Stability of lyophilized sucrose formulations of an IgG1: subvisible particle formation.

Eight lyophilized formulations of a IgG1 monoclonal antibody (MAb) were prepared containing increasing levels of sucrose. In addition, three of the formulations had sorbitol added at a level of 5% w/w relative to sucrose. The samples were stored for up to 4 weeks at 40°C, which is well below the Tg. Upon reconstitution, the levels of subvisible particles were measured using microflow imaging (MFI). The formulation containing no sucrose contained exceedingly high levels of subvisible particles, accounting for as much as 25% of the weight of the protein. Addition of sucrose markedly decreased the number of subvisible particles, with the maximal sucrose:protein weight ratio being 2:1 (the highest level tested). Addition of sorbitol further decreased subvisible particle levels, even for formulations where the sucrose:protein ratio was relatively high. This suggests that even small amounts of a plasticizer like sorbitol can improve the storage stability of a lyophilized antibody formulation, probably by dampening ß-relaxations within the amorphous glass.

Structure, stability, and mobility of a lyophilized IgG1 monoclonal antibody as determined using second-derivative infrared spectroscopy.

There are many aspects of stabilization of lyophilized proteins. Of these various factors, retention of native structure, having sufficient amount of stabilizer to embed the protein within an amorphous matrix, and dampening ß-relaxations have been shown to be critical in optimizing protein stability during storage. In this study, an IgG1 was lyophilized with varying amounts of sucrose. In some formulations, a small amount of sorbitol was added as a plasticizer. The structure of the protein in dried state was monitored using infrared (IR) spectroscopy. The IR spectra indicated increasing retention of the native structure, which correlated with stability as indicated by size-exclusion chromatography as well as micro-flow imaging. Maximal stability was achieved with a 2:1 mass ratio of sucrose to protein, which is more than that would be expected based on earlier studies. Analysis of both high and low frequency bands associated with intramolecular ß-sheet structure provides additional information on the structure of antibodies in the solid state. Finally, there is a correlation between the bandwidth of the ß-sheet bands and the enthalpy of relaxation, suggesting that amide I bands can provide some indication of the degree of coupling to the sugar matrix, as well as structural heterogeneity of the protein.

Death and injury from motor vehicle crashes in Colombia / Muertes y lesiones por accidentes de tráfico en Colombia

We report data on the distribution and determinants of road deaths and injuries for all victims in Colombia, with the aim of defining targets and priorities for highway death prevention in that country and other rapidly urbanizing nations. Using information from Colombia's Fund for the Prevention of Road Injury and the national death registry, we studied data on deaths and injuries from 1991 to 1995 for the nation as a whole and for the country's two largest cities, Santa Fe de Bogotá and Medellín. Deaths and injuries are rising in the nation as a whole. Of the deaths, 75 percent occur in urban areas, and 80 percent are in males. Pedestrians aged 15-34 are a peak subgroup. Thirty-four percent of deaths are attibutable to speeding and/or alcohol consumption. Death tolls are highest at night and on weekends. Specific priority targets for intervention are indicated by the fact that 75 percent of road deaths in Colombia occur in urban areas and that 80 percent of all victims are males

Con el fin de definir objetivos y prioridades para la prevención de las muertes en carretera en Colombia y en otros países que se encuentran en rápido proceso de urbanización, presentamos datos sobre la distribución y determinantes de las muertes y lesiones por accidentes de tráfico en Colombia. Utilizando información del Fondo de Prevención Vial Nacional y del registro nacional de defunciones, estudiamos los datos correspondientes al período comprendido entre 1991 y 1995, tanto en la totalidad del país como en sus dos principales ciudades: Santa Fe de Bogotá y Medellín. En el ámbito nacional, las muertes y lesiones por esta causa están en aumento. En relación con las muertes, 75% ocurrieron en áreas urbanas y 80% de las víctimas fueron varones, cifras que señalan la existencia de objetivos prioritarios específicos para la intervención. El subgrupo más afectado fue el de los peatones de 15 a 34 años de edad. Treinta y cuatro porciento de las muertes fueron atribuibles a exceso de velocidad o consumo de alcohol. El número de víctimas mortales fue más elevado por las noches y en los fines de semana.

Death and injury from motor vehicle crashes in Colombia

We report data on the distribution and determinants of road deaths and injuries for all victims in Colombia, with the aim of defining targets and priorities for highway death prevention in that country and other rapidly urbanizing nations. Using information from Colombia's Fund for the Prevention of Road Injury and the national death registry, we studied data on deaths and injuries from 1991 to 1995 for the nation as a whole and for the country's two largest cities, Santa Fe de Bogotá and Medellín. Deaths and injuries are rising in the nation as a whole. Of the deaths, 75 percent occur in urban areas, and 80 percent are in males. Pedestrians aged 15-34 are a peak subgroup. Thirty-four percent of deaths are attibutable to speeding and/or alcohol consumption. Death tolls are highest at night and on weekends. Specific priority targets for intervention are indicated by the fact that 75 percent of road deaths in Colombia occur in urban areas and that 80 percent of all victims are males