As an outcome of the 2011 Food and Drug Administration Process Validation Guidance, there has been ever increasing interest in the pharmaceutical industry to establish formal Continued Process Verification (CPV) programs for manufacturing processes. There is, however, much confusion over the differences between CPV and the Annual Product Review (APR) process. Most pharmaceutical companies already do some form of trending as part of their APR process. I often get the question, “We already have Annual Product Review in place, why should we go to the trouble of implementing a CPV program?” Annual Product Reviews are just that – annual. A CPV program allows reacting to trends as they occur in real-time. Detecting and correcting unwanted trends or shifts real-time promotes control of the process, reduces waste and maximizes product quality. Allowing as much as a year to go by before detecting and correcting trends and shifts can result in costly recalls and regulatory action.
APR programs typically include some form of data trending, but this trending is usually highly summarized and consists of merely plotting process data on a run chart with specification limits. CPV, on the other hand, is much more involved. In addition to monitoring processes real time or nearly so, CPV monitoring also includes the use of control charts with calculated control limits to signal when a process may be going out of control. Unlike run charts, control charts utilize statistical process control concepts to determine when observed variation in a process exceeds what would be expected for a stable process; that is, a process that is in a state of statistical control. CPV also serves as a valuable input to the APR process. Because data collection and analysis of production data is done on an ongoing basis, there is no need to scramble at the end of the APR reporting cycle to collect and analyze data. Product data can be sourced directly from the CPV database and summarized as needed for inclusion in the APR report. As well as being a regulatory expectation, Continued Process Verification provides a mechanism to react to process shifts and trends in real time in contrast to Annual Product Review (APR) where as much as 12 months may pass before detecting a change in process performance. While there are similarities between CPV and APR, CPV should not be thought of as APR. CPV should serve as a key input to APR where a high level summary of process performance is reported on an annual basis.