FDA remains broken—and mandatory product listing will only make it worseFebruary 17, 2022 | Marc S. Ullman |
Nearly 8 years ago, I published an article reviewing FDA’s failure to enforce the Dietary Supplement Health and Education Act of 1994 (DSHEA), especially in connection with the requirement that new dietary ingredients (NDIs) provide evidence of a reasonable expectation of safety.
I expressed concerns about the potential public health risk posed by knockoffs of NDIs of unknown provenance, likely made with uncontrolled manufacturing processes and containing residual solvents or other impurities; as well as the ongoing failure of FDA to take serious enforcement action against companies that ignore warning letters for the sale of adulterated/spiked/unsafe dietary supplements.
Sadly, it appears very little has changed with the passage of time, and that rather than insisting FDA enforce the laws already on the books, a segment of the dietary supplement industry is prepared to hand the agency unprecedented new powers that supposedly will make enforcement “easier.”
FDA really is broken
During the recently concluded (virtual) annual meeting of the New York State Bar Association’s Food, Drug and Cosmetic Section, I moderated a panel discussion addressing FDA’s failure to respect intellectual property (IP), and the threat to public safety posed by the agency’s inaction and the resulting entry of knockoff ingredients of unknown provenance into the U.S. marketplace.
Among the issues discussed: lack of FDA enforcement action despite receiving evidence that generic forms of beta-alanine imported into the U.S. use manufacturing processes that haven’t been evaluated by FDA, including recombinant technology from E. coli, potentially resulting in unknown impurities that could seriously endanger public health. Remember what happened approximately 30 years ago when a manufacturing change by a single company producing L-tryptophan caused the creation of impurities resulting in multiple deaths?
For now, it seems FDA has determined not to take any serious enforcement action against knockoff ingredients to protect consumer health or stakeholders’ IP rights in the novel ingredients they have researched and documented as safe in NDI notifications to FDA.
In fact, as indicated in an April 28, 2021 letter signed by the then-acting director of FDA’s Office of Dietary Supplement Programs (ODSP), the agency made it quite clear it has no intention to initiate any enforcement action against these knockoff ingredients absent evidence of serious consumer injury—if it would even act then.
FDA lack of (or extremely delayed) enforcement is not limited to a refusal to address the issues posed by knockoff ingredients. In fact, it seems to be the rule when it comes to acting beyond sending a warning letter.
- From 2019 through 2021, FDA issued four warning letters to marketers of illegal products masquerading as dietary supplements containing phenibut, an undeclared active pharmaceutical ingredient. This substance can result in adverse effects, including sedation, respiratory depression and reduced levels of consciousness. The ongoing presence of similar illegal products on the market was documented in a Sept. 22, 2021 letter to FDA from the Center for Science in the Public Interest. (CSPI). Today, it is still possible to find products listed in this letter on the market by using a simple Google search.
- FDA has spent the past several years repeatedly stating CBD is an unlawful ingredient in dietary supplements and foods—and that it is dangerous. In fact, in 2020, FDA issued a warning to consumers that CBD presents a threat of liver injury, can interfere with prescription drugs and poses a threat of male reproductive toxicity. The agency even noted, “CBD has the potential to harm you, and harm can happen even before you become aware of it.” Without commenting on the validity of FDA’s concerns, which have never been withdrawn, the agency has sat back and watched the CBD market continue to grow in the absence of enforcement beyond letter writing. This situation simultaneously creates a regulatory void with no information on safe dosing or regulation of product quality.
- Despite numerous warnings about the dangers to public health posed by kratom, products remain available on the market—and they can be found not on the secret corners of the dark web, but through a simple Google search.
- FDA has established manufacturers have the absolute responsibility to ensure they produce quality products in accordance with GMPs (good manufacturing practices). Yet numerous warning letters and inspections noting the failure of quality systems are allowed to pass before FDA can rouse itself to finally take meaningful steps to enforce the law and protect the public.
Mandatory product listing: The cure may be worse than the illness
Rather than hold FDA to task for these failures, there has been a growing call to grant the agency even more authority over supplements and (at least in theory) illegal products masquerading as supplements by creation of a mandatory product listing (MPL). As envisioned by its proponents, MPL would require companies to list every one of their product labels with FDA and possibly provide other disclosures to the agency. A dietary supplement product would be automatically deemed adulterated if its label was not listed with FDA.
The champions of this legislative scheme present it as a panacea that will cure the market of all of FDA’s enforcement failures. I disagree.
There is the very real threat that FDA could use an MPL as a device to create a premarket approval scheme for dietary supplements. Consider the ramifications of FDA refusing to list N-acetyl-L-cysteine (NAC) products based on its view that NAC is excluded from the definition of a dietary supplement under DSHEA because it was first approved as a drug in 1963. Such refusal could deprive consumers of access to a safe and beneficial ingredient that’s been on the U.S. market in supplements for decades.
In response to the more basic claim that an MPL would make it “easy for the FDA to find companies in violation,” I note the efforts of the panelists at the New York State Bar meeting, the CSPI letter to FDA and the ability to find kratom products on the market through a Google search. This information was not ferreted away in the deepest corners of the dark web. For example, data pertaining to generic forms of beta-alanine—an NDI being manufactured in China—was handed directly to the agency. And does anyone believe the creation of an MPL would suddenly persuade criminals who spike male enhancement products with sildenafil to list the ingredient on their product label and submit the label to FDA, or just go out of business? Finally, how would creation of an MPL change the culture at an agency that permits a decade of inspection failures and warning letters to pass before meaningful enforcement action with actual results is taken against companies that flout GMP requirements?
Sadly, I believe there is no easy fix like creation of a magic MPL that can cure what ails FDA. The agency’s April 28, 2021 letter to Kevin Bell, counsel for Natural Alternatives International Inc. (NAI), demonstrates the agency is broken and has abdicated its responsibilities to protect the public health by effectively regulating dietary supplements, as intended by DSHEA. The FDA letter takes a myopic view of the agency’s enforcement powers at the border and states there is unlikely to be any enforcement activity against knockoff NDIs to protect innovator products or the public health in the absence of serious consumer injuries, or even deaths.
FDA has all of the enforcement authority it needs under DSHEA. A well-written import alert and a few Google searches would provide the agency with a real start on enforcement. FDA is “pretending” it needs MPL in order to target enforcement. Unfortunately, the marketplace and consumers will continue to be at risk until the supplement industry can find a way to come together and persuade lawmakers that a reevaluation of the entire structure and enforcement decision-making process at a broken FDA needs a radical overhaul.
This article appeared on February 16, 2022 on the Natural Products Insider website.
- Marc S. Ullman