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GMP Labeling Lessons

Learn from warning letter enforcement

GMP Labeling Lessons

We can learn a lot from warning letters, especially from GMP-related letters, as they show how FDA investigators interpret regulations. Today’s Warning Letter Wednesday highlights incomplete product specifications and has some unique FDA callouts on supplement labels that are infrequently cited. This shows the importance of a proper supplement label layout, as even small issues can add up and lead to the possibility of a warning letter.

This company was inspected by FDA in 2021 and received some 483s. Learn about the difference between 483s and warning letters here. In my experience, most 483s can be avoided by submitting complete responses before they become a warning letter.

Let’s go into the labeling lessons.

🔷Listing stevia extract. This is surprising as most large reputable companies list their stevia extract as “stevia leaf extract” on supplement labels. This is the fourth warning letter mentioning stevia labeling in the past five years and the second in 2023. Updating how stevia is listed on supplement labels is a good idea.

From warning letter. The (b)(4) and product labels list the ingredient stevia extract (leaves) but do not specify the steviol glycoside. We note your MMR for each product indicates the ingredient is Stevia leaf 97% (Rebaudioside A 97%). The common or usual name for highly purified steviol glycosides depends on the ingredient composition. If the sweetener is purified to contain 95 percent or more of a single steviol glycoside, the specific name of that single steviol glycoside is the common or usual name. For example, the name "rebaudioside A" should be used for ingredients with 95% or more rebaudioside A; the name "stevioside" should be used for ingredients with 95% or more stevioside. If the sweetener is purified to contain 95 percent or more of a mixture of two or more steviol glycosides, the name "steviol glycosides" would be the common or usual name.

🔷Listing zero amounts and <2%DV. Although listing zero amounts in a supplement fact panel is not compliant, even some large companies list sugars as zero in their supplement fact panels. This is one of the major differences between supplements and conventional food labels, as food labels require some zero amounts to be listed. The company was also cited for listing ingredients with <2% daily value. We see this on supplement labels all the time, and personally, I fail to see why it is an issue. For example, if the product contains under 2%DV calcium, but a marketing statement such as "with calcium" is added, then listing <2% daily value may be a good idea. I welcome your feedback.

From warning letter. "The (b)(4) product label declares dietary ingredients with amounts of 0 or percent Daily Values of 0 or <2%. Any (b)(2)-dietary ingredient not present, or in amounts that can be declared as zero in 101.9(c), shall not be declared (e.g., amounts corresponding to less than 2 percent of the RDI for vitamins and minerals) in accordance with 21 CFR 101.36(b)(2)(i).

🔷Listing the correct nutrient measurement. The company was cited for not listing copper in milligram format. This supplement fact panel reference from expert consultant Marian Boardley can be helpful. Thanks, Marian!! 

🔷Listing the "2000 calorie statement" in the fact panel. This is a common label error and is an important reminder that this statement is only "allowed" in a supplement fact panel when items like carbohydrates are present.

From warning letter. The … product bears the following statement: "Percent Daily Values based on a 2,000 calorie diet." This statement is only permitted when the percent of Daily Value is declared for total fat, saturated fat, total carbohydrate, dietary fiber, or protein as required by 21 CFR 101.9(c) and 21 CFR 101.36(b)(2)(iii)(D).

🔷Listing Vitamin D3 instead of Vitamin D. This is an obscure one. Officially, it should be listed as "Vitamin D (as cholecalciferol)," but it is common practice to list "Vitamin D3." This investigator was really a stickler (smiles).

🔷Precautionary allergen statement. This was on an acidified food "supplement" product and shows FDA's thinking about precautionary allergen statements. I ask, "Is there any reason to add to supplement labels?" Also, "Should this be removed from supplement labels?"

From warning letter." The (b)(4) product declares the statement "Manufactured in a facility that processes egg, wheat, milk, soy, tree nuts, peanut, fish & shellfish products." The use of an advisory label such as this is not an acceptable substitute for food allergen control procedures to prevent cross-contact. The firm should make every effort to assure that they and their suppliers have adequate GMPs in place to prevent the un-intentional inclusion of allergens in their products and ingredients."

🔷Improper specifications continue to be cited in warning letters. The company's 483 responses did not include important information. Here FDA cites the company for listing the taste/aroma specification as "meets reference" when it should have been something like "bitter." It seems the company listed the result "meets reference" as the specification. FYI, a better way to list the result is to write what the actual result is such as "bitter." I commonly see these avoidable "minor" errors specification format appear in warning letters.

From warning letter. "the specification for Taste/Aroma states "Meets Reference." "Meets Reference" does not provide a description of the taste or smell that is characteristic of the products."

🔷So, what tipped the scale to a warning letter? I assume it was related to the improper 483 responses that, after five responses, were deemed incomplete. The label issues were probably not enough to attract a warning letter on their own, but having a compliant label can help an inspection go better. Also, uncompliant labels posted on your website may elevate the risk of inspection.

There are a lot more learning lessons in this letter, such as additional improper specification examples. 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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