The agency typically uses a risk based approach in choosing what enforcement battles to fight, though that stance may be shifting a bit based on its recent action regarding the legality of vinpocetine as a dietary ingredient. Nevertheless, the agency historically has not gone after companies based solely on their use of an unusual delivery mode. Supplements are regulated as a subcategory of foods and the method by which they have their systemic effects is supposed to be similar. The definition of a dietary supplement in DSHEA outlines a supplement as something that is taken through the mouth that is meant to be absorbed into the body through the gastrointestinal system.
But attorney Justin Prochnow, a shareholder in the firm Greenberg Traurig, said that hasn’t stopped innovators in the dietary supplement industry from trying all sorts of delivery modes, including nasal sprays, transdermal patches, various forms of anomalous mouth delivery systems and even in one recent case a citizen’s petition to allow a dietary supplement in the form of a suppository.
“I did a recent session at a trade show on the subject of alternative delivery systems. As to the question of which ones are compliant under the law, the answer is none,” Prochnow told NutraIngredients-USA. Prochnow said despite that message, which he said he has delivered a number of times in recent years, companies still approach him wanting opinions on all kinds of delivery innovations, including inhalable supplements.
Pushing the envelope in the mouth
The portion of the delivery mode envelope that is most frequently pushed has to do with alternative modes via the mouth. These consist essentially of two: direct sublingual systems with liquid products meant to be held under the tongue, and mucosal delivery systems with dissolvable films or tablets that are meant to be held in the mouth or on the tongue until they are mostly or completely dissolved. In both cases, the end point of the process is swallowing, but Prochnow said the envelope edge can be crossed depending on the instructions for use provided with the product.
“Sometimes you’ll see somewhat disingenuous instructions, such as those that tell you to hold the dose under your tongue for 15 seconds before swallowing,” he said.
Safety first, precise definitional compliance later
Even though such products technically fall outside of the law, Prochnow said he has not seen warning letters predicated solely on that violation. But if FDA inspects your plant and finds a non-compliant delivery system as one of its observations, the likelihood of a warning letter being issued goes way up.
“I don’t know if I’ve seen a warning letter in which they’ve only addressed a sublingual delivery system and nothing else. But I know of at least half a dozen in which it has been mentioned,” Prochnow said.
Recent warning letter
A recent warning letter issued by FDA illustrates the agency’s approach. It its letter to California company Threshold Enterprises, which markets melatonin products, a progesterone cream and other products as dietary supplements, the agency said “the Act defines the term “dietary supplement” in section 201(ff)(2)(A)(i) of the Act [1 U.S.C. § 321(ff)(2)(A)(i)], as a product that is “intended for ingestion.” Because sublingual products are intended to enter the body directly through the skin or mucosal tissues, they are not dietary supplements and are not foods. Therefore, your firm’s Source Naturals Melatonin products are drugs.”
The agency went on to cite a number of GMP violations that concerned lack of identity specifications and finished product specifications and labeling mistakes. For companies using non-compliant delivery systems, cleaning up after such a warning letter would then require reformulation and repackaging on top of the other things that would need to be done to come into compliance.