How Verve's PMTA Authorization Can Inform New Oral Nicotine PMTAs 

Septmeber 23, 2024

There is an emergent trend of oral nicotine pouches entering various tobacco markets around the world. I felt it might be instructive to review the marketing granted order issued by FDA CTP for the 4 Verve tobacco products in October 2021. The authorization followed the FDA's review of Premarket Tobacco Product Applications (PMTAs) submitted by Altria Client Services LLC on behalf of the U.S. Smokeless Tobacco Company LLC on July 23, 2018. Verve products are oral tobacco products that contain tobacco-derived nicotine, but not cut, ground, powdered, or leaf tobacco. There are two types of Verve products: Discs and Chews. Both are thick and teardrop-shaped, but Discs have a firm texture and Chews have a soft texture.

How Verve's PMTA Authorization Can Inform New Oral Nicotine PMTA Applications

1. Verve's PMTA Authorization

- Provides Insights For → New Oral Nicotine PMTA Applications

- Demonstrates → Appropriate for the Protection of Public Health (APPH)

2. Demonstrating APPH

a. Focus on Reduced Risk

- Evidence Suggests → Verve is less harmful than cigarettes

- Highlights Importance Of → Demonstrating reduced risk in new products

b. Thorough Chemical Analyses and Comparisons

- Applicants Should:

- Quantify → Harmful and Potentially Harmful Constituents (HPHCs)

- Compare → HPHC levels to combustible cigarettes and relevant products

- Provide Data On →

- Nicotine content and delivery

- Pharmacokinetics (e.g., free nicotine levels, pH)

3. Addressing Specific FDA Review Areas

a. Abuse Liability

- FDA Emphasized → Need for abuse liability assessments

- Applicants Should:

- Demonstrate lower abuse liability than cigarettes

- Ensure no appeal to youth or non-users

- Consider pharmacokinetic profiles and potential for misuse

b. Use Patterns and Behavior

- FDA Considered → Real-world use patterns; dual use is common

- Applicants Should:

- Include actual use studies (frequency, duration, concurrent use)

- Address impact of dual/poly use on HPHC exposure

- Conduct in-market surveys on consumer perceptions and behaviors

c. Biomarkers of Exposure (BOE)

- Importance Of → Assessing impact on exposure to harmful compounds

- Applicants Should:

- Conduct BOE studies measuring key biomarkers

- Include exclusive product use groups

- Detail bioanalytical methods used

d. Adverse Health Effects

- FDA Reviewed → Adverse events (AEs) and potential health risks

- Applicants Should:

- Report AEs from trials and post-market data

- Address health risks of ingredients with literature and toxicology data

- Consider misuse implications on AE profiles

e. Population Health Impact

- FDA Evaluated → Impact on initiation, cessation, morbidity, mortality

- Applicants Should:

- Provide data on use likelihood across populations (youth, non-users, etc.)

- Assess potential for reducing cigarette consumption or switching

- Conduct modeling studies on health outcomes

f. Consumer Perception and Understanding

- FDA Considered → Risk perceptions and product understanding

- Applicants Should:

- Include studies on consumer risk and benefit perceptions

- Evaluate comprehension of labeling and marketing for accurate communication

4. Addressing Data Gaps and Limitations

a. Long-Term Health Effects

- Acknowledged → Limitations of pre-market data on long-term effects

- Applicants Should:

- Acknowledge data limitations

- Propose post-market surveillance plans

b. Real-World Use vs. Clinical Trial Settings

- Recognized → Differences affecting dual use and adherence

- Applicants Should:

- Design studies reflecting real-world use

- Consider cost, availability, marketing impacts

c. Generalizability of Findings

- Emphasized → Importance of broader applicability

- Applicants Should:

- Use representative populations and sampling

- Conduct studies across diverse demographics and locations

d. Product Evolution and Modifications

- Noted → Challenges in bridging data from prototypes to final product

- Applicants Should:

- Document product modifications thoroughly

- Provide rationale and supporting data for bridging findings

5. Conclusion

- Emphasize → Reduced risk profile

- Conduct → Comprehensive studies addressing FDA's key review areas

- Proactively Address → Potential data limitations

- Goal → Demonstrate product is appropriate for the protection of public health

Conclusion:

The FDA's authorization of Verve provides valuable lessons for developing new oral nicotine products. Emphasizing reduced risk, conducting comprehensive studies addressing FDA's key review areas, and proactively addressing potential data limitations are crucial for demonstrating that a new oral nicotine product is "appropriate for the protection of the public health."