Article | Scientific Update | Feb 8, 2024

      U.S. regulatory landscape

      While the commercialization of a number of new tobacco and nicotine-containing products has been authorized in the U.S. market for almost a decade, the regulatory landscape in the U.S. faces a series of challenges that, if not overcome, may influence the adoption of these products by adult smokers wishing to move away from cigarettes and their potential impact on public health. In this article, we examine some key regulatory milestones for the commercialization of tobacco and nicotine-containing products in the U.S., as well as two significant challenges in the U.S. regulatory landscape. This article is an excerpt from Scientific Update Issue 18.


      Why regulations on smoke-free products matter

      In the interest of tobacco harm reduction, adult smokers and nicotine users need accurate and non-misleading information about smoke-free products. As we have learned, product information can help them to switch more completely. The U.S. is an example of a country where there are regulatory pathways that are required for the commercialization of and communication about novel smoke-free products, an approach that can help to ensure there is clear substantiation behind statements made across the product category. Despite some of the successes of this approach, the implementation can be complicated. Here, we provide examples from our own applications.  

      Dr. Matthew Holman

      Vice President and Chief Scientific & Regulatory Strategy Officer in our U.S. offices

      Matthew worked for more than 20 years with the U.S. Food and Drug Administration (FDA), most recently as Director of the Office of Science at the Center for Tobacco Products (CTP).


      Key milestones and what they reveal  

      November 2015 was a major milestone within the tobacco industry. It saw the clearance by the U.S. Food and Drug Administration (FDA) of the first tobacco products to be commercialized under the premarket tobacco product application (PMTA), a legal requirement for the introduction of any novel tobacco-containing product into the U.S. market. These products were eight snus smokeless tobacco products sold under the General brand name, by Swedish Match USA, Inc., now a PMI company. While snus was already available in the U.S. market through a number of companies, the eight General Snus products were the first to go through this formal review. Submitted on March 11, 2015, the PMTA took 236 days to be authorized by the FDA, well within expected timeline. 

      Milestones in U.S. Tobacco Regulation for General Snus

      Milestones in U.S. Tobacco Regulation for General Snus.

      With the PMTA review completed, focus then turned to the Modified Risk Tobacco Product (MRTP) review for General Snus products, the application for which had been submitted in June 2014 An MRTP authorization allows the specified product to be marketed with reduced-risk related information. The MRTP review by the FDA took 1,961 days to complete, and in October 2019, the use of the following claim was authorized: “Using General Snus instead of cigarettes puts you at a lower risk of mouth cancer, heart disease, lung cancer, stroke, emphysema, and chronic bronchitis.”  

      MRTP authorizations are valid for up to 5 years, which means that the MRTP authorization for General Snus products will expire in October 2024. Thus, an MRTP renewal application was submitted in July 2023 by Swedish Match. In November 2023, the FDA completed a preliminary review of this application and determined that it met the filing requirements for a tobacco product seeking a modified risk order. As a result, the application was filed and entered the substantive review phase. In early December 2023, the FDA opened a docket and invited public comments on the renewal of existing MRTP orders. At the time of writing, the FDA has not established a closing date for the comment period. The next stage will involve the referral of the MRTP application to the Tobacco Products Scientific Advisory Committee (TPSAC), a group of experts in medicine, medical ethics, science, or technology involving the manufacture, evaluation, or use of tobacco products. No closing date has been communicated for this next stage as well.  

      In May 2017, PMI submitted the PMTA for the tobacco heating system, THS 2.2, commercially known as IQOS 2.4. The FDA granted its authorization—the first heated tobacco product to be authorized under the PMTA in April 2019. The review of the MRTP application for the same product followed.  Submitted in 2016, the MRTP review was completed in July 2020, and PMI was authorized to use the following statements: 

      • “The IQOS system heats tobacco but does not burn it. 
      • This significantly reduces the production of harmful and potentially harmful chemicals. 
      • Scientific studies have shown that switching completely from conventional cigarettes to the IQOS system significantly reduces your body’s exposure to harmful or potentially harmful chemicals.”
      Milestones in U.S. Tobacco Regulation for THS 2.2.

      Milestones in U.S. Tobacco Regulation for THS 2.2.

      This MRTP authorization has a four-year expiration date, which ends in July 2024, and an MRTP renewal was submitted by PMI in July 2023. The FDA accepted this renewal application in September 2023, but did not provide any further response at the time of writing.  


      An increasingly unpredictable market

      One key challenge in the U.S. regulatory environment for tobacco products is the unpredictability in the time it takes the FDA to review marketing applications. PMTA authorizations have been granted by the FDA for 45 products so far, yet around half a million PMTAs are pending review at the FDA, with PMI applications among them. For example, PMTAs for Swedish Match’s oral nicotine products ZYN Flagship and ZYN Ultra have not been processed despite being submitted in March 2020 and November 2021, respectively. The FDA has started reviewing the PMTA for only one variant so far.  

      In October 2023, PMI submitted PMTAs and MRTP applications for a new variant of THS, THS 3.0 commercialized as IQOS Iluma, and the accompanying tobacco sticks commercialized as TEREA. At the time of writing, the FDA has not yet confirmed the acceptance of these applications.  

      As the industry continues to push forwards with innovative smoke-free products, it is becoming increasingly difficult to predict when these products will be allowed to be commercialized in the U.S. market.  


      Unclear evaluating standards

      Another challenge in the U.S. is the standards by which the FDA grants authorizations under the PMTA and MRTP pathways. While the FDA makes its assessments based on the risks and benefits of a tobacco product to the population, including both users and non-users of tobacco products, the requirements for these assessments are available in draft format only and subject to change, for the MRTP process for example, leaving the opportunity for shifting priorities.  

      Because of the current ambiguities around the assessment process, PMI has sought out regulatory experts on the scientific evaluation of tobacco product applications at the FDA to guide us through these applications, and even then, the process remains difficult.  

      As the industry continues to evolve and brings forth more innovative products, the regulatory landscape must adapt to support its growth. Through PMTAs and MRTP applications, the regulatory approach taken by the U.S. has already embraced the harm reduction approach to complement prevention and cessation strategies linked to smoking cigarettes. Such an approach allows more adult smokers to choose lower risk options instead of continuing to smoke, which can have a positive impact on population harm. Reducing authorization timelines and clarifying standard requirements would be important for this approach to truly take hold in the U.S. and make a significant impact on public health.  

      Updates on PMI Science

      Read the Scientific Update magazine

      The Scientific Update magazine is focused on PMI's research and development efforts, milestone studies, industry regulations, and more. View the latest issue, or read the articles online.