The United States is the largest single market for both pharmaceuticals and dietary supplements, and it is governed by the US Food and Drug Administration (FDA). Raised Pharma supports manufacturers and brand owners entering the US: classification, facility registration, dossier and notification preparation, cGMP readiness and labelling review.
More US compliance trouble starts here than anywhere else, so we will be precise.
There is no such thing as an FDA-approved dietary supplement, an FDA-certified facility, or an FDA-approved Drug Master File. FDA has publicly acted against firms issuing misleading “FDA registration certificates.” If a supplier tells you they will get your supplement FDA approved, that is a reason to walk away.
Accurate phrasing exists and is still commercially strong: manufactured in an FDA-registered facility under 21 CFR Part 111 cGMP.
FDA does not approve dietary supplements before they are marketed. That is not the same as unregulated. The obligations are substantial:
A structure/function claim (“supports joint health”) needs no pre-approval, but must be notified to FDA within 30 days after first marketing and must carry this exact disclaimer:
“This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”
The disclaimer has formatting rules — boldface, minimum type size, placed adjacent to the statement with no intervening material, or boxed where it is not adjacent.
Note the direction of travel, because it is widely reported backwards: the NDI notification is 75 days before marketing; the claim notification is 30 days after marketing.
A disease claim is different in kind. A product represented for the treatment, prevention or cure of a disease meets the legal definition of a drug — and becomes an unapproved new drug. This is the single most common trigger for FDA warning letters in the supplement sector.
21 CFR Part 111 governs dietary supplement cGMP. 21 CFR Parts 210 and 211 govern drug cGMP, including OTC drugs.
They are not the same standard, and a Part 111 supplement facility is not qualified to manufacture an OTC drug. If your product carries a monograph active — a sunscreen, an antiseptic, an antacid — it is a drug, and it needs a Part 211 facility and quality system.
This is precisely the line a pharmaceutical CDMO exists to cross. It is also the line that makes a product exportable to the Gulf, where several markets demand pharmaceutical GMP for supplement dosage forms.
The OTC monograph system was reformed by the CARES Act in 2020, replacing rulemaking with administrative orders and introducing OTC Monograph Order Requests. A conforming monograph drug may be marketed without an approved application. An NDA is required where the active ingredient, indication or dosage form has never been marketed OTC, or for a partial prescription-to-OTC switch.
Drug Facts labelling under 21 CFR 201.66 applies to every OTC product, whatever the pathway.
Foreign drug establishments must register with FDA before their drugs are imported, renew annually, and list their known importers. Registration and listing are submitted in SPL XML format, together with a labeler code request that produces your NDC. The NDC is an identifier, not an endorsement — FDA states in capitals that inclusion in the NDC Directory does not denote approval.
One commercial point contract manufacturers often miss: OTC monograph drug facilities, including contract manufacturing facilities, owe an annual OMUFA facility fee. CMO facilities pay a reduced rate. Rates are set annually, so confirm the current figure.
High level: an NDA for a new drug; an ANDA for a generic, requiring sameness to the reference listed drug and demonstrated bioequivalence; a 505(b)(2) where some supporting data comes from studies the applicant did not conduct and has no right of reference to.
A Drug Master File provides confidential detail on facilities, processes or materials. DMFs are not required by statute and are neither approved nor disapproved — they are reviewed only in the context of an application that references them.
Both regimes require one, and they are separate appointments under separate rules. A foreign food or supplement facility must designate a US agent who lives or maintains a place of business in the United States and is physically present there. A foreign drug establishment must identify a US agent who resides or maintains a place of business in the US — and FDA is explicit that a mailbox or answering service does not qualify.
Two patterns dominate the supplement sector, both drawn from real, dated FDA warning letters:
On the drug side, recent letters cite failure to investigate out-of-specification results and batch failures, inadequate laboratory controls, and — notably — failure to test glycerin and propylene glycol for diethylene glycol and ethylene glycol, relying instead on unvalidated supplier certificates of analysis. That last one is currently among FDA’s most aggressively enforced issues, and it is a sourcing and incoming-material control problem before it is a paperwork problem.
FDA regulates supplement labelling. The Federal Trade Commission regulates supplement advertising, and applies its own substantiation standard. A claim that survives FDA scrutiny on a label can still attract FTC action in a marketing campaign. This is a common and expensive blind spot.
Tell us the product, the dosage form and the claims you want to make — the claims usually determine everything else.
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Important: General information about the US regulatory environment, not regulatory or legal advice. FDA guidance changes and several areas referenced here — including the scope of the NDI “chemically altered” exemption — remain governed by draft guidance. No review timelines or fee amounts are stated because they change and are frequently misreported. Classification, notifications, cGMP scope, labelling and claims must be reviewed by a qualified US regulatory professional before marketing. Advertising claims additionally fall under FTC jurisdiction. Last reviewed August 2026.