Choosing the worst-case product and the 10ppm rule


I have 2 questions about cleaning validation in my OSD production line:

Question 1
Our approach on choosing the worst-case product is based on Risk Priority (= Solubility index x toxicity index). My question is that, in my case, there exists: Product A: 25 (Solubility 5 x Toxicity 5) and Product B: 21 (Solubility 7 x Toxicity 3). Which one should I choose as the worst-case product?

Question 2
My current approach on determining the chemical residue limit is based on the following equation:
Equation 1: LSP = Safety Factor x lowest daily therapeutic dose of API / highest max daily dose of drug product
if LSP < 10ppm, then the chemical residue limit is set as:
Equation 2: limit (in ug/cm2) = LSP (in equation 1) x smallest batch size x recovery factor / surface area
Since i always found LSP is much less than 10ppm (i.e. around 0.2 ~ 0.5ppm), I just wondered whether my concept is wrong.

Many thanks for all your reply.

Dear Stanley…

While choosing worst case product, you need to consider potency also. pls look into slide number 36 to 42 of the attached presentation for more information [attach]513[/attach]

Residue limit can be any value more than zero. it depends on your product characteristics.

MACO = [Lowest SINGLE dose of API (previous product) x smallest batch size of next product x safety factor] / maximum DAILY dose of next product

Swab Limit = [MACO x recovery factor ] / [product contact surface area x 100]


managing risk in cleaning validation.pdf (382.7 KB)