Many stakeholders in the USA ENDS sector have been frustrated by the slow progress of the FDA in updating the industry on the status of ENDS PMTA submissions, and the lack of definitive guidance on the minimum requirements for FDA to conduct a substantive review of new tobacco products. So, with a sense of relief rather than joy, stakeholders welcomed the news on October 5th that the FDA had authorised the marketing of the first ENDS product, R.J. Reynolds Vapour Company’s Vuse Solo and three tobacco flavoured cartridges. FDA confirmed RJR Vapour Company had demonstrated that these products were appropriate for the protection of public health (APPH).

However, the news was not all good for RJR Vapour company. Marketing denial orders (MDOs) were issued for the 10 flavoured Vuse Solo cartridges and the menthol flavour remains under FDA substantive review. Although the reason(s) FDA issued MDOs for the flavoured Vuse Solo cartridges is not public knowledge, we can assume that evidence provided in the submission was not sufficient to mitigate the potential for youth initiation, as detailed in data sources such as the 2021 National Youth Tobacco Survey (NYTS).

So, we can all agree this is a start and step in the right direction by FDA. A robust review of the scientific evidence provided by RJR Vapour Company has demonstrated the Vuse Solo product has the potential to help adult smokers to transition to reduced-risk alternatives. We expect that over the next few months more ENDS products will be market authorised by FDA, with flavour options for American smokers potentially extended to menthol. Will FDA authorise any further flavoured ENDS products under the PMTA pathway, such as fruit flavours? The truthful answer is we don’t know at this stage, although it appears the weight of evidence requirements to prove the new flavoured tobacco product is APPH are substantial.

PMTA Final Rule welcomed by ENDS Sector

Watch our PMTA final rule live Q&A from February 2021

Before the announcement of the first ENDS marketing orders through the PMTA pathway, FDA finalised two foundational rules for companies seeking to market new tobacco products. Let’s look at the detail and how this clarity will benefit businesses supplying ENDS products to the US market.

What is the purpose of the PMTA pathway final rule?

In early October 2021, the FDA issued two final rules for the premarket review of new tobacco products. The two foundational rules concerned content, format, and review of Premarket Tobacco Applications (PMTAs) and Substantial Equivalence (SE) Reports. The PMTA pathway is the exclusive pathway for which ENDS manufacturers can seek market authorisation for new products form the FDA. The purpose of the final rule is to provide guidance to PMTA submitters on the minimum basic information needed to determine whether a new tobacco product meets the relevant premarket requirements to implement the Family Smoking Prevention and Tobacco Control Act (2009). The rule was initially issued in draft format by the FDA in January 2021. However, it was withdrawn before publication in the Federal register due to the change in administration following the presidential election in November 2020. The updated final rule has now been published in the federal register, with no substantive changes from the January draft.

What is the minimum requirement for PMTA content?

The information provided in a PMTA submission must be sufficient to demonstrate to the agency that permitting the marketing of the new tobacco product(s) would be “appropriate for the protection of public health” (APPH), as specified in section 910(c) (2) of the Federal Food, Drug, and Cosmetic Act.  FDA evaluates the data provide on the physical aspects of the new tobacco product and the potential impact of the product on public health. The final rule provides guidance on the information an application must include in a PMTA for the FDA to complete a substantive review of an application. Also, the rule formalises the procedures implemented by the FDA for PMTA evaluation, including acceptance, filing and inspections. Amendments to submissions, review time, post marketing requirements for marketing granted orders etc. are also detailed in the final rule. Guidance on the efficient re-submission of PMTAs with supplemental data, potentially of interest to clients subject to MDO for their PMTA submissions, is also included. This may also be utilised by applicants wishing to submit a supplement PMTA for a modified version of the product for which a marketing order has been granted for the original tobacco product.

In brief, the requirements for content are listed below:

  1. General: Describes each section the application must contain.
  2. Format:g., FDA provided forms, comprehensive index, table of content, well organised and legible.
  3. General information:g., Manufacturer name, address, product name, product category, Facility Establishment number(s), summary statements
  4. Descriptive information: Major aspects of new tobacco product, e.g., statement identifying relevant tobacco product standards issued under section 907 of FD&C act.
  5. Samples of new tobacco product(s): For FDA inspection.
  6. Labelling and description of marketing plans: Specimens of proposed labelling for new tobacco product(s), descriptive marketing plans for a least the first year after marketing granted order. Marketing of new tobacco produce must be APPH.
  7. Statement of compliance with 21 CFR part 25: Environmental assessment impact.
  8. Summary: Of all information contained in application.
  9. Product formulation: Components, materials, ingredients, additives, constituents, properties, principles of operation. HPHC constituents’ requirements include contained within, or emitted from, including any reaction of leaching or aging. E.g., constituent name, CAS, unit and variance, samples/replicates, method validation data & rationale, test laboratory details, time between manufacture & testing, storage conditions, test protocols inc. vaping/puffing regimes. Also, details required of design parameters, test data and performance criteria (detailed in tables 21-22 for ENDS products). Product pH & formulation, shelf-life & stability (data assessment at start, middle and end of expected shelf life, methods used, validation reports, accreditation status), product testing and analysis,
  10. Manufacturing: Manufacturing procedures, process control, monitoring procedures, non-conforming products CAPA, and release testing.
  11. Health risk investigations: non-clinical & human subject studies. Health risks to users and non-users (youth, young adults, vulnerable groups), health effects of constituents (inc. HPHCs), toxicology profile of new tobacco product (with discussion of tox. effects of any extractables & leachables that can appear from container closure system and ingredient mixture), pharmacological profile of new tobacco product, health risks compared to existing tobacco products on market, impact on tobacco use behaviour of tobacco product users, abuse liability, actual user use of product, likelihood of dual use, switching likelihood and potential for tobacco users to switch to new product when they would have completely quit tobacco products. Likelihood of non-user, youth initiation and former user re-initiation. Perceptions & intentions for use, human factors influence on product risk, literature review of each type of information listed in section K.
  12. The effects on the population as a whole: Analysis & discussion on how data contained in application establishes new tobacco product is APPH. Overall assessment of likely effect of marketing new tobacco product may have on overall tobacco-related morbidity and mortality.

FDA procedural guidance is also provided for the following:

  • Amendments
  • Withdrawal by applicant
  • Change in ownership of application
  • Supplemental applications
  • Resubmissions
  • FDA review procedure
  • FDA action on an application
  • Issuance of marketing granted order
  • Issuance of marketing denial order
  • Withdrawal of MGO, temporary suspension
  • Post marketing requirements (reporting requirements). E.g., marketing restrictions to mitigate youth exposure to tobacco product advertising, post marketing order being issued.

Is the published final rule substantially different to the withdrawn draft in January?

The final rule is now legally enforceable. There is no material difference between this document and the version published (and withdrawn) in January 2021. FDA did consider and reject the proposal to create a public database which would track the status of all PMTA submissions. FDA believes it is not necessary to create such a database, or such other measures, to ensure adequate public participation or to ensure FDA has access to all potentially relevant information. FDA has also included in the published rule a recommendation that applicants also consider abuse liability and unintended use amongst youth.

So, we hope you’ve found this summary of recent events in the US ENDS sector to be informative. If you like to read the PMTA final rule in full, click on the below link:

Federal Register :: Premarket Tobacco Product Applications and Recordkeeping Requirements

Hall Analytical would be delighted to guide your business through the PMTA process. Please call us to arrange a free consultation.

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