Tobacco Product Analysis; Scientific Workshop; Request for Comments, 33424-33426 [2013-13084]
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Agenda: On July 23, 2013, during the
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Notice of this meeting is given under
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U.S.C. app. 2).
Dated: May 28, 2013.
Jill Hartzler Warner,
Acting Associate Commissioner for Special
Medical Programs.
[FR Doc. 2013–13082 Filed 6–3–13; 8:45 am]
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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.
Notice of public workshop;
request for comments.
ACTION:
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, rollyour-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 https://
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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Federal Register / Vol. 78, No. 107 / Tuesday, June 4, 2013 / Notices
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 https://
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
https://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 https://
www.regulations.gov.
SUPPLEMENTARY INFORMATION:
tkelley on DSK3SPTVN1PROD with NOTICES
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 https://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
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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, Nnitrosonornicotine) (NNN), and 4(methylnitrosamino)-1-(-pyridyl)-1butanone (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 5methylchrysene) 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
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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,
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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 5methylchrysene:
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.
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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
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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 https://
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–0559]
Eli Lilly and Co.; Withdrawal of
Approval of a New Drug Application for
ORAFLEX
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is withdrawing
approval of a new drug application
(NDA) for ORAFLEX (benoxaprofen)
Tablets, held by Eli Lilly and Co. (Lilly),
Lilly Corporate Center, Indianapolis, IN
46285. Lilly has voluntarily requested
that approval of this application be
withdrawn, and has waived its
opportunity for a hearing.
DATES: Effective June 4, 2013.
FOR FURTHER INFORMATION CONTACT:
Martha Nguyen, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 6250,
Silver Spring, MD 20993–0002, 301–
796–3601.
SUPPLEMENTARY INFORMATION: On April
19, 1982, FDA approved ORAFLEX
(benoxaprofen) Tablets, a nonsteroidal
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]]>Agencies
[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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 https://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
[[Page 33425]]
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 https://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 https://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 https://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 https://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 https://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
