Microfiltration is an important process in the pharmaceutical industry. Filter selection and validation is a time-consuming and expensive process. Quality by design approach is important for product safety. The article covers the instrumentalization and process control of a laboratory-scale dead-end microfiltration layout. The layout is a downscale model of the actual production line, and the goal is filter validation and analysis of process parameters, which may influence filter operation. Filter size, fluid pressure, valve plunger speed, and timing issues were considered. The focus is on the identification of the most influential process parameters and their influence on the repeatability of pressure oscillations caused by valve opening. The goal was to find the worst-case scenario regarding pressure oscillations and, consequently, filter energy intake. The layout was designed as compact as possible to reduce pressure losses between the filter and valve. Valve-induced pressure oscillations proved to be prevailing over the water hammer effect. Several filters in sizes between 3.5 cm2 and 6900 cm2 were tested, and some recommendations were suggested for the reduction of energy intake of the filter and to improve the repeatability of the process.