I have recently published a paper on the use of a “visually clean” standard as the sole acceptance criterion in cleaning validation protocols. That publication was based on a presentation at the December 2000 PDA meeting in Washington, D.C. and a similar presentation at the February 2001 Japan PDA meeting in Kyoto, Japan. Since that time I have a slightly different approach to the use of “visually clean” in this manner. This new framework does not invalidate what I have published (and presented numerous times), but rather modifies the framework in which it is presented.
Previously, “visually clean” was presented as an alternative residue limit to the standard dose-based limit (0.001 of the minimum dose of the residue active in a maximum dose of the next manufactured product). On further reflection, I would not present “visually clean” as an alternative residue limit. Rather, the residue limit is still based on the dose-based calculation. Visual examination then becomes the analytical technique to determine that the examined surface has residues below that of the dose-based limit. In essence, this still emphasizes the importance of a dose-based limit, but what changes is the measurement technique. Instead of analyzing a swab or rinse sample by a technique such as HPLC or TOC, a visual examination is used.
This more accurately reflects how visual examination can be used in validation protocols, and particularly emphasizes the fact that when used as a “sole criteria”, a determination of “visually clean” must clearly demonstrate that the residue on the surface is below that level allowed in a dose-based calculation.
This really doesn’t change the steps that one must go through to utilize “visually clean” as the sole acceptance criteria. One still calculates the dose-based surface limit (typically in microg/cm2), and then determines by appropriate lab studies that the residue is clearly visible at or below the dose-based residue limit. Note that this doesn’t mean that one has to exactly determine the lowest level at which the residue is clearly visible (this is also a change from my published paper). For example, if a dose-based limit is calculated as 6.2 microg/cm2, and it can be determined that the target residue is clearly visible on the same surface under equivalent viewing conditions at levels of 3.0, 4.0, 5.0 or even 6.0 microg/cm2, then any determination that a viewed surface was visually clean (under equivalent viewing conditions) would constitute evidence that the residue on the surface was less than 6.2 microg/cm2.
Other conditions for utilizing “visually clean” as the sole acceptance criteria still apply: