Electronic Nicotine Delivery Systems (“ENDS”) in the USA

Implications for Research and Policy

Nathan Cobb, MD Research Investigator, Schroeder Institute

PRESENTED AT: SOCIETY FOR RESEARCH ON NICOTINE AND TOBACCO

BALTIMORE, MD 2/25/2010

Overview

•  Definitions and Characteristics •  Available Data •  Research Implications •  Policy Implications

Electronic Nicotine Delivery Systems

•  Definitions & Characteristics – Common characteristics – Vaporization process – Use – Refilling

Definition

•  WHO –  “designed to deliver nicotine to the lungs” –  “draw a mixture of air and vapours into the respiratory

system” –  “contain electronic vaporization systems, a rechargeable

battery … electronic controls and replaceable cartridges that may contain nicotine and other chemicals”

•  FDA –  “battery powered device that provides inhaled dose of

nicotine by delivering a vaporized propylene glycol/nicotine mixture.”

•  WHO Study Group on Tobacco Regulation. Report on the Scientific Basis of Tobacco Product Regulation: Third Report of a WHO Study Group. 955. 2009. Geneva, Switzerland. •  Westenberger BJ. Evaluation of e-cigarettes. Published FDA correspondence, 5/4/2009. Available at http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm .

Cigarette

•  “A slender roll of cut tobacco enclosed in paper and meant to be smoked …”

•  Etymology: French cigarette, diminutive of cigare cigar, from Spanish cigarro … possibly from the Mayan sik'ar, from sik, tobacco.

New Oxford American Dictionary 2nd edition. Oxford University Press, Inc. 2005.

Sample Devices

Common Components

•  Battery •  Heating element •  Absorbent with solution

– Nicotine – Propylene glycol – Flavorings

Vaporization

•  As propylene glycol (or other alcohol) is heated to 40-65C and forcibly drawn through the device, it vaporizes. – The combination of the negative pressure and

heating causes the vaporization – the exact same process is used to create theatre fog.

– Theoretically, nicotine is carried along in this process.

Use

•  The user inhales, creating negative pressure in the device

•  A mechanical switch enables a heating element. •  Negative pressures draws propylene glycol over

the heating element, causing to it vaporize.

–  Polyethylene  glycol  holds  water  from  breath  vapor,  forming  the  “smoke”,  similar  to  theatrical  fog.  

“Electronic  cigare-e  uses  advanced  microelectronic  technology  and  supercri6cal  physical  atomiza6on  technology  to  atomize  the  high-­‐purity  and  exci6ng  nico6ne  dilu6on  extracted  from  tobacco  into  smoke  for  smoker’s  sucking  and  accordingly  meet  the  needs  of  those  smokers.”  

     -­‐  Smoking  Anywhere  Manual  

Refilling

•  Multiple suppliers of “juice” independent of device manufacturers

•  Marketed for 1-1.3ml refill per cartridge – Current high is 36mg/refill – Single bottle may contains

as much as 1 gram of nicotine in the volume of a shot glass.

Refill Process

Distribution & Sourcing

•  No comprehensive data available •  Most devices appear to be made in China

and then exported/rebranded •  In US, primary distribution appears to be

online and in mall kiosks •  Origin of refill solution and and nicotine

concentrate is unclear – pesticide vrs pharma?

Available Data

•  Device Content and Delivery –  Industry sponsored - Laugesen – FDA & Georgetown/Schroeder

•  Physiologic Effect – Eissenberg 2010

•  Behavioral – None to date

Laugesen Report - 2008

•  Ruyan e-cigarette •  Private company – Health New Zealand

– Activities funded by Ruyan Ltd – Assays done by commercial laboratories

•  Methods – Variety of methods to detect multiple chemical

constituents – Puffing methods poorly described

Laugesen Report - 2008

•  Also found trace levels of TSNAs in the cartridge •  Other compounds detected

– Acetaldehyde – Acetone – Formaldehyde – PAHs

•  Lower levels than cigarettes, but higher than FDA-approved NRT

•  Limitations of FDA testing apply here

Content Testing

•  FDA testing in house (Westenberger) •  GU/SI performed by Arista Labs •  Both groups tested same 2 devices (NJoy High

& Smoking Everywhere High.) •  Tested cartridge content and vapor content for:

– nicotine content –  impurities (TSNA, TSI) – contaminants

Westenberger BJ. Evaluation of e-cigarettes. Published FDA correspondence, 5/4/2009. Available at http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm .

Testing Results - Contaminants

•  FDA –  Tobacco specific nitrosamines (TNSAs) in Njoy, not

Smoking Everywhere in heated cartridge contents –  Diethylene glycol in 1 sample.

•  Georgetown/SI –  butyl acetate, diethyl carbonate, benzoic acid ,

quinoline, dioctyl phthalate 2,6-dimethyl phenol •  Both

–  TSI (cotinine, anabasine, myosmine, B-nicotyrine) in all samples

Vapor Testing

•  FDA 2009 – 100cc puffs via sparging apparatus; each puff

pulled with 100cc syringe through a gas trapping bottle. Contents analyzed using gas chromatography.

•  GU/SI 2009 – 35cc puffs into XAD-4 pads, under ISO

conditions. Pad contents analyzed using gas chromatography.

Testing Results - Nicotine

Nicotine Variability

•  All cartridges yielded less nicotine than labeled.

•  FDA found different contents in identically labeled cartridges (26.8-43.2 mcg).

•  GU/SI found that first 10 puffs yielded approximately 4x nicotine of later puffs

•  Different testing methods yielded markedly different amounts of nicotine per puff.

Eeissenberg

•  Tested serum and craving levels after using 2 brands of ENDS (Njoy and Crown 7; 16mg) against “usual brand”

•  “instructed to puff normally and then puffed ad libitum 10 times (30-s interpuff interval)”

•  Assessment at 5,15,30,45 min, then cycle repeated.

Eissenberg T. Electronic nicotine delivery devices: Ineffective nicotine delivery and craving suppression after acute administration. Tob Control 2010, Feb;19(1):87-8 19.

Testing Results – Serum & Craving

Eissenberg T. Electronic nicotine delivery devices: Ineffective nicotine delivery and craving suppression after acute administration. Tob Control 2010, Feb;19(1):87-8 19.

Testing Results – Serum & Craving

Eissenberg T. Electronic nicotine delivery devices: Ineffective nicotine delivery and craving suppression after acute administration. Tob Control 2010, Feb;19(1):87-8 19.

Wheat from Chaff

•  TSI indicate tobacco origin of the nicotine; they are found in NRTs.

•  Diethylene glycol is the most feared contaminant in PG products, and the cause of several mass poisonings.

•  Nicotine content is highly varied across brands, batches and puffs

Research Implications

•  Safety – Pharmacodynamics

•  Dose delivered, rapidity, serum concentrations? •  Maximum dose feasible?

– Exposure to harmful chemicals leading to health effects such as lung and other cancers through laboratory and human studies

Research Implications

•  Machine Testing •  Consumer behavior •  Device limits (temperature etc)

•  Behavior – Cessation aid – Delaying or subverting smoking cessation – Enticing former smokers to resume smoking – Serving as a gateway for new smokers

Policy Implications

•  When is an ENDS not an ENDS? •  Change the carrier? •  Change the dosing? •  Change the absorption? •  Change the electronics?

•  What defines a “tobacco product”? •  What other drugs could be legally

concentrated and delivered this way?

Policy Implications

•  Most manufacturers have stuck to a harm reduction argument, although a few have made cessation claims.

•  Proponents have argued that by removing the primary carcinogens the “e-cigarette” becomes a less harmful cigarette.

•  Currently, FDA regulation has been blocked in the courts:

Sottera v FDA

“More importantly, it is apparent from Congress's broad definition of "tobacco product" that it intended the Tobacco Act's regulatory scheme to cover far more than the fixed array of traditional tobacco products at issue in Brown & Williamson Tobacco. Both the FLCAA and the CSTHEA only apply to "cigarettes," "little cigars," and "smokeless tobacco," which Congress defined with considerable specificity, yet the Tobacco Act applies to "tobacco products," which Congress defined expansively as "any product made or derived from tobacco that is intended for human consumption.”

Sottera v US FDA, US District Court DC, 1/14/2010

Conclusions

•  Product and manufacturing variability appear to be significant

•  Safety concerns are different and independent from cigarette concerns

•  Definitions and classifications are a challenge for regulation, but should not exempt the products from such.

References

•  Eissenberg T. Electronic nicotine delivery devices: Ineffective nicotine delivery and craving suppression after acute administration. Tob Control 2010, Feb;19(1):87-8 19.

•  Flouris AD, Oikonomou DN. Electronic cigarettes: Miracle or menace? BMJ 2010;340:c311 340.

•  Pauly J, Li Q, Barry MB. Tobacco-Free electronic cigarettes and cigars deliver nicotine and generate concern. Tob Control 2007, Oct;16(5):357 PMCID: PMC259855416.

•  Simpson D. World: E-Cigarettes are here. Tob Control 2009, Apr;18(2):80-1 18 •  Wollscheid KA, Kremzner ME. Electronic cigarettes: safety concerns and regulatory

issues. Am J Health Syst Pharm 2009; 66(19):1740-1742. •  WHO Study Group on Tobacco Regulation. Report on the Scientific Basis of Tobacco

Product Regulation: Third Report of a WHO Study Group. 955. 2009. Geneva, Switzerland, World Health Organization. WHO technical report series.

•  Westenberger BJ. Evaluation of e-cigarettes. Published FDA correspondence, 5/4/2009. Available at http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm172906.htm .

Electronic Nicotine Delivery Systems (“ENDS”) in the USA

Implications for Research and Policy

NATHAN K. COBB, MD 1,2

PETER SHIELDS, MD, PHD 2

JUSTIN BYRON, MA 3

DAVID ABRAMS, PHD 1,3

1 SCHROEDER INSTITUTE FOR TOBACCO RESEARCH AND POLICY STUDIES 2 LOMBARDI CANCER CENTER, GEORGETOWN UNIVERSITY MEDICAL CENTER 3 JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH