The drug preclusion clause excludes an ingredient from use in dietary supplements if that ingredient was in a drug that was “first-to-the-market” or if the ingredient was previously studied for drug uses despite it otherwise qualifying as a lawful dietary ingredient.
The dietary supplements industry has long complained that secret investigational drug filings (FDA does not disclose the date or contents of an investigational new drug application) and indefinite preclusion based on abandoned pharmaceutical research creates significant uncertainty for manufacturers.
FDA has invoked this provision in recent years to exclude several ingredients, including NAC, NMN and CBD. In the case of NAC, the ingredient had been in the supplement market for years without FDA objection, and its use in supplements preceded the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA).
“For decades, this broken drug preclusion process has allowed Washington bureaucrats to threaten lawful dietary supplements that have safely been purchased over the counter for years, stifling innovation and denying Americans access to products they already trust,” said Congresswoman Diana Harshbarger. “My bill delivers the regulatory certainty manufacturers need to innovate and invest with confidence, while establishing transparency and predictability within the drug preclusion framework and preserving consumer access to dietary supplements.”
The bill addresses one of the three key provisions of DSHEA that require legislative amendment, said Scott Bass, principal at Scott Bass Life Sciences LLC and one of the architects of DSHEA.
“The most important here is addressing drugs that have been abandoned, studies that were ended and other examples where drug preclusion should not have been used to stop dietary supplement innovation,” he said.
The key provisions
The Dietary Supplement Innovation Act aims to address five points:
1. Narrow FDA’s ability to exclude ingredients from supplements because they were first approved as drugs or investigated as drugs.
Specifically, a substance could remain eligible for use in foods or dietary supplements if it was marketed in food or supplement-like products before October 15, 1994 (i.e., a grandfathered ingredient). Also eligible are substances marketed as a food or dietary supplement before drug approval, biologic licensure or the start of publicly disclosed Phase 2 or Phase 3 clinical trials.
A substance would also be eligible if its development as a drug was abandoned, which the bill defines as bring “inactive status, withdrawn, or both for a continuous period of at least seven years”.
2. Raise the threshold for triggering drug preclusion by limiting drug preclusion to substances involved in Phase 2 or Phase 3 clinical trials, rather than exploratory or earlier-stage research.
3. Require FDA to consider differences between a drug and a supplement version of an ingredient based on the route of administration, dosage, serving amount, concentration and composition and relative safety profiles in supplement versus drug use.
4. Create a direct pathway to challenge FDA drug-preclusion decisions via the courts and put the burden of proof onto the Agency.
5. Remove drug-preclusion language from the definition of dietary supplement under 201(ff)(3).
‘Thoughtful, balanced legislation’
The Consumer Healthcare Products Association (CHPA), American Herbal Products Association (AHPA) and Council for Responsible Nutrition (CRN) welcomed the announcement.
CRN, which has fought against drug preclusion for years, including filing a Citizen Petition with FDA on the issue, described the Dietary Supplement Innovation Act as “a thoughtful, balanced legislation this issue has needed for years.”
“This bill doesn’t weaken FDA or undermine pharmaceutical innovation,” said Steve Mister, president and CEO of CRN. “Instead, it restores the balance Congress intended when it enacted DSHEA by creating evenhanded, transparent or predictable rules that allow both industries to innovate while protecting consumer access to safe dietary supplements.”
‘This bill misses the key place where change is needed’
On the other hand, Bass said that, since the bill is called the Dietary Supplement Innovation Act, it should address the DSHEA innovation section: 201(ff)(1)(E) [“a dietary supplement for use by man to supplement the diet by increasing the total dietary intake”].
He described the clause as the most critical innovation provision and one that the FDA has both misinterpreted and misapplied, emphasizing the need for a permanent legislative fix. If the dietary supplements sector wants a more open field for critical dietary supplement innovation, he noted, this bill addresses only a tiny slice of that field and misses the key area where change is needed.
“Using a convenient section 301 provision to shoehorn all of this creates a number of issues that probably should be avoided,” Bass said.
“There is a reason that the original 201(ff)(3) was put in the definition section. Either way, it makes little sense to have the main new provision in section 301, the overall FFDCA [Federal Food, Drug, and Cosmetic Act] list of offenses, and then have the explanation on how to apply that new preclusion standard placed in the 400s—the food enforcement/regulatory sections [of the FFDCA].”
A full copy of the bill can be accessed HERE.
