... Puts Nearly Insurmountable Barrier in Front of the Development of Reduced Risk Products by Dr. Michael Siegel Article
The Food and Drug Administration (FDA) has released its draft guidance for industry on applications for modified risk tobacco products. Closely following the statute (section 911 of the Family Smoking Prevention and Tobacco Control Act), the guidance document sets forward the most stringent possible interpretation of the statute, putting every possible barrier in front of the successful development and marketing of reduced risk tobacco products, and making it extremely difficult for such products to enter the market.
The Rest of the Story
1. The guidance makes it almost impossible for new reduced risk products to be successfully developed and marketed.
First, the guidance makes it clear that any new tobacco products designed with the purpose of reducing health risk will be treated as new products. As such, they must not only comply with the requirements of section 911, but they also must successfully apply for a new tobacco product designation under section 910. This is an extremely difficult barrier, as the company must be able to show that the tobacco product is appropriate for the protection of the public's health. This will be virtually impossible, because long-term human studies will almost certainly be required to make such a demonstration, but those studies cannot be carried out unless the product is approved for use. In other words, it is essentially a catch-22 situation.
The implication of this aspect of the guidance is that unless a potential modified risk product was already on the market as of February 15, 2007, it will be nearly impossible to achieve FDA approval.
Thus, the first thing that the guidance does is to essentially preclude the development of new or novel reduced risk products. What the guidance does is basically restrict the playing field to products that were already in existence as of February 15, 2007 (e.g., smokeless tobacco products, dissolvable tobacco, electronic cigarettes, etc.). We are likely to see some applications for these presumably lower-risk existing tobacco products seeking designation as modified risk or reduced exposure products. However, there is a virtually insurmountable barrier in front of the successful development of a new reduced risk tobacco product.
2. The guidance makes it extremely difficult for existing potentially-reduced risk products to successfully achieve modified risk status.
Second, the guidance adopts the strictest possible scientific criteria that must be met for existing products to achieve designation as modified risk products. Most notably, the company must successfully address:
- "The effect the tobacco product and its marketing may have on tobacco use initiation among non-users"; and
- "The effect the tobacco product and its marketing may have on tobacco use behavior among current tobacco users."
Even more specifically, a modified risk product application must:
- "contain scientific evidence regarding the effect the product and its marketing will have on increasing the likelihood that persons who do not use tobacco products will start using the tobacco product that is the subject of the application"; and
- "provide evidence regarding whether the product and its marketing will increase or decrease the likelihood that existing users of tobacco products who would otherwise stop using such products would instead switch to the tobacco product that is the subject of the application."
To make such demonstrations, a company would have to conduct a clinical trial or long-term observational, quasi-experiment in which the potentially reduced risk product was introduced into the market and marketed as a reduced risk product. Then, the company would have to examine the effects on smoking initiation and on reduced quitting, as outlined above.
The key point is that in order to conduct such studies, the company would have to market the product as a reduced risk product. In the absence of such marketing, we will never know the extent to which the product and its marketing will increase the likelihood that nonsmokers might initiate use of the product or that smokers might switch to the product instead of quitting smoking altogether.
But there is a catch-22 here as well. In order to conduct these studies, the company would have to market the product as a reduced risk product. However, the company is prohibited from doing that until and unless it gains approval from the FDA to market it as a reduced risk product!
This catch-22 essentially creates an insurmountable barrier for the successful approval of a modified risk product designation. Take, for example, the case of Camel snus. Suppose that Reynolds American decides that it wants to apply for a modified risk designation for Camel snus. Presumably, it would be quite feasible to show that for the individual user, Camel snus is safer than using cigarettes. However, how can Reynolds obtain data to determine whether or not marketing Camel snus as a safer tobacco product will have an effect on youth smoking initiation? Will widespread advertising campaigns that portray Camel snus as safer than cigarettes lead youth to start using tobacco products, since they now may perceive tobacco products to be safer than before?
There is only one way to find out for sure. And that is to market Camel snus as a reduced risk product and measure any changes in youth tobacco use. No laboratory studies, youth surveys, or consumer perception studies are going to adequately be able to predict youths' actual behavior in the face of a massive marketing campaign for Camel snus as a safer tobacco product. Of course, if Reynolds started marketing Camel snus as a safer tobacco product, it would be in violation of federal law. Hench, the catch-22. And hence, the virtually insurmountable obstacle to the successful designation of a modified risk product.
The following paragraph from the guidance makes it clear just how rigorous the scientific demonstration must be. It also makes it obvious just how impossible it is going to be to conduct studies that allow such a demonstration, especially since the product cannot be marketed in the proposed way until it has been approved:
"The estimates should integrate all of the information regarding the marketing of the product and its potential effects on health, tobacco use behavior and tobacco use initiation to provide an overall assessment of the potential effect that the product’s introduction to the market may have on overall tobacco-related morbidity and mortality. FDA recommends that the applicant estimate the attributable risk of all of the various health effects for various types of individuals in the U.S. population, as well as the total number of individuals of each type. As an illustration, consider a product that an applicant maintains poses one-tenth of the risk of death from lung cancer as compared to smoking cigarettes. FDA recommends that the applicant quantify the potential changes in mortality to the various types of affected individuals in the U.S. population (see bullets below). This would include, among other things, an estimate of the number of smokers who are likely to switch to the product and the subsequent reduction in the number of lives lost due to tobacco use, the number of smokers who may use the product in conjunction with other tobacco products or instead of quitting and the subsequent effect on the number of lives lost due to tobacco use, as well as the number of non-smokers who may initiate use of tobacco with the product and the subsequent increase in the number of lives lost to tobacco use. FDA recommends that a similar approach be used to assess the potential impact on mortality resulting from other diseases, as well as morbidity in the various types of affected individuals in the U.S. population."
The above is a massive research undertaking that could not possibly be done successfully by a single company. It would require a massive research effort from all of the nation's universities over many years, and still could not be accomplished in the absence of actual experiments in which specific products were actually marketed as reduced risk products. Frankly, it's not even clear to me why there is a process for modified risk product applications if the scientific standards are so rigorous that they are virtually impossible to attain.
3. The guidance makes it extremely unattractive for existing potentially-reduced risk products to successfully achieve modified exposure status.
Third, while the guidance does not make it impossible for companies to achieve modified exposure status for a potentially reduced risk product, it makes it extremely unattractive to do so. Why? Because a key provision of the guidance is the following: "Applicants seeking exposure modification orders must also demonstrate that testing of actual consumer perception shows that, as the applicant proposes to label and market the product, consumers will not be misled into believing that the product is or has been demonstrated to be less harmful, or presents or has been demonstrated to present less of a risk of disease than one or more other commercially marketed tobacco products."In other words, you can market a product as being a reduced exposure product, but whatever marketing language you use cannot give consumers the impression that the product is in any way safer than any other tobacco product! But if that's the case, then what reason is there for anyone to switch to your product? Why would anyone shift from the most popular products on the market to your product in the absence of thinking that your product might be safer? And what company would want to go to the expense of putting together a modified exposure application only to have to continue marketing their product the way it is currently marketed?
It's like telling Reynolds, in the above example: "You have shown successfully that Camel snus is almost certainly safer than smoking cigarettes because snus contains no lung toxins and is not inhaled. You have our approval, therefore, to adopt a modified exposure designation for Camel snus. Congratulations! ...
... Oh, by the way. When you market Camel snus, you can't tell people that it is safer than smoking cigarettes. And you can't tell people that it contains no lung toxins because that will lead them to believe that it's safer than cigarettes. You can't tell people that it has fewer identified toxins that cigarettes because they might think it's safer." "So what can we tell people?" Reynolds might then ask.
"That it is an alternative to smoking. Not a safer alternative. Not an alternative that provides reduced levels of carcinogens or reduced levels of toxins. Just an alternative." To which Reynolds might rightly respond: "Well, gee thanks. That's what we're already telling people. What was the whole point behind our reduced exposure application? That was 50 grand down the drain."
The rest of the story, then, is that the FDA guidance on modified risk tobacco products: (1) makes it almost impossible for new reduced risk products to be successfully developed and marketed; (2) makes it extremely difficult for existing potentially-reduced risk products to successfully achieve a modified risk status; and (3) makes it extremely unattractive for existing potentially-reduced risk products to successfully achieve modified exposure status.
Now this is not necessarily the FDA's fault. The FDA is merely interpreting the statute it was given to work with. We have the anti-smoking groups (such as the Campaign for Tobacco-Free Kids and its friends) and the big-name politicians (such as Representative Waxman and Senators Kennedy and Durbin) to thank for the statute which created this inane situation in the first place.