In the process of making submission to add nitrosamine limits on release and at end of shelf life. Have set these limits on the specification in terms of ng/day. All of the development and testing has been done in terms of ng/day - to meet the limits from the EMA for the particular nitrosamine, which are expressed in… ng/day.
An authority has come back and asked for all of the limits and data to be expressed in ppm instead. Has anybody else experienced this? Did you go back to the authority to argue for the use of ng/day.
PPM just seems such an odd unit to use, as it could/would be different for different products with the same API, depending on dose etc.
The ng/day units has already been accepted by some other markets - don’t want different specification limits in different markets solely due to the units being used.
Any advice from experience of this would be much appreciated.
I have only put them in ppm with respect to API. This then keeps it the same from product to product with the same API. This has been widely accepted. I know many of my clients have done the same. I have not heard of regulatory acceptance for ng/day. I’m sure it’s happened, but I haven’t seen it.
This is also in keeping with calculations you see in the FDA guidance, etc.
In contrast, in one of our cases, we have been asked to express all results in ng/day instead of ppb. So this is also a “gap” or “grey zone” (i dont know what to call better) between the Authorities.
However, if we are talking for EU, also EMA Q&A recommends that “Specifications for individual N-nitrosamines should generally include an AI limit expressed in ppm or ppb”. Also CMDh step 2 for confirmatory test outcome is given in “ppm”. So I was a bit surprised.
In any case, what if you expressed results in both ways. That should be also acceptable by your HAs.
Hi all. It depends, when notifying to authorities the results of confirmatory testing, the requirement is to notify both in ng/day and ppm (see screenshot from the Q&A)
But, if we are talking about setting a specification, it has to be done in ppm (or ppb, if the specification is low enough)
