Cleaning Validation Beyond Visual Clean: Proving It with LOD

Visually clean proves nothing

Cleaning validation proves, with data, that residues are below a safe threshold for the next batch.

Three pillars

1. MACO calculation

MACO = (Min dose of previous product × Next batch size × safety factor) / Max daily dose of next product

If MACO < LOD, the analytical LOD becomes the limit — improve the method.

2. Worst case

Lowest solubility, lowest PDE (highest toxicity), hardest-to-clean geometry. Document the scoring matrix.

3. Protocol that survives audit

• Swab recovery >70% per surface/material
• 3 consecutive runs
• Dirty hold & clean hold challenged

Five audit findings to avoid

1. Unqualified swab material
2. Vague sampling area
3. Lab LOD ≠ shop-floor LOD
4. Unchallenged hold times
5. Cosmetic CAPA

Checklist and example as in the French version — method is universal.