E - CIGARETTES: WHAT’S THE REAL MEDICAL INNOVATION BREAKTHROUGH? Dr Kevin Bridgman - Chief Medical Officer & Director Nicovations is a wholly owned subsidiary of BAT

Aims Size and Cause of the Problem Evidence for Tobacco Harm Reduction What Should e-cigarettes Deliver? How to Control Vapour Composition The Need for Standards

The scale of The Problem – the size of The Prize. Declines in developed countries Offset by increases in developing countries / population growth Rate of change reversing Tobacco related mortality projected at 1 billion in 21 st century Ng M et al. JAMA 2014; 311(2): (Accessed 5th Jan 2015)

Tobacco product exposures Rutqvist LE, Curvall M et al 2011; Harm Reduction Journal 8(11) p 1-9 o > 5000 chemicals o 69 Carcinogens o Carbon monoxide o Arsenic o Hydrogen cyanide o Heavy metals GothiaTek ® Standard o Constituent standard o Manufacturing standard o Consumer information chemicals/ (Accessed 27th Jan 2015)

Providing an alternative: Swedish snus Ramström and Wikmans Tobacco Induced Diseases 2014, 12:14 Tobacco related deaths (per 100,000) Men and women Sources: Eurobarometer, Swedish Central Bureau of Statistics – accessed online 28 Nov 2014 Daily use of tobacco (% population) Sweden

Future tobacco and nicotine populations Number of smokers (assuming constant prevalence and medium variant projected population) (Tobacco atlas Ed.3) Number of smokers (assuming impact of harm reduction alternatives with impact similar to Swedish snus experience) * Number of smokers (assuming reduced prevalence of -1.0 % per year, medium variant projected population) (Tobacco atlas Ed.3) American Cancer Society Tobacco Atlas, 3 rd Edition chapter 31 *Swedish Central Bureau of Statistics – accessed online 28 Nov 2014

What should an alternative product deliver?

Anatomy of an electronic cigarette Increasing user options/variability

3 Key factors affect vapour quality

1/ Formulation Composition Pharma grade nicotine Propylene glycol Glycerol Water Flavours (food grade)

Formulations as a source of toxicants: An approach

2/ Device material interactions with the formulation or aerosol Materials testing: Extractables Leachables Mitigation: Materials selection

Mitigation: Compatibility -Right solution viscosity for wicking -Right coil heating profile Dry wicking protection -Alert on empty -Overheat failsafe Thermal decomposition: Both Propylene Glycol and Glycerol known to thermally decompose to toxic carbonyls: Formaldehyde Acetaldehyde Acrolein Acetone 3/ Design and Operating Parameters Kosmider et al Nic Tob Res 2014; doi: /ntr/ntu078

Formulations as a source of toxicants: An approach

In-use vapour quality variation between brands (1/2) Goniewicz (2013): 12 Polish, 1 UK brand, 3 cartridges, 150 puffs Goniewicz et al Tob Control 2013; 0: 1-7. doi: /tobaccocontrol

In-use vapour quality variation between brands (2/2) Goniewicz (2013): 12 Polish, 1 UK brand, 3 cartridges, 150 puffs Goniewicz et al Tob Control 2013; 0: 1-7. doi: /tobaccocontrol

Manufacturing Standards Ohta et al Bunseki Kakagu 2011; 60(10) In-use vapour quality variation within brands Ohta (2011): Japanese brands: 10 samples of each, 3x10 puff sessions

EpiAirway TM tissue is a highly differentiated in vitro human airway culture Cigarette smoke reduced cell viability to 12% at 6hrs Ecigs showed no such decrease and displayed results similar to untreated air controls EpiAirway TM Data – in vitro cytotoxicity model for aerosol exposure Submitted for Publication: Neilson L, Mankus C, Thorne D, Jackson G, DeBay J, Meredith C

E-cigarette standards: Considerations Design -Formulation -Device materials & construction Testing -Electrical testing -Child resistant packaging -Vapour testing -Through use -Through life (stability/shelf-life) Manufacturing -Quality management system to avoid product variability -Release specification

A Compelling Public Health Opportunity Ensure products are: -Attractive to smokers -Meet agreed standards -Meaningfully safer than cigarettes Responsible marketing targeted at adult smokers Distribution freedoms to compete with cigarettes (not pharmacy only) EU Ban OR

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