Query for Maximum daily dose/ dosage

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Dear all,
My query is in the Limit calculation based on dose criteria
As per the formula provided by Fourman, GL & Mullen MV, “Determining cleaning validation acceptance limits for Pharmaceutical Manufacturing operations”.Pharm Technology.17(4), 54-60, 1993

mg of active ingredient in contaminating product’A’ permitted per swabbed surface area = (I/J)*(K/L)U
Where,
I = (1/1000 smallest strength of product A manufactured) expressed as mg/day & based on amount of active present in product’A’
J = Maximum number of dosage units of ProductB_1 taken /day
(Product_B1 is the product manufactured after product’A’,)
K = Number of dosage units per batch of ProductB_1
L= Shared equipment surface(in sq.inch) area in common between Product A & B_1/B_2
U= Swabbed surface area in sq.inch
My Query, is the Parameter ‘J’ this the Maximum Daily dose value or Dosage units??.
Consider the following example.
[Case.1]Product_X_B1, has posology of 10tablets /day, with average weight of 30mg/Tablet
[Case.2]Product_Y_B1, has posology of 1tablet /day, with average weight of 350mg/Tablet
If we assume that both Product_X_B1 and Product_Y_B1 , has same batch size in terms of KG.
which product , I should consider for worst case ‘J’.??

2

Dear T.Arun,

keeping all other variables the same, the product to choose is Y. The contaminated batch is supposed to have incorporated the whole contamination of the equipment, and so, the important parameter is which fraction of the batch, (and thus which fraction of the whole amount of contaminant), is taken by the patient per day. Some comments:

  • The “per day” is a convention as to set a common timebase for all products. Thus products taken once a week have a daily dose of 0,14, although it may sound weird.

  • The worst case to choose (for the limit calculation) is not necessarily the product with the smallest batch size or the maximum daily dosage, but the one with the worst combination of maximum daily dosage, smallest batch size, and highest product exposed surface. A nonexisting “mock product”, which combines the worst case of each of this three parameters may be established.

Best regards

Alfred

3

Dear Alfred,
Thank for your kind reply