Forced degradation re-evaluation when changing API vendor?

[sisay]

Hi all

Currently i have a question regarding forced degradation. One of the purpose of forced degradation is to ensure that the in-house HPLC method is a stability-indicating method.

1. I was wondering that should the forced degradation be re-evaluated when every time changing API vendor for drug product? It may be said that API from different vendors would have different impurity profile which will contribute to different forced degradation results. But, in my opinion, I think forced degradation is to evaluate that if the potential degradation generated from API itself instead of impurity will interfere with quantitating target analyte (impurity or assay). In that case, intrinsic impurity in API will not be a concern.

2. If two APIs in one drug product have different sensitivity to the degradation conditions, i.e., after exposing to degradation condition, one API may be within 5-20% degradation, the other one may be beyond the range. None of the optimal condition can make the degradation level of these two APIs within 5-20%. In this case, how to interpret the chromatograms generated (purity angle/threshold, resolution and impurity level may be the major concern) ?

Hope you can provide me any valuable information and reference for further discussion. Please correct me if I misunderstand the definition of forced degradation. Thank you in advance.

[Mattias]

Hi,

1. I would not repeat forced degradation due to change of API supplier. The molecules have no memory from where they were synthesised

2. That is a tricky situation! I think you will need to stress the two compounds separately (in placebo if possible) to know which degradation product that comes from which substance. But you will also need to stress them together, in case the two compounds can react with each other. But then you will know what all other peaks are.