Harmful/Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke

1. Harmful/Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke Tobacco Product Constituents Subcommittee Meeting June 8, 2010 Corinne G. Husten, MD, MPH Senior Medical Advisor Center for Tobacco Products, FDA

2. Statutory Requirements

3. Tobacco Control Act FDA “shall establish, and periodically revise as appropriate, a list of harmful and potentially harmful constituents, including smoke constituents, to health …..” Sec. 904(e) of the Federal Food, Drug, and Cosmetic Act (FFDCA)

4. Definitions in the Statute • Constituent: no specified definition • Smoke Constituent: “any chemical or chemical compound in mainstream or sidestream tobacco smoke that either transfers from any component of the cigarette to the smoke or that is formed by the combustion or heating of tobacco, additives, or other component of the tobacco product.” (Sec. 900(17) of the FFDCA)

5. Harmful/Potentially Harmful Constituents(H/PH)

6. Draft Guidance: “‘Harmful and Potentially Harmful Constituents’ in Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act” This is a draft guidance and is not for implementation. It was issued for comment purposes only. For the purpose of establishing “a list of harmful and potentially harmful constituents, including smoke constituents, to health in each tobacco product by brand and by quantity in each brand and subbrand,” as required under section 904(e) of the Act, FDA believes that the phrase “harmful and potentially harmful constituent” includes any chemical or chemical compound in a tobacco product or in tobacco smoke: a) that is or potentially is inhaled, ingested, or absorbed into the body; and

7. Draft Guidance: “‘Harmful and Potentially Harmful Constituents’ in Tobacco Products as Used in in Section 904(e) of the Federal Food, Drug, and Cosmetic Act” b) that causes or has the potential to cause direct or indirect harm to users or non-users of tobacco products. Examples of constituents that have the “potential to cause direct harm” to users or non-users of tobacco products include constituents that are toxicants, carcinogens, and addictive chemicals and chemical compounds. Examples of constituents that have the “potential to cause indirect harm” to users or non-users of tobacco products include constituents that may increase the exposure to the harmful effects of a tobacco product constituent by 1) potentially facilitating initiation of the use of tobacco products; 2) potentially impeding cessation of the use of tobacco products; or 3) potentially increasing the intensity of tobacco product use (e.g., frequency of use, amount consumed, depth of inhalation). Another example of a constituent that has the “potential to cause indirect harm” is a constituent that may enhance the harmful effects of a tobacco product constituent.

8. Purpose of the Subcommittee In two subcommittee meetings, • Review the example lists of harmful/potentially harmful constituents developed by other countries • Identify which chemicals or chemical compounds are appropriate for an initial FDA list of harmful/potentially harmful constituents • Identify established methods for measuring each constituent on the initial list • Identify other potentially important information or criteria for measuring the H/PH constituents on the initial list Subcommittees make preliminary recommendations to the full TPSAC regarding specific issues. The full Committee will deliberate on the recommendations from the Subcommittee and make the final recommendations to the Agency on these issues.

9. Questions to the Subcommittee for this meeting • What criteria do you recommend to TPSAC for selecting the H/PH constituents in tobacco products or tobacco smoke (which will be used in developing the initial list)? • What H/PH constituents do you recommend to TPSAC be included on the initial FDA list and how do they meet the criteria? • What established analytical methods do you recommend to TPSAC for assessing the quantity of each H/PH constituent in tobacco products or tobacco smoke?

10. Parameters for the First Subcommittee Meeting • FDA requests that the Subcommittee • Focus on H/PH constituents that are potentially ingested, absorbed or inhaled (e.g., absorbed from the product itself or combustion products that are inhaled) • Focus on chemicals/chemical compounds that are toxicants, carcinogens, or addictive

11. Parameters for the First Subcommittee Meeting • FDA requests that the Subcommittee • Identify the criteria that the Subcommittee will use for determining whether a constituent is a carcinogenic, toxicant, or addictive chemical or chemical compound that you recommend be included on the H/PH list • Identify constituents from the example WHO and country lists that you recommend for the initial FDA H/PH constituent list • Note: Different countries may use the term “constituent” differently, but we ask that the subcommittee have a consistent approach • Review the information from the additional example lists of H/PH constituents developed by various organizations to identify H/PH constituents that may be missing from the example WHO/country lists

12. Parameters for the First Subcommittee Meeting • FDA requests that the Subcommittee • Identify established analytical methods for assessing the quantity of each of the H/PH constituents in tobacco products or tobacco smoke • Focus first on whether methods to assess the quantities of each H/PH constituents exist (such as mass spectrometry) • Leave a detailed discussion of methods until after all the initial questions are answered • Note: There may be more than one established method for a particular constituent. When this is the case, the Subcommittee does not need to identify a single method.

13. Points of Clarification • Asking the Subcommittee to focus on carcinogens, toxicants, and addictive chemicals or chemical compounds does not imply that FDA will not be reviewing other chemicals or chemical compounds for possible inclusion on the H/PH list. • Providing information to the Subcommittee on the four disease outcomes of cancer, cardiovascular disease, respiratory effects, and addiction does not imply that FDA will not be reviewing other disease outcomes for assessing chemicals or chemical compounds for possible inclusion on the H/PH list. • FDA recognizes that H/PH constituents in smokeless tobacco may be under-represented on the example country lists and other organizations’ lists, and the request to use these example lists as a starting point for the Subcommittee’s discussion does not imply that FDA will not be reviewing other chemicals or chemical compounds in smokeless tobacco for possible inclusion on the H/PH list.

14. Recap: Questions to the Subcommittee for this meeting • What criteria do you recommend to TPSAC for selecting the H/PH constituents in tobacco products or tobacco smoke (which will be used in developing the initial list)? • What H/PH constituents do you recommend to TPSAC be included on the initial FDA list and how do they meet the criteria? • What established analytical methods do you recommend to TPSAC for assessing the quantity of each H/PH constituent in tobacco products or tobacco smoke?

15. Clarifying Questions?