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.
OK, over 135 views in a month here, and not one reply. Maybe that means that there is not a conclusive answer.
Anyway, a contributor elsewhere stated
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.
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.
Are you saying that you test ALL the inactive ingredients, fillers, etc. that you use in your finished products using validated methods? Do those methods include assay or just identity ?
So if a filler (like sodium carbonate or sodium citrate) has an NF monograph, you say to run all the NF acceptance tests (they’re assumed or defined as valid tests).
So what about a filler like sodium sulfate or a flavor material which has no USP/NF monograph. Would you develop and validate a test procedure to assay such incoming raw materials as well?
One aspect of this is assuring the integrity of your supply chain. In which case you need to verify the results the supplier is giving you. In our case we verify the test results of all coa results three times to qualify the supplier. Once qualified only periodic verification is required.
Now as for performing all of the test for the API you have to look at the formula it is going in, what the purpose of the API is, What risks are involved. In short, there is no cut and dry answer but with some justification you shouldn’t have to do every test at every receipt.
Justin
[quote=KM-USA]That’s a cryptic and confusing answer.
So if a filler (like sodium carbonate or sodium citrate) has an NF monograph, you say to run all the NF acceptance tests (they’re assumed or defined as valid tests).
So what about a filler like sodium sulfate or a flavor material which has no USP/NF monograph. Would you develop and validate a test procedure to assay such incoming raw materials as well?[/quote]
I agree with Justin. You must have a documented procedure in place to verify your supply chain. It is up to you to determine what is needed but you must have a scientific rationale for that. For critical ingredients that affect human health you would have a higher/more rigorous standard than for excipients that would not affect the efficacy of the product or human health. You should have an SOP in place, and follow and document your internal testing to support the SOP. For example, you may test vs. COA on the first ten batches from a new supplier, then test every 10th batch after that, or perhaps for an ingredient you don’t use frequently you should opt to test every 6 months. These are examples - the reason why no one can give you one answer is because “it depends” on the ingredient, the frequency of use, the risk associated with it, etc.
One other item is that if you use a compendial method you do not need to validate the method but you DO need to verify that you can run the method and obtain correct results. There are various ways to do that (perhaps you can get a certified (e.g., USP) standard and demonstrate you can get acceptable results, perhaps you need to do some limit testing to demonstrate that you can truly pick up a product that fails, etc., etc.).
So for your % ethanol example, you already have a method for testing finished product. If I were you I would have a method for testing incoming material too as if the incoming material is incorrect I have to scrap a lot, write a deviation, whatever which is an enormous waste of time and energy. You may not need to test every lot but you should have some rationale for testing and some data to support it.
[QUOTE=Satish Kapoor]I agree with Coo. You must have a documented procedure in place to verify your supply chain by auditing the vendor .You need to analyse at least some of critical parameters of incoming RM(API) using compendial method, if you use a compendial method you do not need to validate the method but you DO need to verify that you can run the method and obtain correct results, by conducting specificity for Related substances and Precision for assay to demonstrate that you can truly pick up a product that fails, etc., etc.).
You don’t have to validate the incoming Raw materials method. These may be Excipients, APIs, flavors or coating materials, Enzymes. All APIs methods shall be validated or verified by manufacturers. If you supplier is using pharmacopeia method then no need to validate it and should be verified. If they are following Non pharmacopeia method shall be validated. you can procure that method validation documents and review at your end. If you think that method is validated and suitable for quantifying Impurities and product then you can initiate the method transfer between your laboratory and supplier. If the method transfer is successfully completed then you can use that method for your end. Please note API analytical method may vary depend on their manufacturing process or generating the impurities during the manufacturing. Be alert always when you select a new supplier for your raw materials.
Don’t waste your precious time for validate the incoming raw material method validation just do method transfer, shall be documented. Make sure that non pharmacopeia method shall be validated and scientifically justified by your Analytical Research Department.
But as my practice your incoming raw materials shall be tested for all parameters. There is no shortcut. If you are proving that skipping tests is not impact on your product then you do not need to test. But a clear scientific judgment shall be made in this view.
Some times due to urgency of production your microbial analysis may not be completed for incoming raw materials because it will take 5 days. In this time you should have a justification of some batches but you shall analyze at your end. For example starch usually having more moisture and leads to increase the microbial load in your product. So you should perform the micro testing.
Even though your supplier is committed to you to supply the material in well protected transport container but some times container may be damaged and drench with rain water during the transport. But your material receiving personnel and sampling collection people may not be identify that defects because these are only qualitative not quantitative.
These are my industry practice, if any thing wrong kindly correct it.
[quote=Pulla Reddy]But as my practice your incoming raw materials shall be tested for all parameters. There is no shortcut. If you are proving that skipping tests is not impact on your product then you do not need to test. But a clear scientific judgment shall be made in this view.
Even though your supplier is committed to you to supply the material in well protected transport container but some times container may be damaged and drench with rain water during the transport. But your material receiving personnel and sampling collection people may not be identify that defects because these are only qualitative not quantitative.
These are my industry practice, if any thing wrong kindly correct it. Pulla Reddy Karnati.[/quote]
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.
What is required by FDA to do for QC for incoming USP API materials? That apparently is the opinion of the above writer.