Editorial by Al Czap, Publisher
*attributed to C. Little, rooster, date unknown
On July 2, 2011, the U. S. Food and Drug Administration (FDA) published an 86 page draft document – Dietary Supplements: New Dietary Ingredient Notifications and Related Issues – for a ninety day comment period in the Federal Register. This document is specific to new dietary ingredients (NDI) (i.e., dietary ingredients that were not marketed in the United States before October 15, 1994) and is a “Draft Guidance for Industry," which means it contains recommendations that, when finalized, will represent the FDA's current thinking on this topic. This document potentially changes the regulatory status of thousands of ingredients used in dietary supplements, and could result in a large percentage of currently marketed products disappearing from the marketplace. The net health effect for patient consumers, as well as physician practices, may be profound, if the FDA were to finalize this guidance as currently proposed.
On July 26 and 27th, 2011, in Salt Lake City, the United Natural Products Alliance (UNPA) conducted a seminar to educate the Dietary Supplement (DS) Industry about the particulars of the draft guidance. In this relatively non-confrontational setting, manufacturers, ingredient suppliers, and finished product company members received an eye opening presentation on the impact of these new FDA draft guidelines. Presenters included the former Chief of Staff for Senator Orrin G. Hatch (principal negotiator of the Dietary Supplement Health and Education Act [DSHEA]), representatives from the American Herbal Products Association (AHPA) and American Botanical Council (ABC), and industry regulatory and scientific experts, including toxicology experts as well as senior members of the FDA. Dan Fabricant, Ph.D., Director, Division of Dietary Supplement Programs, Center for Food Safety & Applied Nutrition, FDA, gave the keynote speech and his subsequent responses to questions left no doubt that he is guiding the effort by the FDA to ensure full compliance by companies in the DS Industry.
According to DSHEA, DS companies are required to notify the FDA with an NDI notification 75 days prior to marketing any NDI. An NDI is technically any ingredient that was not marketed as a DS prior to the passage of DSHEA in November 1994. Ingredients marketed prior to passage of DSHEA are known as “old dietary ingredients” (ODI). There are approximately 1,460 firms involved in DS, roughly 55,600 DS products currently on the market, and about 1,000 new DS products being introduced to the market each year. The FDA believes that submission and review of NDI notifications are an important preventive control mechanism to ensure that the consumer is not exposed to unnecessary public health risks in the form of new ingredients with unknown safety profiles. They are also concerned because only 700 NDI notifications have been submitted to the FDA in the 16 years since passage of DSHEA. The interpretation of the law by the FDA and the DS industry differs vastly. It remains to be seen how much give and take each side will allow in order to find a working guideline acceptable to both parties.
Areas of discussion will include:
The FDA contends that the necessary proof to establish that an ingredient was marketed prior to DSHEA (i.e., it is an ODI) is the existence of extensive retained records documenting such use and sale. Affidavits without supporting records will not be adequate. The DS industry takes the position that such a requirement does not exist in the language of DSHEA, and that one cannot remove the affidavit process as legal evidence when it exists as such in many other evidentiary findings.
The FDA considers all finished product dosage forms to be the thrust of DSHEA. This means that, in addition to any ingredient not sold prior to DSHEA, an NDI would be required for any ingredient manufacturing change post-DSHEA. This would leave a company selling a finished product containing an ethanol extract of Echinacea post-DSHEA, having to submit an NDI if their pre-DSHEA sales contained only the raw herb or a water extract of Echinacea, as examples. And this DS company would not be able to rely on any sales data from others in the DS industry, despite the fact that hundreds of other manufacturers may have used Echinacea in the ethanol extract form years prior to DSHEA.
The FDA wants each and every finished product with an ingredient not sold prior to DSHEA considered as the basis for NDI, instead of just the ingredient. This means that the FDA does not want to limit NDI requirements to only new ingredient introductions by a DS company, but wants to expand it to include all newly marketed DS products unless they consist only of ODI. Industry views this as a regulatory reach far beyond the intent of DSHEA and as something that amounts to FDA “pre-market approval” of finished products. This will also impose an unnecessary financial burden to the manufacturer, which will ultimately be borne by the consumer. Industry consensus is generally that NDI filing requirements should be for the “ingredient," not the finished product, and that one should be able to utilize any and all data, be it product sales or safety, voluntarily disclosed by other companies in the DS industry.
The FDA requires notification of NDI at least 75 days before introducing a DS containing an NDI. The agency then, within that 75 days, is required to either “acknowledge” the NDI, meaning no objection to marketing of the NDI, or “object” for various reasons, meaning that more data will need to be submitted to the FDA for the ingredient to become an NDI with no FDA objection. The FDA’s new draft guidelines would require that any product containing what they consider to be an NDI, even if the ingredient has been marketed safely for the last 17 years, will need to go through the same NDI process as a newly created ingredient with no safety of use data. If these draft guidelines are finalized as is, there could be many thousands of NDI submissions required by law, all of which will need to be submitted within a few months time. The FDA has assured the DS industry that they will have sufficient staff to process all of these NDI notifications in a reasonable amount of time. The DS industry fears that the FDA will be inundated and overcome with NDI applications similar to what was encountered when Canada’s Health Protection Branch implemented their new labeling requirements. The real potential exists for there to be an overwhelmed process that stretches the timeline of getting existing NDIs back into the marketplace (i.e., ingredients that are currently being used in dietary supplements would become unavailable) and new NDIs into the marketplace. This could stifle innovation, have a major economic impact to the DS industry, and significantly limit consumer access to beneficial DS, especially if the process takes multiple years. One worst case scenario is that consumers wanting to prevent an interruption in their DS regimen would have to buy a three or four year supply of currently used products, with the hope that their supplier would be able to reintroduce the product upon completion of the NDI process prior to their multi-year supply being exhausted.
The FDA contends that the NDI process is strictly in the interest of public safety and cites contamination problems with raw material such as tryptophan in the past as a basis for their thinking. They also consider new NDI requirements to be an important deterrent against the adulteration of DS by companies that are spiking ingredients and finished products with prescription drugs such as sibutramine, analogs of steroids, or erectile dysfunction drugs. The DS industry believes that this constitutes a “whipping boy” approach on both points. Criminals are criminals. It is more than a stretch to believe that companies currently engaging in criminal acts, such as spiking their products with drugs, will submit NDIs that report their criminal acts to the FDA.
If the current version of the FDA draft guidance were to remain as written, physicians who have come to rely on a large pharmacy of effective, safe products would have to adapt to pre-DSHEA limits of therapeutic products, with perhaps a full forty percent of their armamentarium now gone. Patients who have been relying on a specific ingredient or product to manage their condition might suddenly find it completely unavailable. Then, truly, some of the sky would be falling. One only hopes that the draft guidance can be rationally negotiated to find an acceptable outcome for both sides that will ultimately benefit, without unfairly penalizing, the intended beneficiary of DSHEA – the health conscious consumer.
Editor’s Note: The NDI Draft Guidance for Industry can be found here.
