Hello all,
Hope you can help! Currently in ICH 3QD there is a PDE value for silver as an elemental impurity for parental but not for opthalmic (eye) route in the USA.
Can anybody help in advising me in how I would go about calculating a PDE for silver elemtal impurity being administrated in the eye. What is the best approach. Im really struggling!
What data would I need?
Where would I get it from?
Are there any guidances?
What calculations etc /methodology .
As the 'worst case' I would use the PDE obtained for the parenteral route of administration, rather than calculating a likely higher PDE for eye drops. As long as your cleaning procedure and analytical method parenteral PDE should be fine.
Review this for the FDA's current(?) thinking;
http://pqri.org/wp-content/uploads/2015/11/John_Leighton.pdf
If the PDE for opthalmic drops via the eye route of administration is much higher than the parenteral PDE (thus higher acceptance criteria), then you might be able to change to a cheaper analytical method. AAS instead of HPLC for instance. Try contracting with www.affygility.com
According to me, you can use Parental PDE (which will be stringent or equivalent than Ophthalmic; as Parentals are directely administered into the blood.)
In general , route to route extrapolation can be made through the use of bioavailability as per FDAs presentation materials as cited above.
(This may be the case for medicinal product as well as elemental impurity of metal)
Recently ,Barle et al issued the practical papers about the settig of PDE for topical ocular drug and topical otic drug through extrapolation .
For example, please refer to the paper titled as "
Determination and application of the permitted daily exposure PDE for topical ocular drugs in multipurpose manufacturing facilities "
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