Ruggedness of Visible Residue Limits for Cleaning Validation - Pharmaceutical Technology

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Ruggedness of Visible Residue Limits for Cleaning Validation
The author tests the ruggedness of VRL viewing conditions and defines optimal viewing conditions.

Pharmaceutical Technology
Volume 33, Issue 3, pp. 102-111

Results and discussion

Table II: Comparison of visible-residue limit (VRL) data.
Initial versus later VRL determination. Of the original 59 VRLs established (1), the average VRL in this experiment was 1.6 μg/cm2. Three of the four observers agreed on most residue levels, but one observer differed, which resulted in slightly higher VRLs. Of the original set of VRLs, 78% were <2 μg/cm2, but 14% were >4 μg/cm2 (see Table II and Figure 1).

Figure 1: Visible-residue limit (VRL) distribution. (ALL FIGURES ARE COURTESY OF THE AUTHOR.)
Additional VRL determinations increased the experience level, widened the observer pool, and refined the experimental technique. Instead of a small, dedicated group of observers, 20–30 scientists worked on the development compound to establish VRLs. The most significant difference in subsequent VRL determinations, however, was the standardization of the residue-spot preparations using lower spotted residue levels, which resulted in lower VRLs.

Table III: Current visible-residue limit (VRL) data.
Interestingly, variability among the observers decreased even as the observer pool increased. Three major factors led to greater consistency: the initiation of a VRL training program for observers, equipment cleaners, and inspectors; overall increased experience level of the observers; and a more consistent residue-spot preparation technique. Of the additional VRLs established, the average VRL dropped to 0.9 μg/cm2 and 89% of determinations were <2 μg/cm2. Ninety-six percent of the total determinations were <3 μg/cm2, and only 2% were >4 μg/cm2 (see Table II). A t-test comparison of the original and additional VRL data in Figure 1 showed that the data distributions were not equivalent. The additional VRL data with a lower average were statistically different when compared with the original VRL data, which confirmed the effects of experience and technique refinement. The overall average VRL was ultimately <1.1 μg/cm2 for the 253 VRLs (see Table III) because 63% of the VRLs determined were less than the lowest level tested.


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