.9±4.5 percent and high purity analyzed by Thin Layer Chromatography. Adjusting the adsorption conditions increases the productivity of chromatographic operation up to 3.5 fold, indicating that it is feasible in economic terms(AU)

Phase I clinical evaluation of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b in human adult volunteers.

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.

Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine(AU)

Desde 1989, hemos participado en el desarrollo de una vacuna contra el Haemophilus influenzae tipo b. La nueva vacuna se basa en la conjugación de oligosacáridos sintéticos a toxoide tetánico. Nuestros principales objetivos han sido (i) para verificar la viabilidad de la utilización de la síntesis de antígenos y (ii) búsqueda de nuevas alternativas de producción para este importante vacuna infantil. En total, ocho ensayos ya se han realizado con adultos, niños (de 4 a 5 años), y los lactantes. Hemos descrito en este documento los detalles de los dos primeros ensayos clínicos de fase I realizado con voluntarios adultos humanos en virtud de doble ciego, randomizado condiciones. Los participantes recibieron una única inyección intramuscular para evaluar la seguridad y la inmunogenicidad inicial. Hemos encontrado un excelente perfil de seguridad y una respuesta de anticuerpos similar a la observada para el control de vacunas

Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b.

Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.

A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b.

Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.