A. Limiting the level based on toxicity data.
Acceptance criteria for Toxicity can be calculated by using ADI & MACO. But, for this, we need to have the data of Empirical Factor, which is not available all the times. Hence, now-a-days, even FDA is not interested in setting the limits of Toxicity for Cleaning Validation.
Please refer: Mr. LeBlanc guidelines
B) Pharmacological Dose Method:
Safety factor will differ for the application.
For Orals, we can use 1/1000
For Parenterals, we can use 1/1000 to 1/10,000
C. Limiting the level of product which could appear in the following
This limit is purely based on MACO calculation. For some products, even 10 ppm is not acceptable.
With Best Regards,
A) You said in earlier post that " Toxicity levels can not be determined" so i explained the methodology how to calculate the MAC by toxicity data.
B) The safety factor varies depending on the route of administration. Generally a factor of 200 is employed when manufacturing APIs to be administered in oral dosage forms. Safety factor can vary depending on substance/dosage form according to suppose toxicity values from oral administration.
Safety factor for different dosage forms:-
Topicals 10 –- 100
Oral products 100 – -1000
Parenterals 1000 -– 10 000
so for the safer side, usually take 1/1000 as safety factor.
C) MAC derived from 10 ppm approach, it doesn’t means 10 ppm is acceptable limit, it is an approach which came from ICH impurity document.so i think you didn’t get my earlier answer, it just a calculation approach and i will explain it later in detail.
Thanks and best regards