We are looking to increase the amount of flavor excipient in already approved drug formulation. According to SUPAC, complete or partial deletion of a flavor excipient can be reported in the annual report. However, I do not see in the SUPAC by how much the amount can be increased without triggering the PAS submission to FDA. Does it mean there is not limit of how much extra flavor we can add to the formulation as long as we respect IID limits?
Just bumping it up )
Are flavors similar to colors?
The Q&A says "A change in color, either in amount or from one color to another, is a level 3 component and composition change which calls for a prior approval supplement. However, if the color is merely being removed, it is a level 1 change and can be reported in the next annual report."
I am not sure. I could not find anything specifically talking about increasing amount of the same flavor in the formulation.
This may help!
"For products approved with only a range for an excipient, the target may be assumed to be the mid-point of the approved range. If the new target is within the validated range, the change will be a level 1 or 2 change depending on the specific excipient changed and the percent change (see the SUPAC-IR guidance document). The target originally approved remains the target of record; i.e., Level 1 or Level 2 component changes made under SUPAC- IR do not change the target. If the new target is not within the validated range, the proposed target will need a prior approval supplement.
Thank you Narayan.
In our case, we do not have ranges for the excipients. We only have one % composition value for the flavor in our formulation.
Does it mean, if we would like to increase it by any amount it would automatically become PAS?
Yes Valeria, in your case that would be how I would interpret that guidance response language.
As colorant and flavor both are meant just for organoleptic function in the formulation, so theoretically we can consider any increase in flavor concentration as level 3 change, like for colors.
You can consider taking advise from FDA to submit it under CBE 30 or CBE 0 if the flavorant concentration is within IID limits, as then overall safety risk is quite low.
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