UPDATE ON PREMARKET TOBACCO PRODUCT AUTHORIZATION PATHWAY Presented by Ii-Lun Chen, M.D Director Division of Individual Health Science Office of Science, CTP, FDA Disclaimer: This is not a formal dissemination of information by FDA and does not represent Agency position or policy. March 8, 2017
Swedish Match North America MRTPA and PMTA Decisions Focus on PMTA PMTA Informational Session Summary - October 2016 1
BACKGROUND: PREMARKET TOBACCO APPLICATION (PMTA) Before a new tobacco product can be legally marketed (per Section 910(a)(2) of the FD&C Act), a premarket tobacco application must be submitted, reviewed by FDA, and determined to be appropriate for the protection of public health - unless the product is found to be substantially equivalent (SE) to a predicate tobacco product, or the product is found to be exempt from SE. 2
BACKGROUND: PMTA STATUTORY REQUIREMENTS In a PMTA, FDA must determine: Whether permitting this product to be marketed would be appropriate for the protection of the public health The risks and benefits to the population as a whole, including users and nonusers, and The increased or decreased likelihood that existing users of tobacco products will stop using such products and those who do not use tobacco products will start using such products. 3
BACKGROUND: PMTA STATUTORY REQUIREMENTS Per section 910(b)(1), a PMTA must contain: Full reports of all information, published or known to, or which should reasonably be known to, the applicant, concerning investigations that have been made to show the health risks of the tobacco product and whether the tobacco product presents less risk than other tobacco products A full statement of the components, ingredients, additives, properties, and the principle or principles of operation, of such tobacco product A full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and, when relevant, packing and installation of, such tobacco product 4
BACKGROUND: PMTA STATUTORY REQUIREMENTS (CONT.) An identifying reference to any tobacco product standard under section 907 that would be applicable to any aspect of the tobacco product, and either adequate information to show that the aspect of the tobacco product fully meets the tobacco product standard or adequate information to justify any deviation from the standard Specimens of the labeling proposed to be used for such tobacco product The samples of such tobacco product and of components thereof as the Secretary may reasonably require The other information relevant to the subject matter of the application as the Secretary may require 5
PMTA DRAFT GUIDANCES The PMTA draft guidances Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems and Applications for Premarket Review of New Tobacco Products describe FDA s recommendations on how to: Meet the statutory requirements for PMTA content under section 910(b)(1) Present information in a way that helps FDA make its decision on whether to issue a marketing order under 910(c)(1)(A)(i) of the FD&C Act When finalized, these guidances will represent FDA s current thinking on PMTAs for regulated products 6
SWEDISH MATCH NORTH AMERICA (SMNA) 7
GOALS FOR REVIEWING THE SMNA SUBMISSION The overall objective of authorizing new tobacco products to be marketed through the PMTA process is to reduce the morbidity and mortality associated with tobacco use. In evaluating how marketing authorization for these Swedish snus products impacts the current market, FDA considered the possibility that a PMTA order may increase use and initiation of snus due to its perceived favorable profile. Given this possibility, the products impact on health, impact on smoking cessation, impact on snus initiation and uptake, and impact on current ST users was considered in totality. 8
HEALTH IMPACT When used exclusively instead of cigarettes, these snus products offer lower risk of developing respiratory diseases (e.g., COPD, emphysema, chronic bronchitis) and certain cancers (e.g., lung). Assuming that the only users of these products are persons who would have used other ST (smokeless tobacco) products currently on the US market, individuals using these products with lower NNN levels could decrease their excess cancer risk by 90% compared use of moist snuff (market share: 82%), by 67% compared to use of chewing tobacco (market share:15%), by 38% compared to use of US-style snus, and by 92% compared to use of dry snuff. 9
POPULATION IMPACT Data indicate there is limited switching behaviors from exclusive smoking to exclusive smokeless tobacco use. Findings from Tam et al. indicate that in the US, switching from ST use to smoking is more common than switching from smoking to ST use. Nevertheless, limited data suggest that the adoption of snus use in the US is low and, therefore, unlikely to lead to use of other tobacco products. It is anticipated that with the marketing of the proposed products, as described in the PMTAs, there is a low likelihood of nonuser uptake of these products, decreased or delayed cessation, or other significant shifts in user demographics. 10
SCIENTIFIC RATIONALE: PMTA DECISION The products in the SMNA PMTAs may decrease the individual risk among current ST users due to their favorable toxicological profile without posing increased risk to the general population. Current ST users who choose to continue using tobacco products will have additional options for less toxic ST products, thereby potentially decreasing the negative health impact from tobacco product use. 11
PMTA INFORMATIONAL SEMINAR FOR ENDS PRODUCTS 12
PMTA INFORMATIONAL SEMINAR: OCTOBER 2016 OBJECTIVES The PMTA Informational Seminar was developed to assist manufacturers to better understand the scientific principles for evaluating electronic nicotine delivery systems (ENDS) products. The objective was to improve understanding of: FD&C Act requirements for a new tobacco product application General scientific principles and terminology relevant to evaluation of ENDS products as described in the draft guidance on PMTAs for ENDS 13
PMTA INFORMATIONAL SEMINAR: OVERVIEW The PMTA Informational Seminar was held on October 17-18, 2016. Specific seminar topics included: General administrative information Product science evaluation Data sources for potential use Health risk evaluation Role of human factors and labeling Addiction and abuse liability evaluation Impact of initiation, cessation and consumer perception 14
PMTA INFORMATIONAL SEMINAR: GENERAL INFORMATION ENDS PMTA draft guidance is not an FDA-implemented policy. The guidance, when finalized, will communicate FDA's recommendations for submitting a PMTA for ENDS products as well as the general procedures by which FDA intends to review a PMTA. To aid in a successful submission, meetings with the FDA, reviewing guidances, and referencing information in a tobacco product master file may be helpful. Bridging is one of the commonly-used tools that can be used to verify product characteristics through comparability. 15
PMTA INFORMATIONAL SEMINAR: PRODUCT SCIENCE It is important to understand the: Chemistry information relevant to ENDS products, including: ingredients, additives, constituents, collection and analysis of constituents, and product stability Basic engineering principles of product design, product operation, and product manufacturing Toxicology profile of the ingredients in ENDS products, including: dose response, toxicity, routes of exposure, carcinogenicity, and risk assessment An Environmental Assessment is a PMTA requirement. 16
PMTA INFORMATIONAL SEMINAR: DATA SOURCES Data Sources for Potential Use An applicant can use publically available national e-cigarette data to supplement or complement other behavioral information that may be submitted in a PMTA. When performing a literature review, consider including the identification, evaluation, interpretation, and reporting of studies regarding ENDS products. 17
PMTA INFORMATIONAL SEMINAR: HEALTH RISKS Biomarkers of exposure and potential harm may be useful tools to enable a better understanding of potential health impacts within a shorter time frame. The human health impact should be assessed in both users and nonusers. It is important for FDA to understand how consumers and others are impacted by the availability of the product within the world of available tobacco products. 18
TOBACCO PRODUCT MARKET Marketed Tobacco Products Newly Deemed Tobacco Products ENDS Proposed ENDS 19
PMTA INFORMATIONAL SEMINAR: HUMAN FACTORS AND LABELING Consider the use environment, user and user interface when designing a product to maximize the likelihood of correct use and minimize the potential for unintended risk of product use. A PMTA must include a sampling of the proposed label for the new product. 20
PMTA INFORMATIONAL SEMINAR: ADDICTION AND ABUSE LIABILITY Traditional abuse liability assessments are designed to evaluate the likelihood of abuse of a drug, and can also assess the consequences of abuse. Determination of a product s abuse potential/abuse liability is accomplished through multiple lines of evidence. 21
PMTA INFORMATIONAL SEMINAR: INITIATION/ CESSATION General principles suggest that multiple lines of evidence would strengthen an argument related to the likelihood of tobacco product initiation and cessation. Initiation and cessation are defined in different ways. It is important that clear definitions and rationale are provided for how they are being defined in any particular setting in order to support meaningful interpretation of research findings. Youth are particularly susceptible to the initiation of tobacco products; therefore, one of CTP s top priorities is preventing youth from starting to use tobacco. 22
PMTA INFORMATIONAL SEMINAR: CONSUMER PERCEPTION Consumer perceptions are widely accepted in the scientific literature as precursors to use behavior, which may directly inform the likelihood of initiation/cessation among certain groups. Qualitative research provides richer information than what is available through other data collection methods such as surveys or experiments. It is a deeper dive into individuals thoughts, feelings, and behaviors and can help put other sources of data into context. 23
PMTA INFORMATIONAL SEMINAR: SUMMARY Applicants submitting a PMTA must respond to the statutory requirements specified by section 910 of the FD&C Act. FDA must consider whether permitting this product to be marketed would be appropriate for the protection of the public health. In order for FDA to review a tobacco product, it requires sufficient information to describe the product, how it is made, what is the impact if the product goes on the market, what is the impact on users and nonusers, and potential product switching behaviors. No specific studies are required for a PMTA; applicants can use publically available literature and nonclinical or clinical studies. Long-term health outcome studies are not required or expected. 24
QUESTIONS 25