A Lot of Smoke over MRTPs?

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As the industry continues writhing to appease anti-tobacco lobbyists, national regulators, and health authorities alike on all fronts, MRTPs (modified risk tobacco products) may offer at least partial respite from this intensifying onslaught – or do they?

By Thomas Schmid

This could’ve been a rather short article if we had simply stated that currently not one single MRTP has been endorsed by the United States Food and Drug Administration (FDA) or is actively marketed as such anywhere – and then be done with it. But we decided that approach would be too easy and also fail to do justice to a product segment that may sooner or later indeed emerge as a very important new addition to the portfolios of tobacco companies in the US and worldwide.

The Definition

“MRTP” is of course an acronym standing for “modified risk tobacco product”. While this term in itself already gives an overt hint as per the main property such a product must impart, one also has to understand that it has been coined by the FDA. In that respect it wasn’t devised over the course of a lengthy marketing brainstorm at some obscure tobacco firm. There even exists an official FDA definition.

According to Michael Felberbaum, a press officer with FDA’s Office of Media Affairs in White Oak, Maryland, MRTPs are “tobacco products that are sold or distributed for use to reduce harm or the risk of tobacco-related diseases associated with commercially marketed tobacco products.” He added that any person or corporate entity may submit an application seeking an order under section 911(g) of the Federal Food, Drug and Cosmetic Act (a.k.a. FD&C Act) to have their product recognized as an MRTP.

The Conundrum

For such an application to have any chance of approval, the product in question must therefore effectively reduce not only exposure to toxicants contained in regular tobacco but also lower the health risk associated with the consumption of cigarettes or other combustible tobacco products. And naturally enough, these claims must be backed up by rigorous scientific evidence.

Also, since the definition is by all intents and purposes so far only recognized by its originator, the FDA, products that are granted the status can only be sold, distributed, or marketed in the United States as MRTPs; at least until other regulatory bodies elsewhere in the world jump on the bandwagon and adopt the definition as well.

But there is more to it: “At present, no regulatory authority has developed a scientific assessment framework and predictive tests that could be used to assess a tobacco product and determine whether it has potential to reduce the risks of smoking,” explained Joe Thompson, product science director at Imperial Tobacco Limited in Bristol, UK.

So there we have it! On the one hand, tobacco manufacturers may at any time file an application for one or another of their products to be considered for MRTP status. But on the other hand, they are left pretty much in the dark as to exactly what scientific test data they are supposed to submit to support that application. It’s a situation perhaps best described as a “Catch-22”.

The Uphill Battle

Despite the circumstance that to date not one single product has been granted MRTP status in the United States, tobacco companies don’t seem to be particularly discouraged. Practically all of them have for years – sometimes decades – funneled considerable resources into researching and developing potentially reduced risk – or to stick to the erstwhile term, modified risk – alternatives to conventional combustible tobacco products, including cigarettes.

“We have spent over 50 years researching and understanding the causes of diseases related to tobacco use,” said Chris Proctor, chief scientific officer at British American Tobacco (BAT). “Recent developments in technology and shifting consumer demand have made it both possible and commercially viable to develop potentially lower risk alternatives to conventional cigarettes that are acceptable to adult smokers.”

Imperial Tobacco likewise has a long track record of developing products that a government regulatory authority like the FDA may, perhaps, eventually come to regard as compliant with reduced exposure to toxicants and a reduced health risk. The firm also is rather proactively involved with scientific testing procedures that could potentially help regulators establish a definitive assessment framework for future MRTP applications.

“We have developed an in-house testing framework and conducted research into this area, and we continue to seek opportunities to engage with regulators and external bodies to assist them in developing their own assessment frameworks,” asserted Thompson. “The critical step is for a government regulatory authority to clearly define the predicate tests and scientific criteria by which a product can be assessed and endorsed [as an MRTP.”

The Consensus

Because conventional combustible tobacco products will categorically be denied MRTP status for obvious reasons, the question that rightfully arises is: “Which products are possible contenders for a coveted MRTP recognition?”

There is practically no disagreement from either side – neither the manufacturers nor the authorities – that nicotine alone is not the principal culprit causing the health risks commonly associated with tobacco use, Even the UK National Institute for Health & Care Excellence (NICE) stated in its 2013 report that “…most health problems are caused by other components in tobacco smoke, not by the nicotine.” Instead, “it is the toxicants in cigarette smoke that cause the majority of smoking related diseases, like cancer and respiratory diseases…”, as BAT’s Proctor put it; and it’s nothing that we haven’t heard before.

The MRTP Champions

The sensible solution to the dilemma therefore is not to burn tobacco, and that is where the main champions come in: those products most likely to eventually – if ever – be granted MRTP classification. For the time being and until the r&d departments of tobacco companies can come up with something phenomenally better, these primarily comprise e-smoking devices, including vaporizers and heat-not-burn gadgets, and – lo and behold – snus.

“E-vapor products offer the greatest potential as reduced risk products. As the scientific evidence builds supporting the category, and as the technology improves to meet consumer expectations, the market for e-vapor will grow,” explained Thompson. And he might be onto something. Almost since their first emergence in the market not too many years ago, vaporizers – but lately also tobacco heating (a.k.a. heat-not-burn) devices – have been hailed as a healthier alternative to conventional smoking. After all, what the consumer inhales is basically nothing more than a nicotine-laced glycol vapor devoid of harmful tobacco components such as tar and a plethora of carcinogens, if the chorus of manufacturers is to be believed.

To assess the validity of such claims, Imperial is currently conducting a series of clinical trials. “[These trials] will add to the scientific knowledge base of how the products work as reduced risk products,” said Thompson. He added that “as part of our approach to harm reduction we are seeking to gain a medicinal license for [one of our] e-vapor products,” although the company has so far not submitted any MRTP application.

BAT, too, is “currently doing extensive research into the characterization of potential risks associated with tobacco heating products and e-cigarettes,” according to Proctor. The former, of course, work by gently heating tobacco only to the point where nicotine evaporates, but without actually combusting the tobacco itself, thus preventing more harmful substances from actually being inhaled with the smoke.

The company also has already carried out and published research relating to snus, another possible contender for MRTP certification. Not to be confused with chewing tobacco, snus is basically finely ground tobacco enclosed in a small paper or cloth pouch that is inserted behind the cheek by the consumer and left there to develop its stimulating effects. Since nicotine is water soluble, it is then released as the pouch is being soaked in saliva and absorbed by the oral mucosa, supposedly leaving practically all other harmful compounds behind inside the tobacco.

While snus consumption is traditionally a domain of the Nordic countries, this smokeless tobacco alternative is reportedly gradually gaining modest popularity elsewhere, too, perhaps as a defiant response by a certain consumer demographic in the face of ever more stringent restrictions on smoking in public places. Interestingly, Swedish Match North America Inc. has already submitted applications for dozens of its snus tobacco products to the FDA and must thus be considered a forerunner in the less than hurried scramble for MRTP certification.

The Current State of Affairs

Disregarding the admirable efforts by Swedish Match, other tobacco firms are hardly rushing the FDA with their MRTP applications. A race to be the first company to claim a foothold in the MRTP arena is evidently not taking place – at least not yet.

“Since 2009, the FDA has received a mere 17 MRTP applications, including the 10 applications [from Swedish Match]…,” said the FDA’s Michael Felberbaum. He added that of these 17 applications, the agency issued “Refusal to Accept” decisions on 2 and “Refusal to File” decisions on 4. One unnamed company withdrew their application by themselves. “The other 10 all submitted by Swedish Match North America, are currently pending review,” said Felberbaum. Whether Swedish Match will be successful – and it doesn’t look all too promising at this moment – of course solely depends on…

The FDA Procedure

In conformity with its internal regulations, the FDA’s goal is to review and act upon each MRTP application within 360 days of receipt. If the application is accepted, the agency will conduct a filing review to determine whether the application is complete or not, i.e. whether it contains all the items required under Section 911(d) of the FD&C Act. If the application is incomplete, FDA may refuse to file it. If the application is complete, FDA will file the application and begin substantive review.

An order authorizing the marketing of a modified risk tobacco product may be issued if the evidence submitted in the application meets certain requirements as detailed in section 911. FDA may not issue an MRTP order unless it finds that the MRTP will or is expected to benefit the population as a whole. In making this determination, FDA will, for instance, take into account, among other aspects, the increased or decreased likelihood that non-users of tobacco, including young people, will start using the product that is the subject of the MRTP application.

Easy? By no means. Confusing? You bet. Ambiguous? Undoubtedly.

“We may apply to the FDA for MRTP status for some of our new products, if and when it makes commercial and regulatory sense to do so,” concluded Proctor. And we can’t blame him. 

The Swedish Experience

In 2014, Stockholm-based Swedish Match AB submitted 10 applications to the FDA seeking MRTP designation. All of the applications concerned snus products that at the time were marketed in the US by Swedish Match North America. They also were the first applications that have ever been considered complete by the FDA and were thus accepted for further review.

“Snus is a traditional product that has been used in Scandinavia for 200 years, so there is substantial scientific documentation about the health effects among long-term snus users,” explained Dr. Lars E. Rutqvist, senior vice president for scientific affairs at Swedish Match AB. “This research shows unequivocally that use of snus is associated with dramatically less health risks compared to smoking” According to him, the widespread use of snus instead of smoking in Sweden has led to substantial, positive effects on public health with record low rates of tobacco-related disease compared to global prevalence. This phenomenon is often referred to as the “Swedish Experience” and has been been acknowledged worldwide by tobacco scientists, research institutions and NGOs as proof-of-principle for the validity of the concept of tobacco harm reduction. If the FDA should eventually decide to issue a modified risk order for a Swedish snus product, it would indeed constitute a historic event as it would lend further support to the concept of tobacco harm reduction and help pave the way for future MRTP applications for other, more novel tobacco products.

“Undoubtedly, it would also have an impact on decision-makers and regulatory agencies in other parts of the world,” said Dr. Rutqvist, because many of them tend to follow FDA precedence. “However, if the FDA rejects all or some of the applications submitted by Swedish Match, the company would consider the grounds for the rejection and possibly submit further documentation that the agency may require,” Rutqvist said. The ramifications of a negative FDA decision could of course be profound, if not to say devastating. It has been murmured in tobacco industry circles that if Swedish snus cannot meet the standards set by the US Tobacco Control Act for an MRTP, no other product is ever likely to do so.