A US supplement brand is importing EGCG 98% from a Chinese supplier and launching a new SKU. Their regulatory affairs team asks a single question: "Is this EGCG 98% a New Dietary Ingredient (NDI) requiring premarket notification to the FDA?" The supplier says no — it is "the same as green tea, just concentrated." The brand's attorney says the answer is uncertain and the risk of non-compliance is a deemed-adulteration finding under Section 402(f) of the FD&C Act.
Both are partially correct. The legal and regulatory answer to this question — which determines whether a product can legally be sold in the US without a premarket notification — turns on three factual determinations: (1) Was the specific form of the ingredient marketed as a dietary ingredient in the United States before October 15, 1994? (2) Has the manufacturing process "chemically altered" the ingredient relative to its form in the historical food supply? (3) If it is an NDI, has a premarket notification been submitted to FDA at least 75 days before market introduction? Getting these questions wrong — in either direction — costs money: an unnecessary NDI notification consumes $50,000–$300,000 in legal and scientific preparation; an omitted required notification exposes the entire product line to deemed-adulteration status, import detention, and FDA Warning Letters.
This guide resolves the regulatory architecture, the key decision points for green tea extract and EGCG specifically, the 21 CFR 111 cGMP requirements that apply regardless of NDI status, and the supplier regulatory dossier requirements that procurement teams must demand before a US market launch.
The short answer: it depends on the specific form and concentration. Green tea leaves and crude aqueous green tea extracts with a catechin profile consistent with traditional hot-water infusion are strong candidates for pre-DSHEA ("old dietary ingredient") status — they were marketed in the US before October 15, 1994, and have not been chemically altered beyond traditional food processing. These forms likely do NOT require an NDI notification, though the burden of proof lies with the manufacturer to document pre-1994 US market history with contemporaneous written records (not merely an industry association list).
Highly concentrated EGCG isolates (EGCG 95%+) are in a regulatory gray zone. As of June 2026, no NDI notification for EGCG ≥95% appears in the FDA's public NDI notification database. FDA's 2016 revised draft guidance on NDI notifications states that a manufacturing process that "significantly concentrates" or "isolates" a specific constituent of a botanical — particularly when the resulting concentration significantly exceeds what could be achieved by traditional food processing methods (e.g., hot-water extraction of green tea) — may constitute a "chemical alteration" that creates a New Dietary Ingredient. FDA has not formally ruled on EGCG 98% specifically. The first enforcement action targeting high-purity EGCG isolate will define the compliance boundary retroactively for the entire market. Until FDA issues definitive guidance, the conservative compliance position is: treat EGCG ≥90% as a potential NDI and consult regulatory counsel before US market launch.
Regardless of NDI status: Any finished dietary supplement sold in the US containing green tea extract or EGCG must comply with 21 CFR Part 111 (cGMP for dietary supplements). The supplier's manufacturing facility must also meet cGMP standards — and the US brand bears the compliance responsibility, not the overseas supplier.
The Dietary Supplement Health and Education Act of 1994 (DSHEA) — signed into law October 25, 1994 — established the current US regulatory framework for dietary supplements. Under DSHEA, the FDA does not require pre-market approval of dietary supplements as it does for drugs. However, for ingredients not marketed in the US before October 15, 1994 (the New Dietary Ingredient threshold date, set slightly before the act's signing), DSHEA created a premarket notification requirement under Section 413 of the FD&C Act (21 U.S.C. §350b).
The legal standard: A "New Dietary Ingredient" (NDI) is defined in DSHEA as "a dietary ingredient that was not marketed in the United States before October 15, 1994." If a dietary ingredient qualifies as an NDI, the manufacturer or distributor of the NDI or of a dietary supplement containing the NDI must submit a premarket notification to FDA at least 75 days before first marketing — UNLESS the NDI has been "present in the food supply as an article used for food in a form in which the food has not been chemically altered" (FD&C Act §413(a)(1); 21 U.S.C. §350b(a)(1)). The notification must be submitted to FDA's Office of Dietary Supplement Programs (ODSP) and is filed under 21 CFR Part 190.6. The 75-day period begins on the date FDA receives and files the complete notification — not when submitted.
Key regulatory documents: The FDA has published three guidance documents on NDI notifications: (1) Original 1997 NDI regulation (21 CFR 190.6); (2) 2011 draft guidance — "Guidance for Industry: Dietary Supplements: New Dietary Ingredient Notifications and Related Issues" (FDA-2011-D-0376); (3) 2016 revised draft guidance (FDA-2016-D-0340); (4) 2022 draft guidance — "Policy Regarding Certain New Dietary Ingredients and Dietary Supplements" (FDA-2022-D-0281). The 2022 guidance addresses FDA's approach to retroactive NDI compliance and enforcement policy. The 2024 final guidance on NDI notification procedures and timeframes was released in December 2024 by FDA, clarifying procedural requirements without significantly changing the substantive determination framework. None of these guidance documents are legally binding — they represent FDA's current thinking, not law. However, they are FDA's primary tool for enforcement decisions and Warning Letters.
Section 413(a)(1) — The "Food Supply" Exception (no notification required):
"A dietary supplement that contains a new dietary ingredient shall be deemed adulterated under section 402(f) unless it meets one of the following requirements: (1) The dietary supplement contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered."
Section 413(a)(2) — NDI Notification Requirement (when applicable):
"(2) There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or the dietary supplement notifies the Secretary of the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe."
Section 402(f) — Adulteration Consequence:
"A dietary supplement shall be deemed to be adulterated if it is a dietary supplement that contains a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury."
An ingredient is an "Old Dietary Ingredient" (ODI) — not requiring NDI notification — if it was marketed as a dietary ingredient in the United States before October 15, 1994, AND the specific form and concentration marketed matches what is currently being sold. If either of these conditions fails, NDI analysis is required. Key principles from FDA's guidance:
The burden of proof is on the manufacturer: FDA does not maintain an authoritative list of pre-DSHEA dietary ingredients. Each manufacturer is responsible for documenting that their specific ingredient was marketed before October 15, 1994. Industry association lists (e.g., AHPA's Herbs of Commerce) are not sufficient proof — FDA has explicitly stated it does not accept inclusion on such lists as evidence of ODI status. Required documentation: written business records, promotional materials, or press reports with contemporaneous dates prior to October 15, 1994 — including sales records, manufacturing records, commercial invoices, magazine advertisements, mail order catalogues, or sales brochures that establish: (a) marketing took place in the US; (b) the chemical/botanical identity and form of the marketed ingredient; (c) the ingredient was marketed as a dietary ingredient (not as food, drug, or for other non-dietary use).
Affidavits alone are insufficient: FDA has stated that affidavits — sworn statements by company personnel claiming the ingredient was on the market before 1994 — are not sufficient documentation without contemporaneous written records. This is a significant compliance gap for many imported botanical ingredients where the historical US market documentation may not exist or be readily accessible.
The form-specific requirement: ODI status is specific to the form marketed. A crude green tea water extract marketed before 1994 does not automatically confer ODI status on a highly concentrated EGCG isolate produced by chromatographic purification — these are different chemical forms. FDA has indicated that changing the manufacturing process in a way that alters the chemical structure or composition of the ingredient may create a new dietary ingredient even when the starting botanical is an ODI.
Under FD&C Act §413(a)(1), an ingredient present in the food supply "as an article used for food in a form in which the food has not been chemically altered" does not require NDI notification. FDA's guidance defines "chemical alteration" broadly. Examples from FDA's guidance documents that do NOT constitute chemical alteration: drying, milling, tinctures (soaking in aqueous ethanol), standard aqueous extraction. Examples that DO constitute chemical alteration (from FDA's guidance): isolation or purification of a specific constituent to concentrations significantly above what occurs in the whole food; use of solvents other than water or aqueous ethanol that change the constituent ratio; processes that selectively remove or concentrate specific chemical fractions relative to the whole botanical.
The green tea / EGCG-specific analysis: Traditional green tea (hot water infusion) contains EGCG at approximately 15–40 mg per cup, with a catechin ratio of approximately EGCG 50–65% of total catechins, alongside EGC, ECG, EC, GCG, caffeine, amino acids, and other tea polyphenols. A crude aqueous green tea extract that roughly preserves this ratio (while concentrating the solids) is a strong argument for no chemical alteration — it is essentially the same chemical composition as traditional green tea in a more concentrated dry form. However, as concentration increases and the EGCG percentage relative to total extract composition increases (e.g., 50% EGCG, 80% EGCG, 98% EGCG), the argument becomes progressively weaker. At EGCG 98%, the product has been purified to eliminate essentially all other components present in green tea — caffeine, other catechins, amino acids, polysaccharides, chlorophyll — leaving a highly pure single-molecule isolate. FDA's guidance suggests that such "isolation or purification" of a single botanical constituent to this degree may constitute chemical alteration, potentially triggering NDI classification.
The NDI database reality: As of June 2026, no NDI notification for EGCG ≥95% purity appears in FDA's public NDI notification database at regulations.gov. This does not mean the agency has determined EGCG 98% is an ODI — it means no company has tested the regulatory boundary with a formal filing, and FDA has not yet taken enforcement action specifically targeting high-purity EGCG. The absence of NDI filings for a specific ingredient is neither evidence of ODI status nor evidence of regulatory compliance.
When the ODI vs. NDI determination is uncertain — as it is for EGCG 98% — the regulatory options are: (1) Obtain a legal opinion from a US regulatory attorney specializing in dietary supplement law — not a general practice attorney — before market launch. Document this opinion in a compliance file. (2) Request an FDA pre-submission meeting — companies can request informal meetings with FDA's ODSP before submitting an NDI notification to get preliminary feedback on whether a notification is warranted. (3) Submit a voluntary NDI notification — even if ODI status is likely, a voluntary notification creates a documented regulatory record and provides FDA visibility before enforcement. The cost of a voluntary notification ($50,000–$300,000 in preparation) is generally less than the cost of a Warning Letter, import detention, product recall, or class action from an "adulterated" product ruling. (4) Conduct a thorough historical use literature search — if documented evidence of US marketing of a similar form before October 15, 1994, can be found, the ODI position is strengthened. Document and retain this evidence in a regulatory compliance file.
| Green Tea Ingredient Form | Typical EGCG Content | Manufacturing Process | Pre-DSHEA US Market History | Chemical Alteration Risk | NDI Notification Status | cGMP 21 CFR 111 Required? |
|---|---|---|---|---|---|---|
| Whole green tea leaf / powdered leaf | ~2–4% of dry weight | Drying, milling — no chemical solvents; traditional processing | Strong — green tea consumed for centuries; clearly in US commerce pre-1994 | None — same form as traditional food | ODI — no notification required (with adequate pre-1994 documentation) | Yes — for finished supplement manufacture |
| Crude water extract / standardized GTE (20–50% total polyphenols; 30–40% EGCG) | ~20–40% of extract | Aqueous extraction; spray-drying; catechin ratio preserved approximately consistent with traditional hot-water infusion | Likely — green tea water extracts marketed in US supplements in early 1990s | Low — aqueous extraction is traditional; ratio preserved | Likely ODI — document pre-1994 US marketing with contemporaneous records; maintain compliance file | Yes |
| Concentrated GTE (50–80% total catechins; 40–60% EGCG) | ~50–60% of extract | Aqueous or ethanol/water extraction + concentration; catechin ratio moderately altered vs. traditional infusion; caffeine partially removed | Uncertain — concentrated extracts at these levels less clearly documented in pre-1994 US commerce | Moderate — concentration is not "chemical alteration" per se, but selective caffeine removal changes ratio; consult counsel | Gray zone — ODI claim possible with documentation; legal review recommended before US market launch at high EGCG dose | Yes |
| High-purity EGCG isolate (90–95% EGCG) | ~90–95% of extract | Aqueous extraction + chromatographic purification (macroporous resin) + recrystallization; removes all other catechins, caffeine, amino acids; single-molecule isolate | Unlikely — no clear evidence of US pre-1994 commercial marketing of EGCG ≥90% isolate | High — selective isolation of single constituent to >90% purity is a strong argument for chemical alteration under FDA guidance | Likely NDI — no NDI notification in FDA public database; regulatory gray zone; legal counsel required | Yes |
| EGCG 98% (pharmaceutical-grade isolate) | ≥98% EGCG | Full chromatographic + recrystallization purification; functionally pure single compound; zero similarity to traditional green tea compositional profile | No evidence — EGCG 98% at this purity did not exist in commercial US supplement market before 1994 | Very high — complete removal of all other botanical constituents constitutes significant chemical alteration per FDA guidance interpretation | Strong NDI indicator — US brands should consult regulatory counsel; consider voluntary NDI notification before US market launch | Yes |
Table 1 — Green Tea Extract Grades: NDI Status Assessment, Chemical Alteration Risk, and cGMP Requirements
If a dietary supplement contains a New Dietary Ingredient and no NDI notification has been submitted to FDA at least 75 days before marketing — AND the NDI has not been present in the food supply without chemical alteration — the dietary supplement is deemed adulterated by operation of law under Section 402(f) of the FD&C Act. This is not a discretionary enforcement decision by FDA — it is a statutory determination. The practical consequences: (1) The supplement cannot legally be sold in interstate commerce; (2) FDA can initiate import detention under Import Alert 54-07 (adulteration) or 99-41 (botanical ingredients) without physical examination of the shipment — DWPE (Detention Without Physical Examination) can hold a shipment for weeks or months; (3) FDA can issue a Warning Letter demanding immediate removal of the product from the market; (4) FDA can initiate a mandatory recall under Section 415 of the FD&C Act; (5) Private plaintiffs can bring class action lawsuits alleging sale of an adulterated product under state consumer protection laws. Note: submission of an NDI notification — even if FDA later objects — reduces the legal exposure, because the manufacturer has made a good-faith premarket safety disclosure to FDA. An omitted notification provides no such protection.
FDA has issued Warning Letters citing NDI non-compliance in combination with cGMP violations for numerous botanical and dietary supplement products. Common enforcement patterns: (1) Import Alert DWPE (Detention Without Physical Examination) — FDA places a supplier or product on the DWPE list; all shipments from that supplier are detained and refuse admission without physical inspection; shipments can sit in unrefrigerated warehouse conditions for weeks, further degrading EGCG through epimerization and oxidation; (2) Warning Letters citing both cGMP violations (21 CFR Part 111) AND failure to submit required NDI notifications; (3) Consent decrees requiring companies to conduct third-party audits and remediate manufacturing practices before FDA removes import alerts. FDA's 2022 draft guidance specifically addressed the situation where manufacturers have marketed products requiring NDI notifications without having submitted them — FDA offered a pathway for retroactive compliance submissions, signaling active intent to pursue this category of violation. The 2024 final guidance on NDI notification procedures reinforces the 75-day premarket requirement and clarifies that FDA can object to notifications at any time, even after the 75-day period expires, if safety concerns arise.
Scope: 21 CFR Part 111 (Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements) applies to all manufacturers, packagers, labelers, and holders of dietary supplement ingredients sold in the US market — including overseas ingredient suppliers whose products are imported into the United States. The US-based brand bears primary compliance responsibility (as the "manufacturer" under Part 111), but supplier cGMP status directly affects the US brand's ability to pass incoming ingredient testing and maintain their own cGMP compliance.
Key Part 111 requirements applicable to green tea extract / EGCG suppliers:
21 CFR 111.75 — Identity Testing: The US manufacturer must perform identity testing on each lot of dietary ingredient received from each supplier before using it. The testing method must be "specific" to the ingredient — FDA has stated that UV-Vis absorbance alone is not "specific" for identity verification of botanical extracts or EGCG. HPLC with individual catechin quantification is the accepted specific identity test. If the supplier can provide batch-specific HPLC identity data, the US brand can rely on this with appropriate supplier qualification documentation — but cannot eliminate its own identity testing obligation entirely.
21 CFR 111.70 — Specifications: The finished product manufacturer must establish specifications for identity, purity, strength, and composition for each dietary ingredient. These specifications must be documented in writing and used as the basis for incoming goods acceptance/rejection decisions. "Protein ≥90%" and "average MW <2,000 Da" alone do not satisfy Part 111 specification requirements for green tea extract — individual catechin content, residual solvents, heavy metals, and microbiological specifications must all be documented.
21 CFR 111.80–111.87 — Component Testing: The US manufacturer must test or verify testing for: identity (specific test for each component); purity (absence of impurities at harmful levels — heavy metals, residual solvents, pesticides); strength/composition (HPLC-verified catechin profile); and limits for contaminants that may cause the supplement to be adulterated or injurious.
21 CFR 111.14 — Supplier Qualification: The US manufacturer must qualify suppliers from whom they receive dietary ingredients. Supplier qualification includes: written agreements specifying specifications, testing methods, and batch documentation requirements; periodic audits or supplier certification programs; review of supplier COAs against independently established incoming goods testing results.
21 CFR 111.95 — Batch Records: Complete batch production records must be maintained for each batch of supplement produced, including documentation of all dietary ingredients used (with supplier and lot number), in-process testing results, and finished product release testing.
| 21 CFR 111 Requirement | What the Supplier Must Provide | What the US Brand Must Verify Independently | Common Deficiency in FDA Warning Letters |
|---|---|---|---|
| §111.75 Identity Testing | Batch-specific HPLC catechin profile (EGCG, ECG, EGC, EC, GCG individually quantified) with retention time data and chromatogram; botanical Latin binomial (Camellia sinensis L.); plant part stated (leaf) | Perform independent identity test on each incoming lot; HPLC method must be "specific"; cannot rely solely on UV-Vis or total polyphenols | Relying on UV-Vis absorbance for identity; failure to test every incoming lot; accepting supplier COA without independent verification |
| §111.70 Specifications | Documented specification for each analyte: EGCG %, total catechins %, caffeine %, heavy metals (Pb, Cd, As, Hg individually), residual solvents, moisture, microbiology | Establish and document written in-house specifications; use as acceptance/rejection criteria for each lot | Specifications not in writing; specifications that are too vague ("heavy metals: pass" without quantitative limits); no specification for individual catechins |
| §111.80–87 Component Testing | Batch-specific COA with all tested parameters; method references for each test; ICP-MS heavy metals; USP <467> residual solvents; pesticide residues; microbiological counts | Independently test or verify 100% of incoming lots for identity; may conduct reduced testing on purity/strength with supplier qualification program in place (documented) | Failure to test 100% of incoming lots for identity; testing only a subset; relying solely on supplier COA without documented supplier qualification |
| §111.14 Supplier Qualification | cGMP certification (ISO 22000, FSSC 22000, or equivalent); facility audit records or third-party audit report; signed quality agreement; batch-specific COA format consistent with agreed specifications | Qualify each supplier before use; document qualification in a supplier file; requalify periodically (annual or after significant process changes) | No formal supplier qualification program; no written quality agreements with suppliers; using new suppliers without prior qualification |
| §111.95 Batch Records | Provide lot-specific COA linked to production batch number; traceability from raw material receipt through finished production | Maintain complete batch production records linking the supplier lot number used in each finished supplement batch; retain for 1 year past product expiry | Incomplete batch records; inability to link finished product to specific incoming ingredient lots; missing documentation for in-process testing steps |
Table 2 — 21 CFR Part 111 cGMP Requirements: Supplier Obligations and US Brand Verification Responsibilities
1. Identity of the NDI (21 CFR 190.6(b)(1)): For botanicals, the full Latin binomial with author citation (e.g., Camellia sinensis (L.) Kuntze, not just "Camellia sinensis"); plant part used (leaves); extraction/manufacturing process description; chemical characterization of the resulting ingredient (full catechin profile, other chemical constituents); specifications (purity, identity, manufacturing limits).
2. Conditions of use (21 CFR 190.6(b)(2)): Exact recommended daily intake (mg or g); form of the supplement (capsule, tablet, beverage); frequency and duration of use; target population (adults, specific age groups, exclusions); labeling claims and directions for use. FDA has stated that an NDI notification must cover the specific conditions of use — submitting a notification for a lower dose does not protect a higher-dose product using the same ingredient.
3. History of use or other evidence of safety (21 CFR 190.6(b)(3)): This is the most substantive requirement. Acceptable evidence includes: (a) History of use: Published literature documenting the ingredient's history of use in food or dietary supplements; historical human exposure data; traditional use documentation in other countries or cultures; (b) Clinical studies: Human clinical trials (RCTs preferred) at the proposed conditions of use; (c) Toxicological studies: Subchronic and/or chronic toxicity studies (typically 90-day and/or 1-year animal studies); genotoxicity/mutagenicity studies (Ames test, in vitro micronucleus); pharmacokinetics data; (d) Safety basis statement: A written statement by the notifier explaining why the evidence demonstrates the ingredient will be reasonably expected to be safe under the proposed conditions of use.
4. Name and address of the manufacturer/distributor (21 CFR 190.6(b)(4)).
Critical note on EGCG specifically: For EGCG at doses ≥800 mg/day, the EFSA hepatotoxicity evidence (from the EU 2022/2340 regulatory context) is directly relevant to the FDA NDI safety assessment — clinical evidence of ALT/AST elevation at ≥800 mg EGCG/day from interventional trials would need to be addressed in any NDI notification for high-dose EGCG products. FDA would almost certainly request this information as part of its review.
Blue Eyes Biotech supplies EGCG 98% with a complete regulatory compliance package designed to support US-market brands navigating the NDI determination process. We do not claim to provide legal advice — the NDI vs. ODI determination requires regulatory counsel for each brand's specific product and conditions of use. What we provide is the technical and documentation foundation that US-market regulatory counsel needs to make that determination efficiently.
What most overseas suppliers cannot provide — and why it matters: The 2022 FDA guidance on retroactive NDI compliance and the 2024 final guidance on NDI notification procedures both signal active enforcement intent. A brand that sources from an overseas supplier without US regulatory awareness faces: (a) inability to support an NDI submission if required; (b) cGMP deficiency findings during FDA facility inspections that trace back to supplier documentation gaps; (c) DWPE import detention if the supplier's facility is added to an import alert. Our regulatory compliance package is designed to close these gaps.
US Regulatory Compliance Documentation Package:
NDI consultation support: We can connect qualified buyers with US regulatory affairs consultants experienced in NDI submissions for botanical ingredients. The decision to submit an NDI notification — and the preparation of the submission itself — must be led by US regulatory counsel. We provide the manufacturer-side documentation; your US regulatory attorney provides the submission strategy and legal analysis.
Receive FDA facility registration number, cGMP certification, batch-specific Part 111-compliant COA, regulatory status declaration, safety literature summary, and pesticide panel — alongside a 20g analytical sample for your own HPLC verification.
Our regulatory team can provide documentation packages, connect you with US regulatory counsel referrals, and support NDI dossier preparation on the manufacturer documentation side.
Email: [email protected]
Potentially yes — if the specific form and concentration of green tea extract you are using constitutes an NDI (i.e., was not marketed as a dietary ingredient in the US before October 15, 1994, or has been chemically altered from its traditional food supply form), and no NDI notification was submitted, the product is deemed adulterated by operation of law under Section 402(f) regardless of how long it has been sold. Past non-enforcement by FDA does not create legal protection against future enforcement. FDA's 2022 draft guidance specifically addressed retroactive compliance — acknowledging that products requiring NDI notifications have been marketed without submissions — and indicated FDA would consider the timeline of non-compliance in its enforcement discretion. However, FDA explicitly reserved the right to take enforcement action and stated that manufacturers of products requiring NDI notifications should take steps to come into compliance. The recommended immediate action: retain a US dietary supplement regulatory attorney to assess whether your specific product requires an NDI notification, and if so, prepare and submit one. Do not rely on competitor non-compliance as a risk mitigation strategy — FDA may target your specific product category at any time.
NDI notification and GRAS (Generally Recognized As Safe) are two separate regulatory pathways that apply to different product contexts. NDI notification applies to dietary supplement ingredients under DSHEA — it is a premarket notification (not approval) system for supplements specifically. GRAS status applies to ingredients used in conventional foods under the Food Additives Amendment — it is a determination that an ingredient is safe for its intended use in conventional food based on generally available scientific evidence (or expert consensus for substances in use before 1958). They are not interchangeable. A GRAS determination for "catechins from green tea extract" in beverages (such as the FDA GRN 225 filing by Kao Corporation that was withdrawn) does not establish NDI status for the same ingredient in dietary supplements. Conversely, an NDI notification for an EGCG supplement does not constitute GRAS authorization for the same ingredient in conventional food. If you intend to use green tea extract or EGCG in both dietary supplements AND conventional food products, you may need to address both regulatory frameworks separately. Consult regulatory counsel for each product category.
EU Regulation 2022/2340 does not directly determine US NDI status — it is EU law, not US law. However, the scientific evidence underlying EU 2022/2340 — specifically the EFSA 2018 opinion on green tea catechins and hepatotoxicity — is directly relevant to any US NDI safety dossier for EGCG. FDA's NDI safety review requires a "history of use or other evidence of safety" establishing that the ingredient "will reasonably be expected to be safe" at the proposed conditions of use. The EFSA finding that clinical evidence shows statistically significant ALT/AST elevation at ≥800 mg EGCG/day is the type of safety signal FDA would need to see addressed in an NDI notification for high-dose EGCG. Any brand considering a US NDI notification for EGCG at doses approaching or exceeding 400–800 mg/day must include a rigorous hepatotoxicity risk assessment addressing the EFSA evidence in the safety dossier. Failing to acknowledge this evidence in an NDI submission — when it is publicly available — would likely result in an FDA objection letter. In this sense, the EU regulatory framework and the US NDI framework share a common evidentiary base on EGCG hepatotoxicity, even though they operate through different legal mechanisms.
Under 21 CFR 190.6 and Section 413(a)(2) of the FD&C Act, the notification obligation falls on "the manufacturer or distributor of the new dietary ingredient, or of the dietary supplement that contains the new dietary ingredient." This means EITHER the ingredient manufacturer/supplier OR the finished supplement manufacturer/distributor can submit the notification. If the overseas supplier submits an NDI notification covering their specific EGCG ingredient, that notification may protect US brands that use that specific ingredient from that specific supplier — as long as the US brand's product uses the ingredient at or below the conditions of use stated in the supplier's notification, and the US brand's supply chain connects to that specific supplier's notification. In practice: if your overseas EGCG supplier has submitted an NDI notification and received a no-objection letter from FDA, request: (a) the NDI notification number (assigned by FDA upon filing); (b) a copy of the no-objection letter; (c) confirmation that your specific product and dose conditions fall within the scope of the notification. Do not assume that an "NDI-filed" claim from a supplier is accurate without seeing the FDA filing documentation.
"21 CFR 111 compliant" is a claim that the manufacturing facility operates in accordance with FDA's current Good Manufacturing Practice regulations for dietary supplements. The problem: this is a self-declaration unless verified by a third-party audit or FDA inspection. Any supplier can print "21 CFR 111 compliant" on their marketing materials regardless of their actual practices — there is no pre-market FDA certification of cGMP compliance. The meaningful evidence of cGMP compliance is: (a) an NSF/GMP, NSF International, or equivalent third-party cGMP audit certificate with the audit date and scope; (b) no current FDA Warning Letters for cGMP violations at the specific facility; (c) no active import alerts for the facility on FDA's import alert database. Verify these independently — do not rely on the supplier's assertion. For US brands importing from overseas: the US brand bears the compliance responsibility under Part 111 regardless of what the overseas supplier claims. If the overseas supplier's facility is later found to have cGMP violations during an FDA inspection or import examination, the US brand's own cGMP compliance — including their supplier qualification program — will be scrutinized.