Hi everyone,
I am calculating the limit (mcg/g) for a lyophilized drug product. In the risk assessment we need to calculate the limit in ppm for all the elemental impurities class 1, 2a and 3 (injectable DP).
Example of calculation:you should use the PDE published in the ICH-Q3D and then based on the MDD of drug product you get you limit.
Example of calculations, the weight is different before and after lyophilisation and most of time solvent (which contribute to the EIs level in the drug product represent 99% of the formulation).
Exemple of calculation:
For Cd (PDE in ICH-Q3D is 2 mcg/day)
to calculate for lyo product: weight of all ingredients including WFI (bulk solution before lyophilisation) is 3.6g
The limit for Cd will be 2 mcg/3.6 g = 0.55 ppm (mcg/g)
If we consider the lyophilized product, weight is 73.8 mg
The limit for Cd will be 2 mcg/0.073 g=27.1 ppm (mcg/g)
Which limit should be used for the risk assessment?
The bulk of DP limit or the lyophilized powder DP limit?
Thanks and regards,
RK
The final formulation of drug product. Also take into account the number of dose/day.
ICH Q3D published limits both as a PDE and as concentration in teh drug product assuming not more than 10 g per day I believe. I would think it is easiest to just use the expected dosing regimen of the product combined with the metal analysis data to determine the total daily intake for the product. That would be compared to teh ICH Q3D threshold, or potentially the control threshld of 30% of the published value depending on what you are trying to assess here.
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