
[Federal Register Volume 78, Number 107 (Tuesday, June 4, 2013)]
[Notices]
[Pages 33424-33426]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-13084]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0212]


Tobacco Product Analysis; Scientific Workshop; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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    The Food and Drug Administration (FDA), Center for Tobacco 
Products, is announcing a scientific workshop to obtain input on the 
chemical analysis of tobacco products. The analyses of tobacco products 
include developing test methods and evaluating method performance to 
ensure the results of the analyses are reliable and accurate. This 
scientific workshop will focus on understanding the testing of tobacco 
filler and smoke from cigarettes, roll-your-own (RYO) tobacco, and 
smokeless tobacco products for specific chemicals. FDA is also opening 
a public docket to receive comments on these topics.
    Dates and Times: The public workshop will be held on July 30, 2013, 
from 8:30 a.m. to 5:30 p.m., and on July 31, 2013, from 8:30 a.m. to 4 
p.m. Individuals who wish to attend the public workshop must register 
by close of business on July 1, 2013. Submit either electronic or 
written comments to the docket by September 30, 2013.
    Location: The public workshop will be held at 9200 Corporate Blvd., 
Rockville, MD 20850, 1-877-287-1373.
    Contact Person: Janie Kim, Office of Science, Center for Tobacco 
Products, Food and Drug Administration, 9200 Corporate Blvd., 
Rockville, MD, 20850, 1-877-287-1373, FAX: 240-276-3761, email: 
workshop.CTPOS@fda.hhs.gov.
    Registration to Attend the Workshop and Requests for Oral 
Presentations: If you wish to attend the workshop, make an oral 
presentation at the workshop, or view the free webcast, you must 
register by submitting an electronic or written request by July 1, 
2013. Please submit electronic requests to http://surveymonkey.com/s/3RGVYFT. A confirmation email will be sent to your registered email at 
least 2 weeks prior to the workshop date. Those without email access 
may register by contacting Janie Kim (see Contact Person). Please 
provide contact information for each attendee, including name, title, 
affiliation, address, email address, and telephone number. Registration 
is free, but early registration is recommended because seating is 
limited. FDA may limit the number of participants from

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each organization as well as the total number of participants based on 
space limitations. Registrants will receive confirmation once they have 
been accepted for the workshop. Onsite registration on the day of the 
workshop will be based on space availability. If registration reaches 
maximum capacity, FDA will post a notice closing registration for the 
workshop at http://www.fda.gov/TobaccoProducts/NewsEvents/ucm238308.htm.
    There will be opportunities for audience participation at this 
workshop. FDA has included topics for comment in section II of this 
document. FDA will do its best to accommodate requests to speak during 
the workshop sessions, although questions from the audience may be 
limited. In addition, we strongly encourage submitting comments to the 
docket (see Comments).
    If you need special accommodations due to a disability, please 
contact Janie Kim (see Contact Person) at least 7 days before the 
workshop.
    Comments: Regardless of attendance at the public workshop, 
interested persons may submit comments on any of the topics for 
discussion in section II of this document by September 30, 2013. Submit 
electronic comments to http://www.regulations.gov. Submit written 
comments to the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. It 
is only necessary to send one set of comments. Identify comments with 
the docket number found in brackets in the heading of this document. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to 
the docket at http://www.regulations.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In April 2012, FDA held a scientific workshop that focused on 
understanding how tobacco reference products and general testing 
methods are used to analyze tobacco products (77 FR 14814, March 13, 
2012; for more information see http://www.fda.gov/TobaccoProducts/NewsEvents/ucm291530.htm). The scientific workshop that will be held on 
July 30 and July 31, 2013, will focus on understanding the testing of 
tobacco filler and smoke from cigarettes, RYO tobacco, and smokeless 
tobacco products for tar, nicotine, and carbon monoxide (TNCO), 
tobacco-specific nitrosamines (TSNAs), and polycyclic aromatic 
hydrocarbons (PAHs). The workshop will include discussion of the 
analytical methods used for measuring these constituents in tobacco 
products and smoke.
    The workshop will include scientific experts who will present 
scientific and technical information on the testing of tobacco 
products. Such experts could include, but are not limited to, 
scientists from governmental agencies, academia, tobacco product 
manufacturers, and contract testing laboratories.
    FDA is interested in receiving scientific information at the 
workshop and in the docket. Information from the scientific workshop 
may assist us in developing future scientific workshops regarding the 
analysis of tobacco products.

II. Workshop Topics for Discussion

    The scientific workshop will include discussion of the analytical 
methods for measuring the following constituents in tobacco products 
and smoke:
     TNCO in cigarette smoke;
     TSNAs (total TSNAs, N-nitrosonornicotine) (NNN), and 4-
(methylnitrosamino)-1-(-pyridyl)-1-butanone (NNK)) in smoke and tobacco 
filler (i.e., cigarette, RYO, smokeless); and
     PAHs (benzo[a]pyrene, naphthalene, chrysene, 
benz[j]aceanthrylene, benzo[a]anthracene, benzo[b]fluoranthene, 
benzo[k]fluoranthene, benzo[c]phenanthrene, cyclopenta[cd]pyrene, 
dibenz[a,h]anthracene, dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, 
dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, indeno[1,2,3-cd]pyrene, and 5-
methylchrysene) in smoke and tobacco filler (i.e., cigarette, RYO, 
smokeless).
    FDA would like to engage in detailed discussions on chemical test 
methods to understand the principles and aspects of these analyses. 
Aspects of analytical methods encompass solution preparation, 
extraction, separation, detection, and method performance parameters 
with criteria.
    FDA will explore all or some of the following topics during this 
scientific workshop:

A. TNCO in Cigarette Smoke

    1. A description of the different extraction steps used when 
analyzing cigarette smoke for TNCO.
    2. Typical concentration ranges for TNCO and the potential method 
adjustments to accommodate different cigarette strengths and physical 
parameters.
    3. The optimal solvents, extraction solution, standards, and 
reference tobacco product(s) typically used when analyzing TNCO.
    4. The method variability and whether or not it is dependent upon 
different products in your portfolio.
    5. The specific method challenges and limitations when testing 
TNCO, such as environmental moisture, water measurement variability, 
and extraction efficiency.
    6. The major sources of variability (e.g., smoking machine or 
regimen, sample preparation, separation, and detection).

B. TSNAs (Total, NNN, and NNK) in Tobacco Filler (Cigarette, RYO, 
Smokeless) and Cigarette Smoke

    7. The different extraction steps used when analyzing TSNAs in 
tobacco filler, smokeless tobacco, and cigarette smoke particulate.
    8. The optimal solvents, extraction solutions, standards, and 
reference tobacco product(s) needed during the extraction of TSNAs from 
tobacco filler or, as applicable, a Cambridge filter pad.
    9. The rationale for using isotopically labeled internal standards, 
instead of targeted surrogates or external standards for TSNAs. The 
number of isotopically labeled internal standards needed to calculate 
the amount of TSNAs in a sample.
    10. The challenges with isotopically labeled internal standards, 
including: (a) The commercial availability of internal standards or 
their analogs; (b) individual versus (vs.) mixture of internal 
standards; cost of internal standards; (c) deuterated vs. \13\ C 
labeled internal standards; and (d) concerns of proton exchange with 
deuterated labeled internal standards.
    11. The typical concentration ranges for total TSNAs, NNN, and NNK 
and any potential method adjustments to accommodate for different 
cigarette strengths and physical parameters.
    12. The major sources of method variability, e.g., include sources 
from the smoking machine or regimen, sample preparation, separation, 
and detection of different tobacco product types and strengths.
    13. The specific method challenges and limitations when testing NNN 
and NNK.
    14. The differences in separation, detection, and limits of 
detection/quantitation when comparing liquid chromatography/mass 
spectrometry and gas chromatography/thermal energy analyzer for TSNA 
analysis.

C. PAHs in Tobacco Filler (Cigarette, RYO, Smokeless) and Cigarette 
Smoke

    For the PAHs benzo[a]pyrene, naphthalene, chrysene,

[[Page 33426]]

benz[j]aceanthrylene, benzo[a]anthracene, benzo[b]fluoranthene, 
benzo[k]fluoranthene, benzo[c]phenanthrene, cyclopenta[cd]pyrene, 
dibenz[a,h]anthracene, dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, 
dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, indeno[1,2,3-cd]pyrene, and 5-
methylchrysene:
    15. The different extraction steps used when analyzing PAHs in 
tobacco filler, smokeless tobacco, and cigarette smoke particulate and 
any applicable cleanup techniques used.
    16. The optimal solvents, extraction solutions, standards, and 
reference tobacco product(s) needed during the extraction of PAHs from 
tobacco filler or, as applicable, a Cambridge filter pad.
    17. The rationale for using isotopically labeled internal standards 
instead of targeted surrogates or external standards for PAHs. The 
number of isotopically labeled internal standards needed to calculate 
the amount of PAHs in a sample.
    18. The challenges with isotopically labeled internal standards, 
including: (a) The commercial availability of internal standards or 
their analogs; (b) individual vs. mixture of internal standards, cost 
of internal standards; (c) deuterated vs. \13\ C labeled internal 
standards; and (d) concerns of proton exchange with deuterated labeled 
internal standards.
    19. The typical concentration ranges for each of the PAHs listed in 
this document and any potential method adjustments to accommodate for 
different cigarette strengths and physical parameters.
    20. The major sources of method variability, e.g., include sources 
from the smoking machine or regimen, sample preparation, separation, 
and detection of different tobacco product types and strengths.
    21. The different methods necessary to separate and detect for 
PAHs. Provide the number of methods and steps typically used for each 
from extraction to detection.
    22. The specific method challenges and limitations when analyzing 
testing PAHs, including: (a) Isomer separation and identification, (b) 
effects of tobacco blend, and (c) low vs. high molecular weight PAHs 
(volatility and sensitivity).
    23. The differences in separation, detection, and limits of 
detection/quantitation when comparing gas chromatography/mass 
spectrometry, liquid chromatography/ultraviolet detection, and liquid 
chromatography/mass spectrometry for PAH analysis.

D. General Method Testing for TNCO, TSNAs, and PAHs in Tobacco Filler 
(Cigarette, RYO, Smokeless) and Cigarette Smoke

    24. The solution stability for prepared solutions and procedures to 
ensure their integrity.
    25. The typical storage conditions and shelf life (i.e., expiration 
dates) for tobacco product standards and samples.
    26. The standard, reference, or known sample solutions used as 
blanks or for quality control (QC), working, and check standards when 
testing TNCO, TSNAs, and PAHs.
    27. The system suitability and acceptance criteria for each test 
method. The discussion may include calibration, QC, working, 
bracketing, and verification standards, confirmation ion ratio for mass 
spectrometry, chromatographic parameters (i.e., retention times, 
tailing factor, or peak resolution), injector precision, and blanks.
    28. The critical system suitability parameters that are critical 
when testing TNCO, TSNAs, and PAHs.
    29. The actions taken when any system suitability criterion fails, 
including standards, QC, and subsequent sample analyses.
    30. The typical run sequence when testing samples for TNCO, TSNAs, 
and PAHs.
    31. The equations to calculate sample concentrations for TNCO, 
TSNAs, and PAHs.
    32. Examples of chromatograms of reference standards and for 
measured TNCO, TSNAs, and PAHs in tobacco products.

E. Validation or Method Performance for TNCO, TSNAs, and PAHs in 
Tobacco Filler (Cigarette, RYO, Smokeless) and Cigarette Smoke

    33. The specific details when evaluating each validation parameter, 
which may include limit of detection, limit of quantification, method 
detection limit, accuracy, recovery, linearity, range, precision 
(repeatability), and specificity.
    34. The determination of each criterion for each validation 
parameter when evaluating TNCO, TSNAs, and PAHs.
    35. The steps taken when validation parameter criteria are not met.
    36. The validation parameters that are performed with reference 
tobacco products or standards.
    37. The types and strengths of tobacco product samples used during 
validation and method development.
    38. The process taken to revalidate a test method when changes to 
the method (i.e., solvent, extraction method, or column) are made.
    39. The validation process when using a rotary and linear smoking 
machine with a non-intense and intense smoking regimen.
    40. The robustness or ruggedness tests that are conducted for 
extraction efficiency, solution stability, and small changes in 
instrument parameters.

III. Transcripts

    Please be advised that as soon as a transcript is available, it 
will be accessible at http://www.regulations.gov. It may be viewed at 
the Division of Dockets Management (see Comments). A transcript will 
also be available in either hard copy or on CD-ROM, after submission of 
a Freedom of Information request. Written requests are to be sent to 
Division of Freedom of Information (HFI-35), Office of Management 
Programs, Food and Drug Administration, 5600 Fishers Lane, rm. 6-30, 
Rockville, MD 20857.

    Dated: May 24, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-13084 Filed 6-3-13; 8:45 am]
BILLING CODE 4160-01-P


