Ruggedness of Visible Residue Limits for Cleaning Validation - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

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.


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here