Dear All
1. Is it must to analyse the residual solvent in drug product as per <467> which is going to be implemented from july'07. PL. comment.
2. We are having ethanol in our formulation. Is it must to quantify the ethanol by GC or by LOD we can check the content qualitatively. Pl. comment
If you are selling a product that is "USP" grade, then you must either:-
1. Use the method detailed in the monograph for that product, or
2. Validate your chosen method to show that it would deliver the same result as the specified method.
Note that if you deviate from the specified method, then you have to demonstrate that your variations would not affect the results, effectively requiring a method validation
As far as I'm aware, you don't always have to submit the method validation data to the regulatory authority ( but it depends on the status of the drug ), but you do have to have all of the process and data approved by your company's quality group - who will be responsible for showing the data to the regulator or client during any audit. I don't think the USP reviews commercial method validation data, that's the regulator's role.
If the drug is in early phase development, you would submit data with approval applications, but if it's in commercial production you may have to submit data whenever the method is changed. Timing may depend on your regulator. Note that if you wait, and if the reulator doesn't agree that the method is equivalent, a product recall could result, so maybe some companies would immediate submit data on any method changes to the regulator. ...
Note that method validation is not a simple or cheap exercise, a Contract Reseearch Organisation could charge some sum between $10K and $50K to provide all the data and a report suitable for client and regulatory auditors.
With regard to the question of using LOD for ethanol ( which is a Class 3 solvent - low toxicity ), if the method has been validated and you have no other Class 1 or 2 volatile species, then LOD would be acceptable ( I haven't seen the latest USP, but the EP certainly allows LOD and is also based on the ICH guideline, so I'd expect the USP to be the same ).
The LOD method would have to meet the analytical method validation requirements in the ICH guideline text on Validation of Analytical Procedures. LOD ( or an equivalent non-specific method ) is only acceptable for products where only Class 3 solvents are present, otherwise you have to use a solvent-specific method, such as GC.
Please keep having fun,
Bruce Hamilton
