The idea of consistency is fundamental to understanding the expectations (both of industry firms and regulatory agencies) for a cleaning validation program. If we look to dictionary definitions, we can find one definition that consistency is “agreement or harmony between parts of something complex”. While we want our cleaning validation programs to be internally consistent, that just might mean the program fits together. If we just consider internal consistency, it might not be enough in that the program meets any external expectations. So I consider that specific definition partially useful, but partially inadequate for the discussion here. A second dictionary definition is “reliability or uniformity of successive results or events”. This is closer to what we are probably talking about in terms of consistency, in that it is more tied to the results of a cleaning validation program (that is, the results of the specific cleaning process events). If I were to use this second definition, I would place more emphasis on the reliability of results rather than the uniformity of results. Certainly I want data to be uniformly below the calculated acceptance limit, but depending on the sample swab locations (for example), the data may not be numerically the same. Furthermore, there may be an occasional (random) swab sample that is above the calculated acceptance limit, but with adequate justification, I still might judge my cleaning validation program to produce consistent results.
So far, we have just covered issues related to the definition of consistency. We will now turn to the practical considerations. While we want to assure consistency over the lifetime of a cleaning process, I will try to separate out considerations relating to the consistency in the original cleaning validation protocol from lifetime consistency. While our ultimate goal is lifetime, it is important at the end of our original cleaning validation protocol to be able to state clearly that the cleaning process is one that should be consistent over the lifetime of the program.
So, we’ll first cover the consistency of the original validation process. That consistency is demonstrated not only by what is done in the three validation protocols (Phase II) but also what has been done in the design and development of the cleaning process (Phase I). Demonstration of consistency may include:
If all that results in a judgment that the cleaning process is validated, then we are ready to use that cleaning process (for designated products and equipment) going forward.
The next issue is the ongoing confirmation of consistency of the cleaning process during routine use. This may include routine monitoring analytical data for that one event and the lack of cleaning process deviations during that one event. In addition, there may be ongoing trending of routine process monitoring data (like temperature, for example). Finally, it may also include a routine (such as yearly) repeat of one cleaning validation run. These individual assessments may be summarized in a yearly cleaning process assessment report to further document ongoing consistency and control.
To summarize, the idea of consistency as “harmony between parts” is more related to the overall cleaning validation program (the “cleaning validation master plan” and the associated supporting documents). The idea of “reliability of successive events” is more related to individual cleaning process events over time. Both are useful concepts, and understanding the difference may help you better design and execute your cleaning validation program.
With that, here are some caveats.
Copyright © 2024 by Cleaning Validation Technologies