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Determination of Surface Visible Residue Limits on Pharmaceutical Plant Equipment
The minimum amount of residue that can be visually detected on a surface, i.e., visible residue limit (VRL), is demonstrated for a small number of active pharmaceutical ingredients (APIs) on a range of different surface materials typically found in API and drug product manufacturing plants.
Feb 2, 2013 By:
David Ian Fletcher Pharmaceutical Technology
Volume 37,
Issue 2
Table I: Visible residue limit (VRL) data for active pharmaceutical ingredients (APIs) on surface materials of different composition.
Results from the inspections of the plates are summarized in Table I. The observations were generally consistent between the various observers, with all observers in each case reporting the
same conclusion. The residue was considered to be above the VRL only if all observers could detect a residue. In the few instances
where a residue was noted by some, but not all of the observers, the results were indicated as "barely detectable." Where
none of the observers could detect a residue, the result was recorded as "not detected."
Regarding visualization of contamination, three of the APIs dried on the metal to leave a residue in the form of an approximately
even, reddish-brown tarnish. All of the other materials on all surfaces dried to a residue that had the appearance of an evident
white powder. This type of coverage was generally not uniformly distributed on the surface and instead appeared as many dried
droplets or larger areas. This type of coverage was, however, shown in a separate activity involving deliberate soiling of
an actual plant equipment as to how the contamination was deposited in the plant. Accordingly, the plate studies were considered
representative for an assessment of VRLs in the processing equipment.
The following results were recorded regarding the VRLs:
Observations for clear glass, also blue and white enamel, were consistent across all of the different compounds tested in
this study. VRLs for these materials of construction were lowest for blue enamel and clear glass, viewed from either side
of the glass, with all test compounds visible at 10 µg/dm2 . Two of the APIs were tested at lower loadings on these surfaces and were visible at 5 µg/dm2 and also at 2 µg/dm2 with the aid of an additional light source. The absolute VRL thresholds were not determined on these surfaces for any of
these materials because they were out of the scope of this study.
White PTFE exhibited comparatively the highest VRL, with some materials only being detected at 400 µg/dm2 with the aid of additional light source. On this surface, there was significant variance between materials.
On metal, there was variability between VRLs across the range of the test compounds. There was also a clear correlation between
metal-surface roughness and the VRL. Although there were differences in the absolute VRLs for each material, the VRLs for
all test compounds increased with increasing surface roughness. Five of the six APIs were visible on the highly polished surface
of 0.0 µm roughness, at 10 µg/dm2 , whereas only one was visible at 100 µg/dm2 on 1.1-µm surface roughness. There was also some variation in the rate of increase in difficulty in visualizing each compound
with increasing surface roughness.
The contamination was invariably easier to see with the additional portable light source and more obvious when viewed from
an angle of approximately 30–60°. In agreement with previous studies, viewing from directly above the surface was not optimal
due to surface reflections.
David Ian Fletcher, PhD, is lead quality advisor/Lean Sigma Black Belt at AstraZeneca Pharmaceutical Development, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK. David.Fletcher@astrazeneca.com.
Articles by David Ian Fletcher
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