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GMP Labeling Lessons

Incomplete 483 responses lead to warning letter

GMP Labeling Lessons

Dietary supplement labeling and GMP issues lead to a warning letter. We can learn A LOT about how to avoid regulatory issues by understanding this warning letter. Here, I explore key labeling and GMP oversights that the company made as a way to help you avoid the same types of issues in the future. This is why I’ve written Warning Letter Wednesday for 120+ weeks in a row, and I continue to hear good feedback which keeps me going.

First, with some of the labeling violations.

These are minor violations that wouldn’t attract a letter on their own, but they can teach us how to ensure a compliant supplement fact panel is made. The comment about “Other Ingredients” not being allowed in the fact panel is a good one, which I will use when educating clients about label layout compliance.

  • “Supplement Facts label is not enclosed in a box by using hairlines      (21 CFR 101.36(e)(2)).

  • A heavy bar is not placed under the “Serving Per Container” heading      (21 CFR 101.36(e)(6)(i)).

  • A light bar is not placed under the heading “Amount Per Serving” (21      CFR 101.36(e)(7)).

  • A heavy bar is not placed under the final other ingredient (21 CFR      101.36(e)(6)(iii)).

  • The title, “Supplement Facts,” and headings are not bolded (21 CFR      101.36(e)(1)).

  • There is no provision in the regulation for an Other Ingredients      list to appear within the Supplement Facts label.”

Ingredients must be disclosed. There are a lot of redacted statements in the warning letter, but it looks like the company attempted to categorize ingredients “added after the extraction” process as processing aids, which should have been disclosed on the label. Here is a helpful article on the topic. 

Multiple age groups: This is interesting! It shows that the product’s suggested use must match the supplement fact panel. There are directions for different age groups, but the fact panel only lists the amount for one rather than both of the age groups.

From warning letter. “Your product’s Supplement Facts labels do not clearly include all the intended groups with the serving size and nutrition information in separate columns in the Supplement Facts label, as required by 21 CFR 101.36. For example, your …. product’s bottle labeling provides directions for use for adults and children under 3; however, both those intended groups are not declared on your product’s Supplement Facts labels.”

Statement of identity: The bottle reads “Mineral Supplement,” but according to FDA, there is no mineral in the product. Listing “Dietary Supplement” would have avoided this citation.

GMP Violations

There are a lot of GMP violations, such as not having specifications, the quality unit not properly quarantining/releasing components, not documenting equipment cleaning, and not having a two-person documented verification of the weight of ingredients, but there is a lot more. 

I suggest everyone read the full letter

The timeline of events in this letter is interesting. FDA gave this company plenty of chances to “get their GMP act together. FDA inspected the facility from June – August 2023 (OMG, that’s a long inspection) and then tested a nasal product that was likely gathered during the inspection. In late September 2023, FDA had a teleconference with the company where they agreed to recall lots of the nasal product due to high bacteria levels. This led to several GMP violations for citations, such as MMR review procedures, stability, and product release. These are important items for supplement product manufacturing but are essential for any product that goes in the nose, eyes, or ears. 

When I was a contract manufacturer, I remember being asked to make these “drug” types of products, and the answer, due to the higher drug regulatory standard, was always no. This shows that companies should understand the nuances of the regulatory category of products they manufacture, and I expect to see more “cosmetic products masquerading as drug products” cited in the coming year. Here, I write about a topical product that was “turned into a drug” due to its marketing claims.  

Getting back to the timeline, the 483 responses continued from the company until last month when FDA finally determined they needed to issue a warning letter.

Incomplete 483 Responses

Reading this warning letter, the FDA’s comments on the 483 responses made me think this company could have avoided the letter with proper responses. Most, if not all, 483s can be addressed before they turn into warning letters. Learning from letters like this and addressing problems before they escalate can help you stay out of trouble.

Here is a typical incomplete 483 response.

From warning letter. “In your response, you state you will address items within the Supplement Facts label. However, you do not present sufficient evidence to demonstrate corrections. Therefore, your response is insufficient for us to evaluate corrections.”

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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