Tobacco Documents Online

*se Response(Taxicity) Assessment Review of the literature and experimental data to derive the amount of reduction in a particular smoke constituent that would result in a decrease in biological activity. In the absence of such an analysis, our current recommendation is to achieve reductions of 90% or greater. I 6ZC8bLS80Z I 17777 'i-7 'ir _, 7I i'-7 1 i For Difcuwion Puvpau Only

Smo' i. .g and Harm Reduction "We agree with the overwhelming medical and scientific consensus that cigarette smoking causes lung cancer and other serious diseases." gww.nhiljp,morr(s.com "We take the pursuit of harm reduction as a priority. We are pursuing harm reduction in a responsible way. We welcome involvement of the public health community." WSA presentation to WHO "We will develop and launch a conventional cigarette with a significant reduction in potentially harmful smoke constituents by the middle of 2002." State of the Business Address 12/07/00 94£8VL980Z , F«amussim rurposa Only

Ir 5££81~L580Z ' Acceptability Testing Fa Disw.m Pn^µwa. Only

0 I Acceptability Testing ' Concern Level II -Level II + Pii:.3Lilk~i `,l3'.i: IN m -94-Day Inhalation L££8tiL580Z ~ 7„ I I I ~ ~ I Par Diwwrinn Pmpo.e. Only

Acceptability Testing ~- -- - - ~-Y _- ~ ' Concern Level II -Level II + -90-Day Inhalation NtT~ ]fdCmmxiffunlmAkavry The highest tier is concern level III that would include in addition to all the other tests a 90 day inhalation study using rats.

SCoR Product - Timeline • Begin INBIFO Evaluation of 1st Prototype January 2001 • Specifications for 2nd Prototype March 2001 • Make 2nd Prototype INBIFO Samples April 2001 • Begin INBIFO Evaluation of 2nd Prototype May 2001 • Results INBIFO Evaluation of 1st Prototype -January 2002 • Results from INBIFO short-term tests " • Results from INBIFO Evaluation of 2nd Prototype May 2002 • Launch July 2002 • Initiate Human Studies after May 2002 Let me end with the overhead on the timeline for SCoR

These are the steps in the typical risk assessment scheme. It is reasonable to think of the approach to harm reduction in these terms. Hazard identification is the finding of targets to address. In terms of disease categories they are: lung cancer, CVD, and COPD. This can also go beyond that to the identification of targets for reduction in chemistry and in biological tests. This step is conducted by all of WSA. Toxicity Assessment is more commonly known as dose-response assessment. This is the stage where we say how large of a reduction would be meaningful. This step is conducted by all of WSA. Exposure assessment is how much to people take in. This means doing human studies. This step is principally conducted by the human studies group. Risk Characterization is putting it all together. This step is conducted principally by Product Assessment.

Hazard Identification Provide recommendations in order to result in reduced-harm associated with major smoking-related diseases. • smoke constituent(s) targets for reduction/removal • appropriate biological tests. YA.a19GHMVwaWVtimAlmvV ~~~~H+~WN'.+~Y This is the first step-in the Risk Assessment paradigm. Hazard ID involves providing recommendations in order to result in reduced harm associated with major smoking related diseases. Specifically identifying smoke constituent targets to reduce or remove and determine the appropriate biological testing that should be done. A major point is that we are making product changes with the ultimate goal of affecting human health.

Process for Reduced-Harm Product Use and Claims MupYWliryTUb 1 -S~mY.flremhlry 1 -O~nbKFIIY -~~bX ry ~9~LNnanbinFebWn ~ Sp.d.IHCmnWictlen £ g~NVmqdueKn 1 Tab,i(n.aN : T..b,lii..GM 3 E ~ ffi ~ ~ -- ~ 8 euMkMw. TwtlnY . Po~ HumnE~n SM1mETmnHUm.n lmCTamH~~nun ~ V m Mx.~ NWNEILM81uNr ~ E~ Sd~~ € 1 -&wimk.nW ~` -9mewMUea B° EyYlpnbkpy .HemHnnlm F ~ 1 w r.a wtrq f7 6-12 Months 12-36 Months 12-36 Months 5-20 YBSPs iwm:Da~ma.~„~wa. icn.brb.unp~mleer.k~ur.nl wvoa.r..e.~~n This is the version submitted to the IOM. Overview of the process. Similar to FDA approach for drugs where look at safety and efficacy, we are looking at acceptability and reduced harm claims. As always acceptability test and subjective testing and adding additional work as part of claim and accessing human exposure EXAMPLE Provisional Product Claim- May reduce exposure to CO Product Claim - Reduced exposure to CO may decrease risk of CVD Confirmed Product - Claim reduced risk of CVD

Prccess'Fbr Reduced-Harm Product Use and Claims ., ~ AtosptabNity TWs - Smoke Chemistry I - (ien0toxlcity I - Cyiotoxicity I Sub chronicinhalation ( 8pec1N Harm R.ducHon E Speciai Harm Reduction T.sts, if needed ~ Tests, if needed e.g.OrgaN V E ~ System Teating ,5 cc a ~ v ~ Y L a ~ C ~ ~ Q Sub).ctiws T.sting > p, Smoke Paneis Human Exposure Short-Tenn Human Long Term Human M.asur~ro~nt Health ENect Studies Health Effects Studi Epidemiology I - Biomarkers d - Biomarkers of - Hartn Reduction I exposure I Effect Monitoring 6-12 Months 12-36 Months 12-36 Months 5-20 Years Time for testing, not development For Disnwion Purposes Only as! m 6Z£8ti1880Z