Regulatory Insights

What lies ahead for natural products manufacturers and suppliers.

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With many regulatory changes in the natural products industry, for manufacturers and suppliers, it can feel like a shifting maze that seems to adjust every time one begins to become comfortable. Although a map is unavailable, leaders from several industry associations offer some insight about what could be in store.

NDI Notifications
­­In August of 2016, the U.S. Food and Drug Administration (FDA) released a Revised Draft Guidance for New Dietary Ingredient (NDI) Notifications; however, for the industry, there are still major points of contention.

While several members of the American Herbal Products Association (AHPA), based in Silver Springs, MD, have been able to “navigate NDI requirements successfully,” says Michael McGuffin, president of AHPA, the trade group“ has communicated to FDA that the latest version of this guidance is unlikely to achieve the agency’s stated goals of improving the rate of compliance with the NDI notification requirement and the quality of notifications.” One reason in particular may be FDA’s supplement-focused approach to notifications.

In comments submitted to FDA, Loren Israelsen, president of the Salt Lake City, UT-based United Natural Products Alliance (UNPA), points out how the Dietary Supplement Health and Education Act of 1994 (DSHEA) “created an NDI review system focused on the ingredient as the gateway to assess the safety of future dietary supplements,” but FDA would like to “subject over 75,000 dietary supplements and nearly 10,000 dietary ingredients to persistent re-review for safety.” UNPA also noted “the consequences of extending NDI notification to finished dietary supplements would bring a level of cost and a new regulatory burden that will directly affect the level of NDI compliance that FDA seeks,” due to “a recent review of 51,286 dietary supplement SKUs analyzed by Healthnotes, Inc.,” which found, on average, “dietary supplements sold in the U.S. contained 9.5 dietary ingredients.”

Although Andrea Wong, vice president, scientific and regulatory affairs, CRN, based in Washington, D.C. is pleased to see that FDA is willing to develop an authoritative list of pre-DSHEA ingredients and that the Administration will accept master files containing confidential information on NDIs which “will allow for the protection of intellectual property, motivating companies to invest in science and bring scientifically supported branded ingredients to the market.” Another point of contention, says Wong is FDA’s position on synthetic versions of botanical constituents and its narrow interpretation of the definition of “dietary ingredient.” Currently, “the law allows for synthetic copies of botanical constituents to be dietary ingredients; therefore, manufacturers of these ingredients should be given the opportunity to bring the ingredients to market through the NDI notification process,” she explains.

Concurring with Wong, the Austin, TX-based American Botanical Council (ABC) states in comments to FDA, “DSHEA does not explicitly prohibit a synthetic or semi-synthetic compound as a dietary ingredient nor has FDA set forth data to support a safety concern for the use of a synthetic or semi-synthetic copy of an herbal or botanical constituent. ABC continues to emphasize that the safety of an ingredient is the primary consideration and if a synthetic or semi-synthetic compound is chemically identical to the natural compound and has the same level of safety as the natural compound, the ABC supports the availability of the synthetic or semi-synthetic version as a legitimate dietary ingredient.”

Daniel Fabricant, Ph.D., CEO and executive director of the Natural Products Association (NPA), based in Washington, D.C., raises the issue of how FDA seems to go after probiotics heavily. “NPA drafted counterpoints in its comments that rely on what experts deem to show safety at the strain level,” Fabricant says. “However, there are many species of probiotics that should be grandfathered because they have been out in the market for so long despite their strain. FDA seemed to remain heavy handed and singled out probiotic ingredients.”

Dietary Ingredients and the Federal, Food, Drug and Cosmetic Act
According to FDA’s website a dietary ingredient can be one, or any combination, of the following:
• a vitamin
• a mineral
• an herb or other botanical
• an amino acid
• a dietary substance for use by people to supplement the diet by increasing the total dietary intake
• a concentrate, metabolite, or extract

But what should one do if a dietary ingredient that has listings in the NDI database is suddenly excluded from the definition of a dietary supplement because it does not meet the definition of a dietary ingredient?

This scenario is currently happening to the ingredient vinpocetine, which is commonly marketed as a supplement for weight management, increased energy and for improvement of brain function. Though vinpocetine currently has five listings, with the first dating back to July 8, 1997, with a response letter for each that acknowledges no concerns regarding the ingredient or data provided, on September 6, 2016, FDA announced, vinpocetine as ineligible to be a dietary ingredient since it is synthetically produced instead of being a constituent, and in turn did not meet the definition of a dietary ingredient.

Sen. Orrin Hatch, a Republican from Utah, in a letter to then-Commissioner Robert M. Califf, M.D., urged Califf to withdraw the notice in the federal register. “The Dietary Supplement Health and Education Act of 1994 (DSHEA) provides pathways for withdrawing dietary ingredients based on safety concerns,” Orrin wrote, however, no “risk of illness or hazard to the public health” had been cited for the exclusion of the ingredient vinpocetine from the definition of a dietary supplement in the Federal Food, Drug and Cosmetic Act.

Like Hatch, Wong believes since vinpocetine has been marketed for over 20 years and has also undergone five NDI notifications, it should be acknowledged by the agency. Wong is also concerned, “that this decision, if finalized, could discourage companies from developing innovative new ingredients and undergoing the NDI notification process if they know that FDA could simply reverse an acknowledgement of the notification at any time.”

In a NPA press release, Fabricant considers this to be a form of double jeopardy. “To go through the regulatory gate a 2nd time is akin to finishing a round of golf and winning but then having to play a 2nd round while someone charges at you while you hit each golf shot. This sets a very bad precedent and is no environment to conduct business in.”

The Controlled Substances Act
Unlike vinpocetine, mitragynine and 7-hydroxmitragynine are two psychoactive constituents of the plant mitragyna speciosa (kratom) that are untested and unregulated. Native to South East Asia in countries such as Malaysia, kratom has been traditionally used as an analgesic as well as a stimulant and now people have been self medicating with kratom as a way to ween themselves off of prescription opioids. On August 31, 2016, the DEA published in the Federal Register a notice of intent to temporarily place the constituents in the scheduling provisions of the Controlled Substances Act. Following challenges from the public, the notice of intent was withdrawn and a comment period was opened.

Informal comments submitted to DEA, Fabricant stated that, “as former Food and Drug Administration (FDA) officials and regulators of the dietary supplement industry, we can tell you that finished kratom products and raw kratom botanical ingredients have not met the strict standards products and new ingredients must adhere to in order to be marketed to the public and deemed safe for regular use in either our food or our drug supply. Self-medicating with kratom is dangerous without the necessary pre-market approval process set forth by our public health experts at FDA. Even if kratom were delivered as a food, it has never been filed as a new dietary ingredient to FDA’s Center for Food Safety and Applied Nutrition.”

ABC also filed comments to the DEA, but their comments requested that the agency to stop the notice of intent due to the act’s ability to “impede current and future medical research efforts.” In ABC’s formal comments, the evidence cited consisted of the non-profit’s peer-reviewed article on kratom which explained the plant’s benefits to help alleviate the symptoms of opioid withdrawal and the management of pain. According to ABC’s comments, classifying kratom to the Controlled Substances Act would cause hurdles, such as obtaining a registration from the DEA, for the medical research community.

The Near Future
With the compliance date rapidly approaching for the new revisions to the Nutrition and Supplement Facts labels, Wong believes that besides revising their labels, companies should be reformulating their products, as well as paying attention to changes to the daily values and units of measure for several nutrients, the new recordkeeping requirements and the new regulatory definition for dietary fiber.

Fabricant adds, the Nutrition and Supplement Facts Final Rule contained many problems, and because of this we haven’t seen the last on the Final Rule, as well as “NDI guidance, import detentions based on failing to file an NDI, GMPs, and sports nutrition ingredients like DMAA.”
Additionally, with “state acceptance of cannabis for medical purpose and adult-use continuing to expand,” said McGuffin. “The Trump administration has indicated that it may take a tougher stance against states that have legalized cannabis for adult-use.”

Israelsen warns about this year’s implementation of the Food Safety Modernization Act (FSMA) “and the likely use of import alerts to detain non-compliant raw materials now subject to FSMA from entering the country.” This is a problem, he says, because “many foreign suppliers do not understand FSMA and the likely interruptions of supply chains this will cause.”

The last issue that could affect companies which is of particular interest to UNPA is the “continued expansion of synthetic biology, which is the mother of synthetic botanicals. Synthetic biology is the most powerful force driving change in how crops of all kinds are produced, synthesized at astonishing speed, and the resulting materials and ingredients enter our lives in ways and in forms we do not recognize,” said Israelsen. “This includes GMOs, synthetic botanicals, synthetic fragrances, flavors, colors, and a host of other products we know and use daily. Here at UNPA, we sense an urgency to both understand and raise appropriate alarms within the natural products industry of these forces and changes that are coming in order to ‘defend the castle wall’ and protect the integrity of the natural product and organic industries before it may be too late.” WF

Published in WholeFoods Magazine April 2017

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