Ensure 483 responses are complete < Back Incomplete Batch Records & Ingredient Specifications Ensure 483 responses are complete This letter is a great reminder of the basics of Good Manufacturing Practices, starting with developing specifications to ensure the ingredients and products are correct and not contaminated with microbials or heavy metals. FDA inspected this company in January and February last year, and they provided 483 responses over the next couple of months. The findings during the inspection and the incomplete 483 responses led to this warning letter. Ingredient Heavy Metal Specifications: 🔹From warning letter. “You did not provide any heavy metal or microbial test specifications for your Acetyl-glutathione component.” Batch Production Record (BPR) Issues: 🔹From warning letter “A statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing (21 CFR 111.260(f)).” 👉 Asa comments: This is important to identify whether ingredients were added correctly. For example, a lower-than-expected yield could signify missing ingredients or low capsule fill weight. 🔹From warning letter. “Documentation, at the date and time of performance, of labeling operations (21 CFR 111.260(k))” 👉 Asa comments: This is essential to verifying when processes were conducted, which can help identify issues before the product is released to the public. 🔹From warning letter. “An actual or representative label, or a cross-reference to the physical location of the actual or representative label used in production (21 CFR 111.260(k)(2))” 👉 Asa comments: Batch production records are recipes built in conjunction with the product label. Cross-referencing the label is a key part of ensuring the formula and label match. Master Manufacturing Record (MMR) Size: Each formula size should be its own MMR. 🔹From warning letter. “The MMR you provided in your April 8, 2024, response….not specific to a unique formulation of a dietary supplement and is not specific to batch size. Incomplete 483 Responses: The bizarre thing about the warning letter is that it could have been prevented. 🔹From warning letter. “Your response dated April 8, 2024, includes a document titled Returned Product Procedure. However, the procedure does not address the requirement for quality control to conduct a material review and make a disposition decision, as required by 21 CFR 111.510. The procedure states that the food safety officer will perform these activities.” 🔹Here is another reference to an incomplete 483 response. “Your current finished product specification sheet for your Acetyl-glutathione product lists the test method as N/A.” Quality Must Investigate To Prevent Bigger Potential Issues: The following section of the warning letter speaks to a core principle of GMPs: if there is a safety issue due to a product return, the company is required to ensure the return is not related to a problem that affects other batches. This does not need to be complicated, but it should be part of a product complaint or product return SOP. 🔹From warning letter related to the Returned Products Procedure. “Furthermore, the procedure also does not address the requirement that if the reason for a dietary supplement being returned implicates other batches, you must conduct an investigation of the manufacturing processes and each of those other batches to determine compliance with specifications.” There’s a lot more in this warning letter . DATE ORIGINALLY POSTED: 1/22/25 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

< Back Podcast Monday Apr 24, 2023 GMPs and Dietary Supplements: A Conversation With the Experts CHPA Chat If you are in the consumer healthcare industry, you probably know about GMPs, or Good Manufacturing Practices. But what do they specifically mean when it comes to dietary supplements, and how do VMS companies prepare for an FDA inspection? Listen Previous Next

FDA will test suspicious products for drugs < Back Male Enhancement Products Found with Drug-Spiked Ingredients FDA will test suspicious products for drugs FDA has issued two drug-spiked product warning letters this year! This is the type of action I appreciate seeing the FDA do, as this small number of bad actors in the market gives the dietary supplement industry a bad name. Sign up for my weekly Warning Letter Wednesday post. FDA tested these products and found them to contain active ingredients in Viagra and Cialis. The company's product claims about erectile dysfunction likely triggered FDA to test these products, and several ED claims are cited in the warning letters. Erectile dysfunction may be considered a disease claim and should be avoided. But how about libido, sexual performance, and aphrodisiac claims? Do you think these types of statements are structure-function statements? In my opinion, libido-type claims attract FDA attention and require additional testing on Amazon, but they, if substantiated, are likely in the lower-risk category as long as companies are testing to ensure there are no unintentional drug-spiked ingredients. I rarely tell jokes on Warning Letter Wednesday, but I can’t help this one. “Why did the lizard go to the doctor?... He had reptile dysfunction.” In this warning letter , the timeline is perplexing. FDA inspected the manufacturer and conducted a website review in June 2022. FDA tested a product and found the presence of sildenafil which is the active ingredient in Viagra. Then in August 2022, the company issued a recall for one lot of the seven-count product. Two months later FDA issued a public notification warning consumers about these products, and now in January 2023, the company was issued a warning letter. What can we do to help get these drug-spiked products off the markets sooner? This warning letter from yesterday also has an even more bizarre timeline. FDA reviewed the website and potentially tested products in May 2022. In July 2022 FDA issued a public notification warning consumers about the presence of tadalafil in these products. Then, just last month FDA re-reviewed their website and found the company apparently still selling these products, which led to this warning letter. Again I ask, ‘What can we do to help get these drug-spiked products off the markets sooner?’ 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

Scan marketing for “mid-risk” heart health claims < Back IBS & Cholesterol Claims Cited in Warning Letter Scan marketing for “mid-risk” heart health claims This letter primarily cites digestive ailment claims such as Irritable Bowel Syndrome (IBS) and heart health claims such as “lowers cholesterol.” While these types of statements should be avoided, they are not usually enough to tip the scale into a warning letter. Do you want Warning Letter Wednesday delivered weekly to your inbox? Sign up here to join ~500 other regulatory professionals. Here are some key learning opportunities. 🔹Statements related to cholesterol and blood pressure should be avoided. In the past, statements like “lowering cholesterol and blood pressure” were not enough to attract a warning letter unless higher-risk disease words were present, but this seems to be changing. I write about last year’s crackdown on companies making biomarker claims here . I expect this trend to continue, so the learning target here is re-review all marketing and remove statements like these. • Lowers blood pressure • Lower A1C and LDLs • Lower arterial plaque • Lower blood sugar • Lower bad fats 🔹We have always known that Irritable Bowel Syndrome (IBS) is considered a claim, but it’s not commonly cited unless words like Crohn’s Disease are also used. I also suggest using caution when talking about bloating, constipation, and abdominal pain, as they may be symptoms of serious diseases. If accurate a potential risk mitigating factor is talking about occasional abdominal discomfort and attributing bloating to occasional overeating. These strategies help separate normal life events from those related to disease. 🔹The company receiving this warning letter appears to be very small, which again shows that us no one is too small to be off FDA’s radar. 🔹This company also makes statements in testimonials that have been highlighted on the website. When a company engages or calls outs a product review, this then becomes an endorsed testimonial, which is marketing. I write about the endorsement of social media claims here . Read the full warning letter here . 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

High risk “buzzwords” attract FDA/FTC “keyword web crawlers” < Back Step #1 in reducing risk is removing high-risk “buzzwords” High risk “buzzwords” attract FDA/FTC “keyword web crawlers” #WarningLetterWednesday Step #1 in reducing online marketing risk is removing high-risk "buzzwords". These include Alzheimer's, cancer, diabetes, PTSD, opioid support, depression, and of course COVID. Other "buzzwords" include pain, anxiety, inflammation, and arthritis. Today's warning letter is a smorgasbord of "buzzwords". Read it here . Authorities look at the 10,000-foot view of a company's online persona. One "buzzword" will likely not attract a warning letter, but claims on social media, videos, blogs, product reviews, hashtags, and ingredients descriptions elevate risk. The authorities piece them together for one big picture of noncompliance. The more "buzzwords" the higher chance of scrutiny. I suggest removing or replacing them with truthful, accurate, and not misleading options. Examples: Pain <> Discomfort Anxiety <> Mental resilience or balanced mood support Flu <> Seasonal immune support 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

Nutrition fact panels must be in a compliant format < Back Lack of Allergen Labeling Leads to Potential Death Nutrition fact panels must be in a compliant format Allergen labeling regulations are important. They help people with severe allergies avoid products that can make them sick or worse. In this example, the company allegedly did not disclose peanuts and eggs, which led to an anaphylactic death. 👉From warning letter. “On January 23, 2024, after being notified of a consumer complaint received by the FDA regarding an anaphylactic death associated with …. your firm recalled the cookies. The products contained peanuts and eggs but your printed label on the package did not contain an allergen statement or ingredient declaration for peanuts or eggs.” The warning letter goes on to state that there are missing and extra ingredients on the label, which shows that the company’s quality control procedures need a serious review. Disclosing major allergens is easy. Here are the two options. I always prefer the “Contains” option as it’s more apparent to the consumer. 👉The word “Contains” followed by the name of the food source from which the major food allergen is derived, is printed immediately after or adjacent to the list of ingredients, section 403(w)(1)(A) of the Act [21 U.S.C. § 343(w)(1)(A)]; or 👉The common or usual name of the major food allergen in the list of ingredients is followed in parentheses by the name of the food source from which the major food allergen is derived (e.g., “Whey (Milk)”), except the name of the food source is not required when either the common or usual name of the ingredient uses the name of the food source or the name of the food source appears elsewhere in the ingredient list (unless the name of the food source that appears elsewhere in the ingredient list appears as part of the name of an ingredient that is not a major food allergen), section 403(w)(1)(B) of the Act [21 U.S.C. § 343(w)(1)(B)]. The Nutrition Facts Panel (NFP) is also not in the correct format. There are differences between a Supplement Fact Panel and an NFP. This FDA reference is pretty good. 👉From warning letter. “The calorie declaration is not shown bolded and in larger print size, as required by 21 CFR 101.9(d)(1)(iii). b. It lacks the declaration for added sugars, as required by 21 CFR 101.9(c)(6)(iii) c. It lacks the declaration for the required vitamins and minerals, vitamin D and potassium, as required by 21 CFR 101.9(c)(8)(ii)” Here are some examples of compliant NFPs . Read the warning letter here . DATE ORIGINALLY POSTED: 11/27/24 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

Marketing strategies should consider “reasonable consumer expectations” to avoid issues < Back GLP-1 Product Receives Warning Letter Marketing strategies should consider “reasonable consumer expectations” to avoid issues This is one of the cringiest Warning Letter Wednesday posts I've ever written. Wow! This company received a warning letter for making claims that it is better than Ozempic, has FDA approval, does not require a prescription, has no side effects, and is clinically proven in "clinical trials and was approved by the Food and Drug Administration last year." This is the first GLP-1-related "supplement" FDA warning letter. Interestingly, it came in a group of five letters; the other four were companies selling semaglutide (generic Ozempic) labeled as "RESEARCH USE ONLY," but FDA cites their secondary marketing claims as proof of the intended weight loss use. Good detective work FDA! This warning letter is a great study of how implied and express claims cross the compliance limits, such as with the before and after pictures, statements like "Only active GLP-1 is effective GLP-1," and "FDA approved" statements. Here is my opinion on some of the information I've gathered. It is unclear what the ingredients in the product are, but they are marketed as natural and side-effect-free. The product is not labeled as a supplement, but it lists "Clinically Proven" and "Metabolism boost drops for weight management" on the label. The before and after pictures are super cringy and likely violate FTC regulations against deceptive marketing. The product reviews feel doctored, and the entire vibe of the website seems like an AI-generated experiment. It gave me the heebie-jeebies, and I expect the FTC would have a field day with this site. There are other "supplements" for sale on the website, such as THC gummies and weight loss gummies, that are making claims related to anxiety reduction (thanks to Apex Compliance for helping me find these). And much more FDA also cites this company for making "FDA-approved" claims. As we know, supplements are FDA-regulated but not "approved." From warning letter. "webpage for ...includes the image of a blue circle with the claim, "FDA APPROVED" along with the statement,. . . was approved by the Food and Drug Administration last year." Implied GLP-1 statements are cited but they’re probably not the primary reason for this warning letter. From warning letter. “The Science of GLP-1 . . . The effectiveness of … lies in its dual-action approach, addressing intake and expenditure. On one hand, it suppresses appetite, aiding in reduced food consumption and subsequent weight loss. It also slows gastric emptying, prolonging the feeling of fullness over an extended period.” Bashing companies is not my style, as I believe in a "rising tide" and educational approach, as many companies who receive warning letters may not know any better, but this company's marketing feels calculated and intentional. Read the full warning letter here . DATE ORIGINALLY POSTED: 12/18/24 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

Re-review marketing if FDA has inspected you < Back Online Marketing & GMP Lessons Re-review marketing if FDA has inspected you Learning about compliance is fun, and today’s Warning Letter Wednesday has critical teaching opportunities for marketing and GMP compliance. This is yet another example of a company being inspected by FDA; then, many months later, around the time of the inspection close out, FDA looked at the company’s online marketing and found a lot of no-nos. This is an enforcement trend that I write about in more detail here . First, the marketing issues : YouTube videos : Claims made in YouTube videos have been mentioned in three warning letters this year and I expect this trend to continue. Reviewing hours of YouTube videos for compliance concerns is painful, so I developed and patented a technology to help with this . In this warning letter FDA clearly shows the “material connection” or “commercial bridge” by referencing that the company placed its website on the screen. From warning letter. “the URL for your website … appears onscreen during the video and you state: “Very powerful anti-cancer properties…used in conjunction with chemotherapy and other cancer treatments, but not only does it have anti-cancer properties it also has a lot of other properties as well…the way that Taxane works in the body to fight cancer is it causes cell apoptosis in cancer cells.” Biomarker claims continue to be mentioned in warning letters. I go into more detail about this here . From warning letter. “Lowers LDL and Triglyceride Levels” Words with “anti” are disease claims , except for antioxidant and perhaps anti-aging. Words like anti-inflammatory have a risk rating of three out of five (Asa risk scale) which means they are not likely to attract a warning letter on their own, but words like anti-viral are very risky. From warning letter. Dr. Bob’s Parasite Killer is formulated with parasiticidal, anti-fungal, anti-viral, and antibacterial ingredients with the intention of killing everything in the digestive tract. Claims on product labels : We know that all marketing is an extension of the label, but I am still surprised by some of the “on-pack” claims companies put on the product label. No knowledgeable manufacturer would apply labels with these statements. From warning letter. “Dr. Bob’s Parasite Killer is formulated with parasiticidal, anti-fungal, anti-viral, and anti-bacterial ingredients with the intention of killing everything in the digestive tract.” Now the GMP learning opportunities : Component specifications are integral to GMPs, and each raw material must have written specifications. This is to ensure ingredients do not make it into inventory unless they’ve been checked. For example, suppose an ingredient’s visual specification was green and the product came in yellow, or the ingredient did not pass identity testing. In that case, the specification sheet should help catch and document this. From warning letter. “Yuan Zhi is an ingredient in your … but you did not establish such component specifications for Yuan Zhi.” Incomplete 483 responses are too common, and I write more about this here . From warning letter. “you did not provide any supporting documentation, such as copies of your specifications. We are unable to evaluate the adequacy of your corrective action, because you did not provide documentation to support that you have established component and finished product specifications.” Batch Production Records (BPRs) are the “recipe” and should have all adequate information, including copies of labels and cleaning records. Here are some of the items cited in this letter. The description and name of equipment used in producing the batch. This is important so cleaning can be documented. 🔷 The date and time of maintenance, cleaning, and sanitizing of the equipment and processing lines used in producing the batch or a cross-reference to records where this information is retained. 🔷 The unique identifier, such as a lot number and item number for each component, packaging, and label used. 🔷 The identity and weight or measure of each component used [21 CFR 111.260(e)]. A statement of the actual yield or theoretical yield at appropriate phases of processing. This is important to ensure the weight is correct. For example, a high yield could signify an ingredient may have been incorrectly weighed, and this may pose a safety concern. Documentation that the finished dietary supplement meets specifications. Documentation at the time of manufacturing, such as real-time quality checks. This includes bottle weight and label verification. Documentation that quality control personnel reviewed the batch production record and approved and released, or rejected, the batch for distribution. The job of quality is to review and release ingredients, in-process work, and finished products once it has been verified against its specification. Labeling issues were also cited. 🔷 Not listing the capsule in the label’s ingredients 🔷 Not listing the plant part such as ginkgo leaf. 🔷 Not using the standardized common name as described in AHPA’s Herbs of Commerce. Thanks, AHPA, for this resource! 🔷 Incorrect serving size. If the label states, “take 5-8 capsules,” the supplement fact panel must reflect the higher number. 🔷 Listing nutrients with zero amounts, like cholesterol, is not allowed on supplements but is standard for conventional food labels. 🔷 The company was cited for not listing black walnut as a major allergen. I ask, is black walnut a tree nut allergen? 🔷 DSHEA disclaimer: I don’t remember seeing this in a warning letter. The company was cited for apparently not having the DSHEA disclaimer on the label. From Warning Letter. Your … are each misbranded within the meaning of section 403(r)(6) [21 U.S.C. § 343(r)(6)] in that the products make structure-function claims but fail to bear the required dietary supplement disclaimer in accordance with 21 CFR 101.93(b). There are many more labeling items cited. Read the full letter here . 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!

Companies are responsible for co-manufactured products < Back Eye Care (Ophthalmic) Products Under Increased Scrutiny Companies are responsible for co-manufactured products This warning letter is interesting. This is an ophthalmic drug warning letter, but the supplement and cosmetic industries can glean helpful information here. Here, I review these learning opportunities. Claims on website and videos. Timeline: Could the company have avoided a warning letter? Ophthalmic (eye) drug products are under increased scrutiny. Manufacturer and distributor responsibilities Are you interested in a free discussion about high-risk claims on your website? I’ll run my compliance software and share the findings. Book your free session . ● Claims on website and videos. FDA has cited seven companies for claims in YouTube videos this year. What makes this interesting is the videos mentioned in this warning letter were embedded on the webpage rather than just on YouTube. This shows me that FDA is going the extra mile to review videos. Also, some of these videos are old, like this one from 2018. From warning letter. “From your March 16, 2018, YouTube video titled, “MSM Eye Massage (Eye Exercise)” on your… where you demonstrate an eye massage with one of your MSM eye drop products: “This MSM eye massage is great for inflammatory eye conditions, blepharitis, dry-eye, improving the lymph system, and stimulation of tears.” As a side note, Apex Compliance, my monthly compliance software, scans YouTube video transcripts for compliance issues in seconds. Learn more . ● Timeline . FDA tested one of the company’s products and found that it contained microbial contamination, which is very serious for products applied to the eyes. On August 21stof this year, FDA and the company had a virtual meeting, presumably to talk about the contaminated product. A few days later, the company issued a voluntary recall for this and some of their other products. At some point in August FDA reviewed the company’s website and found many drug claims. At some point in August FDA reviewed their website. If the company would have conducted a website compliance check when contacted by FDA, I wonder if they could have avoided a warning letter. ● Manufacturer and distributor responsibilities. This company was using contract manufacturers but apparently did not check their work. Here FDA reminds companies that they are responsible for the products they get made by co-manufacturers. If the company had conducted quality checks, they probably would have caught the microbial contamination before it led to a recall and subsequent warning letter. →From warning letter. “You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities.” FDA also provides a link to this useful guidance document, Contract Manufacturing Arrangements for Drugs: Quality Agreements . ● Ophthalmic drug products are under increased scrutiny. There have been 21 ophthalmic FDA warning letters this year, compared with seven last year. This continued enforcement trend has involved some of the largest companies, such as Amazon. I write more about this . It sounds like the company did not follow the path of an OTC or other drugs. Anything added to the eyes has a high level of danger and should go through proper regulatory channels. →From warning letter. “new drugs may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect…. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 USC 355, is in effect for these products.” Read the full warning 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. Previous Next Get Warning Letter Wednesday in your Inbox Sign-Up Now!