by Willie McKinney, Ph.D., D.A.B.T.
Speed Counts, Including When It Comes to PMTA Applications to the FDA.
Despite the wisdom underlying a famous fable about a hare racing a tortoise, most of the time I’d bet on the hare. Speed counts, including when it comes to PMTA applications to the FDA. Winning authorization quickly by submitting the paperwork as soon as you’re ready and having very few hitches in the application because you understand what the FDA wants will help any company with a new product claim an early and premier space in the marketplace.
The 2020 PMTA authorization of Philip Morris’s IQOS 3 system is a clear example of making an early and strong case for authorization in part by linking to prior research on established products with which the FDA is familiar. It also highlights the need for a PMTA application if a device has had any modifications other than changes to a battery to get UL approval.
We can see Philip Morris’s successful approach reflected in the comments in its Technical Project Lead Review of the new application–commentary from FDA scientists in response to the quality of the application. Here are a few:
Bridging to Previous Products in a PMTA
Scientific review of the application found that the comparison between IQOS 2.4 and the proposed IQOS 3 device is appropriate. The applicant has provided adequate information on the manufacturing process and product quality controls that will help ensure that the IQOS 3 device is manufactured consistently and will meet the applicant’s specifications. The aerosol from the IQOS 3 device has been evaluated and found to be comparable to that from the use of the IQOS 2.4 device. No new exposures or risks for the new device were identified.
Because the new device was based on a device (IQOS 2.4) and a source of nicotine (Marlboro Heatsticks) that had already gone through the PMTA authorization process in 2019, the applicant was able to cite data on the previously authorized products because it could demonstrate that the key elements were very similar or identical. This saved months of work, pushing their authorization ahead of those of their potential competitors.
Overcoming the “New to the U.S.” Problem
The IQOS 3 device is not marketed in the U.S.; however, the applicant has provided user information from the international marketing experience with IQOS 3 as well as consumer reports, complaint, published literature and product safety information. There were no new safety concerns or unexpected adverse experiences identified. The user information from international survey data found no evidence of increased uptake of IQOS by youth or young adults, and IQOS 3 seemed to be more accepted by consumers with a slightly decreased likelihood of dual use with cigarettes as compared to IQOS 2.4. There is no evidence the user population for IQOS 3 will be different from the population who use IQOS 2.4. Although the marketing information provided is not U.S. data, use patterns available for IQOS 2.4 within the U.S. have not raised new concerns regarding product use in youth and young adults. Given the product similarities, there is no evidence of increased risk for youth initiation and use for IQOS 3 as compared to IQOS 2.4.
Again, the applicant was able to bridge to previous research–this time behavioral research–done using a comparable product with a population considered similar to that of the US. Note that the FDA’s main concerns were safety and youth. These are two topics that need to be addressed strongly and directly in any nicotine-related behavioral research.
While it’s critical that manufacturers move quickly to submit their PMTAs, that speed can be canceled by applications that don’t take into account the perspectives that FDA scientists bring to the authorization process. Bridging to previous studies can be a powerful and time-saving tool, but only when the links are explicit, relevant, and scientifically valid.