FDA Waves Stop Sign At Kratom Product Launch After Failed NDI Notification

FDA published an untitled letter the same day it was submitted stating that Industrial Chemicals' website includes statements on kratom's safety as a dietary ingredient and its pending launch of product sales even though the agency in December said an NDI notification the firm submitted in September did not establish safety for the use of mitragynine, an extract from dried kratom leaves, in a supplement branded Mitrasafe.

Industrial Chemicals LLC's planned Feb. 28 launch of a kratom product prompted FDA, in its latest enforcement targeting the herb from a plant similar to coffee, to remind the firm that it has not shown that extract from the ingredient is safe for use in a dietary supplement.

FDA, in an unusual action, on Feb. 26 published an untitled letter the same day it was submitted to Industrial Chemical's advisors stating that the firm's website includes statements on kratom's safety as a dietary ingredient and its pending marketing of kratom even though the agency in December said a new dietary ingredient notification the firm submitted in September did not establish safety for the use of mitragynine, an extract from dried kratom leaves, in a supplement branded Mitrasafe.

"Although your client may have complied with the procedural requirement to submit a pre-market NDI notification for Mitrasafe, meeting this threshold requirement does not relieve your client of the obligation to comply with other legal requirements that apply to Mitrasafe and dietary supplements containing Mitrasafe, such as the prohibition on marketing adulterated dietary ingredients and dietary supplements," said Steven Tave, director of the Office of Dietary Supplement Programs in FDA's Center for Food Safety and Applied Nutrition, in the letter to regulatory consultants FDAImports.com LLC Benjamin L. England & Associates LLC.

Industrial Chemicals, in perhaps an equally unusual move for a supplement manufacturer, makes candidly dismissive statements on a website for Mitrasafe discussing FDA's finding on its NDI notification and the agency's policies for determining whether dietary ingredients are "new" and must be notified to the agency before being used in supplements available in the US and whether an ingredient is shown in a notification to be safe.

'Illogical And Inflexible' NDI Process?

"For kratom, controversy arises and grows simply due to illogical and inflexible government regulations because no one has allegedly, successfully documented retail marketing and sales in the USA prior to 1994 enough for the government’s arbitrary requirement established in law," the Auburn Hills, Mich., firm states on the Mitrasafe website.

The firm says FDA limits the type and amount of information it will accept in NDI notifications to create "a very specific, very defined, process that insures the reasonable expectation of safety with a compliant submission." However, the limit means that a dietary ingredient new to FDA officials "would not be able to make it through the simple act of a compliant [notification] submission."

"It is a bizarre conundrum, natural occurring plants, especially wild harvested plant material, will vary in potency and their mix of constituent elements will vary in content and ratio to each other depending on weather, geography, etc. So, the exact process that was created for the submission of new dietary ingredients, also prevents the submission of all natural, grown in the wild, herbal material that has been safely utilized for thousands of years," says Industrial Chemicals.

Industrial Chemicals' information on mitragynine's history of use "did not establish a basis for the safety of Mitrasafe, and the toxicology studies [the firm] relied on, even if relevant to the ingredient, did not provide evidence supporting a reasonable expectation of safety." – FDA ODSP Director Steven Tave

However, the firm says it developed Mitrasafe as a "very specific" ingredient from isolating "the one singular [kratom] alkaloid that has been tested for the last 60 years over and over by the scientific community, whose scientific studies are public knowledge and readily available to the public. We can prove the exact potency, the exact amount when added to dietary supplements, as required by FDA regulations."

Industrial Chemicals' isn't the only NDI notification mitragynine that FDA has found did not establish safe use for the ingredient, though the agency has not announced concerns that the sponsor of the other notification was planning to market kratom products anyway. The Office of Dietary Supplement Programs in FDA's Center for Food Safety and Applied Nutrition in an April 2017 letter advised a firm identified as American Botanical Corp. that its NDI notification to use mitragynine in a liquid supplement did not establish the ingredient's identity or its history of safe use in the US.

The agency noted recently as it accelerated its initiative to remove kratom from the market that CFSAN has determined that no NDI notification it has received for the herb established its identity, safety or history of use before October 1994, the grandfather date for dietary ingredients already in use to be considered "old" and eligible for use in supplements sold in the US without NDI notifications. (Also see "FDA's Kratom Campaign Turns To Firms Destroying Inventory, Recalling Products" - HBW Insight, 21 Feb, 2018.)

FDA's enforcement against kratom also has accelerated due to concerns by agency officials, including Commissioner Scott Gottlieb, that the herb is promoted by some firms as a natural remedy for treating symptoms of withdrawal from opioid abuse. The agency says substances within kratom, including mitragynine, are opioids and are dangerous if consumed, however, the kratom sector of the supplement industry has dismissed the concern as erroneous and contend the herb has centuries of history as a safe dietary ingredient. (Also see "FDA's Opioid Label For Kratom Called Misbranding By Marketers" - HBW Insight, 7 Feb, 2018.)

Warned On Claims, Too

Claims for kratom as an opioid-withdrawal remedy are also among ODSP Director Tave's points in his letter to Industrial Chemicals.

Tave said claims such as “natural substitute for opium,” “morphine-like effects,” “used as a method of curing addiction for hundreds of years” and “also helps to cover withdrawal symptoms” make Industrial Chemicals' Mitrasafe supplement an unapproved new drug under FDA regulations.

And because FDA considers Mitrasafe a drug intended for treatment of one or more diseases not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner, it is misbranded without adequate directions for its intended purposes, Tave said.

The letter also explains that FDA has completed its review of Industry Chemicals' Mitrasafe NDI notification although the firm has required that it consider additional information. " If you would like for us to consider and respond to additional information related to Mitrasafe, your client should submit a new NDI notification," Tave said.

He also detailed why CFSAN reached its determination on the notification. Industry Chemicals' information "did not adequately describe what Mitrasafe is (its “identity,” which includes structure, composition, and physical and chemical properties)," which precluded linking safety information the firm provided to supporting Mitrasafe's safety, Tave said.

Additionally, "we still had significant safety concerns," he added. The firm's information on mitragynine's history of use "did not establish a basis for the safety of Mitrasafe, and that the toxicology studies [the firm] relied on, even if relevant to the ingredient, did not provide evidence supporting a reasonable expectation of safety."

Tave also noted that one of the rodent toxicology studies included in the notification showed adverse effects at all dose levels. CFSAN's December letter "expressly advised" Industrial Chemicals "that the agency would not consider Mitrasafe or products containing it to be safe, he said.

FDA's enforcement against kratom's use as a dietary ingredient began in 2013 with an advisory to manufacturers against using it in their products, but sales of kratom in crushed or powdered leaves, teas or capsules have continued and the American Kratom Association is lobbying Congress and state lawmakers on keeping the herb on the market. (Also see "Kratom: All Questions On Pre-DSHEA Ingredient Evidence In One Package" - HBW Insight, 16 Oct, 2017.)

The Drug Enforcement Administration in 2017 put on hold a proposal to schedule the active materials in kratom as controlled substances after the overwhelming majority of nearly 23,000 comments opposed the move. The industry association sees FDA's increased enforcement against kratom marketers as a bid to DEA to complete the regulatory procedure to schedule kratom. (Also see "DEA Proposal To Schedule Kratom Stirs Wave Of Opposition" - HBW Insight, 8 Dec, 2016.)

From the editors of the Tan Sheet. Our dietary supplement industry coverage is published in the Rose Sheet, with articles emailed to readers daily and available on this page of the website.