Guidance for Industry
Reporting Harmful and Potentially   
Harmful Constituents in Tobacco  
Products and Tobacco Smoke Under  
Section 904(a)(3) of the Federal Food,  
Drug, and Cosmetic Act   
DRAFT GUIDANCE  
This guidance document is being distributed for comment purposes only. 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication  in  the  Federal  Register  of  the  notice  announcing  the  availability  of  the  draft 
guidance.   Submit comments to the Division of Dockets Management (HFA-305), Food and 
Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD   20852.   Alternatively, 
electronic comments may be submitted to  http://www.regulations.gov.  All comments should be 
identified with the docket number listed in the notice of availability that publishes in the Federal 
Register. 
For questions regarding this draft document, contact the Office of Science in the Center for 
Tobacco Products at 877-CTP-1373 or by e-mail at TobaccoIndustryQuestions@fda.hhs.gov. 
U.S. Department of Health and Human Services   
Food and Drug Administration   
Center for Tobacco Products (CTP)   
March 2012  Guidance for Industry 
Reporting Harmful and Potentially 
Harmful Constituents in Tobacco 
Products and Tobacco Smoke Under 
Section 904(a)(3) of the Federal Food, 
Drug, and Cosmetic Act 
DRAFT GUIDANCE 
Additional copies are available from:  
Food and Drug Administration 
Center for Tobacco Products 
Document Control Center 
Building 71, Room G335 
10903 New Hampshire Avenue 
Silver Spring, MD 20993-0002 
Phone: 240-276-1717 
http://www.fda.gov/tobaccoguidance 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Tobacco Products (CTP) 
March 2012  Contains Nonbinding Recommendations
Draft  Not for Implementation 
TABLE OF CONTENTS 
I.  INTRODUCTION .........................................................................................................................................1 
II.  BACKGROUND............................................................................................................................................2 
III.  HPHCS TO BE REPORTED TO FDA .......................................................................................................3 
IV.  WHO SUBMITS 904(a)(3) REPORTS........................................................................................................5 
V.  WHEN 904(a)(3) REPORTS ARE SUBMITTED TO FDA ......................................................................5 
A.   PRODUCTS MARKETED PRIOR TO JUNE 22, 2012: TOBACCO PRODUCT MANUFACTURERS THAT ARE NOT 
SMALL TOBACCO PRODUCT MANUFACTURERS ...............................................................................................6 
B.   PRODUCTS MARKETED PRIOR TO JUNE 22, 2012: SMALL TOBACCO PRODUCT MANUFACTURERS ..................6 
C.   PRODUCTS FIRST MARKETED ON OR AFTER JUNE 22, 2012.............................................................................6 
VI.  WHAT INFORMATION IS TO BE REPORTED TO FDA .....................................................................7 
A.  MANUFACTURER OR IMPORTER IDENTIFICATION .............................................................................................7 
B.  TOBACCO PRODUCT IDENTIFICATION ..............................................................................................................8 
C.  HPHC QUANTITIES AND TESTING INFORMATION ............................................................................................8 
VII.  HOW 904(a)(3) REPORTS SHOULD BE SUBMITTED..........................................................................9 
i    Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
1 
2 
1
3  Guidance for Industry  
4 
5  Reporting Harmful and Potentially Harmful Constituents in 
6  Tobacco Products and Tobacco Smoke Under Section 904(a)(3) of 
7  the Federal Food, Drug, and Cosmetic Act 
8 
9 
10  This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 
11  thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 
12  bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 
13  the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 
14  staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 
15  the appropriate number listed on the title page of this guidance. 
16 
17 
18 
19  I.  INTRODUCTION 
20 
21  The purpose of this guidance is to assist persons reporting to FDA the quantities of harmful and 
22  potentially harmful constituents (HPHCs) in tobacco products and tobacco smoke under section 
23  904(a)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 387d(a)(3)). In 
24  particular, at this time, while industry is developing laboratory capacity to comply with section 
25  904(a)(3), FDA does not intend to enforce the statutory requirement to provide quantities of all 
26  constituents identified by FDA as HPHCs by June 22, 2012, if manufacturers or importers 
27  complete testing and reporting for an abbreviated list of HPHCs as set forth in this guidance. 
28  Specifically, this guidance document explains: 
29 
30    The statutory requirement for testing and reporting quantities of HPHCs, 
31    What HPHCs will be the focus of FDA enforcement at this time, 
32    Who tests and reports quantities of HPHCs to FDA, 
33    When reports are submitted to FDA, 
34    What information is reported to FDA, and 
35    How reports should be submitted to FDA. 
36 
37  FDAs guidance documents, including this guidance, do not establish legally enforceable 
38  responsibilities. Instead, guidance documents describe the Agencys current thinking on a topic 
39  and should be viewed only as recommendations, unless specific regulatory or statutory 
40  requirements are cited. The use of the word should in Agency guidance documents means that 
41  something is suggested or recommended, but not required. 
42 
 
 
1 This guidance has been prepared by the Office of Science in the Center for Tobacco Products (CTP) at FDA. 
  1  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
43 
44  II.  BACKGROUND 
45 
46  On June 22, 2009, the President signed the Family Smoking Prevention and Tobacco Control Act 
47  (Tobacco Control Act) (Public Law 111-31) into law. The law grants FDA important new 
48  authority to regulate the manufacture, marketing, and distribution of tobacco products to protect 
49  the public health and to reduce tobacco use by minors. It also imposes certain obligations on 
50  industry, including reporting obligations. Among its many provisions, the Tobacco Control Act 
51  added section 904(a)(3) to the FD&C Act. This section requires each tobacco product 
52  manufacturer or importer, or an agent, to begin reporting to FDA on June 22, 2012, all 
53  constituents, including smoke constituents, identified by [FDA] as harmful or potentially harmful 
54  to health in each tobacco product, and as applicable in the smoke of each tobacco product. 
55  Reports must be by brand2 and by quantity in each brand and subbrand. For example, for a 
56  manufacturer using the brand name Acme, separate reports need to be submitted for the 
57  subbrands Acme 100s and Acme Kings. For tobacco products that were not on the market on 
58  the date that the Tobacco Control Act was enacted (June 22, 2009), section 904(c)(1) of the 
59  FD&C Act requires that these reports be submitted to FDA at least 90 days before the product is 
60  delivered for introduction into interstate commerce. 
61 
62  We have taken several steps to identify HPHCs to be reported under section 904(a)(3) of the 
63  FD&C Act. We issued a final guidance discussing our current thinking on the meaning of 
64  harmful and potentially harmful constituent in the context of implementing the HPHC list 
65  requirement.3 In addition, on August 12, 2011, we issued a public notice in the Federal Register 
66  describing the criteria we had tentatively concluded we would use to assist the Agency in 
67  identifying HPHCs, listing 96 HPHCs we identified using those criteria, and asking the public 
68  and interested parties to submit relevant scientific and other information by October 11, 2011 (76 
69  FR 50226). After reviewing comments received in response to this notice, and as directed by 
70  section 904(e) of the FD&C Act, we established the list of HPHCs and published it in the 
71  Federal Register.4 
72 
73  As described in this guidance, we do not intend, at this time, to enforce certain aspects of the 
74  requirements in section 904(a)(3) of the FD&C Act. However, we intend to move toward full 
75  implementation and enforcement of the statutory requirement to report quantities of all HPHCs 
76  on FDAs established list, as appropriate. We anticipate that this guidance will be revised or 
77  withdrawn as we do so. We intend to use the information submitted pursuant to sections 
78  904(a)(3) and 904(c)(1) of the FD&C Act to meet the requirements of section 904(e) of the 
79  FD&C Act regarding a list of HPHCs in each tobacco product by brand and by quantity in each 
80  brand and subbrand. Also, the information will be used to comply with section 904(d)(1) of the 
81  FD&C Act, which requires FDA to publish a list of HPHCs, by brand and by quantity in each 
82  brand and subbrand, in a format that is understandable and not misleading to lay persons. 
 
2 The term brand is defined in section 900(2) of the FD&C Act (21 U.S.C. 387(2)) as a variety of tobacco product 
distinguished by the tobacco used, tar content, nicotine content, flavoring used, size, filtration, packaging, logo, 
registered trademark, brand name, identifiable pattern of colors, or any combination of such attributes. 
3 Available on the Internet at: 
http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/ucm241339.htm.
4 The established list is available on the Internet (under the Regulatory Information heading) at 
http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/default.htm. 
2  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
83 
84  In addition, section 915(a) of the FD&C Act (21 U.S.C. 387o(a)) requires FDA to issue 
85  regulations requiring testing and reporting of tobacco product constituents, ingredients, and 
86  additives, including smoke constituents, by brand and subbrand, that FDA determines should be 
87  tested to protect the public health. Section 915(a) of the FD&C Act calls for FDA to issue these 
88  regulations no later than April 1, 2013. Once regulations promulgated under section 915 of the 
89  FD&C Act become effective, section 904(a)(3) of the FD&C Act requires that a manufacturer, 
90  importer, or agent comply with these regulations in reporting HPHCs. 
91 
92  III.  HPHCs TO BE REPORTED TO FDA 
93 
94  We recognize that industry will have a short time between the establishment of the HPHC list 
95  and June 22, 2012 when the reporting obligations under section 904(a)(3) are effective. We also 
96  recognize that manufacturers or importers (particularly small tobacco product manufacturers5) 
97  may not currently have the in-house laboratory capabilities to test for quantities of HPHCs. 
98  Consequently, manufacturers or importers may rely on contract laboratories for HPHC testing. 
99  Because this will be the first time that tobacco product manufacturers or importers are required 
100  to report quantities of HPHCs, contract laboratories may not be prepared for the large volume of 
101  requests for the testing of quantities of the HPHCs for all brands and subbrands of tobacco 
102  products marketed prior to June 22, 2012. In addition, some contract laboratories may not yet be 
103  able to test for each of the constituents on FDAs established list of HPHCs. However, we think 
104  that within the timeframes described in section V of this guidance, there will be adequate time 
105  for manufacturers or importers, including those relying on contract laboratories, to test and report 
106  on an abbreviated list of HPHCs. Therefore, we do not intend to enforce the requirements to test 
107  and report quantities of all HPHCs on FDAs established list if manufacturers or importers 
108  report, no later than the dates described in section V, quantitative information for the abbreviated 
109  list of HPHCs (Table 1). 
 
 
 
 
 
 
5 The definition of the term small tobacco product manufacturer is discussed in section V.B. 
3  Contains Nonbinding Recommendations
Draft  Not for Implementation 
110 
111  Table 1. Abbreviated List of Harmful and Potentially Harmful Constituents 
  HPHCs in Cigarette  HPHCs in Smokeless  HPHCs in Roll-your-own 
 
  Smoke  Tobacco  Tobacco and Cigarette 
  Filler6 
 
  Acetaldehyde  Acetaldehyde  Ammonia 
  Acrolein  Arsenic  Arsenic 
 
Acrylonitrile  Benzo[a]pyrene  Cadmium 
 
  4-Aminobiphenyl  Cadmium  Nicotine (total) 
   1-Aminonaphthalene  Crotonaldehyde  NNK* 
  2-Aminonaphthalene  Formaldehyde  NNN** 
 
Ammonia  Nicotine (total and free) 
 
  Benzene  NNK* 
  Benzo[a]pyrene  NNN** 
 
  1,3-Butadiene 
  Carbon monoxide 
 
Crotonaldehyde 
 
  Formaldehyde 
 
Isoprene 
 
  Nicotine (total) 
  NNK* 
 
  NNN** 
  Toluene 
  *
  4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 
 
** 
  N-nitrosonornicotine 
112 
113  We identified the HPHCs on this list after considering several factors. We selected constituents 
114  for which testing and analytic methods are well established and widely available. We also 
115  selected constituents that represent several different chemical classes (e.g., polyaromatic 
116  hydrocarbons, tobacco-specific nitrosamines, carbonyl compounds, aromatic amines, metals, and 
117  volatile organic compounds). These constitute a representative sample of the HPHCs on FDAs 
118  established HPHC list, providing a basis for beginning to study regulated tobacco products 
119  pending submission of information for all HPHCs on the established list. Finally, we selected a 
120  small number of constituents so that industry can begin testing and reporting, and FDA can begin 
121  analyzing HPHC information, in a relatively short time. We have identified HPHCs by product 
122  type because different product types may contain different HPHCs. For example, carbon 
123  monoxide is produced during combustion so it is included on the abbreviated list of HPHCs for 
124  cigarette smoke, but not included on the list for smokeless tobacco products, roll-your-own 
125  tobacco, or cigarette filler. 
 
 
6 Roll-your-own tobacco is defined in section 900(15) of the FD&C Act to mean any tobacco product which, 
because of its appearance, type, packaging, or labeling, is suitable for use and likely to be offered to, or purchased 
by, consumers as tobacco for making cigarettes. The term cigarette filler is not defined in the FD&C Act. For 
purposes of this guidance, we intend cigarette filler to mean the cut, ground, powdered, or leaf tobacco that is a 
component of a cigarette. 
4  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
126 
127  IV.  WHO SUBMITS 904(a)(3) REPORTS 
128 
129  Under section 904(a)(3) of the FD&C Act, each tobacco product manufacturer or importer, or 
130  agents thereof must report quantities of HPHCs for tobacco products by brand and subbrand. 
131  We interpret this to mean that domestic manufacturers, or their agents, are to submit the required 
132  HPHC information for products they manufacture. For imported tobacco products, the required 
133  HPHC information is to be submitted by either the foreign manufacturer or the importer, or an 
134  agent, of the product. The definition of tobacco product in section 201(rr)(1) of the FD&C Act 
135  includes any component, part, or accessory of a tobacco product (except for raw materials other 
136  than tobacco used in manufacturing a component, part, or accessory of a tobacco product) (21 
137  U.S.C. 321(rr)(1)). We therefore interpret section 904(a)(3) of the FD&C Act to cover any 
138  regulated tobacco product, whether for sale to consumers or for further manufacturing.7 At this 
139  time, however, we intend to enforce the HPHC reporting requirements for finished tobacco 
140  products for consumer use in the following categories: 
141 
142    Cigarettes (report HPHC quantities in smoke and filler) 
143    Smokeless tobacco (e.g., snus, snuff, plug, chew, loose leaf) 
144    Roll-your-own tobacco 
145 
146  At this time, we do not intend to enforce the requirement to report HPHCs under section 
147  904(a)(3) against manufacturers and importers of other products (e.g., manufacturers of 
148  components sold to manufacturers or to consumers for incorporation into finished tobacco 
149  products for consumer use). We are not aware of established test methods to measure HPHCs in 
150  separated or unincorporated components of tobacco products other than cigarette filler and 
151  roll-your-own tobacco, and we also believe that testing finished products that are ready for 
152  consumer use without further assembly will provide information about the potential exposure of 
153  consumers and others, taking into account the effect of components and product design. If we 
154  find that additional information is needed to protect the public health, we may reconsider these 
155  enforcement policies. 
156 
157  This guidance does not apply to the testing and reporting of quantities of HPHCs for tobacco 
158  products that are not currently subject to Chapter IX of the FD&C Act (see section 901(b) of the 
159  FD&C Act (21 U.S.C. 387a(b))). 
160 
161 
162  V.  WHEN 904(a)(3) REPORTS ARE SUBMITTED TO FDA 
163 
164  Section 904(a)(3) of the FD&C Act requires the reporting of quantities of all HPHCs on FDAs 
165  established list, by brand and subbrand, beginning no later than June 22, 2012. As described in 
166  section III of this guidance, at this time we do not intend to enforce this requirement against 
167  manufacturers or importers of finished tobacco products provided that quantities of the HPHCs 
 
 
7 See the guidance for industry, Listing of Ingredients in Tobacco Products, available on the Internet at 
http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/ucm191982.htm (explaining that 
the definition of tobacco product in the FD&C Act includes components, parts, and accessories of tobacco products, 
whether they are sold for further manufacturing or for consumer use). 
5    Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
168  identified in Table 1 are reported for all of their products, by brand and subbrand, no later than 
169  the dates identified in the following sections. 
170 
171  A.  Products Marketed Prior to June 22, 2012: Tobacco Product Manufacturers 
172  That Are Not Small Tobacco Product Manufacturers 
173 
174  At this time, for a manufacturer or importer (or agents thereof), other than a small tobacco 
175  product manufacturer, we do not intend to enforce the requirement to test and report quantities of 
176  all HPHCs on FDAs established list if manufacturers or importers report quantities of the 
177  HPHCs identified in Table 1 for all of their products, by brand and subbrand, no later than 
178  September 22, 2012. 
179 
180  B.  Products Marketed Prior to June 22, 2012: Small Tobacco Product 
181  Manufacturers 
182 
183  We recognize that small tobacco product manufacturers are unlikely to have their own laboratory 
184  facilities for the testing of HPHCs and are likely to be particularly reliant on contract laboratories 
185  that may have limited capacity at this time. Accordingly, at this time we do not intend to enforce 
186  the requirement for small tobacco product manufacturers to test and report quantities of all 
187  HPHCs on FDAs established list, provided that such a manufacturer report quantities of the 
188  HPHCs identified in Table 1, for all its products, by brand and subbrand, no later than December 
189  22, 2012.8 This additional 3months from the date that other manufacturers will report quantities 
190  of HPHCs should allow contract laboratories sufficient time to complete testing for HPHCs 
191  identified in Table 1 for both large and small tobacco product manufacturers and importers 
192  within the extended timeframes set forth in this guidance. 
193 
194  Section 900(16) of the FD&C Act defines a small tobacco product manufacturer as a tobacco 
195  product manufacturer that employs fewer than 350 employees. For purposes of determining the 
196  number of employees of a manufacturer under the preceding sentence, the employees of a 
197  manufacturer are deemed to include the employees of each entity that controls, is controlled by, 
198  or is under common control with such manufacturer. 9 A small tobacco product manufacturer 
199  submitting 904(a)(3) information should certify on the eSubmitter or paper form (described in 
200  section VII) that it has fewer than 350 employees at the time of submission and should have 
201  documentation available for submission to FDA on request or for inspection to demonstrate that 
202  it meets the statutory definition of a small tobacco product manufacturer. 
203 
204  C.  Products First Marketed On or After June 22, 2012 
205 
 
 
8 Section 915 of the FD&C Act provides that regulations issued under its authority are to have separate compliance 
dates for small tobacco product manufacturers, providing additional time for initial compliance. Section 904(a)(3) of 
the FD&C Act does not contain similar provisions. In addition, section 915(f) of the FD&C Act explicitly states that 
these small tobacco product manufacturer provisions must not be construed to authorize the extension of any 
deadline or otherwise affect any timeframe under any other provision of the FD&C Act. Therefore, an extension in 
time to comply is not required by the FD&C Act. 
9 The definition of a tobacco product manufacturer in the FD&C Act includes any person who imports a finished 
tobacco product for sale or distribution in the United States (section 900(20) of the FD&C Act). Therefore, the 350 
employee threshold applies to importers. 
6    Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
206  For a tobacco product that was not on the market on or after June 22, 2009, section 904(c)(1) of 
207  the FD&C Act requires all tobacco product manufacturers, regardless of their size, to submit 
208  HPHC quantities and other information at least 90 days prior to marketing the product. We do 
209  not intend, at this time, to enforce this requirement in section 904(c)(1) to test and report 
210  quantities of all HPHCs on FDAs established list for products not previously on the market, if a 
211  manufacturer or importer reports quantities for the HPHCs identified in Table 1 of this guidance 
212  at least 90 days prior to marketing the product in the United States. 
213 
214  It is important to remember that the section 904(c)(1) testing and reporting requirement is 
215  separate from the requirements that must be satisfied before you may market a new tobacco 
216  product (sections 905 and 910 of the FD&C Act (21 U.S.C. 387e and 387j)), or modified risk 
217  tobacco product (section 911 of the FD&C Act (21 U.S.C. 387k)). Depending on the nature of a 
218  new tobacco product or modified risk tobacco product, testing and reporting HPHCs on the list in 
219  Table 1 may not be adequate to meet the statutory standards for marketing authorization; 
220  quantities for additional HPHCs may be necessary. This guidance does not represent any 
221  intention to exercise enforcement discretion with respect to the statutory requirements for the 
222  marketing authorization of new tobacco products or modified risk tobacco products. 
223 
224  If the only change to your product after June 22, 2012, is a change to the product label or 
225  labeling that will not alter the quantities of HPHCs found in the tobacco product or its smoke, 
226  you do not need to conduct additional testing to comply with section 904(c)(1) of the FD&C Act. 
227  However, if changes to the product label or labeling include a product name change, then you 
228  must report the name change to FDA so that we may associate the quantities of HPHCs with the 
229  marketed product bearing that brand or subbrand name. 
230 
231 
232  VI.  WHAT INFORMATION IS TO BE REPORTED TO FDA 
233 
234  A.  Manufacturer or Importer Identification 
235 
236  The name and address of each tobacco product manufacturer or importer, and the name and 
237  address of any agent reporting HPHCs on their behalf, are to be submitted along with HPHC 
238  information. FDA requests that you also provide information to assist us in communicating with 
239  you: 
240 
241    Telephone and FAX numbers of the manufacturer or importer; 
242    FDA Establishment Identifier (FEI) number, if known; 
243    A Data Universal Numbering System (D-U-N-S) number for your headquarters, if you 
244  have one; 
245    Contact information for your point of contact including 
246  Title, name, and mailing address; 
o 
247  E-mail address; 
o 
248  Telephone and FAX numbers. 
o 
249 
250  The business entity identifier recognized by the FDA Data Council is the D-U-N-S number. 
251  Providing the site-specific D-U-N-S number for your headquarters will help prevent inaccuracies 
7    Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
252  in FDAs database. Dun & Bradstreet assigns and maintains a database of the D-U-N-S numbers, 
253  which serve as unique identifiers of business entities. Upon application, each business entity is 
254  assigned a distinct site-specific 9-digit D-U-N-S number. If the D-U-N-S number for a location 
255  has not been assigned, a business may obtain one for no cost directly from Dun & Bradstreet 
256  (http://www.dnb.com). 
257 
258  B.  Tobacco Product Identification 
259 
260  Under section 904(a)(3), tobacco product manufacturers or importers are required to submit a 
261  listing of HPHCs for each tobacco product by brand and by quantity in each brand and 
262  subbrand. Each product for which a listing of HPHCs is submitted is to be clearly and uniquely 
263  identified by its brand and subbrand, which includes identifying the type of tobacco product (i.e., 
264  cigarette, smokeless (e.g., snus), or roll-your-own tobacco), and any brand and subbrand names. 
265  Also, include the package size or sizes for each product brand and subbrand. If the package size 
266  will not affect quantities of HPHCs, you do not have to test each package size. FDA also 
267  recommends that a unique product identification number, such as a Universal Product Code, be 
268  included for each product to help the Agency track and file your submission, and communicate 
269  with you about your submission. In addition, we request that you provide the name, mailing 
270  address, telephone number, and FAX number for the testing laboratory or laboratories. 
271 
272  C.  HPHC Quantities and Testing Information 
273 
274  Section 904(a)(3) of the FD&C Act requires the reporting of quantities of HPHCs in each 
275  tobacco product and as applicable in the smoke of each tobacco product. This information is 
276  intended to provide the Agency with information (1) to assist with implementation of the FD&C 
277  Act (e.g., developing tobacco product standards and making substantial equivalence 
278  determinations) and (2) to assist with the publication of a list of HPHCs by brand and subbrand 
279  that is useful for comparing HPHC levels in tobacco products. We therefore understand the 
280  statute to require that quantities must be reported in a manner that provides a basis for 
281  understanding levels of HPHCs in individual tobacco products or their smoke per unit of use, and 
282  for comparing relative quantities of HPHCs associated with different products or their smoke. 
283  Consequently, FDA interprets the term quantity to mean a unit of mass per unit of use (e.g., per 
284  cigarette or per pouch) or a unit of mass per mass of tobacco. For portioned tobacco products, 
285  you should report HPHC quantities per unit of use, and include a measurement of the mean mass 
286  with standard deviation of the mean. For non-portioned tobacco products, (e.g., a container of 
287  loose snuff or of roll-your-own tobacco), you should report HPHC quantities per gram of the 
288  product with standard deviation of the mean. For cigarette smoke, you should report HPHC 
289  quantities per cigarette. HPHC quantities and tobacco mass should be reported in terms of the 
290  International System of Units (e.g., grams, micrograms, nanograms, picograms, or milligrams), 
291  which provides a consistent, reliable system of measurement, and you should use at least three 
292  significant figures.10 
293 
 
 
10 When reporting a quantity, you should round to the last appropriate significant figure. For example, if an HPHC 
quantity is determined to be 54.321 nanograms (ng)/cigarette and the measurement should be expressed as three 
significant figures, then the quantity should be rounded and reported as 54.3 ng/cigarette. It would not be 
appropriate to report the quantity as 50.0 ng/cigarette or 54.0 ng/cigarette. 
  8  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
294  Section 904(a)(3) is also intended to provide information that is representative of your product as 
295  marketed. Use a testing protocol to measure HPHCs in tobacco products or tobacco smoke that 
296  involves appropriate sampling techniques to select samples for testing, and provides reproducible 
297  results based on multiple measurements. In reporting quantities derived from such tests, we 
298  believe it is necessary to include a statement of average values and variability among these 
299  multiple measurements. Therefore, you are to report the mean mass and a measure of the 
300  variability among multiple measurements. We strongly recommend that you provide the standard 
301  deviation of the mean to report variability and that you report the number of replicate 
302  measurements made in determining the mean mass and standard deviation. For portioned 
303  products, you also are to include a statement of the mean mass of tobacco in each product and a 
304  measure of the variability among multiple measurements. We strongly recommend using 
305  standard deviation of the mean to describe the variability among measurements. 
306 
307  With respect to the requirement in section 904(a)(3) that manufacturers and importers report 
308  quantities of HPHCs in the smoke of each tobacco product, we note that different smoking 
309  regimens (e.g., intense or non-intense)11 are designed to collect different amounts of smoke from 
310  a given tobacco product for analysis and would be expected to provide a range of quantities of 
311  HPHC levels for the smoke of a given tobacco product. Therefore, we believe that information 
312  about the smoking regimen that was used to determine reported HPHC values is necessary for 
313  the interpretation and comparison of HPHC quantities reported, and you are to include this 
314  information in your report. FDA recommends that you also provide information on the smoking 
315  machine used to collect mainstream smoke (i.e., linear or rotary). 
316 
317  We recommend that the quantity of each HPHC in cigarette smoke be determined by both the 
318  non-intense and intense smoking regimens. The two smoking regimens are expected to provide 
319  the Agency with information about different deliveries of HPHCs possible for each tobacco 
320  product. FDA recommends seven replicates for the determination of quantities for all HPHCs, 
321  except nicotine and carbon monoxide in cigarette smoke. For nicotine and carbon monoxide in 
322  cigarette smoke, we recommend 20 replicates. 
323 
324  FDA also recommends that the following information be submitted for each HPHC, which will 
325  aid FDA in evaluating the data: 
326 
327    Number of replicate measurements; 
328    Date (or date range) of testing; 
329    Date (or date range) when the tested product was manufactured; and 
330    Analytical methods used to extract, separate, and detect the HPHCs. 
331 
332  For smokeless tobacco products, FDA recommends that you use the CDC method to calculate 
333  free nicotine (74 FR 712, January 7, 2009). 
334 
335 
336  VII.  HOW 904(a)(3) REPORTS SHOULD BE SUBMITTED 
337 
 
11 By intense smoking regimen we mean Canadian Intense, Health Canada Test Method T-401, and by non-intense 
smoking regimen we mean ISO 3308:2008 and ISO 5387:2000. 
9  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
338  The FDA eSubmitter tool is an electronic application designed to streamline the data entry and 
339  submission process for reporting HPHCs. Users of the eSubmitter tool first download and install 
340  the computer application and then enter all data. To facilitate data entry in relevant sections, 
341  users can populate an Excel file and import data into eSubmitter. The tool alerts the user if there 
342  is missing information. The eSubmitter tool is available at 
343  http://www.fda.gov/ForIndustry/FDAeSubmitter. 
344  Users of the eSubmitter tool can use the FDA Electronic Submissions Gateway (ESG) to 
345  securely submit their report to CTP and receive an automatic acknowledgement of FDA receipt. 
346  The FDA ESG is used across FDA as the portal for receipt of electronic regulatory submissions. 
347  The FDA ESG system requires users to apply for a free account before submitting data, a process 
348  which can take one to three weeks. FDA therefore urges the user to apply for ESG accounts well 
349  in advance of the deadline for data submission. Once approved, the user can send all submissions 
350  to CTP using the eSubmitter tool and FDA ESG. Instructions on obtaining an ESG account are 
351  available at http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/ucm188949.htm. 
352 
353  Although electronic submission is not required, FDA strongly encourages electronic submission 
354  for efficient and timely data submission and management. If an electronic submission is not 
355  possible or practical, an alternative tool for paper submissions is available at 
356  www.fda.gov/tobaccoinfoindustry. If the ESG is not used, submissions can be mailed to: 
357 
358  Food and Drug Administration 
359  Center for Tobacco Products 
360  Document Control Center 
361  Building 71, Room G335 
362  10903 New Hampshire Avenue 
363    Silver Spring, MD 20993-0002  
364 
365 
366 
10