Evaluation of the influence of open and closed-ampoule technologies on particulate matter in small-volume parenterals.

Abstract

SVP in glass ampoules are manufactured using two main different technological production processes: the open-ampoule process (O) and the closed-ampoule process (C). In principle, the open-ampoule production technology should lead to better controlled production process. To test this hypothesis and quantify the possible qualitative differences in the manufactured ampoules, a suitable experimental design was set up. The two ampoule production processes have been compared on the basis of the visible particulate burden. Two batches of ampoules filled with water for injections were produced for each type of process, following conventional industrial procedures. Two samples of 20,000 units were taken from each batch and inspected with different automatic inspection systems: two Brevetti CEA machines (S1, S2--light scattering) and two EISAI machines (S3, S4--light absorbtion). The comparison between the processes was based on the rejection percentage. On both inspection machines the open-ampoule production samples present rejection percentages (ranging from 0.154% to 1.248% rejection percentages) which, on average, are lower than those detected in closed-ampoule production (ranging from 1.434% to 3.86% rejection percentages). The difference between the two processes is even more marked if we also consider the data obtained using inspection machines S3 and S4. The substantial differences in performance of the four inspection machines stress the need to provide for adequate validation procedures.