Selling supplements in the US: the complete compliance guide

The US is the world's largest supplement market, and its regulatory model is distinctly different from the EU's. Dietary supplements in the US operate under a framework where products do not need pre-market approval, but manufacturers carry the full burden of safety, manufacturing quality, accurate labeling, and substantiated claims — with serious consequences for getting it wrong. This guide gives the complete picture of US supplement compliance and how the right software keeps a brand on the right side of it.

The US framework: DSHEA

US dietary supplements are governed by a framework that treats them as a category of food, not drugs. Products generally do not require pre-market approval, but this freedom comes with responsibility: the manufacturer is accountable for the product's safety, for manufacturing it properly, for labeling it accurately, and for being able to substantiate every claim. The absence of pre-approval does not mean the absence of rules — it means the rules are enforced after the fact, often severely.

Understanding this shifts the mindset: compliance is your responsibility to build in, and software that helps you do so systematically is how you carry that burden reliably.

The Supplement Facts panel

US supplements carry the Supplement Facts panel, with its own format, its Daily Values, and its conventions for dietary ingredients — distinct from the EU's nutrition presentation. The percentages are calculated against US Daily Values, which differ from EU reference values, so the same product shows different numbers on a US label than an EU one. Generating an accurate Supplement Facts panel from the formula, with the right Daily Values, is core to US compliance.

New dietary ingredients and GRAS

A central US question is whether an ingredient is a new dietary ingredient (NDI) — one not marketed before the cutoff — which may require notification before use, or whether it is generally recognised as safe (GRAS) for its use. Knowing the status of each ingredient, and whether an NDI notification is needed, is a key compliance step. Using an ingredient without the right status or notification is a significant risk.

21 CFR Part 111: cGMP

US supplements must be made under current Good Manufacturing Practice, defined in 21 CFR Part 111. This governs the manufacturing process, including master manufacturing records and batch records — the documentation proving each batch was made correctly. The record-keeping, testing, and quality discipline cGMP requires is substantial, and the structured records a good system maintains support exactly this.

Structure-function vs disease claims

The claims line in the US is sharp: supplements may make structure-function claims (how an ingredient affects the body's structure or function) but not disease claims (that a product treats, cures, or prevents a disease). Crossing that line turns a supplement into an unapproved drug in the eyes of regulators. Knowing which side of the line a claim falls on, and keeping claims to permitted structure-function statements, is essential.

FTC substantiation

Beyond the line between claim types, every claim must be substantiated — backed by adequate evidence — a requirement enforced by the FTC for advertising. A claim you cannot support is a liability regardless of its wording. Tying claims to the evidence and to what the formula actually delivers is what keeps US marketing defensible.

Heavy metals, Prop 65, and contaminants

Contaminant limits, especially heavy metals, matter in the US, and California's Proposition 65 adds specific warning requirements tied to certain substances above defined levels. Knowing your product's contaminant load and whether Prop 65 warnings apply is part of selling compliantly, particularly into California.

Selling on Amazon and the platform layer

For many US brands, Amazon and major retailers add a layer on top of the regulations — their own documentation, labeling, and compliance requirements, often stricter than the legal minimum. Meeting both the regulatory rules and the platform's requirements is the practical reality of the US market, and being able to produce the documentation each demands is part of the job.

How software keeps you compliant

US compliance places the burden on the manufacturer to build it in, across the Supplement Facts panel, ingredient status, cGMP records, the claim line, substantiation, and contaminants. Software that generates the right panel, flags ingredient status, maintains the manufacturing and batch records, ties claims to evidence, and tracks contaminants turns that burden into systematic, supported practice rather than hopeful manual effort.

The takeaway

US supplement compliance places the full burden on the manufacturer — accurate Supplement Facts, correct NDI/GRAS status, 21 CFR 111 cGMP records, structure-function claims that stay on the right side of the disease line, FTC substantiation, and contaminant limits, plus the platform requirements of Amazon and retailers. Software that builds these into how you formulate and document is how a brand carries that burden reliably. Sell into the US with compliance designed in.

Lemoniq generates the Supplement Facts panel, flags ingredient status, ties claims to the formula, and maintains the records — so US compliance is systematic. See what Lemoniq can do for your US compliance