Validation of USP monographs

[cody84]

Is it necessary to fully validate USP methods? Or is a method verification acceptable.
I am trying to validate the CHG solution monograph for 2 of our products and am having a lot of trouble with the related compounds as none of them are identified in any literature I can find and therefore I can only use the USP standard ($620/50 mg) for the validation which is not preferable due to cost.

Thanks for any info!

[tom jupille]

I believe that USP methods are considered validated by definition. So long as you meet the system suitability requirements, you should be OK.

[krickos]

I believe that USP methods are considered validated by definition. So long as you meet the system suitability requirements, you should be OK.

Will expand a bit on Toms post. You need to test the procedure locally and document it. Also one typically also expect a statement in the documentation that the procedure is suiteble for detecting the impurities in your product (regardless if they are known but unidentified or identified).

If there is a corresponding monograph in Ph Eur/BP you might get lucky and find information around known/identified impurities. Generally also Ph Eur reference standards tend to be cheaper than USP.

[danko]

Cody84,

If you see unknown/unidentified compounds in your products, you are supposed to identify them thus characterizing these products. There are both USP, EP etc. guidelines on that particular matter.
Please don’t send unknown compounds on the marked.

Best Regards

[krickos]

Might have misunderstood the question.
.....I can only use the USP standard ($620/50 mg) for the validation which is not preferable due to cost.

As long as you use the monograph I can not see that you get away from using the USP standard unless you qualify your own primary or secondary reference standard against the USP standard.

The Ph Eur standards are cheaper (79euros/50mg) and is supposed to come with a reference chromatogram in this case, the Ph Eur monographs contains more information about know impurities, however the procedure is not similar to the USP procedure so unsure on how informations you can extract from Ph Eur. But it could be intresting to compare both procedure and see if one is more suiteble than the other, also injecting both references on both procedures can be intresting as the references contains mixes of impurities.

[cody84]

Thanks everyone for the replies!

We've been making and testing this product for years now. Previously they had just verified the method. Now for some reason they want me to validate the current method without changing it. I think they got concerned because we recently had our FDA audit.

The CHG Related Substance standard from USP contains all of the related compounds, but USP said it is just used to test the resolution of your system and so they have not identified the compounds. Because of this I can't spike solutions with each impurity, so it is making this validation really complicated. The spec for RC is no more than 3% of the peak area of CHG.
I think I will try to spike with known amounts of CHG into the resolution solution, but it will be hard to get the exact % amounts I need for Accuracy and Range and such.

[cody84]

Great news! I checked our British pharma and it has 4 of the impurities and their names and structures and also my manager is very happy to hear their standards are much cheaper and come with documentation! Thanks!!

[W Kruse]

We are an API company. Our customers are demanding at least a verification as part of their submission requirements. Trust me, this is becoming tedious. Sometimes the verifications have a quick turn around.

Wanda

[krickos]

Cody: Glad to hear that you found want youwanted, though I think your management is going a bit over the top here.

Wanda: I do not follow your argument. You typically verify and document the suitability of the pharmacopiea procedure once (until procedure is significantly changed), you typically do not redo it just because you get a new customer. Or do you rather mean that you customers want your impuirty profile (ICH Q7a requirement to have one) or are the pharmacopiea procedures you work with very often changed:?:

[W Kruse]

I obviously did not include all details pertaining to my comment. It was meant strictly as an observation of what our customers are demanding

The philosophy was that since methods were compendial, you brought them in house and used them, no verification need, no report. Often the methods were handed to our quality analysts for them to figure out. You can imagine that this approach was not the best. any fixes after implementation often went into memos or monthly reports.

Fortunately those of us who have had to fix these messes, along with support from external papers and symposia, management has allowed us the time and money to fix methods up front and document in reports that can be easily accessed.

method verification is done only once unless there are column changes.

[krickos]

Right Wanda,

I fully understand, have been in similar situations.