USP Methods/cGMP Regulations

[Must remain anonymous]

Our company just purchased a line of OTC products to go with ours. We have had similar OTC products, with same actives, for 25 years, and have always used the USP procedure on ours. Now, with the acquisition of the new brand names, our QA department insists that the USP assays are for the active ingredients themselves, and cannot be used as is for assay of the finished products unless the USP procedure is validated for the finished products themselves. Previous to this (and per my department SOP), USP and other compendial methods were taken as not needing validation, just needing a verification that the procedure works in the products. Does anyone out there really know, or can offer some expert advice? I think our QA may be trying to exert their "power", or is tremendously afraid of putting a document in our cGMP file and having to "defend" the science.

[tom jupille]

Presumably, you have been inspected / audited by the FDA at some point during those 25 years. If that SOP was in place, and if it passed muster with the FDA, then "if it ain't broke, don't fix it".

[Must remain anonymous]

Mr. Jupille: our company's products of this type have been manufactured at co-packers for at least a dozen years, and either no FDA inspector ever questioned their assay procedure, or was OK with it, but there is no way to know. As to the newly-acquired products: yes, their (former) facilities were inspected by the FDA numerous times, and there was never an issue about this (and, apparently, this is considered a "universal" procedure for this active). But my company's QA department is "special". They didn't have an SOP in place detailing that they were just using the USP procedure either, or their rational for using that procedure.

[tom jupille]

Strictly speaking, your QA people are correct. There is no guarantee that that there isn't something in your formulation that would interfere with / invalidate the USP procedure. That said, I find it hard to visualize that these products have been made and analyzed for over a decade without having an SOP in place on how the analysis is carried out. Someone needs to go over the documentation history on this stuff before a "feco-ventillary collision" occurs.

[DR]

You will have to revalidate.

As mentioned, you are dealing with a new formulation so you have to revisit (at least) all aspects of the validation that deal with specificity and accuracy. You should also repeat your forced deg. studies as you may not have the same impurity profile as with the legacy product. If the new formulation is pretty much the same as what you had adn the sample prep. is about the same, you may be able to skirt some robustness work.

[Alfred88]

Dear all:
I agree with DR and Tom. USP monographs are mostly for pure materials, and the assays (if exist) are for pure materials. Monographs for compounded products with active ingredient(s) are rare!

If you use the assay method directly from USP for your products, the matrix may interfere with the assay, and alter the results. We have had many problems with USP methods that did not work for our products. We had to develop the methods internally (of course, we do the validation!).

As quoted by anonymous, "the USP assays are for the active ingredients themselves, and cannot be used as is for assay of the finished products unless the USP procedure is validated for the finished products themselves," I agree completely with your QA's position. Perhaps you must enhance compliance, by validating USP methods on your finished products. It is good practice to check system suit, and accuracy.

Alfred.

[AdrianF]

It seems to me that sometimes when it comes to validation, commonsense goes out the window - it has taken us over a year to validate a CDS - Empower!

If we took the same view when buying a car it would stand in the drive for a six months before it was let out on the road!

[DR]

- it has taken us over a year to validate a CDS - Empower!

Is this because you're validating all of your custom fields & calculations before you use it? [/hijack]

[AdrianF]

I wasn't involved in the validation so I can't answer that question. My point was the validation industry seems to have taken on a life of its own. I the past I have impemented a CDS system - we boughtit put on the bench read the manual and started using it - took a week or two. If control samples were OK we assumed the system was OK especially as it was being used by 1000s of others. Will laboratories be validating Vista when it arrives?