Case 1:20-cv-00393-LMB-TCB Document 1406-9 Filed 08/12/22 Page 1 of 4 PageID# 35109
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`Exhibit 9
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`Case 1:20-cv-00393-LMB-TCB Document 1406-9 Filed 08/12/22 Page 2 of 4 PageID# 35110
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`Submission to Tobacco Products Scientific Advisory Committee
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`Caryn Cohen M.S.
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`Office of Science
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`Center for Tobacco Products
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`Food and Drug Administration
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`Document Control Center
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`Bldg. 71, Rm. G335, 10903
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`New Hampshire Ave.
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`Silver Spring, MD 20993-0002
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`To:
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`For:
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`Tobacco Products Scientific Advisory Committee (TPSAC)
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`TPSAC meeting 24-25th January 2018
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`Subject:
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`Modified Risk Tobacco Product Applications: Applications for 1005 system
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`with Marlboro Heatsticks, 1005 system with Marlboro Smooth Menthol
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`Heatsticks, and 1005 system with Marlboro Fresh Menthol Heatsticks [link]
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`Federal register:
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`82 FR 27487 15 June 2017
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`Submission date: 14 December 2017
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`Submission by:
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`David B. Abrams
`Professor
`Department of Social and Behavioral Sciences
`NYU College of Global Public Health
`New York University
`U nited States
`
`Frank Baeyens
`Professor of Psychology
`U niversity of Leuven
`Belgium
`
`Scott D. Bailin, JD
`Health Policy Consultant,
`Former Vice President and Legislative Counsel,
`American Heart Association
`United States
`
`Clive D. Bates
`Director, Counterfactual, London, Former
`Director Action on Smoking and Health,
`London
`United Kingdom
`
`Brian L. Carter
`Director of Scientific Communications
`Consumer Advocates for Smoke-free
`Alternatives Association
`U nited States
`
`Karl Fagerstrom
`President Fagerstrom Consulting AB
`Vaxholm
`Sweden
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`Konstantinos Farsalinos, M.D.
`Researcher
`Onassis Cardiac Surgery Center, Athens
`U niversity of Patras,
`Greece
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`Marewa Glover
`Professor, School of Health Sciences
`College of Health
`Massey University
`New Zealand
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`Page 1 of 20
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`1199_RESP00011600
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`PX-439
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`Case 1:20-cv-00393-LMB-TCB Document 1406-9 Filed 08/12/22 Page 3 of 4 PageID# 35111
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`Submission to Tobacco Products Scientific Advisory Committee
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`the primary causes of disease and other harms listed in these warnings. It is essential that relevant
`warnings are used — these statutory default warnings are not applicable, and no evidence exists to
`support their use. They would be misleading and damaging.
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`We argue that, beyond reasonable doubt, the IQOS and Heatstick products under evaluation create
`substantially reduced toxic exposures to users than cigarette smoking, and that implausible and
`u nknown mechanisms would be required for this substantial reduction in exposure not to translate into
`less risk of harm or reduced risks of tobacco-related diseases. Accordingly, we think that the three
`claims should be accepted as framed and tested by the applicant and the relevant orders made as soon
`as possible. A lengthy delay in deciding the application simply means more smoking, disease and death
`w hile smokers wait to have access to and proper information about a low-risk alternative to smoking.
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`Do the statements convey the magnitude of risk reduction? Our main concern is that the claims
`requested are too weak given the likely magnitude of exposure and risk reduction. For example, the
`phrase "presents less risk" could be understood as 5% less, 30% less, 70% less, or 90% less — and only
`the last of these is likely to be approximately correct. If consumers misperceive the extent of risk-
`reduction, then the result is likely to be more smoking than there otherwise would be.
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`2 Health impacts and relative risk of 1Q05
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`We consider that the IQOS product is a reduced-risk tobacco product creating exposures substantially
`lower than equivalent cigarette smoking. The magnitude of reduction in exposures and results of cell
`studies and human clinical trials justifies a conclusion, again, that the product will create substantially
`reduced risk and harm in users who switch from cigarette smoking.
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`The basis for this is the extensive science base developed by the manufacturer and published in high
`q uality peer-reviewed journals specializing in regulatory science. We consider the case rests on four
`main strands:
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`1. The physical and chemical processes involved are completely different to smoking.
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`2. The toxicity of the IQOS aerosol is far less than cigarette smoke.
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`3. Biomarkers of toxin exposure are substantially and rapidly reduced after switching from smoking to
`heated tobacco use.
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`4. Reduced exposure is expected to be translated to reduced harm and disease risk
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`2.1 The physical and chemical process involved are completely different
`Heated tobacco products have an inherently different design to cigarettes and operate at much lower
`temperatures. According to data from the manufacturer, the heated product design allows for electrical
`heating of the tobacco stick to reach a maximum temperature of 350°C (660°F). This compares to the
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`Case 1:20-cv-00393-LMB-TCB Document 1406-9 Filed 08/12/22 Page 4 of 4 PageID# 35112
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`Submission to Tobacco Products Scientific Advisory Committee
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`high combustion temperature of tobacco cigarettes, reaching up to 900°C (1650°F) during a puff,5 that
`create the mixture of solid and liquid particles and toxic gases. The lower temperature range is
`specifically designed to avoid combustion and the resulting toxic emissions. Several of the most harmful
`toxic chemicals in smoke are products of combustion,678 therefore, avoiding the combustion processes
`is expected to reduce the toxicity of the aerosol.
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`2.2 The chemical profile and toxicity of 1Q05 aerosol is different from cigarette smoke
`Evidence published from the manufacturer has clearly shown that the potentially toxic emissions from
`1005 are substantially lower compared to tobacco cigarettes.
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`Schaller et a19 evaluated 1005 aerosol for the presence of 59 compounds, including 54 priority toxicants
`in tobacco smoke that have been listed by authorities such as the World Health Organization, the U.S.
`Food and Drug Administration and Health Canada (Harmful and Potentially Harmful Chemicals —
`HPHC5).8 Different puffing regimes were tested, including ISO regime, Health Canada Intense regime and
`more intense puffing conditions, up to 110 mL puff volume and 4.5 seconds puff duration. Substantial
`reductions in toxic emissions, ranging from 60-99% for different compounds, compared to a
`standardized tobacco cigarette (3R4F) was observed.
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`Similar differences were observed recently in another study by the manufacturer comparing 1005 with
`commercial tobacco cigarettes.' Additionally, cytotoxicity and mutagenicity studies identified an 85-
`95% reduction in the potencies of 1005 compared to 3R4F cigarettes. The levels of nicotine emitted to
`the aerosol of 1005 were approximately 30% lower compared to 3R4F cigarettes using Health Canada
`Intense puffing regime. The latter finding was recently verified in an independent study comparing 1005
`with commercially-available tobacco cigarettes.' Additionally, it was found that the unused tobacco
`stick of 1005 contains similar concentration of nicotine as the tobacco of regular cigarettes, suggesting
`that nicotine is not added to the tobacco stick.
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`5 Baker RR. Smoke generation inside a burning cigarette: modifying combustion to develop cigarettes that may be less
`hazardous to health. Prog. Energy Combust. Sci. 2006;32:373-385. [link]
`6 U.S.DHSS. How Tobacco Smoke Causes Disease The Biology and Behavioral Basis for Smoking-Attributable Disease A Report
`of the Surgeon General. Public Health. U.S. Dept. of Health and Human Services, Public Health Service, Office of the Surgeon
`General; 2010. 792 p. [link]
`7 White JL, Conner BT, Perfetti TA, Bombick BR, Avalos JT, Fowler KW, et al. Effect of pyrolysis temperature on the
`m utagenicity smoke condensate of tobacco. Food Chem Toxicol. 2001;39:499-505. [link]
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`8 McGrath TE, Wooten JB, Geoffrey Chan W, Hajaligol MR. Formation of polycyclic aromatic hydrocarbons from tobacco: The
`link between low temperature residual solid (char) and PAH formation. Food Chem Toxicol. 2007 Jun;45(6):1039-50. [link]
`9 Schaller J-P, Keller D, Poget L, Pratte P, Kaelin E, McHugh D, et al. Evaluation of the Tobacco Heating System 2.2. Part 2:
`Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regul Toxicol Pharmacol. 2016 Nov
`30;81 Suppl 2:S27-47. [link]
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`10
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`11
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`Jaccard G, Tafin Djoko D, Moennikes 0, Jeannet C, Kondylis A, Belushkin M. Comparative assessment of HPHC yields in the
`Tobacco Heating System THS2.2 and commercial cigarettes. Regul Toxicol Pharmacol. 2017 Aug 14;90:1-8. [link]
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`Farsalinos KE, Yannovits N, Sarri T, Voudris V, Poulas K. Nicotine delivery to the aerosol of a heat-not-burn tobacco product:
`comparison with a tobacco cigarette and e-cigarettes. Nicotine Tob Res. 2017 Jun 16 .[Iink]
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