21 CFR 1114 & 1107: What FDA Requires From Your Nicotine Supplier

On October 5, 2021, FDA published two final rules that permanently changed the documentation requirements for every nicotine product sold in the United States. 21 CFR Part 1114 (86 FR 55300) governs Premarket Tobacco Product Applications. 21 CFR Part 1107 (86 FR 55224) governs Substantial Equivalence Reports. Both took effect November 4, 2021. Updated submission forms became mandatory January 2, 2026.

These are not new proposals. They are the law. And on February 26, 2026, the Fifth Circuit Court of Appeals upheld the PMTA rule in a unanimous panel decision, eliminating the last realistic legal challenge to the framework.

If you manufacture nicotine pouches, e-liquids, or NRT products in the US, your PMTA or SE submission must name every ingredient supplier by name, list every CAS number, and document purity grades with acceptance ranges. A supplier change triggers a new filing. Incomplete ingredient documentation is one of the most common reasons PMTAs receive deficiency letters.

Here is what these two rules actually require, and what your nicotine supplier needs to deliver.

Two Rules, One Compliance Framework

FDA finalized both rules simultaneously to create an integrated premarket review system. Understanding which rule applies to your product determines which documentation pathway you follow.

21 CFR Part 1114: The PMTA Rule

The PMTA pathway applies to all electronic nicotine delivery systems (ENDS), nicotine pouches, and any new tobacco product that cannot demonstrate substantial equivalence to a predicate. For ENDS products specifically, PMTA is the only route to market. There is no SE pathway, no product standard, and no fixed numerical threshold for the "appropriate for the protection of public health" (APPH) standard.

The rule establishes content, format, and review procedures across five subparts:

• Subpart B defines submission criteria, content requirements, and supplemental application procedures
• Subpart C governs FDA review and action timelines
• Subpart D covers postmarket restrictions and reporting
• Subpart E addresses record retention, confidentiality, and electronic submission requirements

Every PMTA must include: physical product specifications, all components and ingredients, additives and constituents, toxicological profiles, manufacturing details, packaging and labeling information, consumer perception research, and marketing plans. The application must demonstrate that marketing the product is appropriate for the protection of public health under Section 910(c)(2) of the FD&C Act.

21 CFR Part 1107: The SE Rule

The Substantial Equivalence pathway applies to cigarettes, smokeless tobacco, cigars, hookah tobacco, and roll-your-own tobacco. Applicants must demonstrate that the new product either has the same characteristics as a predicate product or that any differences do not raise different questions about public health.

SE Reports require documentation of all tobacco, substances, compounds, and additives contained within or added to tobacco, paper, filter, or any other component. This includes compounds "reasonably expected to be formed through chemical reaction during manufacturing," such as nicotine-related nitrosamines.

The scope extends to container closure systems, even when externally sourced, and to software or assembly of materials that affect product performance, composition, constituents, or characteristics.

What Changed on January 2, 2026

As of January 2, 2026, all PMTA and SE submissions must use FDA's updated web-based application forms. Applications submitted in outdated formats are subject to Refuse to Accept (RTA) decisions. Any manufacturer updating or filing an application must work in the new format. This deadline is not discretionary.

The Ingredient Documentation Requirements That Cascade to Your Supplier

Both rules create documentation obligations that flow directly upstream to ingredient suppliers. When your customer files a PMTA or SE Report, every ingredient in your product must be documented to the following specifications.

What FDA Requires for Every Ingredient

For each ingredient in a PMTA or SE submission, the application must include:

1. Ingredient name (IUPAC or common name)
2. CAS number for chemical identification
3. Purity and grade with documented acceptance ranges
4. Supplier name identified in the application
5. Target quantity and range with unit of measure (mg/mL or mg/unit)
6. Contaminant limits with qualitative and quantitative confirmation

For nicotine specifically, FDA expects USP/EP grade documentation as the standard in PMTA ingredient submissions. The Certificate of Analysis must include grade certification, assay percentage, and full impurity profile. At the February 2026 FDA roundtable with small ENDS manufacturers, the agency confirmed that nicotine specifications must include "clear targets, acceptance ranges, batch release data, and in-process controls."

This is not a suggestion. FDA stated at that same roundtable that "quality systems must be demonstrably operational" with completed documentation proving the system functions in actual manufacturing.

HPHC Testing and Characterization

The nicotine ingredient's contribution to the finished product's Harmful and Potentially Harmful Constituents (HPHC) profile must be documentable. This includes Tobacco Specific Nitrosamines (TSNAs) and any carbonyls or other HPHCs relevant to the specific product format.

PMTA submissions must include validated HPHC testing methods with laboratory accreditation information. The testing burden does not end at submission: stability data covering beginning, middle, and end of the claimed shelf life must demonstrate that ingredient specifications hold over time.

The Supplier Change Trigger

This is the requirement that catches manufacturers off guard. Under both rules, changes in supplier materials or ingredient sourcing that affect product characteristics require new premarket notification. You cannot swap nicotine suppliers mid-production and maintain the same marketing authorization. Every supplier named in the application is locked into that authorization unless a new filing is submitted and accepted.

For manufacturers running nicotine salt formulations across multiple product lines, this means the choice of supplier is not just a procurement decision. It is a regulatory commitment that persists for the life of the product authorization. This is one reason why choosing a nicotine supplier requires evaluating regulatory readiness alongside price and lead times.

What the Fifth Circuit Ruling Means for Compliance Planning

On February 26, 2026, the Fifth Circuit Court of Appeals upheld the 2021 PMTA final rule in a unanimous panel decision. The ruling addressed two key challenges from industry:

Health-risk investigation disclosure is mandatory. The court found that the requirement to disclose all known health-risk investigation information is mandated by the Tobacco Control Act itself. FDA cannot waive it by regulation, and applicants cannot avoid it. Every PMTA must include this information.

No relief for small manufacturers. The court found FDA's Regulatory Flexibility Act certification reasonable. The American Vapor Manufacturers Association had lobbied for a streamlined process for small manufacturers. FDA rejected those requests in the final rule text, and the Fifth Circuit agreed.

The practical consequence: there is no pending legal challenge that could weaken these documentation requirements. Manufacturers and suppliers should plan for these rules as permanent infrastructure. For a detailed breakdown of how these requirements affect your PMTA filing, see PMTA Requirements: How Your Nicotine Source Affects FDA Submissions.

Tobacco Product Master Files: Your Supplier's Direct Line to FDA

A Tobacco Product Master File (TPMF) is a confidential submission that an ingredient supplier files directly with FDA. It contains proprietary ingredient and composition data that the manufacturer then cross-references in their PMTA or SE Report.

The benefit is structural. A supplier with a current TPMF on file allows manufacturers to satisfy ingredient documentation requirements without requiring the supplier to disclose trade secrets to the applicant or the public. The manufacturer references the TPMF; FDA reviews the underlying data directly.

A supplier without a TPMF forces the manufacturer to independently document all ingredient details, typically with less precision and no confidentiality protection for the supplier's formulations. In a regulatory environment where FDA scrutinizes every data point in the ingredient section, that gap is consequential.

How FDA Pre-Approval Inspections Trace Back to Your Supplier

FDA pre-approval inspections examine the entire manufacturing chain. The inspection scope includes:

• Master Manufacturing Records (MMRs) documenting every production step
• Batch Production Records (BPRs) for each lot
• Non-conformance investigations and root cause analyses
• Corrective and Preventive Actions (CAPAs) for out-of-specification materials
• Quality Unit assessments of incoming component suitability

Every one of these inspection targets requires supplier documentation. When FDA reviews your Quality Unit's assessment of incoming nicotine ingredients, they expect to see CoAs with batch-level traceability, specifications with acceptance ranges, and evidence that out-of-spec materials were caught and handled.

If your nicotine supplier cannot produce this documentation on demand, your manufacturer customer faces an inspection finding. That finding goes into the PMTA review record. It does not go away.

The Pipeline of Rules That Will Tighten Further

21 CFR 1114 and 1107 are the foundation, but FDA has proposed additional rules that will increase documentation requirements:

Tobacco Product Manufacturing Practices (TPMP). Proposed in March 2023, this rule would introduce GMP-like standards including design controls, quality systems, and full traceability of all components, parts, ingredients, additives, and materials. Comment period closed October 2023. Finalization is expected to advance in 2026.

ACE Submission Tracking Number. This proposed rule would require importers to provide a PMTA Submission Tracking Number at the port of entry through the Automated Commercial Environment system. Every physical shipment would link to a specific regulatory authorization.

Administrative detention. This proposed rule would allow FDA to detain suspected adulterated or misbranded tobacco products during inspections.

Congress has appropriated at least $200 million in tobacco user-fee funds toward enforcement against unauthorized products, including enhanced port-of-entry controls and a federal multi-agency task force. The enforcement trajectory is toward more scrutiny, not less. Manufacturers whose supply chain documentation is already audit-ready will navigate this environment with fewer disruptions.

Building a Supplier Documentation Package That Survives FDA Review

Based on the requirements in both finalized rules and the direction of proposed regulations, a compliant nicotine supplier documentation package should include:

Document	Requirement Source	Purpose
Certificate of Analysis (batch-level)	21 CFR 1114, ENDS PMTA Guidance	Purity, grade, impurity profile per lot
CAS number and IUPAC name	21 CFR 1114 §1114.7, 21 CFR 1107	Chemical identity for FDA submission
Acceptance ranges and targets	FDA Feb 2026 roundtable guidance	Batch release specifications
HPHC characterization data	21 CFR 1114, ENDS PMTA Guidance	Nicotine contribution to HPHC profile
Stability data	21 CFR 1114, ENDS PMTA Guidance	Shelf-life specification maintenance
GMP/quality system documentation	21 CFR 1114, TPMP (proposed)	Manufacturing partner audit evidence
Tobacco Product Master File	FDA TPMF program	Confidential supplier data for cross-reference
Supply chain traceability records	21 CFR 1114, TPMP (proposed)	Raw material origin through delivery

A supplier that can deliver this package on request, with batch-level granularity and current certifications, reduces your regulatory risk at every stage: initial filing, FDA information requests during review, and pre-approval inspection.

A supplier that cannot is a gap in your application that FDA will find.

NicAlliance provides USP/EP grade nicotine and nicotine salt formulations with full documentation support for PMTA and SE submissions. Every batch ships with a Certificate of Analysis, and our US-based supply chain with a certified manufacturing partner is built for the traceability standards these rules require. If your current supplier documentation has gaps, request a sample with full CoA and compare it against what FDA expects.

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