As per guideline, the limit setting should be practical achievable. How to interpret this statement? What is an achievable limits?
We have a product, Due to the minimum dose is too low. The allowable 0.1% carryover will results in a limit about 0.008µg/cm². And it is always fail for some parts. On the other hand the LD50 for this API is relatively high (more than 200mg/KG). Is it acceptable to increase the limit to certain level (such as 0.05µg/cm²)? Thank you.
Dear b0b,
in my opinion there are not too many ways out. If your validation policy states to use the minimum dose, you cannot switch over to use the LD50 because you get a limit too low. Additionally, I’m not sure if the limit calculated with the LD50 and the safety factor that applies, will not give you an even lower limit. Not knowing which the active is, I would try justifying a higher limit through the pharmacological action of the active, if possible. As an example, we have the case of Vitamin D3, where the daily dosage is only 10 µg which gives unreasonably low limits. In this case, we used a safety factor of 0,01 instead of 0,001 because there is no possibility of harming anybody with even a gross contamination with Vitamin D3, and the ingestion of Vitamin D3 with the milk of a cup of coffee is 100 times greater than the ingestion of Vitamin D3 as a contamination calculated with this safety factor. Same applies to all actives that are used as food additives, dietary supplements, dimethicone, etc. As a comment: 0,008 µ/cm² is a quite usual limit, take into account that sampling 100 cm² you get 0,8 µg in the sample, which is near a lot of therapeutic dosages.
Best regards
Alfred.