Is it necessary to carry out validation tests on model mixtures prepared using both substances, or is it enough to use one substance for testing?
What validation tests should be carried out for an "alternative" substance only? If there is a quantitative method: what validation tests should be checked, for example?
Is it necessary to use a risk-based approach to determine validation tests when registering a new alternative substance during revalidation?
I'm really looking forward to your response, thank You for your attention!
If formulation is same, components of formulation are same only manufacturers are different have same specifications then no need for analytical method validation if method is already validate.
Yes, as per ICH Q2! What do you call a 'model mixture'? Even a different supplier or manufacturer can have a different impurity profile or supply a hydrate.
Thank you for your answers, Saeed Ayaz Khan , Bruce Neagle !
Bruce Neagle The model mixture is a mixture of an active ingredient (active pharmaceutical substance) and a placebo in the proportions of a drug.
The problem is that in ICH Q2 there are no clear guidelines about the scope of validation tests with the second (alternative) substance. But there is a message about the need for revalidation when the substance changes: "Furthermore revalidation may be necessary in the following circumstances: • changes in the synthesis of the drug substance"
I just want to understand to what scope it is necessary to perform validation tests with the second substance.
Of course you will have to perform a QA audit of the new manufacturer's facility, but you could have a limited method validation (which should include specificity, linearity (which you could derive the LOD and LOQ), repeatability... Don't be surprised if the impurity profile is different since it is dependent on the manufacturing process. You should also put the finished drug product that is using the new manufacturer's API, on stability.
You're welcome. Your 'forced degradation' (FD) studies will tell you how the API reacts under extreme conditions (acid, base, heat, light, oxidation, info for you QA audit) particularly degradation and pathways. Many active ingredients have been esterified (example Vitamin A Acetate from Vitamin A Alcohol) so they are more stable.
Consult the guideline PA/PH/OMCL (13) 82 R5 available on the internet.
In the case of alternative/different API manufacturers are intended to be used for the same drug product:
1. If API manufacturing process, specified and actual impurities, polymorph are the same so it's easier but it is rear case.
2. If either API process is different or specified or actual impurities or polymorph are different they will need to be taken into account during DP method validation. It's possible to combine in the same validation. For stability indicating method validation may be possible to implement risk-based approach
3. Stability study for DP being manufactured from each API supplier for both cases 1 and 2. You can probably implement risk based approach (matrix)
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