The concepts of "clean-hold time" and "dirty-hold time" have been part of cleaning validation since its inception. Clean hold time is generally considered to be the time between the completion of cleaning and the initiation of the subsequent manufacturing operation. Dirty hold time can begin when the clean equipment is initially soiled, but more often is defined as the time between the end of manufacturing and the beginning of the cleaning process. Intuitively, it makes sense to be concerned about both hold times. Dirty equipment is harder to clean the longer the hold time, and clean equipment has a greater chance of becoming soiled as hold time increases.
In its Guide to Inspection of Validation of Cleaning Processes, the US Food and Drug Administration considers identifying and controlling the length of time between the end of processing and each cleaning step to be critical elements of the cleaning processes (1). FDA also expects pharmaceutical companies to demonstrate that routine cleaning and storage of equipment does not allow for microbial proliferation. The European Union expects companies to provide a validation master plan with clearly defined and documented validation program elements (2). Health Canada looks for companies to describe the interval between the end of production and the beginning of the cleaning procedures as well timeframes and conditions for the storage of clean equipment that do not allow for microbial proliferation (3). Finally, the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) guideline looks for documentation of both dirty- and clean-hold times (4). The general practice among industry is to routinely document and track equipment-hold times to ensure ongoing compliance.