注射用メシル酸ナファモスタット製剤の先発および後発医薬品におけるロット間品質試験

抄録

Very little quality information is available for generic pharmaceutical preparations and this is particularly so for injectable preparations for which few quality studies have been conducted. With this in mind, we conducted an inter-lot quality variation investigation on nafamostat mesilate preparations for both the original and generic products and compared the results. The investigation involved measuring amounts of impurities other than those of the active ingredient by high performance liquid chromatography.
For the nine generic products investigated, impurity amounts were about 2.4 times that of the original (min. 2.0 times-max. 3.1 times). We determined that these differences were not due to hydrolysates of the active ingredient but to unknown substances since the amounts of these unknown substances in the generic products were about 5.7 times (min. 4.7 times-max. 8.0 times) their amount in the original product.
Concerning inter-lot variation (maximum value-minimum value), we found that the variation in total impurity amounts for the generic products was 1.8 times (min. 0.7 times-max. 2.8 times) that of the original product, while the variation in unknown substance amounts for the generics was 3.1 times (min. 1.0 times-max.4.6 times) that for the original.
The results of the present study suggest that it is necessary to take inter-lot variation into account in evaluating the quality of generic products. They also suggest that the higher contents of unknown impurities in the generics could be a cause of the in-circuit precipitation which has been reported with generic versions of nafamostat mesilate during blood purification in the clinical setting.