2016 FDA Warning Letters: Top Takeaways (So Far)

Aug 18, 2016

  • Reading FDA Form 483 warning letters is akin to trolling online celebrity mugshots: “They busted who for what?!” But familiarizing yourself with these letters should be more than just an exercise in gawking; warning letters are a valuable window into how FDA is scrutinizing the dietary supplement industry and, in return, how well (or not) the supplement industry is adhering to current good manufacturing practices (cGMPs). Simply put, FDA warning letters are a cautionary lesson for marketers and manufacturers who prefer to avoid getting such letters in the first place.

    To recap, the Federal Food, Drug and Cosmetic Act (FD&C) authorizes FDA to inspect supplement manufacturing facilities. If, during an inspection, FDA uncovers “any failure to meet the minimum requirements listed in 21 CFR, Part 111, or, technically, any failure to meet the current industry standard, whether provided for in 21 CFR, Part 111, or not,” said failure winds up on an FDA Form 483, or 483 for short, says Cynthia A. Ipach, president, Compliance Insight Inc. (Fairfield, OH). “Failing to remediate the problem listed,” she adds, “or to respond adequately to a 483 can result in the further regulatory action of a Warning Letter.”

    So, just how is industry compliance these days? “This is a tough one to answer,” says Justin J. Prochnow, shareholder, Greenberg Traurig LLP (Denver, CO). “We routinely assist companies with responding to 483 observations,” he says, and while he doesn’t think the number of letters is increasing, his sense is that, if nothing else, “the number of inspections has remained steady, if not increased.”

    Cheryl Luther, DC, general manager, dietary supplements and functional beverages, NSF International (Ann Arbor, MI), believes there’s been “an uptick” in the number of 483s issued over the past year, if not actual warning letters. “This is partly due to the lack of trust that the government’s regulatory agencies have in industry’s ability regulate itself,” she notes, though she emphasizes that “dietary supplement companies are striving to restore and maintain brand integrity by demonstrating their commitment to producing safer products for their customers.”

    Injecting some cold, hard data into the discussion, Ipach claims that a brief search of FDA warning letters to dietary supplement manufacturers reveals 19 such letters issued in the first half of 2016, compared to 27 in 2015 and 44 in all of 2014.

    So far, so good?

    That depends—not only on how the year’s second half goes, but on the nature of the observations noted in the letters, as well. And though complete 483 summaries for 2016 won’t drop until 2017, Ipach says that common themes in the warning letters released thus far run to misbranding due to misrepresentations in labeling; failure to establish or follow standard operating procedures (SOPs) or quality-control responsibilities; and failure to establish, follow, or provide sufficient specifications and batch production records (BPRs).

    So, just a bunch of technicalities, then? Not as far as Ipach is concerned. “This is not a matter of i-dotting and t-crossing,” she says. “Based on these observations, the industry continues to struggle with the same issues.” After all, when a “technicality” involves failing to document contamination or what’s in a batch of product, people can be harmed.

    Says Ipach, “Dietary supplement manufacturers need to focus on and provide training on the regulations.” But on the bright side, she adds, if all the documentation failures merely reflect the missteps of new companies entering the market, the future may bode well.

    Here’s a look at some recent FDA warning letters, and why you should care. (Nutritional Outlook thanks Marc Ullman, of counsel, Rivkin Radler, and his FYI Newsletter for collecting and sharing the letters.)


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  • Hemp CBD

    It’s no secret that as more localities legalize marijuana and “medible” products gain steam, FDA will be clamping down on dietary supplement and functional food manufacturers who appear to be taking advantage of the “Wild West” atmosphere.

    That’s just what the agency did on February 4, 2016, when it sent warning letters to eight companies marketing foods and dietary supplements containing cannabidiol, or CBD—a non-psychoactive cousin of the tetrahydrocannabinol (THC) found in Cannabis sativa.

    This isn’t the first time FDA has slapped the wrists of companies marketing CBD supplements. But while previous warnings called out marketers for making improper health claims, the current crop of letters focus on a more serious issue—namely, questioning the legitimacy of CBD as a dietary ingredient entirely. Because CBD is the subject of two drug applications currently under consideration, the agency says that CBD could be “outside the definition of a dietary supplement.” The takeaway for CBD firms? Be careful, and stay tuned.

    Photo © iStockphoto.com/AlenaPaulus

  • Picamilon, DMBA, and Weight Management

    A corner of the supplement industry familiar with scrutiny is the weight-loss sector. High-profile FDA actions coupled with an overweight nation’s desperation to shed pounds has focused special attention—from Congress, no less—on products that promise more than they deliver and contain ingredients they shouldn’t.

    So when FDA sent warning letters on March 31, 2016, to Nutraclipse Inc. and M4 Nutrition Companies about the unauthorized presence of methylsynephrine, 1,3-dimethylbutylamine (DMBA) and picamilon in their weight-loss supplements, it must have given Senator Claire McCaskill (D-MO) cause to smile.

    Why? The senator last year asked ten major retailers to pull picamilon-containing supplements from their shelves while also chiding FDA for its inaction on the ingredient, which is a derivative of GAMA (gamma-aminobutyric acid) and nicotinic acid developed in 1969 in the Soviet Union as a pharmaceutical.

    Photo © iStockphoto.com/shirhan

  • Anti-Aging and Skincare

    Is getting old a disease? It sure feels like it. And as far as FDA is concerned, it might as well be, for the agency sent a warning letter on July 15, 2016 to Annmarie Gianni Skin Care for making what the agency deemed drug claims on its website.

    In question were the company’s Repair Serum, Anti-Aging Eye Cream, and Anti-Aging Serum, for which web copy touted benefits ranging from “helps prolong and regenerate the skin cell” (Anti-Aging Serum) and “boosts cell regeneration” (Anti-Aging Eye Cream) to “ideal for treating: sun spots, age spots, acne scarring, hyperpigmentation” (Repair Serum).

    Such claims were a bridge too far for FDA, which determined that they established the products as drugs “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or articles intended to affect the structure or any function of the human body.”

    Photo © iStockphoto.com/imagestock

  • Pet Supplements

    Sleep soundly knowing that FDA has Fido’s back. For the agency doesn’t just police dietary supplements for us human animals; it keeps an eye on products marketed for the rest of the animal kingdom, too.

    Case in point: On December 17, 2015, Advantage Biosciences Inc. received an FDA warning letter regarding its marketing of nutritional supplements for animals: Resvantage Canine, Resvantage Feline, and Resvantage Equine.

    Taking exception to claims that the products “provide an effective new therapy for treating type II diabetes,” “can be used as a cancer therapy by itself or combined with other therapies,” and “consistently prolong the life of several different animal groups,” the agency classified the products as new animal drugs “not generally recognized among experts…as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling.”

    Photo © iStockphoto.com/travellinglight

  • Brain Health

    Interest in brain-health dietary supplements is growing fast, but supplement manufacturers marketing toward this class of cognitively concerned consumers best beware what they say—and where they say it.

    Witness the warning letter FDA sent to MPH Nutrition LLC on October 1, 2015. The agency apparently did an inventory of the company’s entire website, citing claims made for its Re:Mind Recover omega-3 product not only in web copy but in videos, white papers—even “likes” on its Facebook page. In sum, it determined the claims made regarding “concussion recovery” to be “therapeutic” and, therefore, sufficient to establish the product as a drug.

    Photo © iStockphoto.com/Yakobchuk

  • A Cure for Hangovers?

    The best cure for a hangover is time. But FDA found a company—Life Support Development Ltd.—claiming that its Life Support Hangover Relief supplement could do the job just as well, if not better.

    In a warning letter dated September 17, 2015, FDA called out the company for marketing Life Support Hangover Relief as an unapproved new drug. It pointed to statements that the product’s “cutting-edge formula contains an extract from the fruit of the Japanese Raisin Tree, known specifically to aid in the recovery from alcohol intoxication,” and that the product “can protect the liver and brain from damage.”

    But that’s not all. The letter went on to enumerate almost a dozen cGMP violations observed during a facilities inspection, not least of which were failures to collect and hold reserve samples of each lot of packaged product, or to maintain its physical plant in a clean and sanitary condition.

    Photo © iStockphoto.com/BartekSzewczyk

  • New Dietary Ingredient

    Still unsure about exactly which ingredients are considered to be a new dietary ingredient (NDI)? Join the club. FDA itself has yet to release its final NDI guidance, and until it does, supplement marketers are left to follow the shorthand that if a substance wasn’t marketed in the United States in a dietary supplement before October 15, 1994, it is, in fact, an NDI.

    This matters—a lot—because FDA requires marketers of products containing NDIs to notify the agency about the ingredients, providing evidence that the products can reasonably be assumed to be safe. Failure to do so whilst still sending products into interstate commerce can earn the marketer an FDA warning letter like the one that went to Rightway Nutrition Marketing LLC on March 7, 2016.

    Pointing to the presence of Acacia rigidula powder in the company’s Green Coffee Bean Extract +Energy supplement, FDA declared the powder an NDI and thus cited the product as adulterated under the terms of the Federal Food, Drug and Cosmetic Act.

    Photo © iStockphoto.com

  • The Role of the Contract Manufacturer

    There are plenty of ways that a dietary supplement marketer could run afoul of FDA. But one area that “still seems not to be clear to many companies,” says Justin J. Prochnow, shareholder, Greenberg Traurig LLP (Denver, CO), is the balance of responsibility between private-label owners and the contract manufacturers who produce products for them.

    For even if someone else is doing the manufacturing for you—and, presumably, the recordkeeping and due diligence that FDA requires—label owners “are still obligated to ensure that products are being manufactured pursuant to the GMPs,” Prochnow says.

    Or, as FDA said in a bill of particulars sent to Tibetan Herbal Balance Inc. on January 1, 2016, “Although your firm may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, contract out its ultimate responsibility” to ensure that supplements comply with cGMP requirements.” The lesson? A reminder that, at the end of the day, the manufacturer is ultimately responsible for adherence to GMPs—or the lack thereof.

    Kimberly J. Decker writes for the food and nutrition industries from her base in the San Francisco area, where she enjoys eating food as much as she does writing about it.

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