I am in the process of putting together a matrix for cleaning validation. Currently we use the dose criteria formula for determing acceptance criteria. I ran into the following problem though.
Product A (first product):
Daily Dose = 2g/day
% of Active = 0.09%
Product B (second product):
Times per day = 2
Daily Dose = 120g/day
Batch Size 1100 kg
Common Surface Area = 16914 sq.in.
Rinse amount = 250kg
Rinse Area = 16914 sq.in.
Due to the small amount of active in the first product followed by a large daily dose in the second product the rinse value comes out to low.
Using these values I am getting acceptance criteria that we can’t test for. I have looked into using different formulas (Maco, RDL) but am unable to determine how to tie in the active percentage into the formulas.
Our analytical lab does not test for finished product they only test for active ingredient.
In my opinion, the analysis of the rinsewater after washing the equipment is not a suitable way to demonstrate the validity of your cleaning procedure. Actually, it is accepted only as a routine monitoring method having previously been correlated with other sampling methods. The problem is that using the rinsewater as “sampling medium” is equivalent to assume that it removes consistently all the contamination, which is exactly what you want to demonstrate and thus not suitable as hypothesis. In the worst case, the washing/rinsing procedure is completely useless, all the contamination remains in the equipment, and you will find no contamination in the rinsewater and will happily (and erroneously) conclude that the cleaning procedure is successful! Even worse, normally you choose as the worst case for the contaminant the active that is least soluble in water or the washing/rinsing solution, thus inherently spoiling the use of the rinsewater as sampling method.
The best way to demonstrate the absence of contamination is sampling directly the surface of the equipment, either swabbing with a solvent which readily dissolves the contaminating active, or sampling by rinsing with a small volume of this solvent (not water!) parts that cannot be swabbed (mesh screens are a classical example for this). And before sticking to a sampling method, conduct a recovery test!
[quote=CLARGORD]I am in the process of putting together a matrix for cleaning validation. Currently we use the dose criteria formula for determing acceptance criteria. I ran into the following problem though.
Product A (first product):
Daily Dose = 2g/day
% of Active = 0.09%
Product B (second product):
Times per day = 2
Daily Dose = 120g/day
Batch Size 1100 kg
Common Surface Area = 16914 sq.in.
Rinse amount = 250kg
Rinse Area = 16914 sq.in.
Due to the small amount of active in the first product followed by a large daily dose in the second product the rinse value comes out to low.
Using these values I am getting acceptance criteria that we can’t test for. I have looked into using different formulas (Maco, RDL) but am unable to determine how to tie in the active percentage into the formulas.
Our analytical lab does not test for finished product they only test for active ingredient.[/quote]
Dear Mr. CLARGORD
Here are some of the suggestions for you. First of all reduce your rinse volume as much as it is possible. Because high rinse volume means less concentrated your residue. So, if you can reduce the rinse volume then you will get more concentrated residue and that might help you.
Secondly ensure that your recovery is more than 50%. However more than 80% will be better. If you have recovery less than 50% then your sampling method is not working and you are getting diluted rinse sample with your residue. If so, then develop a suitable sampling method having recovery more than 80%. May be you need to rinse with a soluble solvent that can increase your recovery or you need to consider the swab method as it is direct sampling method and from my experience swab method is better than rinse method. If your swab method is still sampling the residue that can not be quantified by your analytical method then you can chose the options of increasing the sampling area to sample more residue in your swab.
Thirdly, if all are not working then you should work out for developing another analytical method that have a limit of quantitation that can quantify your residue.