validation of method:drug substance and drug product

[scio2]

Hi do i need full validaiton moving from drug substance to drug product

[paroma]

Hi, really the work to do isn’t to validate a method that is good working on API assay, but to demonstrate that it’s suitable for the assay in a formulated product. Surely you haven‘t to repeat tests for precision, linearity and robustness if you already collected this data for API assay, but you must evaluate the recovery of the sample treatment procedure, verify the absence of chromatografic interferences and an overall accuracy vs standard. Usually I repeat also an evaluation af the intermediate precision between different analysts, to be sure that results cannot be affected by changes in lab handling.

[Bruce Hamilton]

I suspect you should talk to your quality people.

I'd be very wary of backtracking a formulated drug product assay to the drug substance assay, as you, or your supplier, should already have had a validated drug substance assay to make the product.

Please keep having fun,

Bruce Hamilton

[adam]

Remember that, until the time of the Phase 3 IND, the requirement is for "partial validation". You don't have to have the method completely validated.

What we generally do, in my company, is assume that the validation of the drug product covers the drug substance during Phase 1 and 2. Than when it is time for phase 3, you will have to do some additional work that is focussed strictly on the drug substance: validation of precision with drug substance prep, forced deg of drug substance, LOD/LOQ of drug substance method (which may be different becuase you have less excipient noise) etc.