Altria Group, Inc. · NYSE:MO
Altria — Tobacco Science Research Conference 2019
20 slides from Altria's conference presentation, Sep 17, 2019
Slide 1: Preclinical Testing Of Flavors In E-vapor Products, Part 2: Preparation And Stability
Preclinical Testing Of Flavors In E-vapor Products, Part 2: Preparation And Stability Characterization Of Representative Flavor Mixtures Cameron R. Smith Tobacco Science Research Conference September 17, 2019 C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 1
Slide 2: Overview of Session
Overview of Session ▪ Part 1: Selection of Representative Flavor Mixtures Using a Structural Grouping Approach (Kim Ehman) ▪ Part 2: Preparation and Stability Characterization of Representative Flavor Mixtures (Cameron Smith) ▪ Part 3: In Vitro Cytotoxicity and Genotoxicity of Representative Flavor
Slide 3: Preclinical Testing of Flavors in E-vapor Products: Overview
Preclinical Testing of Flavors in E-vapor Products: Overview Selection Process Preclinical Preparation, Application Characterization & Ketones Stability E-Vapor Industry Terpenes Acids 5000+ Flavors PG1 Part 38 FlavorsIn-vitro Part 2 VG Acetals Phenols 200-300 Nicotine 38 Flavors Esters Pyridines Al
Slide 4: Objectives
Objectives ▪ Maximize the shelf life of flavor mixtures to avoid repetitive and time consuming batch characterization necessary in preclinical studies ▪ Evaluate the effectiveness of our shelf life stability strategy using gas chromatography-mass spectrometry (GC-MS) C. Smith l Regulatory Affairs l
Slide 5: Definition: Pre-blends
Definition: Pre-blends ▪ Basic concept: concentrated ingredients (flavors) are diluted and combined to make a final mixture or product ▪ Pre-blends (or concentrates) are commonly used in the food and beverage manufacturing industry due to prolonged shelf life, reduced packaging volume, and lower dis
Slide 6: Study Design
Study Design Longer Stability Shorter Stability Pre-blend I – 22 Pre-blend II – 7 Dilute with PG, VG, PG Nicotine VG Pre-blend III – 2 Nicotine 38 Flavors Pre-blend IV – 6 Pre-blend V – 1 Test Formulation C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 6
Slide 7: Pre-blend Categorization
Pre-blend Categorization ▪ Evaluated reactivity of compounds based on functional group characteristics - Alcohols < Aldehydes, Ketones & Esters < Enolizable Aldehydes & Ketones < α,β-unsaturated Ketones & Aldehydes < Acids and Bases ▪ Grouped compounds in minimum number of categories as possible to
Slide 8: Pre-blend Categories
Pre-blend Categories Aldehydes, Alcohols, Acetals, Ketones, Hydrocarbons – 22 Flavors I I – A,B,C α,β-unsaturated GroupsElectrophilic Volatility Ketones & Concentration & Aldehydes – 7 Flavors II Enolizable nucleophilic β-Dicarbonyls, Ketones & Esters – 2 Flavors III Basic Compounds – 6 Flavors IV A
Slide 9: Study Design
Study Design ▪ 1 Month Stability for Pre-blends - Refrigerated and Room Temperature Conditions ▪ 10 Days Stability for Test Formulations (All 38 Flavors) - Refrigerated and Room Temperature Conditions ▪ Acceptance Criteria - Pre-blends – ± 15% of initial value - Test Formulations – ± 20% of the init
Slide 10: Percent of Initial Concentration: Pre-Blend I
Pre-Blend IC Aldehydes, Alcohols, Acetals, Ketones, Hydrocarbons 120% Refrigerated Room Temp. a-pinene Percent of Initial Concentration 110% isoamyl alcohol 100% 90% benzyl alcohol 80% 2-methoxy-4-methylphenol 70% d-nonalactone 60% ethyl vanillin 50% 0 1 2 3 4 Time Points (weeks) C. Smith l Regulato
Slide 11: Percent of Initial Concentration: Ethyl Vanillin Stability
Pre-Blend IC Ethyl Vanillin Stability 120% Refrigerated Room Temp. Ethyl Vanillin Ethyl Vanillin 110% Percent of Initial Concentration PG Acetal 100% 90% 80% 70% 60% 50% 0 1 2 3 4 Time Point (weeks) C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 11
Slide 12: Percent of Initial Concentration: Pre-blend II
Pre-blend II Electrophilic α,β-unsaturated Ketones & Aldehydes 120% Refrigerated Room Temp. (E,Z)-2,6-nonadienal Percent of Initial Concentration 110% ketoisophorone 100% piperitone 90% ethyl maltol 80% furaneol 70% methyl cinnamate 60% dihydroactinidiolide 50% 0 1 2 3 4 Time Point (weeks) C. Smith
Slide 13: Percent of Initial Concentration: (E,Z)-2,6-Nonadienal Stability
Pre-blend II 120% Percent of Initial Concentration (E,Z)-2,6-Nonadienal Stability 110% (E,Z)-2,6-Nonadienal (E,Z)-2,6-Nonadienal PG Acetal 100% < 24 hrs. 90% Relatively Stable 80% 70% 60% Refrigerated Room Temp. 50% 0 1 2 3 4 Time Point (weeks) (E,Z)-2,6-Nonadienal Initial Time Point – 73% lower tha
Slide 14: Ethyl Maltol & Furaneol Stability
Pre-blend II Ethyl Maltol & Furaneol Stability Instrument Column Issue 120% Start End Percent of Initial Concentration ethyl maltol 110% 100% 90% furaneol 80% 70% 60% Refrigerated Room Temp. 50% 0 1 2 3 4 Time Point (weeks) C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019
Slide 15: Percent of Initial Concentration: Pre-blends IA, IB, III, IV
130% Pre-blend IA Pre-blend IB 130% Percent of Initial Concentration Percent of Initial Concentration 120% 120% 110% 110% 100% 100% 90% 90% 80% 80% 70% 70% 0 1 2 3 4 0 1 2 3 4 Time Point (weeks) Time Point (weeks) 130% Pre-blend III 130% Pre-blend IV Percent of Initial Concentration Percent of Initi
Slide 16: Study Design
Study Design Longer Stability Shorter Stability Pre-blend I – 22 Pre-blend II – 7 Dilute with PG, VG, PG Nicotine VG Pre-blend III – 2 Nicotine 38 Flavors Pre-blend IV – 6 Pre-blend V – 1 Test Formulation C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Final 16
Slide 17: Test Formulation with Nicotine - Refrigerated
Test Formulation with Nicotine - Refrigerated Pre-blend T0 T1IA - 1 day T2 - 7 days T3 - 11 days T0 T1 - 1 day T2 - 7 days T3 - 11 days (± 1 day) (± 1 day) (± 1 day) (± 1 day) Pre-blend IA Compounds Pre-blend II Compounds p-cymene 100% 97% 96% 97% (E,Z)-2,6-nonadienal 100% 94% 89% 79% 1-penten-3-one
Slide 18: Test Formulation without Nicotine - Refrigerated
Test Formulation without Nicotine - Refrigerated T2 - 7 days T3 - 11 days T2 - 7 days T3 - 11 days T0 T1 - 1 day T0 T1 - 1 day (± 1 day) (± 1 day) (± 1 day) (± 1 day) Pre-blend IA Compounds Pre-blend II Compounds p-cymene 100% 102% 104% 94% (E,Z)-2,6-nonadienal 100% 98% 99% 92% 1-penten-3-one 100% 9
Slide 19: Conclusion
Conclusion ▪ The use of pre-blends can substantially simplify the timely preparation and characterization necessary for preclinical testing ▪ Depending on the test formulation ingredients, pre-blends can be stable for a matter of months in refrigerated conditions ▪ All test formulation flavor ingred
Slide 20: Acknowledgements
Acknowledgements Altria Client Services, Richmond, Virginia, USA John H. Miller IV Niti Shah Ashutosh Kumar K. Monica Lee PMI R&D, Neuchâtel, Switzerland Felix Frauendorfer Philippe Guy Pierrick Diana, Anneke Glabasnia C. Smith l Regulatory Affairs l Altria Client Services l TSRC Sept 17, 2019 l Fin
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