Dietary Supplement Innovation Act Targets FDA's Drug Preclusion Clause
核心洞察
Rep. Diana Harshbarger introduced the Dietary Supplement Innovation Act (搜索) to narrow FDA's use of the DSHEA drug preclusion clause against supplement ingredients.
The bill would limit preclusion to substances in Phase 2 or Phase 3 trials and allow ingredients from abandoned drug programs back on the market.
FDA has invoked the provision to exclude ingredients including NAC, NMN (搜索) and CBD, drawing long-standing industry complaints about secrecy and uncertainty.
A newly introduced bill in the U.S. House of Representatives aims to rewrite the drug preclusion clause of the Dietary Supplement Health and Education Act (DSHEA), a provision that has allowed the U.S. Food and Drug Administration to exclude ingredients from the dietary supplement market because they were first studied or approved as drugs.
The Dietary Supplement Innovation Act (搜索), introduced by Rep. Diana Harshbarger, R-Tenn., seeks to narrow FDA's authority to exclude ingredients from supplements on the basis that they were first approved as drugs or investigated as drugs. Harshbarger said the current system was "built on ambiguous standards" that allows the agency to "declare dietary supplements illegal even if they have been on the shelves for years."
"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," Harshbarger said. "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."
How the Clause Has Been Applied
Under DSHEA, a substance investigated as a drug before it came to market as a supplement must remain in the drug realm. The clause was included in the original DSHEA negotiations as a way to protect investments made in drug discovery and development, preventing a supplement ingredient developer from bringing a product to market ahead of a lengthy drug development process. If a developer could demonstrate that a dietary ingredient was on the market first, its future as a supplement was assured — the coexistence of prescription and supplement forms of omega-3s is cited as a primary example.
Industry observers, however, have objected to how FDA has interpreted the clause, arguing that manufacturers are left in the dark until late in development about whether a previous Investigational New Drug (IND) application is on file. FDA does not disclose the date or contents of an IND application, and indefinite preclusion based on abandoned pharmaceutical research creates what the industry describes as significant uncertainty for manufacturers.
FDA has invoked the provision in recent years to exclude several ingredients, including NAC, NMN (搜索) and CBD. In the case of NAC, the ingredient had been on the supplement market for years without FDA objection, and its use in supplements preceded the passage of DSHEA in 1994. In the case of the anti-aging ingredient NMN (beta-nicotinamide mononucleotide, or β-NMN), FDA ruled the ingredient was precluded from supplements because of an IND it had previously approved for the Chinese company Metro International Biotech (搜索) — a decision that came long after supplement ingredient development had begun and significant investments had been made.
Industry sources have also flagged the possibility that drug preclusion could keep an ingredient off supplement shelves even if a drug company abandons its development efforts, raising fears the clause could be used in an anticompetitive fashion.
Five Core Provisions
The Dietary Supplement Innovation Act (搜索) addresses five points:
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Narrowing FDA's exclusion authority. 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 (a grandfathered ingredient). 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 would also be eligible, as would substances whose development as a drug was abandoned — defined in the bill as being "inactive status, withdrawn, or both for a continuous period of at least seven years."
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Raising the preclusion threshold. Drug preclusion would be limited to substances involved in Phase 2 or Phase 3 clinical trials, rather than exploratory or earlier-stage research.
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Requiring comparative assessment. FDA would have to consider differences between a drug and a supplement version of an ingredient based on route of administration, dosage, serving amount, concentration and composition, and relative safety profiles in supplement versus drug use.
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Creating a judicial pathway. The bill would establish a direct pathway to challenge FDA drug-preclusion decisions in court and place the burden of proof on the agency.
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Removing preclusion language from the supplement definition. The bill would strike drug-preclusion language from the definition of dietary supplement under section 201(ff)(3).
Industry Support
The Consumer Healthcare Products Association (搜索) (CHPA), the American Herbal Products Association (搜索) (AHPA) and the Council for Responsible Nutrition (搜索) (CRN) welcomed the announcement. CRN, which has fought drug preclusion for years, including filing a Citizen Petition with FDA on the issue, described the bill 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."
AHPA President and CEO Graham Rigby said botanical dietary supplement innovation depends on clearly defined pathways that allow safe herbs and natural products to reach consumers. "Representative Harshbarger's legislation would help restore the balance Congress intended under DSHEA and better ensure that drug development does not unnecessarily foreclose legitimate dietary supplement innovation," Rigby said.
CHPA President and CEO Scott Melville said the bill "provides much-needed regulatory certainty, and helps ensure consumer access keeps pace with innovation."
According to a joint statement from the trade associations, the bill would preserve access to ingredients marketed in foods or dietary supplements prior to Oct. 15, 1994; clarify when drug preclusion applies so ingredients in discontinued or inactive drug development programs are not blocked forever; provide greater regulatory predictability for manufacturers, researchers and consumers; help ensure innovative ingredients are not unnecessarily excluded when no approved drug reaches the market; balance protection of pharmaceutical research against consumer access; reduce costly and resource-intensive disputes; and streamline the pathway for FDA to allow both dietary supplements and drugs with the same ingredient at the agency's discretion under predictable rules and procedures.
A Partial Fix, One Architect Argues
Scott Bass, principal at Scott Bass Life Sciences LLC and one of the architects of DSHEA, said the bill addresses one of the three key provisions of DSHEA that require legislative amendment. "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.
Bass nonetheless argued that a bill named the Dietary Supplement Innovation Act (搜索) should address the DSHEA innovation section, 201(ff)(1)(E), which covers "a dietary supplement for use by man to supplement the diet by increasing the total dietary intake." He described that clause as the most critical innovation provision and one that FDA has both misinterpreted and misapplied, emphasizing the need for a permanent legislative fix. If the supplements sector wants a more open field for critical dietary supplement innovation, he said, 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]."