Regulatory and safety science

Rulemaking activity

Rulemaking on the core food and supplement parts peaked in 2016; Part 190 has appeared in six documents in 32 years

Federal Register rules and proposed rules that cite each part, by year, 1994–2026; select a year to sortFederal Register data

Source: federalregister.gov API, documents of type Rule and Proposed Rule whose CFR references list the part, yearly counts, retrieved October 24, 2026. Corrections and technical amendments count as documents.

Data table

Federal Register rules and proposed rules citing each part, 1994–2026 (years with zero omitted)
Part	Total	Documents by year
21 CFR 1	180	1996: 2, 1997: 1, 1998: 1, 1999: 2, 2001: 2, 2002: 2, 2003: 14, 2004: 16, 2005: 8, 2006: 2, 2008: 4, 2009: 1, 2010: 4, 2011: 4, 2012: 4, 2013: 19, 2014: 12, 2015: 11, 2016: 17, 2017: 6, 2018: 10, 2019: 2, 2020: 13, 2021: 2, 2022: 8, 2023: 6, 2024: 4, 2025: 2, 2026: 1
21 CFR 11	47	1997: 1, 2000: 1, 2003: 1, 2004: 1, 2005: 1, 2006: 2, 2011: 4, 2014: 2, 2015: 10, 2016: 10, 2017: 6, 2018: 3, 2019: 1, 2020: 2, 2021: 1, 2023: 1
21 CFR 101	327	1994: 5, 1995: 16, 1996: 36, 1997: 30, 1998: 33, 1999: 18, 2000: 15, 2001: 4, 2002: 8, 2003: 9, 2004: 6, 2005: 12, 2006: 9, 2007: 11, 2008: 8, 2009: 2, 2010: 4, 2011: 8, 2012: 2, 2013: 1, 2014: 10, 2015: 11, 2016: 23, 2017: 9, 2018: 11, 2019: 6, 2020: 6, 2021: 1, 2022: 4, 2023: 4, 2024: 2, 2025: 3
21 CFR 111	28	1995: 2, 1997: 4, 1999: 2, 2000: 1, 2003: 8, 2007: 3, 2008: 2, 2015: 1, 2016: 3, 2018: 2
21 CFR 117	52	2013: 11, 2014: 3, 2015: 5, 2016: 9, 2017: 4, 2018: 7, 2019: 3, 2020: 2, 2022: 2, 2024: 2, 2025: 2, 2026: 2
21 CFR 170	34	1995: 4, 1996: 4, 1997: 3, 2000: 3, 2002: 2, 2004: 1, 2006: 1, 2007: 2, 2010: 2, 2015: 1, 2016: 2, 2017: 2, 2019: 1, 2022: 3, 2023: 1, 2024: 1, 2026: 1
21 CFR 190	6	1996: 1, 1997: 1, 2001: 1, 2010: 1, 2022: 1, 2023: 1
7 CFR 205	162	1997: 1, 1998: 4, 2000: 5, 2001: 1, 2003: 4, 2005: 5, 2006: 6, 2007: 8, 2008: 6, 2009: 1, 2010: 10, 2011: 11, 2012: 14, 2013: 8, 2014: 4, 2015: 7, 2016: 7, 2017: 10, 2018: 9, 2019: 7, 2020: 6, 2021: 5, 2022: 9, 2023: 7, 2024: 3, 2025: 2, 2026: 2

Labeling (Part 101) appears in 327 documents; the supplement CGMP rule (Part 111) in 28. See the CFR atlas.

In this section

Nine pages cover the pathways, the evidence and the legal questions behind them

All categories

Legal status and questions for counsel

Category, drug exclusion, Proposition 65, sanctions, Lacey Act, CITES and IP. Not legal advice.

Legal status →

Dietary supplements

NDIN strategy and dossiers

Eligibility, the 75-day notification, FDA's 2026 guidance, GLP and master files.

NDIN pathway →

Quality

USP, ICH and certificates of analysis

Botanical standards, relying on a supplier's COA (21 CFR 111.75), supplier scoring.

Quality standards →

Safety science

Toxicology and exposure

Nonclinical studies, reference points, exposure margins, ADME and interactions.

Toxicology →

Human evidence

Clinical research

Study design, power, ethics oversight, registration and IND triggers.

Clinical research →

Foods and beverages

GRAS and food ingredients

Food additive petitions, GRAS notices, the 2026 proposal, color additives.

Food pathways →

Cosmetics

Cosmetic safety and MoCRA

Registration, listing, safety substantiation, adverse events, cosmetic or drug.

Cosmetics →

All agencies

CFR atlas

Every federal rule set from field to label, with a part finder.

CFR atlas →

Outside the U.S.

International market access

EU novel foods, Canadian licences, Australian listing, Japanese function claims.

International →

Compliance map

The same botanical extract faces a different statute, premarket step and manufacturing rule in each U.S. product category

Intended use, shown by labeling and marketing, decides the category. FDA approves drugs and color additives before marketing; it does not approve dietary supplements, dietary ingredients or cosmetics.

Intended use routes a botanical extract into one of five U.S. lanes, and a disease claim can move it into the drug laneStatute and regulation

Sources: 21 U.S.C. 321(f), (g), (i), (s), (ff); 350b; 355(a); 355h; 379e (Cornell LII, accessed Oct 22, 2026). 21 CFR Parts 1 Subpart L, 101, 111, 117, 170, 171, 190, 210, 211, 312, 314, 701, 740 (eCFR, current to Oct 21, 2026). FDA Small Entity Compliance Guide for Part 111 (2010) on ingredient suppliers. FDA, “FDA Authority Over Cosmetics” (content current as of Nov 18, 2025).

Full compliance map (text version)

U.S. compliance map by product category: statute, key regulations, premarket requirement, quality regime and claims rules
Category	Statute and definition	Key regulations	Premarket requirement	Quality regime	Claims rules
Dietary supplements	FD&C Act § 201(ff); new dietary ingredients under § 413 (21 U.S.C. 350b)	21 CFR Part 111 (CGMP); 21 CFR 190.6 (NDI notification); 21 CFR 101.93 (statements); Part 1, Subpart L (FSVP) for importers	No FDA approval. A notification at least 75 days before marketing for a new dietary ingredient, unless every ingredient meets the food-supply exception	Part 111 for anyone who manufactures, packages, labels or holds a dietary supplement	Structure/function statements: notify FDA within 30 days of first marketing, carry the required disclaimer, hold substantiation. A disease claim makes the product a drug unless it is an authorized health claim
Bulk dietary ingredients	Dietary ingredients are food under the FD&C Act	21 CFR Part 117 (CGMP; hazard analysis and preventive controls unless exempt)	The NDI manufacturer or distributor may file the NDIN	Generally Part 117. Part 111 applies if the ingredient goes to a firm that only packages or labels it, or directly to consumers	Marketing copy, websites included, can establish an intended use that makes the product a drug
Conventional foods and beverages	§ 201(f) food; § 201(s) food additive; § 409; § 721 color additives	21 CFR Part 117; Parts 170–171 (food additives, GRAS); Part 101 (labeling); Parts 70–74 (color additives)	A food additive needs an FDA regulation, obtained by petition, unless its use is GRAS or otherwise excluded. Color additives must be listed. GRAS notification is voluntary today; a rule to make it mandatory was proposed in August 2026	Part 117	Nutrient content and health claims follow 21 CFR 101.13 and 101.14. A claim to treat or prevent disease outside an authorized health claim can make the food a drug
Cosmetics	§ 201(i) cosmetic; Chapter VI as amended by MoCRA (2022)	21 CFR Part 701 (labeling); Part 740 (warnings); color additive listings	No FDA approval except for color additives. Facility registration and product listing under MoCRA	MoCRA requires a GMP rule; none has been proposed. FDA has a draft cosmetic GMP guidance	Intended use decides cosmetic or drug. Claims to treat disease or to affect the structure or function of the body make it a drug
Drugs, including OTC	§ 201(g) drug; § 505 new drug approval; § 505G OTC monographs	21 CFR Parts 210/211 (CGMP); Part 312 (IND); Part 314 (applications)	A new drug needs an approved application. Certain OTC drugs may be marketed under monograph conditions	Parts 210/211; a drug made without them is adulterated (§ 501(a)(2)(B))	Claims must match the approved application or the monograph

Regulatory intelligence

Since March 2024 FDA finalized two NDI guidances, proposed mandatory GRAS notices and withdrew the talc testing proposal

Since 2022 most tracked actions concern cosmetics; two cosmetic rules are overdue and the GRAS proposal is open for commentStatus as of Oct 22, 2026

Federal Register documents, FDA guidance pages, FDA's MoCRA page and eCFR, as cited in the table below. The PFAS report (Dec 29, 2025) and earlier deadlines are listed in the table.

Show the table (20 rows): Regulatory intelligence tracker, newest first, with status as of October 22, 2026

Regulatory intelligence tracker, newest first, with status as of October 22, 2026
Date	Document	Status	What it means for ingredient developers
Oct 19–20, 2026	NDI notifications: identity and safety information about the NDI (91 FR 66336; docket FDA-2025-D-6501)	Final guidance	Finalizes Sections VI.A–VI.C of the 2016 revised draft as a stand-alone document. The rest of that draft, including when a notification is required, remains draft.
Aug 11, 2026	Substances Generally Recognized as Safe (91 FR 51834; docket FDA-2025-N-3262)	Proposed rule	Would make GRAS notices mandatory, with exceptions and a time-limited streamlined route for substances already in commerce. Comments are due December 9, 2026. Self-affirmed GRAS remains lawful today.
Dec 29, 2025	Cosmetic GMP final rule (FD&C Act § 606)	No proposed rule	The statutory deadlines for a proposed rule (Dec 29, 2024) and a final rule (Dec 29, 2025) have passed with no rule published. FDA's draft cosmetic GMP guidance is the current reference.
Dec 29, 2025	FDA report on PFAS in cosmetic products (MoCRA § 3506)	Published	A required report on PFAS use and safety evidence in cosmetics; it creates no new obligation by itself.
Nov 28, 2025	Testing methods for asbestos in talc-containing cosmetics (proposed Dec 27, 2024, 89 FR 105490; withdrawn 90 FR 54603)	Withdrawn	No replacement proposal has been published. FDA cited comments that “warrant further consideration and assessment.”
Mar 10, 2025	HHS directive to explore eliminating the self-affirmed GRAS pathway	Policy announcement	A direction to FDA to explore rulemaking; it led to the August 2026 proposal and changed no rule by itself.
Dec 29, 2024	Cosmetic label contact information (FD&C Act § 609(a))	Statute in effect	Labels must carry domestic contact information for adverse-event reports.
Jul 1, 2024	Cosmetic facility registration and product listing (§ 607)	Statute in effect	FDA's enforcement-discretion period ended; registration renews every two years and listings are updated annually.
Jun 29, 2024	Fragrance allergen labeling rule (§ 609(b))	No proposed rule	The statutory deadline for a proposed rule has passed; no proposal has been published.
Apr 4, 2024	NDIN master files for dietary supplements (89 FR 23599; docket FDA-2024-D-0706)	Draft guidance	Describes master files and letters of authorization. Not for implementation; no final version has been issued.
Mar 5–6, 2024	NDI notification procedures and timeframes (89 FR 16003; docket FDA-2023-D-5280)	Final guidance	Submission mechanics, FDA response letters, incomplete notifications, confidentiality and pre-submission meetings.
Dec 29, 2023	Cosmetic safety substantiation (§ 608) and serious adverse-event reporting (§ 605)	Statute in effect	The responsible person must keep records of adequate safety substantiation and report serious adverse events within 15 business days.
Dec 29, 2022	Modernization of Cosmetics Regulation Act (Pub. L. 117-328)	Statute	In FDA's words, “the most significant expansion of FDA's authority to regulate cosmetics” since the FD&C Act of 1938.
Dec 9, 2022	IND exemptions for studies of lawfully marketed foods, supplements and cosmetics (87 FR 75536)	Proposed rule	Comments closed March 9, 2023; no final rule has been published.
Aug 17, 2016	GRAS notification final rule (81 FR 54960; 21 CFR Part 170, Subpart E)	Final regulation	The voluntary GRAS notice procedure in force today. FDA responds within 180 days of filing, extendable by 90 days.
Aug 12, 2016	NDI notifications and related issues, revised draft (81 FR 53486; docket FDA-2011-D-0376)	Draft guidance	Remaining sections cover what an NDI is, “chemically altered,” definitions and the decision tree. Revised October 2026 to show what was finalized.
Nov 27, 2015	Foreign Supplier Verification Programs (80 FR 74226; 21 CFR Part 1, Subpart L)	Final regulation	Importers verify foreign suppliers; § 1.511 modifies the duties for dietary supplements and their components. See the FSVP summary under global ingredients.
Sep 17, 2015	Preventive controls for human food (80 FR 55908; 21 CFR Part 117)	Final regulation	Applies to dietary-ingredient operations; the § 117.5(e) exemption covers finished supplements made under Part 111, not bulk ingredients.
Jun 25, 2007	Dietary supplement CGMP (72 FR 34752; 21 CFR Part 111)	Final regulation	Applies to anyone who manufactures, packages, labels or holds a dietary supplement.
Oct 25, 1994	Dietary Supplement Health and Education Act (Pub. L. 103-417)	Statute	Created FD&C Act § 413: an ingredient not marketed before October 15, 1994 is a new dietary ingredient.

Sources: Federal Register documents cited in each row (federalregister.gov API, Oct 22, 2026); FDA guidance pages and FDA's MoCRA page (content current as of Aug 10, 2026); eCFR (current to Oct 21, 2026); HHS press release, Mar 10, 2025. Full citations under Sources below.

Explanation, details and sources

Status as of October 22, 2026, checked against the Federal Register, eCFR and FDA pages. Final guidance is still a recommendation; a proposed rule binds no one until finalized.

Enforcement record

One in five dietary-supplement food recall records since 2012 was Class I, the most serious class

FDA food recall records whose product description says “dietary supplement”, by year and recall classopenFDA data

Source: openFDA food enforcement reports API, search of product descriptions for “dietary supplement”, 585 records in 244 recall events, data last updated October 14, 2026, retrieved October 24, 2026. Class definitions: 21 CFR 7.3(m).

Data table

Food recall records with “dietary supplement” in the product description, by report year and class
Year	Class I	Class II	Class III	Total
2012	4	5	3	12
2013	12	67	28	107
2014	33	26	0	59
2015	1	39	4	44
2016	9	32	11	52
2017	15	94	5	114
2018	7	16	4	27
2019	1	10	6	17
2020	4	8	11	23
2021	16	12	5	33
2022	1	8	1	10
2023	1	14	6	21
2024	2	5	3	10
2025	2	13	23	38
2026	9	9	0	18
Total	117	358	110	585

Class I means a reasonable probability of serious adverse health consequences or death (21 CFR 7.3(m)(1)).

Explanation, details and sources

A record is one product in a recall event, so one event can contribute several records. The text search finds products whose description includes the words “dietary supplement”; products described otherwise are missed, and drug recalls of products sold as supplements are in openFDA's drug data (see legal status). openFDA states that its data are not validated for clinical decisions. Reasons named in the records, by keyword: undeclared allergen 157 records, microbial contamination 46, lead or other metals 13.

Precision

Twelve pairs that are often treated as equivalent, and are not

Twelve distinctions EUTECNIQ would keep in every proposal and reportRegulation FDA guidance

Sources: 21 CFR 190.6(f); FDA NDI procedures guidance (March 2024); FDA NDIN master-file draft guidance (April 2024); 21 CFR 170.30 and 21 U.S.C. 321(s); FDA MoCRA page; ILAC-P8:11/2023 on accreditation scope; 21 CFR 111.1, 210.1, 211.1; FDA guidance statements on nonbinding effect.

Text version of the twelve pairs

NDIN acknowledgement≠FDA approval or a finding of safety
FDA silence after 75 days≠A finding that the ingredient is safe (21 CFR 190.6(f))
NDIN master file≠An FDA review, authorization or endorsement
GRAS conclusion≠Authorization for every use, product category or country
Cosmetic registration or listing≠FDA approval of the product
ISO/IEC 17025 accreditation≠GMP compliance, or competence outside the accredited scope
Supplement CGMP (21 CFR Part 111)≠Pharmaceutical CGMP (21 CFR Parts 210/211)
Traditional use≠Clinical proof of benefit
Preclinical biological activity≠Efficacy in people
Experimental formulation improvement≠Proven safety of the new form
Final FDA guidance≠A binding requirement
U.S. regulatory status≠Authorization in the EU, Canada, Australia or Japan

Risk-to-evidence framework

Beyond a common baseline, an ingredient's own risk profile should decide which evidence is generated

Every ingredient starts from the same baseline; each risk driver adds evidence at specific stages, and four add a stop-or-go gateEUTECNIQ proposal

Framework: EUTECNIQ proposal drawing on FDA final guidance (October 2026), Sections IV, V.3, VII, VIII.2, IX and Appendix A; 21 CFR 190.6; Parts 111 and 117. The full table below lists each evidence item. A planning tool, not a safety assessment.

Full framework: every risk driver, the evidence it adds and its decision gate

Risk-to-evidence framework table
Risk driver	Evidence added, by stage	Decision gate	Basis
Baseline (every ingredient)	Identity confirmed against authenticated reference material; written specifications Contaminant limits and test methods suited to the source; supplier qualification Review of published toxicology and history of use Highest total daily intake under the proposed conditions of use (EDI) Adverse-event information from published use; human studies only if a gap remains Legal category, pathway and claims review		21 CFR 190.6; Parts 111/117; FDA final guidance IV, VI, IX
Several species, chemotypes or plant parts trade under the same name	Orthogonal identity tests (microscopy plus a chromatographic fingerprint) and named adulterant species excluded	Stop if identity cannot be confirmed or an adulterant cannot be excluded	FDA final guidance IV.10
Composition varies with region, season or harvest	Multi-lot compositional data; marker ranges and specification limits set from batch data Intake of key constituents estimated at the upper end of the range		FDA final guidance IV.2, IV.13
Extraction or purification concentrates or changes the material	Process description, concentration ratio and marker levels relative to the starting material Comparability with the material in existing studies; bridging rationale or new studies Possible “chemically altered” question for NDI status, referred to counsel		FDA final guidance IV.13, VII.4; 2016 draft IV.B
Metals, pesticides or mycotoxins plausible for the crop or region	Validated methods and limits for elemental contaminants, pesticide residues and mycotoxins; testing frequency set by risk		FDA final guidance IV.13; EUTECNIQ practice
High microbial load in the raw material or a water-based process	Microbial limits, and a process step or test that controls them		EUTECNIQ practice
Process residues: solvents, processing aids or degradation products	Specifications for residual solvents other than water Stability-indicating methods for degradation products		FDA final guidance IV.13
Toxins known in the same species, genus or family	Targeted assays showing the absence or level of those toxins Hazard characterization for any toxin that is present	Stop or reformulate if the toxin cannot be controlled	FDA final guidance IV.12
Intake above documented historical exposure, or no history of use	Studies from FDA's Standard Safety Testing Table to fill the gap, such as a genetic toxicity battery and a 90-day study NOAEL-based margin of safety, ADI and EDI/ADI ratio		FDA final guidance VII, IX, Appendix A
Genotoxicity alert or an equivocal genetic toxicity result	Follow-up testing; a positive result calls for further studies such as carcinogenicity	Go or no-go before further investment	FDA final guidance VII.6
Nanoscale or other engineered delivery form	Particle or droplet size distribution and its stability Nano-specific safety evidence; data on the conventional form alone are unlikely to suffice Contact FDA before submitting a notification		FDA final guidance VIII.2
Pharmacologically active constituents likely taken with medicines	In vitro screening for metabolizing-enzyme and transporter inhibition and induction Clinical interaction study if screening shows a relevant signal Label warnings considered	Label, restrict the population or stop if a relevant interaction is confirmed	EUTECNIQ practice
Intended for, or likely used in, pregnancy, lactation or children	One-generation reproductive study becomes relevant Intake per kilogram of body weight for the target group Population limits in labeling		FDA final guidance VII.1, Appendix A
Combined with other active ingredients in the finished product	Margin of safety for each ingredient and for the finished product Tolerability of the finished product where gaps remain Each new dietary ingredient addressed in the safety narrative		FDA final guidance V.3, IX

Explanation, details and sources

Select what applies to an ingredient. The framework shows which stages of development gain evidence requirements and where a stop-or-go decision falls. It is a planning tool, not a safety assessment.

Who does what

EUTECNIQ would plan and integrate the evidence; specialist partners would generate regulated data and counsel would give legal opinions

Each activity stays with the party qualified and accountable for itProposed division of work

EUTECNIQ proposal. EUTECNIQ has no laboratory, studies or submissions of its own.

Text version of the division of work

Proposed division of regulatory and safety work between EUTECNIQ, external partners and the client or counsel
Activity	EUTECNIQ (proposed)	Qualified external partner	Client or counsel
Pathway assessment	Scientific facts: identity, history, process, intended use		Counsel gives the legal conclusion
Identity, characterization and contaminants	Methods, specifications, data review; in-house testing once a laboratory exists	Accredited contract laboratories until then
Nonclinical toxicology	Study selection, protocol review, monitoring, interpretation	Contract research organizations, GLP where chosen	Client funds and owns the data
Human studies	Design input and safety-endpoint planning	Clinical sites and IRBs	Sponsor
Dossier and safety narrative	Drafting, calculations, document control		Notifier signs and submits
Submission and FDA contact	Technical support		Notifier or its agent

Mapping an ingredient's pathway?

EUTECNIQ is in formation and welcomes early conversations with ingredient suppliers, brands and scientific partners about pathway and evidence planning.

Start a conversation NDIN pathway