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

0.0 0.3 0.6 0.9 1.2 1.5 1.8

Cardiovascular Disease

Pulmonary Disease

Lung cancer

million deaths

Do e-cigarettes generate lower levels of harmful or potentially harmful substances?

ToxicantRange 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, μg 0.2–5.61 1.6–52 0.2

Acetaldehyde, μg 0.11–1.36 52–140 0.11

Acrolein, μg 0.07–4.19 2.4–62 ND

o-Methylbenzaldehyde, μg 0.13–0.71 … 0.07

Toluene, μg ND–0.63 8.3–70 ND

p,m-xylene, μg ND–0.2 … ND

NNN, ng ND–0.00043 0.0005–0.19 ND

NNK, ng ND–0.00283 0.012–0.11 ND

Cadmium, ng ND–0.022 … 0.003

Nickel, ng 0.011–0.029 … 0.019

Lead, ng 0.003–0.057 … 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, JDGeneral Counsel, Chief Compliance Officer

Agenda1. 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