FDA Regulation of Tobacco Washington, DC October 21, 2015 What is Relative Risk-a look at the Continuum of Harm Aruni Bhatnagar, PhD, Professor, University of Louisville, Volunteer, American Heart Association Patricia I. Kovacevic, General Counsel and Chief Compliance Officer, Nicopure Labs LLC, The Halo Company Moderated by Scott Ballin, JD, Health Policy Consultant

Tobacco Product Harm Reduction: The Cardiovascular Perspective Aruni Bhatnagar, Ph.D. Professor of Medicine University of Louisville Louisville, KY

Cardiovascular Disease is the Leading Cause of Death in Smokers Cardiovascular Disease Pulmonary Disease Lung cancer million deaths

Do e-cigarettes generate lower levels of harmful or potentially harmful substances? Toxicant Range in Content in Aerosol From 12 E-Cigarette Samples per 15 Puffs* Range in Content in Conventional Cigarette Micrograms in Mainstream Smoke From 1 Cigarette Content in Nicotine Inhaler Mist per 15 Puffs* Formaldehyde, μg0.2– –520.2 Acetaldehyde, μg0.11–1.3652– Acrolein, μg0.07– –62ND o-Methylbenzaldehyde, μg0.13–0.71…0.07 Toluene, μgND– –70ND p,m-xylene, μgND–0.2…ND NNN, ngND– –0.19ND NNK, ngND– –0.11ND Cadmium, ngND–0.022…0.003 Nickel, ng0.011–0.029…0.019 Lead, ng0.003–0.057…0.004 Goniewicz et al., Tob Control (2014) 23:133

E-cigarettes generate particulate matter Fuoco et al., Environ Pollution (2014) 84:523 E-cigarettes Conventional cigarettes Main mode around 150 nm, smaller mode at 10 nm 20-27% particles are estimated to be deposited in the circulatory system and organs Higher e-liquid nicotine content associated with higher number of particles Longer puffing time results in more particles Mainstream aerosol has a particle size distribution of 165 nm 25-35% particles are likely to be deposited in tissues

Are e-cigarettes reduced harm products? Harm depends on the level of exposure, which might increase with persistent e-cigarette use For conventional cigarettes, the dose response for cardiovascular mortality is non-linear Most of the risk of smoking is at low doses: 80 % of the harm at <3 cigarettes/day Pope et al., Circulation (2009) 120:941

Nicotine is not an innocuous drug E-cigarettes contain very low levels of carcinogenic alkaloid NNK Trace levels of nornicotine, anatabine, and anabasine (1-2 % of nicotine) Variable doses of nicotine Nicotine is a psychoactive and vasoactive drug Increases heart rate and blood pressure Enhances cognition and suppresses appetite Affects release and metabolism of neurotransmitters such as dopamine, norepinephrine and epinephrine Relatively non-toxic, but long-term effects remain unknown

E-cigarettes and public health Acceptance of e-cigarettes has the potential to reverse social norm Efficacy as cessation aid is unclear (some studies have shown that they are as effective as other nicotine replacement therapies) Some surveys report that a majority of e-cigarette users completely replaced tobacco cigarettes with e-cigarettes Dual use persists at moderately high levels E-cigarette use could increase nicotine addiction and could promote smoking Harm = toxicity x usage, if toxicity is decreased, but use is higher then there is little harm reduction.

FDA’s current tobacco regulatory scheme and harm reduction Patricia I. Kovacevic, JD General Counsel, Chief Compliance Officer

Agenda 1.Very, very brief overview of the Tobacco Control Act and how it will apply to nicotine-containing vaping products (i.e., though deeming) 2.Where is deeming now, why is it important? 3.Do current FDA legislation/regulation/guidances take into account different risk profiles of products? 4.What should we strive for from a regulatory point of view for recognition of the risk continuum? 5.Are there constructive regulatory solutions? 6.How can the industry, public health and academia shape regulation? 7.Immediate opportunities