Setting Cleaning Validation Acceptance Limits for Topical Formulations - Pharmaceutical Technology

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Setting Cleaning Validation Acceptance Limits for Topical Formulations
There is a need for current cleaning validation methods to be used for topical formulations. The authors highlight the issues and challenges encountered.

Pharmaceutical Technology
Volume 32, Issue 1

MACO = (0.35 mg/day 200,000 FTUs 25.0 cm2 /swab) / (162.0 FTUs/day 6000 cm2 ) =1.80 mg/swab

Other criteria

Other criteria typically used in the industry include 10 ppm criterion and visually clean criterion. The former is based on the assumption that not more than 10 ppm of any pharmaceutical ingredient should appear in any other product, and the latter is not an assumption but rather a fixed value of 0.1 mg/25 cm2 swab area obtained after performing spiking studies. The lowest value obtained from all the MACO calculations based on different criteria is then selected as the acceptance limit for active A1.


The determination of MACO for a pharmaceutical agent to the subsequently manufactured product is an inexact science. Each approach has its own set of assumptions and limitations. Any firm that relies on MACO values for their cleaning validation studies must understand the assumptions used in deriving the MACO values. It is the responsibility of pharmaceutical manufacturers and cleaning validation scientists tasked with setting MACO values to estimate a value that is safe for consumers without being so demanding that resources are spent unnecessarily.

M. Ovais* is a pharmaceutical scientist, Xepa-Soul Pattinson (M) Sdn Bhd, 1-5, Cheng Industrial Estate, 75250 Melaka, Malaysia, tel. 006063351515, fax 006063355829,

Lai Yeo Lian is the innovation and development manager at Xepa-Soul Pattinson (M),

*To whom all correspondence should be addressed.

Submitted: June 5, 2007. Accepted:July 26, 2007


1. FDA, Guide to Inspections of Validation of Cleaning Processes, Division of Investigations, Office of Regional Operations, Office of Regulatory Affairs (Rockville, MD), July 1993.

2. G.L. Fourman and M.V. Mullen, "Determining Cleaning Validation Acceptance Limits for Pharmaceutical Manufacturing Operations," Pharm. Technol. 17 (4), 54–60 (1993).

3. D.A. LeBlanc, "Establishing Scientifically Justified Acceptance Criteria for Cleaning Validation of Finished Drug Products," Pharm. Technol. 22 (10), 136–148 (1998).

4. R.J. Forsyth and D.V.Haynes, "Cleaning Validation in a Pharmaceutical Research Facility," Pharm. Technol. 22 (9), 104–112, (1998).

5. J. Agalloco, "Points to Consider in the Validation of Equipment Cleaning Procedures," J. Paren. Sci. Technol. 46 (5), 163–168 (1992).

6. C.C. Long and A.Y. Finlay, "The Finger-Tip Unit–A New Practical Measure," Clin. and Experim. Dermatol. 16 (6), 444–447 (1991).

7. European Commission Health and Consumer Protection Directorate-General, The SCCP's Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 6th revision, adopted by the SCCNFP during the 10th plenary meeting Dec. 19, 2006.

8. D.B. Layton et al., "Deriving Allowable Daily Intakes for Systemic Toxicants Lacking Chronic Toxicity Data," Regul. Toxicol. and Pharmacol. 7, 96–112 (1987).


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