Chromatography Forum

Our QA has asked me to post for your expert opinions. Our company makes finished OTC pharmaceuticals in USA. We purchase USP API materials and put those into over the counter pharmaceutical products.

The question is: do our QC test procedures for the incoming API need to be validated (or use the USP assay procedure), or just to show that the incoming material meets our own company standard of quality - as we do not sell the API, just finished goods containing that API? And those API materials are already certified by their manufacturer as meeting USP requirements.

We develop and validate our own test procedures for the API in the finished products (what we actually sell) as per ICH/USP/cGMP etc.

Thanks.

Yes you need to test the API and all other raw materials using validated methods. You are responsible for what you put into your drug product. Purchasing a USP-API assures you that it was manufactured using cGMP processes.

In my "expert" opinion, if your QA department really asked for the opinions of the (generally) anonymous users of an internet forum to help set company testing policy, you need a new QA department (or a new job).

I'm not trying to be snarky - I would be seriously concerned if I were you, they should know this stuff.

In my "expert" opinion, if your QA department really asked for the opinions of the (generally) anonymous users of an internet forum to help set company testing policy, you need a new QA department (or a new job).

I'm not trying to be snarky - I would be seriously concerned if I were you, they should know this stuff.

Have to agree with DR there.

To answer the question in general around monograph APIs, provided that your drug product file refer to an API with a specification that only referers to a USP monograph, it is enough to verify and document that the relevant analytical procedures are suiteble, in other words, no full validation is required unless there is a problem, see like USP chapter <1225> or something like that, CFR has a similar intention.

It does not matter if you make/sell/broke/buy the API or excipients for that matter, your QP/company is utterly responsible for all ingredients relaesed to be used in the manufacturing of the drug product. If your comany has no control of the supply chain, it will eventually blow up in your face.

I agree, I would be cautious too. I was once offered a QC manager position at a company getting it's feet wet in manufacturing GMP OTC products. I had 5 years or less experience, I knew enough not to take a management position.

I didn't know is not an excuse that goes over well with the FDA..hello 483, recalled product..

If you haven't validated your method, where is the proof that it is working properly? The system suit isn't enough, that's just an easy check of some parameters to indicate if the system 9or some part of it at least) is or isn't up the spout.

You are responsible for what you put into your drug product.

It does not matter if you make/sell/broke/buy the API or excipients for that matter, your QP/company is utterly responsible for all ingredients relaesed to be used in the manufacturing of the drug product. If your company has no control of the supply chain, it will eventually blow up in your face.

Thank you for your responses. Following that line of reasoning then, since our company purchases alcohol to use as active in hand sanitizer products, shouldn't we need to assay the incoming alcohol for % ethanol even though there is no USP active range in the monograph (guessing due to the varied strengths and denaturants) before we put it into a finished product? Right now we don't assay the incoming alcohol for either % ethanol or to even to make sure it's the right denatured formula, I think that's a gap. Opinions, please. We have validated the ethanol assay for the finished products we sell. There is a USP assay (USP 611) but % ethanol is not defined in the monograph. Thanks.

I'm reviving this old thread.

I have contacted USP, and the person in charge of the alcohol monograph seems "surprised" that we didn't know that USP assumes everyone "knows" that specific gravity is used as the incoming alcohol purity check (even though it's not in the monograph, and not especially specific, essentially assumes only water and alcohol present. So we did initiate that.

So the new question is: currently we assay for strength and identification of incoming USP-grade API ingeredients, then we make OTC products containing these. Someone inquired whether we should be performing ALL the USP-listed tests on all batches of USP API raw materials.
1. What is required by FDA to do for QC for incoming USP API materials?

2. What do most similar companies do?

Thanks.

Right now we don't assay the incoming alcohol for either % ethanol or to even to make sure it's the right denatured formula

Denatured with what?
Most denatured alcohol is denatured with methanol, which is something I don't want to be smearing haphazardly on my hands or on children's hands. Unless you're getting stuff that's specifically denatured with isopropanol, it might be time for a new supply.

1. What is required by FDA to do for QC for incoming USP API materials?

Characterization and identification of all materials that do not have primary identification performed by the direct supplier and clearly outlined on their C of A.

2. What do most similar companies do?

FTIR, LC retention time testing, Mass Spectrometry.

You're generally also required to check for degradants and related substances in more complex molecules
(Ethanol, not so much... but aspartame is a good example, as it is not terribly shelf-stable in solution)

NDIR takes a bit of setting up but is becoming a mainstream solvent QC testing technique. You can get ID an mositure content in one, not sure if it could also look at the denaturing agent (which could be 5-10% methanol, or 0.1% t-butanol, not sure what else is used). In another job we had a Perkin Elmer which wasn't bad but the after-sales was the usual weakness. No sample prep required though.