Help Clarifying MACO Value for 10ppm Criteria

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Hi everyone,

Just looking for some clarification on the MACO calculation for the 10ppm acceptance criteria…

Is the final carryover value in terms of mg of API OR mg of product??

The PIC/s guideline states:

  • No more than 10ppm of any product will appear in another product.
However, for example, say the final 10ppm MACO calculation gave a 5mg allowable carryover of product 'A' into product 'B' is that:

a) 5mg of the complete formulation of product ‘A’ allowed to carryover into product ‘B’?

OR

b) 5mg of the active ingredient (API) contained in product ‘A’ allowed to carryover into product ‘B’?

Any help clearing this up for me would be greatly appreciated, thanks!

Josephine Miles

2

Dear Josephine,

My understanding is that it is a), 5g of the complete formulation of A in B.
Assuming that you also took the complete formulation of B as 100%, of course.

If you take the API into account with the 10 ppm rule, I would expect strange values for the MACO at extreme changeovers including very high and very low dosage forms (I did not calculate any scenario, just a gut feeling).

The alternate “rule” - actually only an example given by PIC/S -, the 0.1 % min dose/max dose criterion, takes care of the “API-load” of your products.10 ppm is a simple arbitrary default value (without much of a rationale) that does not take into account the dosage of the API. It was probably thought as a correction where dose/dose considerations gave ridiculously high MACOs.

Michel

3

In my opinion and my experience, I consider only API as the contaminant. So, 5 mg of API can be allowed into next product.
Except API, other ingredients (excipients, colorants, WFI etc) cannot show pharmacological effect at lower concentrations. Hence, consider only API as the contaminant.

Regards
Veerraju

4

I am also agree to ramyaraj725