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Noncompliant Testing Methods Lead to Warning Letter

Use qualified reference samples

Noncompliant Testing Methods Lead to Warning Letter

This company received 483s for GMP violations relating to testing methods and specifications. 

They were inspected in late 2021 and early 2022 and sent FDA five 483 responses last year. It seems these responses were not satisfactory, which led to this warning letter.

There are numerous learning opportunities here.

🔷One of the violations was not having a strength test on a softgel product. It seems the company once had this, but it was removed 👉“at the request of the customer, as documented in your change control document.”
A key learning lesson here is contract manufacturers should be flexible with their customers to a limit. Obviously, completely removing this test from the softgel specifications was a bad idea. Who knows, perhaps they could have found a more suitable strength test to satisfy GMP requirements and the customer.

🔷Unqualified reference standards are cited in this warning letter. The company was testing samples using FTIR, but the reference samples were not verified, which means they were likely from previous batches and not a purchased verified material. I will admit this is how I used to test identity circa 2010-ish.
👉From warning letter. “Identity testing using FTIR to compare the sample spectrum to an unverified reference sample is not an appropriate scientifically valid method”

🔷Identity testing in the finished product was brought up again, and this is a trend to watch. FDA requires the identity of each ingredient to be tested before blending and in the finished product. This is straightforward for some items but is costly and challenging if there are numerous botanical ingredients, as this requires developing expensive testing methods. I am unsure if this is the case in today’s #WarningLetterWednesday, but this is not the last time we will hear about this rigid pharmaceutical interpretation of supplement GMPs. I write about this here.

🔷Proving test method suitability is starting to appear in 483s and now in warning letters. This means that the FDA is asking why specific test methods are used. In the past, relying on a third-party lab for this was sufficient, but now, having suitability documentation on file for each method your lab uses is a good idea.

Read the full letter

Disclaimer: The educational information provided here is for informational purposes only. Contact an attorney for specific legal advice. Rule #1 in compliance is to ensure marketing is truthful and not misleading.

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