On May 19, 2020, FDA (U.S. Food and Drug Administration) published a proposed Guidance Document announcing its intention to adopt a “Policy Regarding Certain New Dietary Ingredients and Dietary Supplements Subject to the Requirement for Premarket Notification: Guidance for Industry” (The Draft Guidance). This document announced FDA’s intent to consider, pending public comment, a six month suspension of suspending against companies that fail to comply with (21 U.S.C. 350b(a)), which provides, among other things, for the notification of FDA at least 75 days before the introduction or delivery for introduction into interstate commerce of a dietary supplement that contains a new dietary ingredient (NDI). According to the Agency, the primary purpose of such notifications is to permit FDA to assess the safety profile of any NDI prior to introduction into the market. Given FDA’s longstanding failure to enforce the law pertaining to NDIs, this appears to be a highly misguided Guidance. The Guidance and FDA’s failure to enforce, however, should not be taken as a signal to companies that compliance is not necessary.
A Misguided Guidance
As written, The Dietary Supplement Health and Education Act (DSHEA) requires that any dietary ingredient that was not on the market prior to October 1994 be the subject of a notification demonstrating a “reasonable expectation of safety” for its intended use prior to being introduced into the market. This process was established by the Congress more than 25 years ago as a means to ensure that ingredient suppliers had sufficient information to be confident that anything “new” introduced into the market would be safe for its intended use—but without creating a preapproval system blocking entry to market absent FDA consent. Hence, the dietary supplement industry operates within a system that requires notification of FDA rather than express agency approval.
In the Draft Guidance, FDA proposes to exercise enforcement discretion and not take any action against companies that have failed to submit a required NDIN (new dietary ingredient notification) for a period of 180 days. The Guidance does not explain any legal basis for FDA to announce that it will simply not enforce a portion of the Federal Food, Drug and Cosmetic Act designed to ensure that NDIs do not pose a threat to the public health. The requirement for FDA review of safety data for NDIs has been in place since October 1994 (over 27 years) when the DSHEA was enacted. The final regulation concerning the form of the submission of NDINs to FDA—21 CFR 190.6—was finalized on Oct. 23, 1997 (nearly 25 years ago). Twenty-five years after promulgation of a final rule setting for the requirements for submission of a NDIN, FDA is now seemingly announcing its intention not to enforce.
Incredibly, the Draft Guidance states that FDA “estimate[s] that more than 4,600 notifications should have been submitted and were not,” citing speculation as to this number presented by a former Director of the Office of Dietary Supplement Programs. While it is unclear if there is any actual basis for this number, it seems incredible that an agency charged with protecting the public health, has allowed anything approaching this number of violative products to enter the marketplace in the absence of evidence that there is a reasonable expectation of safety for their intended use. What is the point of publicly announcing an intention not to enforce the law in an area that FDA has failed to effectively police for nearly 25 years?
The answer to that question may be that we are witnessing an exercise of regulatory legerdemain designed to distract from FDA’s abject failure to enforce the law as it relates to NDINs and instead focus blame on the dietary supplement industry. The Draft Guidance claims to be intended “to help ensure that consumers have access to safe dietary ingredients and dietary supplements, while addressing and controlling the risks that are presented by failure to file an NDI notification.” Yet, by its own admission, FDA (in a shocking emperor has no clothes admission) claims that there are approximately 4,600 ingredients presently on the market that have failed to file an NDIN—after a quarter-century of non-enforcement, how does it protect the public health to formally announce that the Agency will continue to not enforce for a period of 180 days, after it takes the time to evaluate comments submitted within 60 days of publication of the Draft Guidance? (In effect, we are looking at well over a year before the formal 180-day non-enforcement period ends).
Over the past decade, clients of our firm have presented FDA with evidence of “copycat” or “knock-off” ingredients seeking to trade on their work in submitting a fulsome NDIN demonstrating the safety of the NDIs they wish to introduce to the U.S. market. The evidence presented to FDA concerning various knockoff ingredients documented the presence of unknown peaks on HPLC (high performance liquid chromatography) chromatograms reminiscent of those associated with the l-tryptophan disaster; the presence of residual formaldehyde; and the presence of e-coli. FDA was provided with information documenting the identity of the entities importing these potentially dangerous ingredients into the United States and asked to take enforcement action, including issuing an Import Alert, necessary to protect the public health. The Agency declined to take action. Considering these potential safety concerns, how are these ingredients included within the scope of FDA’s enforcement discretion? This abysmal history should give pause to anyone considering the point of the Draft Guidance.
Incredibly, the Draft Guidance fails to make any definitive commitment to end FDA’s failure to enforce that law relating to NDINs. What is the point of 180 days of enforcement discretion to file an NDI, if the agency does not make an explicit statement that continued violators can expect strong and meaningful enforcement when the discretion period ends? In the absence of such a commitment followed by actual action, the Draft Guidance serves no purpose other than presenting “regulatory theater” designed to make it appear that FDA is doing something when, in fact, it will continue to do nothing.
Safety First
Despite FDA’s failure to enforce the law as it relates to NDINs, there are compelling reasons for companies introducing a NDI to the market to take appropriate steps to ensure that their new ingredients are safe. These include taking responsibility for protecting the public health by making sure that your ingredient is safe, reducing the risk of injuring a consumer and facing product liability litigation (including the risk of punitive damages) and even having to deal with class action claims for placing an unsafe ingredient on the market. Failure to take steps to be in compliance can also create a risk of loss of insurance coverage as most policies exclude coverage for illegal acts.
Companies introducing a new dietary ingredient to the market actually have several options. The most obvious is the NDIN process. While FDA enforcement has been lax (or non-existent), the Agency has greatly improved its handling of NDINs. Pre-notification meetings are now common so that it is possible to get a preliminary idea of what the Agency is expecting in a submission and whether there are potential complicating issues with an ingredient. While there remains some lack of clarity as to exactly what FDA expects as far as data demonstrating a “reasonable expectation of safety,” there are a number of well qualified consultants who are knowledgeable in this area and working with experienced Counsel can place companies in the best possible position to for a successful NDIN.
Alternatively, DSHEA permits the use of an NDI in cases where the ingredient has been present in the food supply as an article used for food in a non-chemically altered form. Significantly, FDA has stated that there is no geographic limitation to where the ingredient has been “present in the food supply.” Thus, for example, a company that is interested in bringing an NDI into the U.S. that has been legally present in a food or supplement in a foreign country does not need to submit an NDIN prior to use. It is, however, imperative that there be a solid data set (toxicology reports, evidence of extended use without adverse event reports) supporting the safety of the ingredient.
Another viable option to satisfying the “present in the food supply” is to conduct a GRAS (generally recognized as safe) assessment of the ingredient. GRAS is the standard which new food ingredients are required to satisfy before being sold in the United States. A GRAS assessment involves review of all available safety data for an ingredient by a panel of qualified experts, usually consisting of toxicologists and other food scientists. A conclusion that an ingredient is GRAS can be finalized through an affirmation which is held by the company (Self-Affirmed GRAS) or through the preparation of a formal document detailing all of the data that leads to a conclusion that the ingredient is safe. Much like the NDIN process, FDA will participate in a pre-GRAS notification meeting if one is requested. Once the GRAS status of an ingredient is established, we believe that it should be marketed in conventional food before use in dietary supplements in order to satisfy the “present in the food supply” requirement.
As companies consider these options, it is also important to consider that GRAS status requires publication of all (or almost all) safety data in order to satisfy the “general recognition” requirement. On the other hand, it is possible for a successful NDIN to be based entirely on proprietary data, which can be marked confidential and withheld from disclosure to potential competitors.
One final point for ingredient suppliers to consider is that submitting an NDIN or conducting a GRAS assessment is the protection that these steps will provide against “the DHSEA Blocking Provision.” This is the part of DSHEA that states that if an “article” (ingredient) was either approved as a drug or the subject of publicly disclosed study as an Investigational New Drug prior to its use in food or supplements, the ingredient prohibited from such use. This part of DHSEA can cause any number of complications to the introduction of NDIs, including where a company has studied its ingredient as a potential drug before deciding to go market for use in supplements. There is also concern that some of the newly identified constituents of hemp that are currently being marketed without “dotting every I and crossing every T” could be blocked from the market if a pharma company undertakes research on one of these constituents.
Conclusion
While FDA’s NDI amnesty guidance may be misguided, there remain compelling reasons to take all appropriate steps to ensure that any truly new ingredient being introduced into the marketplace is safe. FDA’s failure to enforce this aspect of the law is a grave disservice both to industry and consumers. The burden of ensuring that dietary ingredients are appropriately offered for sale in dietary supplements thus falls almost entirely on the industry. Whether a company chooses to submit a NDIN or pursue GRAS status is an important decision that should be made in consultation with qualified experts and regulatory counsel. NIE
Marc S. Ullman represents clients in matters relating to all aspects of Food and Drug Administration and Drug Enforcement Administration matters, regulatory issues, Federal Trade Commission proceedings and litigation. He practiced with one of New York’s leading white collar criminal defense firms for ten years, where he represented clients in both federal and state prosecutions, as well as numerous related civil matters and other litigations. He can be reached at [email protected].
