Selection of MDD in Finished product

Hi,
If I am working on single nitrosamine impurity for combination (two APIs) of finished product and out of them one (API) content has high MDD and other (API) has low MDD content, also based on information, I concluded that possible single nitrosamine impurity generated only from low MDD API.

So, for limit calculation purpose (AI/MDD), which MDD should be taken ? (Low MDD API or High MDD API)

Thank you.

if the query relates to EU/EEA, then you can refer to the EMA qualoty Q&As part I, where there is a specific reference to this.
" Fixed Dose Combination products (FDC)

For [medicinal products] containing more than one [active substance], the calculated threshold should be based on the maximum daily dose (MDD) described in the SPC of the FDC(s) under evaluation. The FDC(s) are indeed developed in a specific ratio of [active substances] composing the [medicinal product] and therefore considering the MDD of an [active substance] in mono-component [medicinal products] would not be appropriate.

If an unidentified impurity cannot be assigned to one of the [active substances] in the FDC it has to be compared to the signals of all [active substances] in order to verify whether the respective [ICH] identification threshold is exceeded or not. If exceeded, the impurity should be identified and assigned to the signal of the respective [active substance]. If not exceeded, the specification limit should be set with reference to the [active substance] that would ensure the lowest amount/exposure to the patient."

2 Likes