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.