Cleaning Validation

Cleaning Validation Acceptance Limits Calculation

Cleaning Validation Acceptance Limits Calculation made easy

This PharmAdvice developed fully validated Microsoft Excel spreadsheet application offers

fast, easy to use reliable calculation of acceptable cleaning residues for

APIs
considering the overall equipment train
using the 1/1000 dose criterion and the 10 ppm criterion
graphical overview on common surface area
electronic signatures
audittrail

Cleaning validation is an essential part of GMP production. During GMP Inspections cleaning validation is
often challenged versus established guidance documents e.g.

FDA: Guide to inspections of validation of cleaning processes (July 1993)

CEFIC - Active Pharmaceutical Ingredients Committee (APIC): Cleaning
Validation in Active pharmaceutical Ingredient manufacturing plants
(1999)
PIC: Principles of Qualification and Validation in Pharmaceutical
Manufacture - Recommendations on Cleaning Validation. (ref. Document
PR 1/ 99 March 1999)

Residue acceptance limits are calculated using

- the 1/1000 dose criterion =
[ (1/1000 of smallest dose) / (maximum number of dosage units of next product taken per day)] *
[(batch size of next product / common surface area)] * (sampled surface area)

- the 10 ppm criterion =

(10 mg) *[ (batch size next product kg) / Common surface area)] * (sampled surface area)

- the visually clean criterion

A common major deficiency discovered during GMP audits is that companies do not consider the complete
equipment train, but limit their calculation to one production step only. At the end of the day this may
cause an accumulation of residues during the manufacturing process e.g. in a solid dosage form
manufacturing process involving dispensing, sieving, granulation, tableting, dedusting, coating, inspecting
and blister packaging may have a 10 ppm residue and the overall residue may be 80 ppm. The underlying
cause most often is that it is very time consuming to calculate all the possible combinations contributing
the common product contacting surfaces.

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