Validation of a high voltage leak detector for use with pharmaceutical blow-fill-seal containers--a practical approach.

Proposed requirements for pharmaceutical package integrity testing outlined in the EU Guide for Sterile Medicinal Products may make it necessary to evaluate and validate alternate ways to perform 100% leak inspection. One such method is high voltage leak detection (HVLD). Even though HVLD has been used for glass ampoules and vials for years, qualification and validation strategies are not well established. In this article, we describe and discuss our practical approach to validation and the protocols used to qualify and validate a high voltage leak detector for use with blow-fill-seal containers. For this work, we used laser drilled pinholes as a model for pinholes produced during manufacturing and defined a "window diagram." This diagram allowed us to plot the parameters of influence and the settings of the HVLD in an easy to visualize pictorial display. In the validation step, we initially determined the most sensitive standard integrity test for our product and container design from the available choices, the vacuum chamber, dye bath and microbial challenge visual inspection tests. In the next phase of our work, the HVLD was crossed-validated against the most sensitive of these tests, the dye bath visual inspection test. This was accomplished with a large number of containers mixed with deliberately defective ampoules. Our conclusion from this work is that the HVLD is an appropriate and feasible integrity test for 100% inspection of blow-fill-seal containers.