Vague FDA Guidance Fails to Provide a Roadmap to Dietary Supplement Misbranding Minefield

In part one of this series, we presented the current landscape regarding misbranding in the dietary supplement space and FDA enforcement activity. Claims of misbranding related to insignificant levels of impurities and other byproducts put the dietary supplement industry in a difficult position.

However, the notion that products should not contain any impurities or byproducts simply lacks any logical support. In this article, we expand on these concepts by examining how impurities in pharmaceuticals and food products can be acceptable to FDA while the agency inexplicably takes the opposite position with respect to dietary supplements.

By refusing to provide detailed guidance on impurities to the dietary supplement industry, FDA has left open the possibility of enforcement actions against dietary supplement entities predicated on an arbitrary system. If pharmaceuticals are allowed to contain impurities or other byproducts based on FDA’s reasoning that not all levels of impurities pose a risk to consumer health, why is this same standard not applied to dietary supplement products?

Sandoz: Impurities are okay in pharmaceuticals

As seen in the recent Sandoz Inc. v. Becerra decision (57 F.4^th 272 [D.C. Cir. 2023]), the potential for arbitrary enforcement related to dietary supplement misbranding contrasts starkly with FDA’s position on impurities in pharmaceutical products.

The federal appeals court in Sandoz sought to determine whether known impurities in an FDA-approved drug would also be considered “approved” by the agency in order to enforce a drug manufacturer’s “new chemical entity exclusivity” rights. In this case, Sandoz Inc., a drug manufacturer, brought an action against the Secretary of Health and Human Services (“HHS”) to challenge FDA’s decision in 2012 that the drug Aubagio was eligible for new chemical entity exclusivity. Sandoz had requested approval for a generic equivalent of Aubagio.

Under the Hatch-Waxman Act, a prescription drug may maintain “new chemical entity exclusivity” for a certain period before generic brands are allowed on the market, if no active ingredient in a drug has been previously approved by FDA. The only active ingredient in Aubagio, which is used to treat patients with relapsing multiple sclerosis, is teriflunomide. Sandoz argued Aubagio did not meet the conditions for new chemical entity exclusivity because teriflunomide was previously “approved” as an impurity in a rheumatoid arthritis drug called Arava that FDA approved in 1998.

Arava is comprised of another ingredient known as leflunomide, which FDA identified as the sole active ingredient in that drug. However, when Arava is manufactured and stored, the leflunomide molecules break down into teriflunomide. FDA even characterized teriflunomide as an “impurity” and allowed Arava to contain up to 3.5 percent teriflunomide.

In deciding for HHS, the court accepted FDA’s argument that teriflunomide was not an “active” ingredient in Arava, and therefore was not considered a previously approved ingredient. However, this case stands for much more than affirming that only active ingredients in a drug product may be considered “approved” in a new drug product.

In this case, FDA openly acknowledged and allowed for certain levels of impurities in drug products, which already face a much higher burden of regulation and testing than dietary supplements. Furthermore, this case shows that FDA allows for known impurities that may be byproducts of chemical breakdowns in a product that were not necessarily included to serve a therapeutic function.