As per ICHQ3D Class 1 & 2A elements should be assessed even though those are not intentionally added or used in the process.
Can we need to test those elements
or
can we justify by theoretical approach like those are not used in the process & the equipment, packing material coming into contact are not consists those class 1 & 2A elements.
Please guide…
Touchy subject! You can state in your documentation (risk analysis?) that you do not add these molecules and they are not chemically similar to molecules that you are using (therefore they are not potential degradants). In addition, as proof, you can take a sample of your drug product and send it out to a contract lab for a USP <467> (or European equivalent) analysis by GC.
Here the case is Drug Substance.
As a API manufacture, how can i support to formulator to comply ICHQ3D?
Please elaborate…
The only thing you can do is confirm in writing that you do not use these prohibited solvents and send a sample of the API out to a contract lab for USP <467> analysis (headspace GC if I remember).
The formulator may have use excipients that have become contaminated with these solvents (thus the changes mandating drug products be analysed). They may be tracing the issue (the reason behind their discussion).
Also if memory serves (doubtful sometimes), these prohibited solvents were used back in the 70’s in order to precipitate and purify many API’s (when many patents were issued). Be sure your manufacturing process does not use them!
Hi Boomer,
My question is about Elemental impurities[Metals]…ICHQ3D.
It’s new, in which case I will let someone else answer.
There is a discussion on Linkedin too. See link below.
As an API manufacturer you should assure that the produced product is free from Elemental Impurities.
Class 1 and 2A shall be analysed and limits shall be same or below the ICH/EU/USP recommended limits w.r.t TTC and Maximum Dosage of the API produced.
Coming to other elements if any elements like Metal catalysts or any other elements are forming during the manufacturing the API you should set the limits and have to analyse it.
All these shall be analysed on ICPMS / ICPOES or highest sensitivity instruments because these limits would be normally in ppms.
You shall evaluate from the beginning of the Raw Materials using in your API process and list out the elements and develop a method, validate it and use this method to detect the elements levels in your API.
Based on the trend you may include in your release specification or keep as an Skip test. That is up to your choice and firms policy .
Please be sure you have complete evaluation as per ICHQ3.
Pulla Reddy Karnati.