If White House policy is to regulate with a lighter touch, does it stand to reason that inspectors on the ground might be less inclined to dole out Form 483s for what some would argue are nominal violations?
With a new administration in office and new leadership guiding FDA, it’s only natural to wonder if the regulatory environment for dietary supplements, as it relates to current good manufacturing practices (GMP) enforcement, will change-and if so, in what direction. After all, Donald J. Trump got elected president in no small part thanks to promises of “smarter”-that is to say, more lenient-regulation.
As the tea-leaf readers try to tease out where FDA may be headed on GMP enforcement, one subject of study is the pace and nature of Form 483 letters documenting concerns observed during supplement facility inspections. Why? Because if White House policy is to regulate with a lighter touch, it stands to reason that inspectors on the ground might be less inclined to dole out Form 483s for what some would argue are nominal violations.
Another consideration: Brutal budget cuts to agencies like FDA might make it harder for officials to do their jobs, regardless of whether they were aiming to do so with vigor or with an eye toward easing the weight of those “burdensome” regulations.
Too Soon to Tell
So how do things actually look on the ground? “To be honest,” says Lisa Glymph Lattimore, technical manager, dietary supplements, NSF International (Ann Arbor, MI), “I think it’s too early to analyze and interpret short-term enforcement trends.”
Marc Ullman, of counsel, Rivkin Radler (Uniondale, NY), agrees, adding that with so many of FDA’s sub-commissioner leadership spots still staffed by holdovers from the pre-Trump era, “Changes in policy or enforcement approach likely wouldn’t be seen until there’s turnover in these positions.”
Thus it looks for now like business as usual-which in the case of FDA means the usual slowness. Indeed, though “there doesn’t seem to be any change in the agency’s tone or level of cGMP enforcement since the Trump administration came in,” Ullman says, “to the extent that I’ve noticed any change at FDA, I’d say that the pace of any new initiatives by the agency has gone from its usual glacial speed to virtually nonexistent.”
One In, Two Out
But while Justin J. Prochnow, shareholder, Greenberg Traurig LLP (Denver, CO), also believes that “the passage of regulations, guidance, and other more overarching action has definitely experienced a slowdown,” he thinks it might be for reasons more complicated than the typical bureaucratic sclerosis.
“Clearly, FDA under the Trump administration has been given orders to slow down any actions initiated under the previous administration,” Prochnow says. This is no surprise, as the White House made clear from the start that it favored a policy of “one in, two out,” meaning that each new law or regulation passed must come at the expense of two existing regulations-a strategy that “has certainly slowed down efforts that had been underway,” Prochnow says.
A case in point is FDA’s request for public comments on the most recent version of the agency’s new dietary ingredient (NDI) draft guidance; changes to the definition of the term healthy under 21 CFR, Part 101.65(d), of the Food, Drug and Cosmetic Act (FD&C Act); and several questions pertaining to the definition of natural, Prochnow continues. “None of those actions is likely to move forward quickly at this time,” he says. What’s more, menu labeling requirements that were set to go into effect on May 5, 2017, and changes to the Nutrition Facts Panel that were set to take effect next July have also been delayed. “Yet companies continue to be inspected by FDA compliance officers, have products inspected at Customs, and otherwise experience day-to-day regulation in substantially the same manner,” he says.
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No Uptick, No Letup
And what of inspectors’ use of FDA’s Form 483? Known as a “483” for short, the form documents any failure of a manufacturer to meet the minimum requirements listed in 21 CFR 111. Failure to correct problems listed in a 483, or to respond to FDA adequately, may land one in the path of further regulatory action in the form of an “official” FDA warning letter.
Which is unwelcome news for any supplement company. So it might be some relief to hear that, as far as Ullman can tell, “things appear to be fairly steady” with regard to the Trump FDA’s treatment of 483s so far: no massive uptick, and no wished-for letup, either.
Then again, Ullman notes that manufacturers wishing for a regulatory letup might do well to reconsider what they wish for. After all, even if FDA’s conduct of inspections seems to be the same as it ever was, “I think that industry should be grateful for this,” he concludes. “Any noticeable letup would only benefit the scofflaws who are frequently the cause of our headaches in the media and at FDA.”
GMPs Always Matter
In other words, be grateful for regulatory blessings in disguise-and don’t get complacent. For despite uncertainty as to FDA’s future moves, one thing we can be sure of is that GMPs still matter-as they should. “Regardless of the enforcement trends, supplement manufacturers need to remain vigilant and committed to ensuring compliance with GMP requirements,” Glymph Lattimore says. And with several new provisions of the Food Safety Modernization Act (FSMA) now going into effect for supplement makers, “we’ll likely see increased enforcement of the FSMA requirements in the coming year,” she adds.
FDA is even soliciting consumers for help. On July 25 of this year, the agency, through its official blog FDA Voice, called upon the public to report supplement products that don’t work as advertised, produce adverse effects, bear false or overstated claims, or simply aren’t as pure or safe as they claim to be. The lesson: “The industry needs to continue demonstrating its ability to self-regulate,” Glymph Lattimore says, whether it sees a surge in 483s or not.
Ahead, here’s a look at some recent FDA warning letters and what they tell us about agency enforcement. (Thanks to Marc Ullman, of counsel, Rivkin Radler, and his FYI Service Newsletter for collecting and sharing the letters.)
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Clean Up Your Acts
GMPs are the backbone of safe and successful supplement production. And, not surprisingly, the task of ensuring that companies comply with them occupies much of an FDA inspector’s time when taking the measure of how a plant is operating. But there’s a reason that keeping up with GMPs is so time consuming, both for inspectors and for companies: they’re complicated, lengthy, and surprisingly easy to run afoul of.
That’s what Unique EnCapsulation Technology LLC (Landing, NJ) learned in an FDA warning letter dated January 17, 2017. The letter called out GMP violations ranging from i-dotting and t-crossing matters-failing to include an actual or representative product label in batch production records, for instance-to more serious violations, such as not rejecting a supplement or product component that didn’t meet established specifications, as well as water test results indicating the presence of yeast and mold.
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Misbranded It by That Much
If your idea of a misbranded dietary supplement is one that, for instance, promotes itself as being made primarily of ingredient X but actually contains very little X and a whole lot more of Y, you’re not thinking creatively enough. And you’re certainly not thinking like an FDA inspector. Those inspectors will label a supplement as misbranded for a whole lot of reasons, many of which are far more subtle than simply marketing a product that isn’t what it says it is.
For example, Morhaim Pharmalab Inc. (Miami) received an FDA letter dated May 16, 2017, noting a host of misbranding violations related to its Vital Procollagen product. Among the violations: failing to declare all the common or “usual” names of ingredients, not identifying the part of the plant that’s the source of the product’s botanical ingredients, out-of-spec nutrition information, and even failure to include a domestic address or phone number for the company on the label. Oops!
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A Drug by Any Other Name…
When is a dietary supplement not a dietary supplement? When it makes claims-either on pack or online-that FDA deems sufficient to tip the product into drug territory. And that’s not something you want FDA to have to do.
Witness the case of Black Seed Herb Inc. (Liberty, NY), which received a letter from FDA dated July 11, 2017, stating that disease claims for its Diabalance Herbal Blood Sugar Balance Tablets, Quick Slim with pure Hoodia Gordonii Capsules, BHealthy Black Seed Bitter Melon 90 Veggie Capsules, and Black Seed w/ Olive Leaf/Garlic Capsules “establish that these products are drugs under section 201(g)(1)(B) of the Act [21 U.S.C. § 321(g)(1)(B)] because they are intended for use in the cure, mitigation, treatment, or prevention of disease.” .
Some of the disputed claims seem relatively innocuous-“Sweet Sunnah QuickSlim is an all-natural formula that…attacks obesity…”; “The main focus of the herbs within Diabalance is blood sugar balancing…”-but as far as FDA is concerned, they qualify the products as “new drugs” prohibited from legal introduction into interstate commerce absent prior FDA approval. .
“This is a good example of a typical letter to a dietary supplement company for what I call the trifecta of warning letter bases: disease claims, GMP violations, and labeling violations,” says Justin J. Prochnow, shareholder, Greenberg Traurig LLP. “Such letters are pretty common in that companies receiving such letters generally have deficiencies in all three areas.”
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Brace for the Cure
When it comes to unauthorized drug claims, FDA may have a particular beef with products promising to cure, treat, mitigate, or otherwise address cancer. According to the agency’s consumer updates page, FDA sent out warning letters in April 2017 to 14 companies advising them to change or remove fraudulent web statements promising to do just that. “If the companies don’t comply,” the page declared, “the FDA may take further legal action to prevent their products from reaching consumers.”
Yet companies continue to play upon consumers’ fear of this complex disease. Exhibit A: Nature’s Health Company LLC (Hoover, AL) presents an “anecdotal history” on its website of an incident in which a tea containing the same four ingredients as are in the company’s Ojibwa Herbal Tea Formula “somehow seemed to cause the different organs in the body to ‘normalize,’ helping the body’s own immune system to fight and correct whatever was wrong” once a cancer-stricken nurse consumed them.
We know: Huh? Fortunately, the claim was enough to raise FDA’s hackles. Further, says Prochnow, “Companies need to understand that any information put out there by the company on any platform may be viewed by the FDA as evidence of the true intent of the company to sell products.”
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There’s nothing willy-nilly about how FDA monitors which ingredients are permitted in dietary supplements. To wit, Section 201(ff)(1) of the FD&C Act defines “dietary ingredient” as “a vitamin; mineral; amino acid; herb or other botanical; dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any dietary ingredient from the preceding categories.”
So when AndroPharm LLC (Boca Raton, FL) decided to formulate 2,17a-dimethyl-17b-hydroxy-5a-androst-1-en-3-one and 17b-hydroxy-2a, 17b-dimethyl-5a-androstan-3-one-azine into its Sten Z product, and methyl-1-etiocholenolol-epietiocholanolone into a product called M1 Alpha, it was asking for trouble.
Both ingredients are synthetic steroids and do not constitute dietary ingredients as per section 201(ff)(1) of the FD&C Act. So in a letter dated June 5, 2017, FDA pronounced the products not dietary supplements and sternly requested that the company follow up with the appropriate actions. As Prochnow notes, letters like that “reinforce the need for companies to ensure that all ingredients in dietary supplements are permissible dietary ingredients, or if they’re new dietary ingredients that the proper notification is filed with FDA unless the ingredients are exempt.”
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Don’t Pass the Buck
It’s so tempting to leave all this legal and regulatory rigmarole to the friendly contract manufacturers who help keep our industry humming. But as Nature’s Vision Inc. (Portage, MI) learned in an FDA letter dated May 1, 2017, it’s not so easy to pass the buck.
In the letter, FDA noted that though Nature’s Vision contracts out the production of its supplements to a third-party manufacturer, the former maintained “no documentation of product specifications or certificates of analysis for the product received, and [has] not performed any audit or engaged in any other activity to determine the acceptability of the manufacturer to manufacture [its] dietary supplement products, or to ensure the quality of the dietary supplements received and that the products are packaged and labeled as specified in the master manufacturing record.”
This will not do! FDA says it best: “Although a firm may contract out certain dietary supplement manufacturing, packaging, and/or labeling operations, it cannot contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement CGMP requirements.” Let that be a lesson.
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