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

Residue appearance


Figure 3: Effect of concentration on residue appearance.
Standard preparation for residue spots involved pipetting 100 μL of sample solution or suspension onto a material coupon. This volume of methanol consistently supplied a circular residue spot of approximately 5 cm. in diameter, which was nearly equal to the swabbed 25-cm2 area. As sample concentrations decreased, residue appearance changed from being uniform to that of a ring (see Figures 3 and 4).


Figure 4: Effect of concentration on residue appearance.
To determine the effect of spotting volume, 60 μL of the lowest spotted solution was pipetted along with 0, 20, 40, 60, 80, and 100 μL of methanol. The lowest concentration was used because the appearance of the residue near VRL was the primary area of interest. The appearance of the different volumes had little effect on the appearance of the residue around VRL. All of the residues were similar, but, as expected, the rings became larger with the increased volume (see Figure 5). Eventually, larger volumes of spotting solvent would make the ring too dilute to detect, but the area of the ring at that point would be significantly larger than the swab area of 25 cm2.


Figure 5: Effect of volume on residue appearance (6-μg sample).
The appearance of residues near VRL concentration, it was concluded, are expected to take on the appearance of a ring. If the residue has a uniform appearance, it is most likely well above the VRL limit.

Conclusion

The ruggedness of VRL viewing conditions has been tested, and optimal viewing conditions have been defined. Studies established the ruggedness of VRL determination among multiple observers at different sites, showed the relationship between VRLs of formulations and individual components, and assessed the effects of residue appearance on VRL preparation parameters. The research also highlighted the value of a VRL training program for all involved personnel.

Acknowledgment

The author gratefully acknowledges colleagues at the respective sites who generated VRL data and participated in the multisite study.

Richard Forsyth is a consultant for Cleaning Validation and GMP Topics, tel. 610.948.2970,

Submitted: June 25 2008. Accepted: June 30, 2008.




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References

1. R.J. Forsyth and V. Van Nostrand, "Visible Residue Limit for Cleaning Validation and its Potential Application in a Pharmaceutical Research Facility," Pharm. Technol. 28 (10), 58–72 (2004).

2. R.J. Forsyth and V. Van Nostrand, "Application of Visible Residue Limit for Cleaning Validation in a Pharmaceutical Manufacturing Facility," Pharm. Technol. 29 (10), 152–161 (2005).

3. R.J. Forsyth and V. Van Nostrand, "The Use of Visible Residue Limit for Introduction of New Compounds in a Pharmaceutical Research Facility," Pharm. Technol. 29 (4), 134–140 (2005).

4. R.J. Forsyth, J.L. Hartman, and V. Van Nostrand, "Risk-Management Assessment of Visible Residue Limits in Cleaning Validation," Pharm. Technol. 31 (4), 134–140 (2007).

5. R.J. Forsyth et al., "Correlation of Visible Residue Limits with Swab Results for Cleaning Validation," Pharm. Technol. 30 (11), 90–100 (2006).


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