Comment to FDA - IQOS Systems Modified Risk Tobacco Product Applications
Comment by The Heartland Institute on IQOS Modified Risk Tobacco Product Application
Dr. Scott Gottlieb
U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
Re: Docket No. FDA-2017-D-3001: Modified Risk Tobacco Product Applications for IQOS Heating Systems
August 18, 2017
Dear Commissioner Gottlieb:
There are an estimated 39 million adult smokers in the United States, and smoking may cause up to 480,000 deaths per year. If such rates persist, estimates suggest over 9.6 million Americans will die from smoking-related illnesses over the next 20 years.
Billions of dollars have been spent on campaigns to reduce smoking rates, yet public health advocates’ only message to smokers has simply been, “Quit or die.”
A third and much more realistic option is tobacco harm reduction, “which explicitly includes the continued use of tobacco or nicotine, and is designed to reduce the health effects of tobacco use.”
It is the smoke produced by burning tobacco, not the ingestion of nicotine, that ought to be the target of public health campaigns. Tobacco harm reduction efforts educate smokers about alternative nicotine delivery systems—including smokeless tobacco, such as snus, electronic nicotine delivery systems, and heat-not-burn (HNB) cigarettes, all of which are reduced-risk products (RRPs).
Nicotine is one of the most intensively studied drugs in history, and research has consistently shown it to be a main driver of traditional tobacco cigarette use. However, even though nicotine has proven to be addictive, it is not considered a highly hazardous drug. It does not cause cancer, and it does not play any significant role in pulmonary or cardiovascular diseases. Nicotine is a mild stimulant and/or relaxant and has many of the same properties as caffeine, another plant-derived addictive substance consumed by Americans in a wide variety of products.
Nicotine abstention, like caffeine abstention, is uncomfortable and sometimes “unachievable for many users.” Both nicotine and caffeine are stimulants that enhance concentration and mental performance, encourage a sense of well-being, and elevate mood. Both raise heart rates and blood pressure levels transiently during use. Neither is directly responsible for cancer, emphysema, or heart disease.
According to the Tobacco Advisory Group of the Royal College of Physicians, “Nicotine itself is not especially hazardous, and if nicotine could be provided in a form that is as acceptable and effective as a cigarette substitute, millions of lives could be saved.”
Tobacco harm reduction products provide satisfying doses of nicotine that mimic the physiological and psychological sensations of smoking and are less harmful. Such products “empower smokers to gain control over the consequences of their nicotine addiction.”
It is also important to note the Food and Drug Administration (FDA) understands the greatest harm produced by cigarettes is linked to the high temperatures of combustion, which produces thousands of toxic compounds that, when inhaled hundreds of thousands of times over a smoking career, leads to many smoking-related diseases.
HNB technology is a unique tobacco harm reduction tool because it has the “ability to regulate and distill flavor and nicotine at lower temperatures.” Several brands have been introduced and tested in various international markets.
In addition to iQOS by Philip Morris International (PMI), Reynolds American, Inc. tested Revo, an HNB with a hot charcoal tip that heats tobacco and a glycerin solvent, creating flavor. British American Tobacco has two HNB technologies: iFuse is a “hybrid” that heats liquid into a vapor, which then flows through tobacco at temperatures around 200 to 400 degrees Celsius, and Glo heats tobacco to approximately 240 degrees Celsius.
Studies have compared HNB products by analyzing the “presence and relative concentrations of harmful and potentially harmful constituents (HPHCs).” In 2011, FDA’s Center for Tobacco Products identified 93 HPHCs in tobacco products and smoke, and distinguished 18 as “essential to evaluate.”
A 2016 study published in Toxicology in Vitro provided a “comparative assessment of the biological impact of heated tobacco aerosol from the tobacco heating system … and smoke from a combustible cigarette.” The study examined bronchial epithelial cultures exposed to iQOS vapor and found significant reductions in biological markers compared to when cigarette smoke is regularly inhaled.
Through its new iQOS HNB device, PMI’s “key aspiration [is] to demonstrate that [its] products have a risk reduction profile approaching that of cessation.” PMI has conducted and published numerous studies of four different platforms of RRPs, including two e-vapor products and two HNB systems. PMI has also created a rigorous evaluation process to assess the health impacts of HNB, including a risk assessment model, conducted using rodents, to address cardiovascular disease, chronic obstructive pulmonary disease (COPD), and lung cancer.
Comparing rodents exposed to cigarette smoke to those exposed to a HNB aerosol, PMI Science analyzed pulmonary function, tissue morphology, lung inflammation, and molecular network perturbations, all of which are associated with COPD. Their findings suggest exposure to RRPs can significantly lower the risk of COPD and that iQOS is an effective tobacco harm reduction tool.9
RRPs, including HNB, must be recognized by FDA as tobacco harm reduction tools. PMI Science has provided FDA with a comprehensive assessment of their product and should be permitted to place it on the market as a cigarette substitute.
In the 2009 Family Smoking Prevention and Tobacco Control Act, FDA created a modified risk tobacco product (MRTP) applications, which provide companies an opportunity to submit their products to “FDA to evaluate whether a tobacco product may be sold or distributed for use to reduce harm or the risk of tobacco-related disease.” Since then, not one application has been approved by FDA. In the first applications brought to the regulatory body, FDA denied Swedish Match North America Inc.’s MRTP application regarding snus smokeless tobacco, in December of 2016. Numerous studies suggest that snus is significantly less harmful than tobacco cigarettes, and ought to qualify as a RRP. Should FDA approve iQOS, the agency will be noting the importance of such products for tobacco harm reduction purposes.
On July 28, you noted that “we need to envision … a world where less harmful alternative forms [of tobacco], efficiently delivering satisfying levels of nicotine, are available for those adults who need or want them …” As a regulatory body that aims to protect public health, FDA should encourage the development of safer and more satisfying cigarette substitutes, facilitate fact-based communications about their relative risks, and make them available to U.S. smokers who may be unable or unwilling to achieve complete nicotine and tobacco abstinence on their own.
State Government Relations Manager
The Heartland Institute
 Brad Rodu, et al., “Vaping, E-cigarettes, and Public Policy Toward Alternatives to Smoking,” The Heartland Institute, February 20, 2017, p. 12-13, https://www.heartland.org/publications-resources/publications/vaping-e-cigarettes-and-public-policy-toward-alternatives-to-smoking.
 Brad Rodu, For Smokers Only: How Smokeless Tobacco Can Save Your Life (Los Angeles, CA: Sumner Books, 1995), p. 29
 Harm Reduction in Nicotine Addiction: Helping People Who Can’t Quit, Royal College of Physicians, October 2007, https://shop.rcplondon.ac.uk/collections/books-1/products/harm-reduction-in-nicotine-addiction-helping-people-who-cant-quit?variant=6509405637.
 Riccardo Polosa, et al., “A Fresh Look at Tobacco Harm Reduction: The Case for the Electronic Cigarette,” Harm Reduction Journal 10 (October 2013), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850892.
 Edward Anselm, “Tobacco Harm Reduction Potential for ‘Heat Not Burn,’” R Street Institute, February 2017, https://www.rstreet.org/wp-content/uploads/2017/02/85.pdf.
 Anita R. Iskandar et al., “A Systems Toxicology Approach for Comparative Assessment: Biological Impact of an Aerosol from a Candidate Modified-Risk Tobacco Product and Cigarette Smoke on Human Organotypic Bronchial Epithelial Cultures,” Toxicology in Vitro, March 2017, http://www.sciencedirect.com/science/article/pii/S0887233316302314.
 “Building the Evidence for RRPS,” PMI Science, https://www.pmiscience.com/our-goals/building-evidence-rrps.
9 “Testing a Prototypic RRP in an in Vivo Model of COPD,” PMI Science, https://www.pmiscience.com/toxicological-assessment/systems-toxicology/experimental-data-production/vivo-systems/testing.
 “FDA Takes Action on Applications Seeking to Market Modified Risk Tobacco Products,” Food and Drug Administration, December 14, 2016, https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm533219.htm.