Limit calculation for cytotoxic products

How to calculate the residue limit for cytotoxic product by considering toxicity of the product ?

Dear Mr Tapan Kumar Panda,

Before I answer to your post, I would like to know if you are manufacturing any known cytotoxic product with other (i.e. non-cytotoxic) products or the product (which you are referring to) is manufactured in a dedicated facility.

In order to determine residue limits for cytotoxic products we need to understand what the regulations (ICH/FDA) say about the issue. PIC/S regulation for cleaning validation (PIC/S PI 006: Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation) states that “For certain allergenic ingredients, penicillins, cephalosporins or potent steroids and cytotoxics, the limit should be below the limit of detection by best available analytical methods. In practice this may mean that dedicated plants are used for these products.”

From the above it is very clear that we need to have a dedicated facility for the product concerned. If we need to determine residue limit for a cytotoxic contaminant in any of the non-cytotoxic product we would require an anlytical method which have the lowest possible “limit of detection (LOD)” and the residue which is detected should be lower than this LOD. Hence, in this case the residue limit for a cytotoxic contaminant is not calculated rather made as low as possible (which means lower the limit, better it is). The manufacturer need to provide the justification for the analytical method used (i.e. the method selected is the best possible method avaliable and the LOD is the lowest) for detection and quantitation of residues.

Hope the reply is of some use.