Altria Group, Inc. · NYSE:MO
Altria — 2018 CORESTA Congress
21 slides from Altria's conference presentation, Oct 24, 2018
Slide 1: Modification of Standardized Methods for the Measurement of Nicotine in Very Low Nicotine Content Cigarettes
Modification of Standardized Methods for the Measurement of Nicotine in Very Low Nicotine Content Cigarettes Anthony Brown, Matt Melvin, Yezdi Pithawalla, Jennifer Smith, Karl Wagner Altria Client Services LLC, 601 E. Jackson St., Richmond, VA 23219, U.S.A. Kiana Manson, Jay Pierotti, Hui Liu, Kerry
Slide 2: FDA – Tobacco Product Standard for Nicotine Level of Combusted Cigarettes – ANPRM
FDA – Tobacco Product Standard for Nicotine Level of Combusted Cigarettes – ANPRM Altria Client Services LLC | Regulatory Sciences | Anthony Brown | October 24, 2018 | Final | ST29 - 2018 CORESTA | 2
Slide 3: FDA – Tobacco Product Standard for Nicotine Level of Combusted Cigarettes – ANPRM
FDA – Tobacco Product Standard for Nicotine Level of Combusted Cigarettes – ANPRM Potential Scope: Cigarette Pipe Cigarettes Cigars Tobacco Tobacco Roll your Bidis & Waterpipe own (RYO) Kreteks Tobacco Potential Maximum Nicotine Level for cigarette tobacco filler: 0.3 - 0.5 mg/g Potential Analytical
Slide 4: Commercial Cigarette Fillers vs Proposed Maximum Nicotine Level in ANPRM
Commercial Cigarette Fillers vs Proposed Maximum Nicotine Level in ANPRM 25 Nicotine in filler (mg/g) 20 15 10 5 0 Proposed A B C D E F G H Max Nicotine Commercial Cigarette Fillers Level in ANPRM Altria Client Services LLC | Regulatory Sciences | Anthony Brown | October 24, 2018 | Final | ST29 - 20
Slide 5: Analytical Testing Method – ANPRM
Analytical Testing Method – ANPRM FDA asked: Should the proposed tobacco product standard specify a method for the analysis of nicotine? FDA believes the test method should: 1. Provide consistent results across accredited testing facilities 2. Demonstrate a high level of specificity, accuracy, and p
Slide 6: Three Pillars of Effective Analytical Testing
Three Pillars of Effective Analytical Testing Consensus Laboratory Proficiency Certified Tobacco Standardized Methods Testing Reference Materials Altria Client Services LLC | Regulatory Sciences | Anthony Brown | October 24, 2018 | Final | ST29 - 2018 CORESTA | 6
Slide 7: List of Analytical Testing Methods – ANPRM
List of Analytical Testing Methods – ANPRM 12 methods referenced in ANPRM Only two consensus CRM 35, Continuous Flow Analysis (Filler) standardized test methods GC-FID (Filler) referenced in ANPRM GC-MS confirmatory method (Filler) GC-MS using SPME (Filler) CRM 87, GC-MS (Filler) published Other f
Slide 8: Standardized Methods for Nicotine
Standardized Methods for Nicotine Filler Smoke CRM No 62: 2005 CRM No 87: 2018 ISO 10315: 2013 Determination of nicotine in Determination of Determination of nicotine tobacco and tobacco nicotine in tobacco in smoke condensates - products by gas products by GC-MS Gas chromatographic chromatographic
Slide 9: Determination of Nicotine in Tobacco Filler
Determination of Nicotine in Tobacco Filler Methods CRM No 62 – GC-FID Calibration range 5.0 – 40 mg/g CRM No 87 – GC/MS Calibration range 0.64 – 64 mg/g Repeatability and reproducibility values Determined through interlaboratory collaborative studies Range of nicotine levels in a variet
Slide 10: ALCS Modifications of CRM No 62 and CRM No 87
ALCS Modifications of CRM No 62 and CRM No 87 Modified Modified Parameter CRM 62 CRM 87 CRM 62 CRM 87 LOQ (mg/g) 5.0 0.02 0.64 0.064 Calibration range (mg/g) 5 to 40 0.02 to 40 0.64 to 64 0.064 to 64 Injection mode split splitless split split Regression model equal 1/x 1/x 1/x Sample mass : Extract
Slide 11: Validation Results – ALCS Modifications
Validation Results – ALCS Modifications Modified Modified Modified Parameter CRM 62 CRM 62 CRM 87 MTBE Hexane LOQ (mg/g) 0.02 0.02 0.064 S:N ratio 19 34 152 % Deviation at LOQ (n=6) 3% 9% 14% Instrument precision at LOQ (n=6) 1.2% 0.9% 1.1% Calibration range (mg/g) 0.02 to 40 0.02 to 40 0.064 to 64
Slide 12: SRM NIST 3222 Cigarette Tobacco Filler
SRM NIST 3222 Cigarette Tobacco Filler Prepared from air cured, low nicotine tobacco Processed and supplied by 22nd Century Group, Inc. Developed through NIST and FDA Center for Tobacco Products Certified value for nicotine: 0.117 ± 0.018 mg/g Based on 5 distinct data sets from NIST and CDC
Slide 13: Sample Results – ALCS Modifications
Sample Results – ALCS Modifications SRM NIST 3222a CRM 62 CRM 62 CRM 87 Air cured, low nicotine filler MTBE Hexane Nicotine (mg/g) “as-is” (n=15) 0.154 ± 0.009 0.149 ± 0.019 0.170 ± 0.015 %Recovery from Fortification (n=3) 94% 90% 88% Intermediate Precision (n=15) 5.8% 12.6% 8.9% RT1b CRM 62 CRM 62
Slide 14: Standardized Methods for Nicotine
Standardized Methods for Nicotine Filler Smoke CRM No 62: 2005 CRM No 87: 2018 ISO 10315: 2013 Determination of nicotine in Determination of Determination of nicotine tobacco and tobacco nicotine in tobacco in smoke condensates - products by gas products by GC-MS Gas chromatographic chromatographic
Slide 15: SPECTRUM Cigarettes
SPECTRUM Cigarettes ® 23 Different cigarette configurations Manufactured by 22nd Century Group, Inc. Distributed by Research Triangle Institute Reported range of nicotine in filler1 0.28 – 25 mg/g Reported range of nicotine in smoke2 0.01 -1.68 mg/cigt Available through NIDA’s drug supply progra
Slide 16: Determination of Nicotine in Smoke
Determination of Nicotine in Smoke Method ISO 10315 – GC-FID Calibration range 0.08 – 8.00 mg/cigt Repeatability and reproducibility values Determined through interlaboratory collaborative studies Range of nicotine in a variety of traditional cigarettes: 0.09 – 1.41 mg/cigt SPECTRUM® Cigaret
Slide 17: ALCS Modifications of ISO 10315
ALCS Modifications of ISO 10315 Modified Method ISO 10315 ISO 10315 LOQ (mg/cigt) 0.08 0.01 Calibration range (mg/cigt) 0.08 to 8 0.01 to 2 Injection mode split split Regression model equal 1/x Y-intercept include ignore Extraction volume 20 ml 10 ml Modified method calibration range brackets VLNC c
Slide 18: Validation Results – ALCS Modifications
Validation Results – ALCS Modifications Parameter Modified ISO 10315 LOQ (mg/cigt) 0.01 S:N ratio at LOQ (n=30) 15.9 % Deviation at LOQ (n=6) 2% Instrument precision at LOQ (n=6) < 1% Calibration range (mg/cigt) 0.01 to 2.00 Linear regression (r2) ≥ 0.995 Altria Client Services LLC | Regulatory Scie
Slide 19: ISO Smoke Yields – ALCS Modifications
ISO Smoke Yields – ALCS Modifications NIST 3222 cigarette filler was used to make handmade cigarettes NIST 3222 (n=5) TPM Nicotine %RSD Air cured, low nicotine filler (mg/cigt) (mg/cigt) High Yield 10.5 0.019 8% Med Yield TPM 6.1 0.013 Nicotine 17% Cigarette (mg/cigt)b %RSD Low Yielda 3.3 (mg/cigt)
Slide 20: Conclusions
Conclusions Existing standardized methods are not fit for the analysis of VLNC tobacco products Standardized methods can be modified for the analysis of nicotine in VLNC tobacco products Future steps Create VLNC reference products Standardize methods that include VLNC products Establish
Slide 21: For copies of this presentation visit the Altria's Science Website
For copies of this presentation visit the Altria’s Science Website at www.altria.com/alcs-science Altria Client Services LLC | Regulatory Sciences | Anthony Brown | October 24, 2018 | Final | ST29 - 2018 CORESTA | 21