The Devil’s in the Regulations Impact on Product Testing May 18, 2009 Richard G. Higby President / Managing Director

 An independent, ISO 17025:2005 accredited laboratory (A2LA, UKAS) specializing in the characterization of tobacco and tobacco smoke  Locations: Richmond, VA; Kingston upon Thames  Founded: April 2000  Ownership: Molins PLC

Pick any two…

 Annual registration of products  Testing requirements (passage + 24 months)  Data submission (passage + 36 months)

 Ingredients  Tar, nicotine yield  Smoke constituents ◦ Mainstream ◦ Side stream  Tobacco constituents  All brands

 “Brand” distinguished by: ◦ Tobacco (blend) ◦ Tar content (yield) ◦ Nicotine content (yield) ◦ Flavor (menthol, non-characterizing flavor) ◦ Size (King, 100, slim, etc.) ◦ Filtration (non-filter, charcoal) Every stick and blend variant manufactured is a “brand”

Smoke Constituents Blend A Kings Full flavor RegularLights Ultra Lights Full flavor MentholLights Ultra Lights 100s Full flavor RegularLights Ultra Lights Menthol Full flavor Lights Ultra Lights ABC Tobacco  Blend B Kings Regular Full flavor Lights Ultra Lights Menthol Full flavor Lights Ultra Lights 100s Regular Full flavor Lights Ultra Lights Menthol Full flavor Lights Ultra Lights Total12

 Health Canada  ANVISA – Brazil  WHO –TFI ◦ Framework Convention on Tobacco Control ◦ TobReg ◦ TobLabNet

Health Canada/ANVISATobReg  Ammonia  Aromatic amines (4)  Benzo[a]pyrene  Carbonyls (9)  Eugenol  Hydrogen cyanide  Mercury  Metals (6)  Nitrosamines (4)  NOx  Organics (5)  Phenolics (7)  Semivolatiles (3)  Tar, nicotine, CO  Aromatic amines (2)  Benzo[a]pyrene  Carbonyls (3)  Hydrogen cyanide  Mercury  Metals (6)  Nitrosamines (4)  NOx  Benzene  1,3-butadiene  Ethylene oxide  Tar, Nicotine/free nicotine, CO

Health Canada/ANVISATobReg  Ammonia  Aromatic amines (4)  Benzo[a]pyrene  Carbon monoxide  Carbonyls (9)  Hydrogen cyanide  Mercury  Metals (6)  Nitrosamines (4)  NOx  Organics (5)  Phenolics (7)  Semivolatiles (3)  Tar and nicotine

Health Canada/ANVISATobReg  Alkaloids (5)  Ammonia  Benzo[a]pyrene  Eugenol  Humectants (3)  Metals (7)  Nitrate  Nitrosamines (4)  pH  Propionate  Sorbic acid  Triacetin

 FTC Smoking (35/60/2; 24h conditioning)  ISO Smoking (35/60/2; 48h conditioning)  “Canadian” Intense Smoking (45/30/2; 100% vent blocking)  “Massachusetts” smoking (45/30/2; 50% vent blocking)  Other methods yet to be defined

Health Canada/ANVISATobReg  Smoke constituents ◦ Mainstream methods (14) ◦ Mainstream constituents (47) ◦ Side stream methods (14) ◦ Side stream constituents (45)  Tobacco constituents ◦ Methods (12) ◦ Constituents (27)  Smoking regimes (2) Total Methods (40) Total Endpoints (121)  Smoke constituents ◦ Mainstream methods (10) ◦ Mainstream constituents (24)

 Health Canada ◦ In vitro assays are required to measure:  Cytotoxicity (neutral red uptake assay)  Mutagenicity (Ames Salmonella assay)  Genotoxicity (micronucleus)  Family Smoking Prevention and Tobacco Control Act ◦ Toxicology is mentioned in terms of reduced harm products

 ISO 17025:2005 ◦ Laboratories are accredited in accordance with the recognized International Standard ISO/IEC 17025:2005 General Requirements for the Competence of Testing and calibration Laboratories. This accreditation demonstrates technical competence for a defined scope and the operation of a laboratory quality management system (refer to joint ISO-ILAC-IAF Communiqué dated 18 June 2005).  Good Laboratory Practices (GLP) ◦ Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for pharmaceuticals (only preclinical studies), agrochemicals, cosmetics, food additives, feed additives and contaminants, novel foods, biocides, detergents etc.... GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments.

 ISO 17025:2005 ◦ 22 quality procedures  Good Laboratory Practices ◦ 104 standard operating procedures

 United States Lobbying activity surrounding the bill to grant the US Food and Drug Administration regulatory control over tobacco products, which passed the House in a vote on April 2nd and will be taken up by the Senate Health, Education, Labor and Pensions HELP Committee this week, was intense in the first quarter of 2009, with Altria, the lone industry player to support the measure, spending $4.29 million on the FDA bill and a couple of other pieces of tobacco legislation, while rivals Reynolds American and Lorillard paid lobbyists $1.59 million and $850,000, respectively, in that period, according to Federal lobbying records. (Washington Post 05/11)

 Clinical use trials ◦ E.g. 100 smokers with puff profiling  Toxicology ◦ In vitro assays  Cytotoxicity  Neutral red uptake assay  Clastogenicity  Micronucleus, sister chromatid exchange  Mutagenicity  Ames Salmonella assay ◦ Other assays  Inflammation