2018-01121. Agency Information Collection Activities; Proposed Collection; Comment Request; Draft Guidance for Industry: Modified Risk Tobacco Product Applications

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on “Draft Guidance for Industry: Modified Risk Tobacco Product Applications” (MRTPA).

DATES:

Submit either electronic or written comments on the collection of information by March 26, 2018.

ADDRESSES:

You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before March 26, 2018. The https://www.regulations.gov electronic filing system will accept comments until midnight Eastern Time at the end of March 26, 2018. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date.

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2012-D-0071 for “Draft Guidance for Industry: Modified Risk Tobacco Product Applications” Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.gpo.gov/​fdsys/​pkg/​FR-2015-09-18/​pdf/​2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Amber Sanford, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-8867, [e-mail].

SUPPLEMENTARY INFORMATION:

Under the PRA (44 U.S.C. 3501-3520), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. “Collection of information” is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document.

With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology.

Draft Guidance for Industry: Modified Risk Tobacco Product Applications

OMB Control Number 0910—NEW

In the Federal Register of April 3, 2012 (77 FR 20026), FDA published a notice of availability including the PRA analysis. FDA is republishing the paperwork analysis with updates to satisfy the requirements of the PRA.

This draft guidance describes the information that the Federal Food, Drug, and Cosmetic Act (FD&C Act) requires in an MRTPA submission as well as FDA's recommendations regarding the scientific evidence that should be contained in a MRTPA for FDA to make an assessment and conduct an ongoing review of modified risk tobacco products (MRTPs). The draft guidance also permits the filing of a single application for any MRTP that is also a new tobacco product under section 910 of the FD&C Act (21 U.S.C. 387k). The draft guidance discusses, among other things: (1) Who submits MRTPAs; (2) when to submit a MRTPA; (3) what information section 911 of the FD&C Act (21 U.S.C. 387j) requires applicants to submit in a MRTPA; (4) what scientific evidence FDA recommends applicants include in a MRTPA; (5) what information should be collected through postmarket surveillance and studies; and (6) how to organize and submit a MRTPA. The purpose of the proposed information collection is to allow FDA to collect statutorily mandated information regarding modified risk tobacco products and other information that will facilitate FDA's effective and efficient review of MRTPAs.

Modified risk tobacco products are tobacco products that are sold or distributed for use to reduce harm or the risk of tobacco-related disease associated with commercially marketed tobacco products (section 911(b)(1) of the FD&C Act). No person may introduce or deliver for introduction into interstate commerce any MRTP unless an order issued pursuant to section 911(g) is effective with respect to that product (section 911(a) of the FD&C Act).

Under section 911(d) of the FD&C Act, a MRTPA must contain:

• A description of the proposed product and any proposed advertising and labeling;
• The conditions for using the product;
• The formulation of the product;
• Sample product labels and labeling;
• All documents (including underlying scientific information) relating to research findings conducted, supported, or possessed by the tobacco product manufacturer relating to the effect of the product on tobacco-related diseases and health-related conditions, including information both favorable and unfavorable to the ability of the product to reduce risk or exposure and relating to human health;
• Data and information on how consumers actually use the tobacco product; and
• Such other information as the Secretary may require.

Further, FDA's regulation implementing the National Environmental Policy Act of 1969 requires that “[a]ll applications or petitions requesting agency action require the submission of an [environmental assessment] or a claim of categorical exclusion” (21 CFR 25.15(a)).

Section 911(g) of the FD&C Act describes the demonstrations applicants must make to obtain an order from FDA. Section 911(g)(1) and (2) of the FD&C Act set forth two bases for FDA to issue an order.

A “risk modification order” is an order permitting the introduction or delivery for introduction into interstate commerce of a tobacco product that FDA has found meets the criteria for an order under section 911(g)(1) of the FD&C Act. In order for FDA to issue a risk modification order under section 911(g)(1) of the FD&C Act, the applicant must demonstrate that the proposed modified risk tobacco product, as it is actually used by consumers, will:

• Significantly reduce harm and the risk of tobacco-related disease to individual tobacco users and
• Benefit the health of the population as a whole taking into account both users of tobacco products and persons who do not currently use tobacco products.

An “exposure modification order” is an order permitting the introduction or delivery for introduction into interstate commerce of a tobacco product that reduces or eliminates exposure to a substance and for which the available scientific evidence suggests that a measurable and substantial reduction in morbidity and mortality is likely to be demonstrated in future studies. In order for FDA to issue an exposure modification order, the applicant must satisfy all of the criteria for issuance of an order under section 911(g)(2) of the FD&C Act.

FDA may issue an exposure modification order under section 911(g)(2) of the FD&C Act (the “special rule”) if it determines that the applicant has demonstrated that:

• Such an order would be appropriate to promote the public health;
• Any aspect of the label, labeling, and advertising for the product that would cause the product to be a MRTP is limited to an explicit or implicit representation that the tobacco product or its smoke does not contain or is free of a substance or contains a reduced level of a substance, or presents a reduced exposure to a substance in tobacco smoke;
• Scientific evidence is not available and, using the best available scientific methods, cannot be made available without conducting long-term epidemiological studies for an application to meet the standards for obtaining an order under section 911(g)(1); and
• The scientific evidence that is available without conducting long-term epidemiological studies demonstrates that a measurable and substantial reduction in morbidity or mortality among individual tobacco users is reasonably likely in subsequent studies (section 911(g)(2)(A) of the FD&C Act).

Furthermore, for FDA to issue an exposure modification order, FDA must find that the applicant has demonstrated that:

• The magnitude of overall reductions in exposure to the substance or substances, which are the subject of the application is substantial, such substance or substances are harmful, and the product as actually used exposes consumers to the specified reduced level of the substance or substances;
• The product as actually used by consumers will not expose them to higher levels of other harmful substances compared to the similar types of tobacco products then on the market unless such increases are minimal and the reasonably likely overall impact of use of the product remains a substantial and measurable reduction in overall morbidity and mortality among individual tobacco users;
• Testing of actual consumer perception shows that, as the applicant proposes to label and market the product, consumers will not be misled into believing that the product is or has been demonstrated to be less harmful, or presents or has been demonstrated to present less of a risk of disease than one or more other commercially marketed tobacco products; and
• Issuance of the exposure modification order is expected to benefit the health of the population as a whole taking into account both users of tobacco products and persons who do not currently use tobacco products (section 911(g)(2)(B) of the FD&C Act).

In evaluating the benefit to health of individuals and of the population as a whole under section 911(g)(1) and (2) of the FD&C Act, FDA must take into account:

• The relative health risks the MRTP presents to individuals;
• The increased or decreased likelihood that existing tobacco product users who would otherwise stop using such products will switch to using the modified risk tobacco product;
• The increased or decreased likelihood that persons who do not use tobacco products will start using the modified risk tobacco product;
• The risks and benefits to persons from the use of the MRTP compared to the use of smoking cessation drug or device products approved by FDA to treat nicotine dependence; and
• Comments, data, and information submitted to FDA by interested persons (section 911(g)(4) of the FD&C Act).

Furthermore, FDA must ensure that the advertising and labeling of the MRTP enable the public to comprehend the information concerning modified risk and to understand the relative significance of such information in the context of total health and in relation to all of the tobacco-related diseases and health conditions (section 911(h)(1) of the FD&C Act).

FDA intends to determine whether it will issue an order under section 911(g) within 360 days after the receipt of a complete application and will issue such an order only if the application satisfies all the applicable requirements in section 911 of the FD&C Act.

A risk modification order issued under section 911(g)(1) will be effective for the period of time specified in the order issued by FDA (section 911(h)(4) of the FD&C Act). An applicant to whom a risk modification order is issued under section 911(g)(1) must conduct postmarket surveillance and studies (section 911(i)(1) of the FD&C Act).

An exposure modification order issued under section 911(g)(2) of the FD&C Act will be effective for a term of not more than 5 years. FDA may renew an exposure modification order if the applicant files a new application, and FDA finds that the requirements for such order under section 911(g)(2) continue to be satisfied (section 911(g)(2)(C)(i) of the FD&C Act). Further, an exposure modification order will be conditioned on the applicant's agreement to conduct postmarket surveillance and studies and to submit the results of such surveillance and studies to FDA annually (section 911(g)(2)(C)(ii) and (iii) of the FD&C Act).

The postmarket surveillance and studies that all applicants who receive orders are required to conduct are intended to determine the effect of issuance of an order on consumer perception, behavior, and health, and enable FDA to review the accuracy of the determinations upon which an order was based (section 911(g)(2)(C)(ii) and 911(i)(1) of the FD&C Act). An applicant who receives a risk modification order must also conduct postmarket surveillance and studies that provide information FDA determines is otherwise necessary regarding the use or health risks involving the tobacco product (section 911(i)(1) of the FD&C Act).

If the proposed MRTP is a new tobacco product within the meaning of section 910(a)(1), the new tobacco product must satisfy any applicable premarket review requirements under section 910 of the FD&C Act, in addition to any requirements under section 911 of the FD&C Act. A new tobacco product must be found to be substantially equivalent, exempt from the requirement to obtain a substantial equivalence determination, or have a marketing authorization order under section 910(c)(1)(A)(i) of the FD&C Act. The collections of information relating to premarket review described in the “Guidance for Industry: Section 905(j) Reports: Demonstrating Substantial Evidence for Tobacco Products” (OMB control number 0910-0673), 21 CFR part 1107 (“Establishment Registration, Product Listing, and Substantial Equivalence Reports”) (OMB control number 0910-0684), and “Deeming Tobacco Products To Be Subject to the FD&C Act ” (OMB control number 0910-0768) have been previously approved by OMB. An applicant may file the appropriate report or application to satisfy any applicable premarket review requirements and a separate application under section 911 of the FD&C Act. To the extent data or information contained in the premarket review portion of the application is also relevant to or required for the modified risk determination, FDA encourages the applicant to cross-reference that data or information rather than duplicate it in the modified risk portion of the application. Additionally, due to the many similarities between the content requirements of sections 910(b)(1) (for premarket tobacco applications (PMTAs)) and 911(d) (for MRTPAs) of the FD&C Act, we recommend submitting a single application to seek both a marketing order under section 910 of the FD&C Act and a modified risk order under section 911 of the FD&C Act. The single application must include the information required for premarket review under section 910(b) of the FD&C Act, as well as the information required to support issuance of an order under section 911(g) of the FD&C Act.

Description of Respondents: The respondents to this collection of information are applicants who are responsible for creating and submitting MRTP applications and who wish to obtain an FDA order to allow them to market their product. While it is expected that many of the respondents will be manufacturers, respondents could include importers, distributors, and retailers of tobacco products.

FDA estimates the burden of this collection of information as follows:

Table 1—Estimated Annual Reporting Burden ¹

Activity	Number of respondents	Number of responses per respondent	Total annual responses	Average burden per response	Total hours
MRTPA (section 911(d) of FD&C Act)	3	1	3	10,000	30,000
Environmental analysis (21 CFR 25.15)	3	1	3	320	960
Request for a meeting prior to submitting a MRTPA	8	1	8	40	320
All activities related to postmarket surveillance studies, including submission of protocols, conduct of studies, and annual reporting (section 911(g)(2)(C)(ii), 911(i)(1) and (2))	5	1	5	5,000	25,000
Requests for renewal (section 911(g)(2)(C)(i) and 911(h)(4))	1	1	1	1,000	1,000
Total Hours					57,280
1 There are no capital costs or operating and maintenance costs associated with this collection of information.

Table 1 describes the annual reporting burden as a result of submitting a MRTPA. FDA estimates that it will receive three MPRTAs annually and that it will take the applicant 10,000 hours per response to conduct studies and collect the information needed to support an MRTPA. FDA is also including an estimation of the burden associated with preparing environmental analyses. FDA estimates that it will take an additional 320 hours to prepare any environmental analyses. FDA encourages persons considering developing a MRTPA to meet with the Center for Tobacco Products to discuss MRTPA submission and investigational requirements. FDA anticipates that eight respondents considering developing MRTPAs may request meetings with FDA. FDA estimates it will take 40 hours per response to prepare a meeting request, including background information.

Section 911 of the FD&C Act requires applicants to whom FDA issues orders to conduct postmarket surveillance and studies and submit relevant information to FDA on an annual basis. Applicants must submit and receive FDA approval of surveillance protocols. FDA estimates that it will take 5,000 hours per response to collect and submit the protocol information to FDA, conduct the postmarket surveillance and studies and to submit results of postmarket surveillance and studies to FDA annually. FDA expects five respondents to carry out postmarket surveillance and studies annually.

Because orders issued under section 911(g) of the FD&C Act are valid for only a set number of years, FDA expects applicants will submit requests for renewal. Because the dates on which orders are issued and the length of the period for which the order is valid will vary, FDA expects one request for renewal annually. FDA estimates that it will take 1,000 hours to prepare the request for renewal.

The estimated total burden hours for this collection of information is estimated to be 57,280. These burden estimates were computed using FDA staff expertise and by reviewing comments received from recent FDA information collections for other tobacco-related initiatives. In addition, FDA notes that due to the many similarities between the content requirements of sections 910(b)(1) (from PMTAs) and 911(d) (for MRTPAs) of the FD&C Act, and the likelihood that many respondents will submit joint PMTAs and MRTPAs, or cross-reference the applications, that part of the collection of information burden for respondents submitting an MRTPA will be captured in the preparation of the PMTA.

Dated: January 17, 2018.

Leslie Kux,

Associate Commissioner for Policy.