ABSTRACT
Objetivo: identificar los riesgos generales en la etapa de limpieza de los cambios de campaña de una planta multipropósito para productos biológicos, así como proponer acciones de control para mitigarlos, garantizando enfocar la atención sobre los riesgos no aceptados identificados y sus escenarios.Métodos: se aplicó el análisis de riesgos de calidad, usando la herramienta análisis de modo y efectos de fallas, lo cual permitió la identificación de los riesgos asociados a la contaminación y sus escenarios, así como accionar de forma proactiva teniendo en cuenta los resultados del cálculo del número de prioridad de riesgo. Resultados: se demostró que los residuos de producto e higienizante comprometen la etapa de limpieza. Se propusieron acciones que deben ser documentadas en los procedimientos de limpieza de los equipos no dedicados. Conclusiones: se identificaron los riesgos generales y sus escenarios. Las acciones de control de riesgos implementadas mitigaron a más del 50 por ciento del número de prioridad de riesgo total para garantizar la efectividad de la operación de cambio de campaña como parte del cumplimiento de las Buenas Prácticas de Fabricación
Objective: to identify the general risks in the cleaning phase during changeover in a multiproduct plant for biological products and to put forward control actions to reduce them, guaranteeing to focus attention on the unacceptable identified risks and their scenarios. Methods: aquality risk analysis using the tool called Failure Mode and Effect Analysis was made, which allowed identifying pollution-associated risks and their settings, and working proactively according to the results of the risk priority number estimation. Results: it was proven that the product and the cleaning agent residues may compromise the cleaning phase. Several actions that should be documented in the cleaning procedures of non-dedicated equipment were then suggested. Conclusions: the general risks as well as their settings were identified. The implemented risk management actions reduced total risk priority number values by over 50 percent in order to assure the effectiveness of the changeover operation as part of the compliant requirements for Good Manufacturing Practices
Subject(s)
Biological Contamination , Risk AssessmentABSTRACT
We studied the capacity of an API-rHBsAg purification process to eliminate DNA contamination from yeast-host cell. Firstly, was demonstrated consistency of manufacturing purification process to remove DNA, from (3.9 + - 1.9)108 pg/dose in starting material to (3.4 + - 1.6) pg/dose, equivalent to 8.2 log in Active Pharmaceutical Ingredient (API), measuring DNA quantity in several unit operations along manufacturing process for twenty batches, five consecutive in 2000, 2001, 2003 and 2005. These values for API, lower than 10 pg/dose, accomplish current WHO requirements for Hepatitis B vaccines obtaining by recombinant DNA technology (WHO, 1989; European Pharmacopoeia, 2001a). The main removal factor for manufacturing process, equivalent to 6.4-log, was reached in negative anion-exchange chromatography. Then, the capacity of immunoaffinity chromatography and positive anion-exchange chromatography to remove chromosomal DNA purified from yeast-host cell was assessed using a scaled-down chromatographic process which was shown to yield product meeting purity criteria set for the manufacturing process. Log10 reductions for DNA through the immunoaffinity chromatography and positive anion-exchange chromatography were 7.3 + - 0.1, and 5.8 + - 0.1 respectively. Overall, these studies indicate that total DNA clearance factor for API-rHBsAg manufacturing process was 19.4 log, 2.4 times higher than the real DNA contamination, indicating that API-rHBsAg manufacturing as described here have sufficient DNA reducing capacity to achieved a high margin of DNA safety.