Determination of Surface Visible Residue Limits on Pharmaceutical Plant Equipment - Pharmaceutical Technology

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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.


Pharmaceutical Technology
Volume 37, Issue 2

Conclusion

In addition to the various factors previously shown to affect VRL (such as viewing angle, distance, and lighting conditions), the new data in this study indicate that there is also a large variation in the VRL across different surface types, both in terms of materials for construction and, in the case of metal surfaces, the roughness. The data also provide supplementary evidence that the VRL varies with individual compounds, thereby further adding to the repository of knowledge concerning the effectiveness of the visual-inspection process during cleaning as well as helping to define the scope of applicability. If visual examination is to be used as the sole criterion for ensuring equipment cleanliness, a wide range of factors need to be considered. For example, where equipment is constructed from more than one material type, the absolute surface areas for each type of material should be taken into consideration in calculating the maximum theoretical residual contamination level.

The relationship between metal-surface roughness and VRL indicates the importance of knowing the roughness for each equipment item in order to determine the maximum potential contamination level accurately. Accordingly, any procedural use of "visibly clean" as a pass criterion should be supported by periodic checks of the surface roughness to ensure that the basis for acceptance is not compromised. Metal-surface roughness is a factor to be considered for any user requirement specification when ordering new equipment.

In view of the variability in VRLs on some surfaces between different compounds, in a multiproduct plant, it is necessary to conduct a test on each new material to determine the individual VRL. This test is particularly important as currently there is no evident predictor of VRL from any physical or chemical property of the subject material. The test is straightforward and significantly more rapid to perform than development of a swab or rinse method.

The above data offer definite potential for improving the efficiency and accuracy of the cleaning process by using VRLs alone. The limitations should, however, be recognized and the risk assessed on a case-by-case basis (i.e., the applicability under potentially different lighting and access conditions in the plants should be risk-assessed). Even if visual inspection, supported by the above data, is not directly used as a basis for total plant-cleaning verification, it may prove useful for individual items of equipment, or as an aid to deviation investigations.

References

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2. D.A Leblanc, J.Pharm. Sci. Technol. 56 (1), 31–36 (2002).

3. FDA, Guide to Inspection of Cleaning processes, Division of Field Investigations, Office of Regional Operations, Office of Regulatory Affairs, (Rockville, MD, July 2004).

4. R.J Forsyth, V. Van Nostrand, and G.P Martin, Pharm. Technol. 28 (10), 58–72 (2004).

5. R.J Forsyth and V. Van Nostrand, Pharm. Technol. 29 (4), 134–140 (2005).

6. R.J Forsyth and V. Van Nostrand, Pharm. Technol. 29 (10), 152–161 (2005).

7. R.J Forsyth, J. Hartman, and V. Van Nostrand, Pharm. Technol. 30 (10), 104–114 (2006).

8. G.L Fourman and M.V.Mullen, Pharm. Technol. 17 (4), 54–60 (1993).

9. R.J. Forsyth, Pharm. Technol. 35 (3), 122–128 (2011).

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.
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