Open manipulation

Any step in which the product path, a container or a connection is opened to the surrounding air, such as pipetting in a biosafety cabinet or uncapping a flask. In aseptic and cell therapy manufacturing, the number of open manipulations is a main driver of contamination risk, so process design aims to replace them with closed systems and sterile connections. An open aseptic step normally needs a Grade A environment, which in a conventional cleanroom sits in a Grade B background. Counting the open steps in a Japanese partner's process description is a quick way to gauge its contamination risk.