PMTA After FDA v. Wages and White Lion: What Applicants Need Now

The U.S. Supreme Court’s decision in FDA v. Wages and White Lion Investments, LLC, issued on April 2, 2025, is an important development for companies seeking FDA authorization for new tobacco products.

The case involved FDA’s denial of marketing applications for flavored electronic nicotine delivery system (ENDS) products. The Supreme Court ultimately vacated the Fifth Circuit’s judgment and held that FDA’s denial orders were sufficiently consistent with the agency’s earlier guidance regarding scientific evidence, comparative efficacy, and device type.

For PMTA applicants, the decision reinforces an important practical lesson:

Applicants need to build a complete, product-specific scientific record that directly addresses the statutory Appropriate for the Protection of the Public Health (APPH) standard.

The decision does not create a new PMTA pathway or eliminate FDA’s existing requirements.

And in 2026, applicants also need to account for another important development: FDA has announced that it intends to evaluate changes to the current PMTA regulatory framework, potentially including new rulemaking. Until those changes are made, FDA says it will continue processing PMTAs under the current statutory and regulatory framework.

What Was FDA v. Wages and White Lion About?

The case involved applications submitted by manufacturers seeking authorization for flavored e-liquids used with open-system electronic cigarettes.

FDA denied the applications after determining that the manufacturers had not provided sufficient scientific evidence demonstrating that marketing the products would be appropriate for the protection of the public health.

The applicants challenged the denials, arguing in part that FDA had applied standards that were inconsistent with its earlier guidance.

The Fifth Circuit agreed with the applicants and found that FDA had acted arbitrarily and capriciously.

The Supreme Court reversed that conclusion.

The Court determined that FDA’s denial orders were sufficiently consistent with its prior guidance regarding:

• Scientific evidence
• Comparative efficacy
• Device type

The Court also recognized FDA’s broad discretion under the Tobacco Control Act to determine what types of scientific evidence may be sufficient to demonstrate that a product meets the APPH standard.

What Did the Supreme Court Actually Decide?

The decision is important, but it should not be interpreted as a blanket approval of FDA’s PMTA practices.

The Court held that the particular FDA denial orders challenged in the case did not violate the Administrative Procedure Act under the change-in-position doctrine.

The Court explained that agencies may change policies when they provide a reasoned explanation, acknowledge the change, and consider serious reliance interests where applicable.

In this case, however, the Court concluded that FDA’s decisions were sufficiently consistent with its earlier guidance.

This distinction matters for applicants.

Wages and White Lion does not mean that FDA can deny a PMTA without explaining its reasoning.

It also does not mean that applicants can submit less scientific evidence.

Instead, the decision reinforces the importance of understanding the evidence FDA expects and connecting that evidence to the specific product being reviewed.

The APPH Standard Remains the Core of PMTA Review

Under the Tobacco Control Act, FDA must determine whether allowing a new tobacco product to be marketed would be appropriate for the protection of the public health.

FDA considers the risks and benefits to the population as a whole.

This includes both:

• People who currently use tobacco products
• People who do not currently use tobacco products

FDA also considers whether current tobacco users are more or less likely to stop using tobacco products and whether non-users are more or less likely to begin using tobacco products if the proposed product is marketed.

This means a PMTA cannot focus exclusively on whether a product is potentially less harmful than cigarettes.

The applicant must present evidence addressing the product’s overall population-level impact.

What Does This Mean for PMTA Applicants?

Applicants should build their submissions around a clear scientific and regulatory argument.

The application should allow FDA to understand:

What is the product?

Who will use it?

How will people use it?

What are the product’s risks?

What potential benefits exist for current tobacco users?

What is the likelihood of initiation among non-users?

What evidence supports these conclusions?

How will marketing and distribution affect the population-level balance?

The more clearly these questions are connected, the easier it is for FDA to evaluate the application.

Scientific Evidence Needs to Be Product-Specific

One of the most important lessons from Wages and White Lion concerns scientific evidence.

The Supreme Court recognized that the Tobacco Control Act allows FDA to determine what types of evidence are sufficient in a particular application. The statute permits either well-controlled investigations or other valid scientific evidence when sufficient to support the statutory finding.

This means applicants should not assume that one type of study automatically guarantees authorization.

A PMTA’s evidence should be:

• Scientifically credible
• Relevant to the product
• Relevant to the intended population
• Appropriate for the questions FDA needs to answer
• Internally consistent
• Supported by the overall application

Do You Always Need a Randomized Controlled Trial?

Not necessarily.

The Supreme Court noted that FDA’s statutory authority includes consideration of “other evidence” when it is sufficiently valid and rigorous.

However, applicants should not interpret this as meaning that minimal evidence is sufficient.

The practical question is:

Does the totality of evidence adequately demonstrate that marketing the specific product would be appropriate for the protection of the public health?

Applicants should therefore develop an evidence strategy before generating individual studies.

Comparative Evidence Still Matters

The Wages and White Lion case also involved FDA’s evaluation of comparative evidence.

FDA had expected applicants to provide comparisons between their proposed products and other relevant tobacco products.

The Supreme Court concluded that FDA’s comparative-efficacy approach was consistent with the agency’s earlier guidance and the statutory framework.

For applicants, this means a PMTA should not evaluate the proposed product in isolation.

Depending on the product, relevant comparisons may include:

• Combustible cigarettes
• Products within the same tobacco category
• Products within the same subcategory
• Other relevant tobacco products
• Potential predicate or comparator products

The appropriate comparisons depend on the product and the regulatory questions being addressed.

Flavors Require Careful Population-Level Analysis

Flavor was a major issue in Wages and White Lion.

FDA’s decisions relied heavily on concerns that certain flavors could appeal to youth and increase initiation.

The Supreme Court recognized FDA’s consideration of evidence that youth demand had shifted across device types and concluded that FDA had a reasonable basis for considering flavor an important factor.

Applicants with flavored products should therefore pay particular attention to evidence concerning:

• Youth appeal
• Adult consumer appeal
• Initiation
• Use patterns
• Switching
• Cessation
• Dual use
• Product perceptions
• Marketing exposure

A statement that a flavor is popular among adult consumers is not, by itself, enough to establish the population-level benefit required by the statute.

Marketing Plans Still Matter

One particularly important aspect of the case involved marketing plans.

FDA had previously described marketing plans as an important part of the PMTA process but did not evaluate the applicants’ marketing plans in the challenged decisions.

The Supreme Court’s decision did not establish that marketing plans are irrelevant.

Instead, the Court addressed the specific legal issue presented by the agency’s failure to consider those plans and the Fifth Circuit’s treatment of that error.

Applicants should therefore continue to take marketing and distribution controls seriously.

A strong PMTA should explain how the proposed marketing strategy is designed to:

• Reach the intended adult population
• Reduce youth exposure
• Control advertising
• Control distribution
• Reduce unauthorized sales
• Prevent marketing practices that could increase youth initiation

Marketing controls should be supported by actual implementation plans rather than general statements of intent.

Manufacturing Information Still Matters

A PMTA is not only a toxicology or clinical science submission.

FDA considers the methods, facilities, and controls used to manufacture, process, and pack the new tobacco product as part of its overall evaluation.

Applicants should therefore maintain strong documentation covering:

• Product composition
• Components and ingredients
• Manufacturing processes
• Process controls
• Specifications
• Quality controls
• Packaging
• Labeling
• Manufacturing facilities
• Quality systems
• Product consistency

The manufacturing section should support the broader scientific story presented in the PMTA.

Product Characterization Remains Critical

Applicants should clearly establish what the product is.

Product characterization may include information concerning:

• Components
• Ingredients
• Additives
• Nicotine
• Chemical constituents
• Emissions
• Physical characteristics
• Product performance
• Stability
• Manufacturing variability

FDA needs to understand the product being evaluated and whether the product tested in studies is representative of the product proposed for commercial marketing.

Any disconnect between test articles and commercial products can create significant regulatory questions.

Environmental Information Is Also Part of the Process

Applicants should not overlook environmental requirements.

FDA’s PMTA process can include an environmental assessment or an applicable claim of categorical exclusion, depending on the circumstances.

FDA’s current PMTA process identifies environmental information as a potential component of the application review process.

Applicants should ensure that environmental documentation is complete and consistent with the proposed product and manufacturing activities.

What FDA Is Looking for in a PMTA Today

FDA’s current PMTA framework still requires applications to satisfy the content and format requirements established under the PMTA final rule.

FDA states that a PMTA must include the information required under Section 910(b) of the FD&C Act and 21 CFR Part 1114.

The review process generally includes:

Acceptance Review → Filing Review → Scientific/Application Review → FDA Action

FDA may issue:

• Refuse to Accept correspondence
• Refuse to File correspondence
• Deficiency letters
• Environmental information requests
• Marketing Granted Orders
• Marketing Denial Orders

Understanding these stages is essential when preparing a submission.

FDA’s PMTA Framework Is Also Evolving in 2026

There is another major development applicants need to consider.

On September 28, 2026, FDA announced that it intends to evaluate changes to the PMTA regulatory framework, including potentially initiating new rulemaking to replace the current framework.

FDA cited its experience implementing the 2021 PMTA rule, changes in the tobacco marketplace, the development of an illicit and unregulated market, and the pace of new product introductions as reasons for evaluating the framework.

However, FDA also made clear that this does not mean the existing PMTA framework has been suspended.

The agency says it will continue to:

• Process PMTA submissions
• Conduct premarket reviews
• Issue regulatory decisions
• Apply the statutory APPH standard

until any future changes are made through the appropriate process.

For applicants, the practical message is simple:

Do not wait for a future PMTA rule to begin preparing a compliant application.

Current PMTA Submission Requirements Still Apply

FDA’s current submission requirements remain important.

Applicants must use the appropriate FDA forms and provide the information necessary for FDA to process and review the application.

FDA currently recommends using CTP Portal NextGen for PMTA submissions.

FDA has also announced that applicants should use the web-based forms in CTP Portal NextGen by November 14, 2026; after that date, eSubmitter will no longer be available for PMTA and SE submissions, although PDF submissions may remain available for applicants unable to submit electronically.

Applicants should therefore confirm that they are using the latest forms and current submission procedures before filing.

What Applicants Should Do Now

1. Start With an Evidence Gap Assessment

Review the existing PMTA evidence and identify areas where the scientific record may be weak.

Ask:

• What does the evidence demonstrate?
• What does it not demonstrate?
• Which conclusions are supported directly?
• Which conclusions depend on assumptions?
• Are the studies representative of the marketed product?

2. Build the APPH Argument Before Finalizing the Data Package

Do not treat APPH as a conclusion added at the end of the application.

Build the argument throughout the submission.

The evidence should connect:

Product → Exposure → Risks → Benefits → User behavior → Non-user behavior → Population impact

3. Strengthen Comparative Evidence

Identify appropriate comparator products and explain why those comparisons are scientifically and regulatorily relevant.

Do not rely on generic claims that a product is “safer.”

Explain the specific evidence supporting the comparison.

4. Evaluate Youth and Adult Use

For products where youth appeal is a concern, applicants should carefully evaluate:

• Youth appeal
• Adult appeal
• Initiation
• Switching
• Continued use
• Dual use
• Cessation
• Marketing exposure

The population-level analysis should address both users and non-users.

5. Review Marketing Controls

Ensure that the marketing plan is specific enough to demonstrate how the applicant intends to control the risk of youth access and exposure.

6. Verify Product Consistency

Confirm that:

Commercial product = Test product = Manufacturing specifications = PMTA description

Any material discrepancy can create questions during FDA review.

7. Prepare for Deficiency Questions

FDA may request additional information during application review.

Applicants should maintain organized source documentation so that responses can be prepared efficiently.

A response should directly address the question rather than simply referring FDA back to large sections of the original application.

A Practical PMTA Readiness Checklist

Before submission, applicants should confirm:

☐ Product identity and classification are clearly established

☐ Product composition is fully characterized

☐ Components and ingredients are documented

☐ Manufacturing processes and controls are documented

☐ Product specifications are established

☐ Toxicology and constituent data are appropriately supported

☐ Human health evidence is relevant to the product

☐ Adult use and switching evidence is addressed

☐ Youth initiation and appeal are addressed

☐ Comparative evidence is appropriately developed

☐ Marketing and distribution controls are documented

☐ Labeling is complete and consistent

☐ Environmental information is addressed

☐ APPH analysis connects the evidence across the application

☐ Current FDA forms are being used

☐ Application structure meets 21 CFR Part 1114 requirements

☐ Supporting records are organized and retrievable

The Bottom Line

The Supreme Court’s decision in FDA v. Wages and White Lion did not create an easier PMTA pathway.

Instead, it confirmed that FDA has significant discretion in evaluating what scientific evidence is sufficient to determine whether a new tobacco product is appropriate for the protection of the public health, while also addressing the specific question of whether FDA’s challenged decisions were inconsistent with its prior guidance.

For applicants, the practical takeaway is to build PMTAs around a complete, product-specific, scientifically defensible APPH argument.

That means going beyond product characterization and toxicology.

Applicants should demonstrate how the product’s risks and potential benefits affect the population as a whole, including current tobacco users and non-users, while addressing product use, switching, initiation, youth appeal, marketing, manufacturing, and other relevant evidence.

And because FDA is now evaluating potential changes to the PMTA regulatory framework, applicants should monitor future rulemaking without assuming that current requirements have disappeared. FDA has confirmed that it will continue processing PMTAs under the existing statutory framework while any future changes are considered.

For companies preparing a PMTA in 2026, the safest strategy is:

Build to the current requirements, strengthen the evidence, and monitor the regulatory framework for change.

Need Help With PMTA Preparation?

JJCC Group helps tobacco and nicotine-product companies develop and strengthen PMTA strategies, assess scientific and regulatory gaps, organize application documentation, and prepare submissions aligned with FDA requirements.

If your company is preparing a new PMTA, responding to FDA deficiencies, or evaluating an existing application after the Wages and White Lion decision, a focused regulatory assessment can help identify areas that need attention before FDA review.