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. On February 26, 2026, the Fifth Circuit Court of Appeals upheld the PMTA rule in a unanimous panel decision. That is not the end of the litigation, though. A separate small-business challenge to the same rule is live and on appeal, and the section below explains what it does and does not put at risk.

If you manufacture nicotine pouches, e-liquids, or NRT products in the US, your PMTA or SE submission must name every ingredient supplier, list every CAS number, and document purity grades with acceptance ranges. A supplier change does not automatically trigger a new filing, but a change that alters the product's characteristics does, and proving which one you have is on you. Incomplete ingredient documentation is a common reason applications draw deficiency letters, although FDA does not publish a breakdown of deficiency causes.

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

In December 2025 FDA launched web versions of its premarket application forms (Forms FDA 4057, 4057a, 3965 and 3965a). As of January 2, 2026, applicants must use the current version of those forms.

Two clarifications matter here, because this deadline is often described more absolutely than it is. The web-based versions are not compulsory: updated PDF versions of the same forms remain available and can still be filed through CTP's Document Control Center or uploaded via eSubmitter. What is no longer accepted is the superseded version of the form. And FDA's stated position is that it generally intends to refuse to accept applications that do not use the latest forms or do not complete them properly. That is an enforcement intention rather than a statutory bar, but it is not a gate worth testing.

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

One distinction is worth drawing carefully, because it is usually blurred. The rule does not mandate a pharmacopoeial grade. 21 CFR 1114.7(i) requires the applicant to state the purity or grade and the supplier. It does not say that grade must be USP or EP. USP/EP grade documentation is the reference point most applicants use because it gives the stated grade an externally defined meaning a reviewer can check against a published monograph, rather than a number the applicant defined for itself. That is a strong practical reason to specify it, not a legal one.

A Certificate of Analysis that does the job carries grade certification, assay percentage, and the full impurity profile. At FDA's February 2026 roundtable with small ENDS manufacturers, the agency pressed the same point: nicotine specifications should carry clear targets and acceptance ranges, supported by real batch release data and in-process controls.

The roundtable readout was equally blunt about the difference between a quality system on paper and one in operation. SOPs and templates are not enough on their own. FDA expects completed documentation showing the system worked 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 point that catches manufacturers off guard, and it is narrower than the way it usually gets repeated. Changing suppliers is not itself a regulated event. What is regulated is a modification to the product. Under section 910(a)(1) of the FD&C Act, a change in a component, part, constituent, ingredient, or in the content, delivery or form of nicotine creates a new tobacco product that needs its own authorization. A supplier change that carries no change in the material's characteristics does not, on the face of the statute, require a new filing.

The practical problem is evidentiary. You have to be able to demonstrate that nothing moved, specification by specification, against a filed application that names the original supplier. That is why a supplier switch should be treated as something you evidence against the filed specification, not as a free procurement move.

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 challengers, a group of e-liquid manufacturers and the United States Vaping Association, argued that FDA had improperly leaned on the economic analysis from its 2016 deeming rule and had failed to weigh less burdensome alternatives. The panel rejected both arguments.

The practical consequence is narrower than "the rule is now untouchable." The Fifth Circuit closed one line of attack. It did not close all of them. In June 2026 the US District Court for the Middle District of Florida granted a preliminary injunction in Zest Brands LLC v. FDA, finding the plaintiffs likely to succeed on a claim that FDA's small-business certification for this same 2021 PMTA rule was facially false under the Regulatory Flexibility Act. That relief runs only to those plaintiffs' own products, and FDA has appealed to the Eleventh Circuit.

Two things follow. Nothing in that case touches the ingredient documentation requirements themselves, and no court has stayed them, so the sourcing obligations described here are the ones in force today. But the framework is under live challenge, so "permanent infrastructure" overstates it. Build to the rule as written, and watch the Eleventh Circuit. 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:

Each of the three below is a proposal. None of them is in force, and none of them creates an obligation you have to meet today.

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. The comment period closed in 2023. As of August 2026 FDA has not issued a final rule, more than three years after the proposal.

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, linking every physical shipment to a specific regulatory authorization. Comments closed October 15, 2024. No final rule has issued as of August 2026, and supplying the tracking number remains optional.

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

Section 772 of the FY2026 appropriations legislation directs FDA to spend at least $200 million of tobacco user-fee collections on ENDS enforcement, including enhanced port-of-entry controls and $2 million for a DOJ-led 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:

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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