The Tobacco Vapor Electronic Cigarette Association (TVECA) has obtained a copy of the FDA electronic cigarette deeming regulations that were sent to the Office of Management and Budget (OMB) for final approval before promulgation, as well as a draft of the guidance that the agency intends to release in conjunction with the deeming regulations. The guidance relates to the recommended procedure for filing pre-market tobacco product applications (PMTA's). The TVECA has made the PMTA guidance publicly available on its web site, but did not make the deeming regulations available upon the request of the FDA.
The following commentary is based on my review of the PMTA draft guidance document. Although I have not yet reviewed the actual deeming regulations, it is possible, from analyzing the guidance, to infer the basic approach that the FDA has decided to take regarding the regulation of electronic cigarettes and vaping products. Once the deeming regulations are released, I will continue to analyze them and provide additional commentary, including any clarifications of the following commentary if they are necessary. However, the approach the FDA is taking appears clear from the draft guidance.
Caveat: This commentary is based solely on my review of the PMTA draft guidance. It is possible, although unlikely, that the actual deeming regulations include exemptions or modified provisions for certain small businesses. I had originally made a decision to postpone my commentary on the draft guidance document until the deeming regulations were released in their entirety, in order to avoid any error in case there are exemptions in the deeming regulations. However, I have made the decision to publish the commentary now because by the time the deeming regulations are released, it will be too late to change them. I believe that the risks associated with the possibility that the fine details of the deeming regulations render invalid my commentary below are far outweighed by the benefits of making this information available to the public so that interested parties can provide meaningful feedback to the OMB to inform a properly informed review of the regulations.
Now is the time when interested parties must understand the regulatory strategy that the FDA intends to take, and the implications of such a strategy, so that they can potentially provide comments to the Office on Management and Budget's Office of Information and Regulatory Affairs (OIRA), which has the authority to require changes in the regulations if it is unable to make "a reasoned determination that the benefits of a regulation justify the costs." In addition, as there are at least 34 scheduled meetings of interested parties with the OMB, I am publishing this commentary now to allow those groups to provide more informed advice and recommendations to the OMB, rather than having to guess about the approach that the FDA intends to take with respect to the regulation of electronic cigarettes.
According to the OIRA web site:
"Outside parties may provide written comments to the OIRA Administrator on a rule that is under review. If a rule is at OIRA for review, interested parties can provide comments by email at OIRA_submission@omb.eop.gov. In the email please specify the name of the rule and the regulatory identification number (RIN) as specified in the docket for the rule on www.reginfo.gov.
Outside parties may also request a meeting with the Administrator, or his/her designee. If you would like to request a meeting to provide views on a rule being reviewed at OIRA, email: Mabel_E._Echols@omb.eop.gov or call 202-395-6880 to schedule."
The regulatory identification number (RIN) for the deeming regulations is 0910-AG38.
Note: There are currently 34 scheduled meetings of interested parties with OIRA. The OIRA web site lists each of these meetings and who requested the meeting. After the meeting, the OIRA will list the meeting attendees and any public documents. A number of tobacco companies and electronic cigarette businesses or groups have already scheduled meetings, but so have several public health groups which have argued for stringent regulation of e-cigarettes, including the American Heart Association, American Academy of Pediatrics, American Thoracic Society, and Campaign for Tobacco-Free Kids.
Analysis of the FDA's Regulatory Approach
It is clear from the guidance that the approach the FDA is taking is as follows:
1. All electronic cigarette products that are sold directly to consumers (including e-liquids and vaping devices) will be required to submit a pre-market tobacco application which must be approved by the FDA in order for the product to stay on the market (it can remain on the market pending review of the application). The FDA has decided to use February 15, 2007 as the grandfather date for these regulations, and since no product currently on the market can be deemed "substantially equivalent" to products on the market eight years ago, all products will have to submit a PMTA. Products that are sold to wholesalers and retailers (i.e., not offered for sale directly to consumers) will not be required to submit a PMTA.
2. The PMTA must demonstrate that the product in question is beneficial to the public's health, taking into account not only the effects on smokers who use the product, but also the impact on nonsmokers - especially youth - who might initiate use of the product.
3. While a single PMTA may be submitted for multiple products, the demonstration in #2 must be made for every product individually. Different flavorings and different nicotine strengths constitute separate products. Thus, if a vape shop sells 100 flavors of e-liquids, and each is offered at four levels of nicotine, that shop will have to demonstrate for each of the 400 products that offering it for sale to the public will benefit the public's health. All of the requirements which I describe below apply to each separate e-liquid.
4. Vaping devices are also considered tobacco products. Thus, if a vaping shop offers for sale 20 different types of vaping devices, it will have to demonstrate for each device that offering it for sale will benefit the public's health. All of the requirements which I describe below apply to each separate device.
5. The PMTA should include the following information (this is just a partial list of the most cumbersome aspects of the application):
In general, for each product (meaning each flavoring/strength combination):
- research findings on the health effects of the product;
- research findings on the effect of the product on tobacco use among users of the product;
- research findings on the effect of the product on tobacco use initiation among youth; and
- research findings on the impact of the product on the population as a whole.
- a complete laboratory analysis of the constituents of the aerosol, with quantification of the concentrations of at least 29 specific chemicals;
- the health risks of the product compared to never using a tobacco product;
- the likelihood of youth initiating tobacco use with the new product;
- the likelihood of former smokers re-initiating tobacco use with the new product;
- the likelihood that consumers who initiate use of the product will later switch to more hazardous tobacco products;
- the likelihood that consumers will use the product along with other tobacco products;
- the likelihood of smokers switching to the product instead of quitting completely or trying to quit with an FDA-approved medication; and
- a discussion explaining how the data above demonstrate that the introduction of the product into the market will contribute to the protection of the public's health.
- For the laboratory testing, at least 10 samples from three different batches need to be tested;
- The testing must be done under a variety of conditions of use, such as varying voltages, and under conditions of intense and non-intense use;
- If a vaping device is the product in question, it must be tested with a range of e-liquids;
- If an e-liquid is the product in question, it must be tested with a range of vaping devices;
- For e-liquids and vaping devices, the shelf life must be determined under varying conditions of temperature and moisture;
- Changes in the aerosol flow rate and the constituents of the aerosol need to be tested over the life span of the e-liquid or vaping device;
- All existing studies on the safety and use of the product must be submitted, including the results of all clinical and non-clinical investigations;
- For any clinical studies of the product, the study sponsor must obtain an IND (investigational new drug) prior to initiating the research;
- In general, non-clinical studies are not enough to support the conclusion that a product is appropriate for the protection of the public's health - clinical studies of each product are generally necessary;
- For each product, genotoxicity and cytotoxicity studies are recommended;
- A thorough literature review should be conducted;
- The toxicological profile of each aerosol constituent should be provided - if no information is already available, toxicology studies need to be conducted;
- For each constituent of the aerosol, the particle size in the aerosol should be determined, as well as the deposition of through inhalation;
- For each constituent, the implications of the particle size and deposition during inhalation should be analyzed in terms of potential toxicity;
- Animal testing may be necessary to determine potential toxicity;
- For each aerosol constituent, the health effects of that chemical should be studied - both changes in physiological measurements and laboratory values (such as inflammatory markers) should be investigated;
- If there are no existing data on the toxicity of a particular chemical component of the aerosol, then computation modeling studies should be conducted using surrogate (i.e., similar) chemical structures;
- Consumer perception studies are highly recommended;
- Studies of the potential use of the product by nonsmokers (including youth) and existing smokers is highly recommended. Such studies must be related to the product itself or a similar product. Thus, an open-system vaping device could not submit information on the results of a study involving a first-generation cig-a-like product, and vice versa; and
- Puff topography studies should be included in the application.
- E-cigarette companies and businesses will not be allowed to market these products for smoking cessation; and
- Therefore, no smoking cessation claims will be allowed for any of these products.
Implications of the FDA's Regulatory Approach
1. The most important implication of the FDA's regulatory approach for electronic cigarettes is that the FDA has apparently decided that electronic cigarettes pose a much greater threat to the health of the public than the extremely toxic tobacco cigarettes which are killing more than 400,000 Americans each year. This is evident by the fact that the agency is requiring an unduly expensive and burdensome process for every single electronic cigarette or vaping device and e-liquid to remain on the market, while the agency gave a free pass for all of the existing tobacco cigarette brands. Tobacco cigarettes can continue to kill hundreds of thousands of consumers each year with few additional restrictions or safety requirements, while the much, much safer electronic cigarettes must go through a nearly impossible, expensive, and burdensome application process.
2. The successful submission of a PMTA will be nearly impossible. Just look at it this way: In order to submit a successful application, one must demonstrate the overall benefits of your product outweigh any risks, including the possible initiation of nicotine use by nonsmokers or former smokers. One must identify the individual and population-level benefits and risks and have a mechanism to model these effects over time in order to determine and quantify the net effect on the population's long-term health. However, in the tobacco control community, there exists no consensus on any one aspect of the potential benefits and risks. For example, some tobacco control scientists have argued that e-cigarettes impede smoking cessation, while others (myself included) have argued that e-cigarettes aid smoking cessation. With this degree of disagreement within the public health community, how the hell is a manufacturer possibly expected to wade through the quagmire in order to provide a demonstration of net public health benefits or risks? If scientists with 30 or more years of experience in tobacco control cannot agree upon even the individual benefits of e-cigarettes, how can a vape shop owner possibly be expected to demonstrate the long-term health consequences of allowing his particular e-cigarette product onto the market?
Moreover, there is no existing model to weigh potential risks and benefits, even if they could be quantified. For example, suppose a product could demonstrate a 15% rate of smoking cessation using the product, but that comes at the expense of 3% of youth initiating nicotine use with that product, of which 32.6% of the youth progress to cigarette smoking. How do you calculate and then weigh the risks and benefits? Is this going to result in a positive or negative net long-term public health benefit? This is an exceedingly complex question. If researchers with 30 years of experience in modeling health risks associated with changes in smoking policies cannot provide an answer, how can we expect a vape shop owner to provide the answer?
3. Putting together a PMTA will be prohibitively expensive and resource-intensive for all but the largest companies. Suppose a vape shop sells 100 flavors of e-liquid, and each comes at three nicotine levels. That vape shop owner is going to have to submit 300 PMTAs, each one demonstrating the toxicological properties, vapor constituents, health effects, consumer use, vaping topography, risk of youth initiation, and overall risk benefit ratio for that product. The time alone required to assemble the application is itself prohibitive, but when you consider the cost of just doing the laboratory analyses, no vape shop in the country is going to be able to afford it.
4. The regulations will result in the decimation of the e-cigarette industry and put thousands of e-cigarette entrepreneurs and shops out of business. There will be a major contraction of the industry as only the tobacco companies and perhaps the largest of the independent e-cigarette companies will be able to survive the burdensome regulatory process. In the long-term, these regulations will cause e-cigarette sales to plateau, ending the possibility that vaping devices could transform the nicotine market by creating a major shift from combustible tobacco products to much safer forms of nicotine delivery. This will be destructive to the public's health, both in the short- and long-term.
5. The regulations will create a monstrous bureaucracy, tying up thousands of hours of FDA time that could be better used to confront the smoking epidemic, which actually would save lives. Moreover, the creation of this bureaucracy will not directly protect the public's health. Instead, the FDA should have simply promulgated a set of uniform safety standards and regulations that would have immediately protected the public's health, putting an immediate end to battery explosions and other problems. These standards should have included basic quality control requirements, battery safety, and temperature/voltage regulation to prevent the formation of hazardous degradation products such as formaldehyde.
6. The regulations will essentially force the e-cigarette companies and businesses to lie to their customers by hiding from them the fact that these products were originally designed to help people quit smoking and that thousands of consumers have successfully quit smoking with these products. E-cigarette companies and businesses will not be able to communicate the truth and instead will have to rely on other "benefits" of e-cigarette use in their marketing, such as their sexiness, use by celebrities, or coolness. This marketing is much more likely to appeal to kids than truthfully informing consumers that these products were devised for the express purpose of helping people get off toxic cigarettes by providing a much safer alternative form of nicotine.
The Rest of the Story
The rest of the story is that FDA must be out of its mind. These deeming regulations should really be called "The Cigarette Protection Act of 2015." The regulations are an embarrassment to public health. They create stringent requirements for electronic cigarettes, while allowing the much more toxic real cigarettes to remain on the market, unencumbered and unchallenged by competing products that are much safer and that could have otherwise transformed the nicotine market away from combustible tobacco products, thus saving thousands of lives.
The regulations will decimate the e-cigarette industry, forcing thousands of small vapor shops and e-cigarette sellers out of business. This will no doubt result in many vapers returning to cigarette smokers and many potential quitters from trying to quit using these products.
After acknowledging that there is a continuum of risk among nicotine-containing products, with e-cigarettes at the opposite end of the spectrum from tobacco cigarettes, the FDA has chosen to ignore the risk differences and instead, to treat e-cigarettes much more stringently than tobacco cigarettes. To stay on the market, Marlboro cigarettes had to do nothing at all. But to stay on the market, much safer Vuse e-cigarettes, which have been shown to have very low emissions with non-detectable levels of all the major chemicals of concern, will have to conduct extensive research, both clinical and non-clinical studies, spending millions of dollars, in order to stay on the market for the long-term.
The regulations will also force e-cigarette companies and businesses to lie about the primary purpose and benefit of their products (an aspect of the regulations that I believe violates the free speech rights of the companies and could be successfully challenged in court).
Finally, the regulations do nothing to directly address the known hazards of electronic cigarettes to users, such as lack of battery safety which has resulted in battery explosions, and the presence of carcinogens like formaldehyde in the vapor which could have been prevented by setting standards for proper regulation of voltage and/or temperature.
I can only hope that the OIRA will disapprove the regulations, requiring major changes in the regulatory approach that bring it in line with the concept of public health. Otherwise, thousands of innocent people are going to be harmed in the short-term, and perhaps millions in the long-term.