Tag: PMTA

To better understand the U.S. premarket tobacco product application process, turn to astrophysics.

By George Gay

Like many people, I was fascinated earlier this year to see the first-ever image indicating the presence of a black hole—one in the Messier 87 galaxy, 55 million light years from Earth. Since it is not possible to “see” a black hole, the image was of its event horizon where all known physical laws collapse and where stuff pops into and out of reality. One of the most illuminating comments I read about the image was provided by The Guardian’s science correspondent, Hannah Devlin, who wrote, “At the event horizon, light is bent in a perfect loop around the black hole, meaning if you stood there, you would be able to see the back of your own head.”

Obtaining the image required a huge effort, but I wonder if the scientists involved didn’t miss a trick. Couldn’t they have looked closer to home if they wanted to study a region where stuff pops into and out of reality? During a presentation on the U.S. vapor industry at the electronic nicotine-delivery systems (ENDS) conference in London, U.K., in June, I definitely formed the idea that timelines were dropping into and out of reality across some sort of event horizon, and, by the end of it, I’m sure that I got at least a glimpse of the back of my own head. This sense of confusion wasn’t caused by the presentation, which was good, but by the time warping effects of the U.S. Food and Drug Administration’s (FDA) shuffling of deadlines for the submission of premarket tobacco product applications (PMTAs) by ENDS product manufacturers, largely in response to external pressures.

At the time of the presentation, the deadline issue was before the District Court in Maryland, but, on July 11, that court ordered the FDA to require that manufacturers of ENDS products (and certain other products) file PMTAs within 10 months of the order (by May 12, 2020) for any products placed on the market on or before Aug. 8, 2016, the date after which no new products have been allowed to launch without a PMTA but after which many have, presumably because we have been operating on that event horizon.

The story behind the court case and the order is beyond the scope of this piece, but the situation, as it stands, seems to be that because of the enormous costs—millions of dollars per product variant, as I understand it—involved in submitting PMTAs, the time necessary to do so and the limited time available to do so, the U.S. market for ENDS products could be reduced in fairly short order to IQOS (the only ENDS product—officially a cigarette, I believe, as far as the FDA is concerned but one characterized as a legally undefined noncombustible cigarette—to have been granted a PMTA), devices supplied by companies willing to run the gauntlet of the law until such time as they are closed down, and, eventually, a handful of yet-to-be-launched products belonging to companies with bottomless pockets.

Although the deadline for the submission of PMTAs was once set by the FDA as 2022, and though the granting of PMTAs has proved to be a painfully slow process, in responding to the court order, the FDA seemed not to be too bothered about the task ahead. In a 1,100-word statement (mostly given over to anguished cries about having to protect young people from vaping), acting FDA Commissioner Norman Sharpless’ only suggestions that time might be short appeared when he said the FDA stood ready to accelerate the review of e-cigarettes and other new tobacco products and when he added that manufacturers didn’t need to wait 10 months to act. Of course, some manufacturers will have already made moves toward preparing PMTAs, and the court order allows products to remain on the market for up to a year while the FDA considers those PMTAs. The main reason the FDA is probably not alarmed at the situation, though, is because it knows that the cost of preparing a PMTA is way beyond the reach of most companies.

REGULATORY GUIDANCE

Meanwhile, back at the event horizon, the FDA was said to issue policy and regulatory guidance documents in relation to such things as PMTAs that, if I have this correctly, are not binding but are binding, though not necessarily enforced. Another presentation on how to keep products in the U.S. market had it that a guidance document was not legally binding, but complying with it was a really good idea unless you had a brilliant alternative way of staying on the right side of the regulatory issue for which the guidance was issued, which seemed like another way of saying that they were and were not binding. Otherwise, staying in the U.S. market, which was said to offer significant growth opportunities, meant rationalizing your product portfolio, having a plan and an awful lot of spending money, and moving expeditiously. Presumably, even more expeditiously following the court order.

It is illuminating that while tobacco products—deemed, presumably during a meeting held at some event horizon, to include ENDS—were made the responsibility of the FDA so that their control could be governed by the application of science, that governance seems to have slipped—inevitably, I would suggest—largely into the hands of politicians, nongovernmental organizations, pressure groups and the courts.

Let’s not forget the parents concerned about the use of ENDS products by young people—part of what conference delegates learned was the “kiddification” of the U.S. The conference was told that pressure by parents was causing some head teachers to close school bathrooms, presumably to prevent the youngsters from using such facilities for vaping.

My goodness. Once you learn about such alternative realities, you know you’re looking at the back of your own head. I mean, where are these youngsters doing the things that bathrooms are provided for? Holding on will cause more physical damage—on what the FDA would refer to as an individual level—than any amount of vaping, while not holding on and not using the bathroom facilities will lead—on a population level—to a mighty unpleasant and unhygienic state of affairs.

Meanwhile, on this side of the event horizon, the conference was given a briefing about the activities of the e-cigarette unit of the U.K.’s Medicines and Healthcare products Regulatory Agency, including those necessary to prepare for a post-Brexit U.K. The agency is responsible for operating the national product notification system under the EU’s Tobacco Products Directive (TPD), publishing a list of notified products, operating an adverse reactions system and reviewing safety reports of products in use. In addition, the unit provides systems for intelligence gathering, online market surveillance and product removal in collaboration with e-cigarette stakeholders.

There are reportedly 39,000 products accepted for U.K. supply and more than 55,000 products notified for the U.K. via the EU Common Entry Gate, an IT tool designed to ensure uniform reporting. The unit has reportedly received 59 adverse reaction (yellow card) reports detailing 170 adverse reactions and 11 referrals relating to the safety and quality of products. In addition, it has received about 100 referrals from enforcement agencies while, in 2018–2019, it disseminated more than 500 intelligence referrals to external agencies. As a result of collaboration with enforcement agencies, more than 700 unnotified product listings have been removed from the online marketplace since December 2018.

CONVERGENCE OF REGULATIONS

Looking at the bigger picture, another presentation included a world map that showed where bans are in force on nicotine-containing electronic cigarettes—a map that seemed to indicate that countries of the southern hemisphere are keener on such bans than those of the northern hemisphere. Whether this phenomenon has something to do with the trade winds, I don’t know, but it is no surprise that regulatory burdens in respect of these products are seen as being greater in countries of the southern hemisphere than in those of the northern hemisphere, though in this case, with the inclusion of regulations that stop short of bans, the south/north division is less marked. Apparently, the worldwide trend is away from bans but toward more regulation and more restrictions, with countries around the world gradually becoming more similar in their regulatory approach to ENDS products.

Of course, the idea that regulations comprise a burden has meaning only if those regulations are unnecessarily restrictive and if they are adhered to by those operating within the marketplace. In the U.S., the law that has banned the launch of new-to-the-market and updated ENDS products without a PMTA since Aug. 8, 2016 seems to have been widely ignored. And in the EU, the TPD provision that limits nicotine-containing e-liquid refills to 10 mL is being circumvented by “short-fills,” which basically provide consumers with a way of mixing their own higher quantity liquids, conveniently and accurately, without busting the ban on the sale of nicotine-containing e-liquids above 10 mL. Apparently, short-fills account for more than half of the sales of refills in the top three EU markets—the U.K., Germany and France—taken together. They can have consequences for taxation in those countries where tax is applied to e-liquids.

Quite what you make of such a circumvention or of the illicit products launched in the U.S. will be down to your view on law and order. There seemed to be a current of opinion at the conference that because not enough official action was being taken against offenders, the advantage was falling to irresponsible operators. This view is all well and good, and as long as those who hold it abide by all the laws of their countries, they may reasonably pat themselves on the back for being such upstanding citizens. But if, for instance, they regularly drive at speeds that exceed the legal limits and park where they shouldn’t, they are simply hypocrites.

My view is that while everybody should abide by the law, it has to be expected that some won’t when, for instance, those laws are, in the case of the 10 mL e-liquid limit, simply silly and, in the case of the PMTA requirement, seemingly unnecessarily loaded in favor of one group (big companies) over another (small companies).

Some regulations are seen as not being burdensome but rather as essential, but those tend to be the kind that help to ensure certain standards are adhered to—that products available to the consumer are of a certain quality. Looked at from one point of view, this is important because the vapor industry is controversial, and it shouldn’t hand its opponents ammunition. The same can be said of the cannabidiol industry, which, as is becoming increasingly common at such events, also got a look-in at the conference. Looked at from another direction, the imposition of inappropriate standards could be anti-competitive and anti-innovative, so it is vital that those involved in deciding on standards are representative of a broad spectrum of interests.

STANDARDS

One presentation had it that standards aim to facilitate international trade and protect consumers. It is, of course, important to protect consumers from overly risky products, but what about protecting them from a reduction in innovative products that might be caused by the sort of internationalization that has encouraged huge consolidation in the tobacco industry? You must ask yourself whether the tobacco consumer has been well served in those tobacco markets that have been reduced to the products offered by just a few major manufacturers, all with basically the same outlook. Encouraging international trade in vapor products might be the last thing that is needed. Certainly, it cannot be taken as a given that it is a good thing, and it certainly raises to new heights the importance of getting the balance right of those involved in determining standards.

Of course, when standards are being developed, an eye must be kept on whether they would be measurable in a meaningful way. Once standards have been agreed on, repeatable methods of measuring whether those standards are being adhered to have to be developed. It was useful that the conference included a presentation on the part that the Cooperation Centre for Scientific Research Relative to Tobacco (Coresta) is playing in this field, which apparently includes work that other organizations are unlikely to do. Coresta has the advantage of being made up of a wide range of organizations with expertise from different sectors and of having a track record of supporting—though not being involved in—the development of international standards.

The importance of testing regimes was also underlined by presentations on safety and toxicology aspects of e-liquids, an introduction to extractable and leachable testing of ENDS devices, and the uniformity measurement of aerosol delivery in tobacco-heating products.

On a more prosaic level, the conference was given a rundown of what is generally seen as the U.K.’s vaping dichotomy, whereby the public health community has a positive approach to vaping but that positivity is not fully reflected in public beliefs and actions. Different presentations had it that the vaping prevalence in the U.K. has been stable since 2015, that 26 percent of people in the U.K. believe that vaping is as harmful or more harmful than smoking, and that 40 percent of smokers have not tried vaping. While smoking prevalence is at a record low, 15 percent of the adult population, or 7.4 million people, are said to smoke while 11 percent of mothers are still smoking at the end of their pregnancies.

However, a presentation by a healthcare professional shed some light on this situation and suggested that there really was no mystery here. Part of the problem is that while those at the top of the healthcare pole have accepted the positive role that vaping can have in encouraging people not to smoke, that message is not necessarily reaching those below. There is, in other words, a gap between healthcare policy and practice caused in part by a mismatch between national health goals and funding for those goals. This has resulted in a lack of knowledge among healthcare professionals at the sharp end.

There are also the well-known hurdles of a media ready to relay vaping scare stories, no matter how slender their links are to reality, and lazy private and public sectors that hitch vaping bans onto public smoking bans without, it would seem, the slightest regard for the fact that these are very different activities. In other words, having returned to the event horizon, they seem to be content just to stare at the backs of their own heads.