The First 10 Years: Reflecting on Opportunities and Challenges of the Tobacco Products Scientific Advisory Committee of the United States Food and Drug Administration

Figures & data

Figure 1. TPSAC membership and functioning structure from 2010 to 2019.

Figure 2. Number of TPSAC meetings, 2010–2019 (n = 25). Notes: We present the total number of meetings by year. Several meetings covered multiple topics.

Figure 3. Number of open hearing public speakers by scientific topic (n = 178).

Table 1. Process Questions Posed to TPSAC by the FDA from 2010 to 2019 (n = 16 meetings).

Topic	Meeting date	Process questions to TPSAC
Menthol	March 30–31, 2010	Are there any specific questions around menthol that industry should address at the next meeting? What other information does the committee need in order to meet its statutory requirement? Are there agenda items that should be included in future meetings pertaining to menthol? What support does the committee need to complete its report and recommendations by the statutory deadline?
HPHCs	June 8–9, 2010 Questions to the Dissolvable Tobacco Product Subcommittee	What criteria do you recommend to TPSAC for selecting the HPHCs in tobacco products or tobacco smoke (which will be used in developing the initial list)? What HPHCs do you recommend to TPSAC be included on the initial FDA list and how do they meet the criteria? Which smoking regimen or regimens does the subcommittee recommend to be used by TPSAC to measure HPHCs? What established analytical methods do you recommend to TPSAC for assessing the quantity of each HPHC in tobacco products or tobacco smoke? What scientific parameters need to be considered in choosing methods to be used? What are your scientific recommendations on: sampling, based on information about variability of products? smoking regimens? What are your scientific recommendations on how values should be normalized: By product unit (per can or stick) By volume (smoke volume, gram of smokeless) By nicotine or tar content
HPHCs	July 7, 2010 Questions to the Dissolvable Tobacco Product Subcommittee	See above
Menthol	July 15–16, 2010	In light of the July 15–16, 2010, TPSAC presentations, what future presentations would you like to request from industry on: Characterization of menthol in cigarettes, clinical effects of menthol in cigarettes, biomarkers of disease risks, marketing data, and population effects of menthol in cigarettes?
Menthol	September 27, 2010	Questions to be addressed in the final report: What is the impact of menthol cigarettes on public health, including such use among children, African Americans, Hispanics, and other racial/ethnic minority groups? What recommendations, if any, does TPSAC have for the FDA regarding menthol cigarettes?
Menthol	November 18, 2010	Are the questions proposed by the chapters 1 and 2 writing working groups the scientific questions that should be addressed in the report? Does the committee agree with the proposed approach for evaluating the scientific evidence? (e.g., using the concept of equipoise, the evidence is sufficient/insufficient to conclude that the relationship is more likely than not, at least as likely, more likely, insufficient)
Menthol	January 10–11, 2011	What suggestions does TPSAC have regarding the proposed model? What suggestions does TPSAC have regarding the general approach to the review of the evidence? What suggestions does TPSAC have regarding the strength of evidence criteria? What suggestions does TPSAC have regarding the approach outlined by each of the chapter writing groups?
Menthol	March 2, 2011	What comments do you have regarding the proposed model? What feedback does TPSAC have regarding draft chapters 3 and 6?
Dissolvable tobacco products	July 22, 2011	Discuss the possible public health impact relating to: marketing of dissolvable tobacco products. perception and use of dissolvable tobacco products by children and adults. abuse liability of dissolvable tobacco products. health risks of dissolvable tobacco products. risk of accidental ingestion of dissolvable tobacco products. features of dissolvable tobacco products that may contribute to tobacco initiation. features of dissolvable tobacco products that may lead tobacco users to singular or dual use of dissolvable tobacco products instead of quitting. What additional topics, if any, would you like the FDA to ask the tobacco industry to present on at the next TPSAC meeting? Are you aware of any available information or research that you would like the FDA to request to be presented to the TPSAC to help inform the report and recommendations on dissolvable tobacco products?
Dissolvable tobacco products	January 18–20, 2012	Regarding the data from Sweden on smokeless tobacco products, discuss what, if any, extrapolations can be made: to use of dissolvable tobacco products. from the impact of the use of traditional smokeless tobacco on oral health to the impact of the use of dissolvable tobacco products on oral health. What factors may limit making these extrapolations? With respect to the peer reviewed articles on dissolvable tobacco products, please discuss: What scientific findings are more strongly supported by the literature? What information gaps exist in the literature? What additional research would inform an evaluation of the public health impact of dissolvable tobacco products? What surveillance activities should be implemented to monitor poison events associated with dissolvable tobacco products? Discuss whether dissolvable tobacco products increase overall initiation for the use of tobacco products and what further research would inform this question. What evidence, if any, is there that dissolvable tobacco products encourage initiation of use of tobacco products generally? What design features of dissolvable tobacco products encourage or discourage use by current nonusers of tobacco products? In what way, if any, does initiation of use of dissolvable tobacco products encourage eventual use of other forms of tobacco? Discuss youth perceptions of dissolvable tobacco products and what further research would inform this question. What do children and adolescents think about dissolvable tobacco products and how might this affect use of the product? What are the characteristics of dissolvable tobacco products that make them more or less appealing to children and adolescents, including users and nonusers of tobacco products? How do youth perceptions of dissolvable tobacco products compare to their perceptions of cigarettes and other smokeless tobacco products? Which, if any, specific population groups are more likely to use dissolvable tobacco products? Discuss adults’ perceptions of dissolvable tobacco products and what further research would inform this question. What do adults think about dissolvable tobacco products and how might that affect use of the product? What are the characteristics of dissolvable tobacco products that make them more or less appealing to adults, including users and nonusers of tobacco products? How do adults’ perceptions of dissolvable tobacco products compare to their perceptions of cigarettes and other smokeless tobacco products? Which, if any, specific populations are more likely to use dissolvable tobacco products? Discuss dual use of dissolvable tobacco products with other tobacco products and what further research would inform understanding of this issue. To what extent are dissolvable tobacco products used in conjunction with other tobacco products by children, adolescents, and adults? How are dissolvable tobacco products used by children and adolescents in conjunction with other tobacco products (i.e., dual use)? How are dissolvable tobacco products used by adults in conjunction with other tobacco products (i.e., dual use)? What role, if any, does marketing play in promoting exclusive or dual use of dissolvable tobacco products? Discuss potential abuse liability of dissolvable tobacco products and what further research would inform this question. How do the nicotine levels and different rates of nicotine delivery impact the abuse liability of dissolvable tobacco products? In what ways, if any, do the design characteristics of dissolvable tobacco products or their packaging encourage or discourage use by targeted users? What aspects, if any, of the design characteristics of dissolvable tobacco products encourage or discourage use by nontargeted populations? What aspects, if any, of the design characteristics of dissolvable tobacco products encourage or discourage use in ways other than as stated by the manufacturer? In what ways, if any, could the abuse liability of dissolvable tobacco products be reduced? How does the abuse liability of dissolvable tobacco products compare to that of other tobacco products? Discuss cessation rates as related to dissolvable tobacco products and what further research would inform this question. How are the tobacco cessation rates associated with use of dissolvable tobacco products related to the tobacco cessation rates for users of other tobacco products? How does cessation differ among adolescents and adults with dissolvable tobacco products compared with other tobacco products? What evidence, if any, suggests that children, adolescents, and adults delay tobacco cessation by using dissolvable tobacco products? What evidence, if any, suggests that dissolvable tobacco products alter tobacco cessation for users of other types of tobacco products (i.e., do users switch to dissolvable tobacco products rather than quit)? Discuss the morbidity and mortality associated with the use of dissolvable tobacco products and what further research would inform this question. How does the morbidity and mortality associated with use of dissolvable tobacco products differ compared to that associated with use of other tobacco products? Discuss the toxicity related to dissolvable tobacco products. What are the key toxicities of concern for dissolvable tobacco products that may require toxicity testing in in vitro and/or in vivo toxicology models? What are the most applicable model(s) for toxicity testing of dissolvable tobacco products? In Vitro toxicity testing In vivo toxicity testing Discuss the marketing strategies currently used to promote dissolvable tobacco products and what further research would inform this question. Who is the target audience of dissolvable tobacco product marketing? What are the primary messages used in dissolvable tobacco product marketing? How does the marketing of dissolvable tobacco products affect consumer perceptions of the product? How is the marketing of dissolvable tobacco products similar to and different from that of other tobacco products? Discuss the public health impact, if any, and what further research would inform understanding of: Risk of accidental ingestion of dissolvable tobacco products. Safety of package design of dissolvable tobacco products. Topography of use of dissolvable tobacco products. Youth perception of dissolvable tobacco products. Impact of the use of dissolvable tobacco on cardiovascular health. How knowledge of the impact of the use of chronic nicotine replacement therapy on health could inform the use of dissolvable tobacco products.
Dissolvable tobacco products	March 1, 2012	Regarding the summary of TPSAC’s consideration of dissolvable tobacco products, please be prepared to discuss in detail at the meeting what changes should be made to any part of the document. In particular, do you have any disagreements or concerns regarding the key findings from the evidence review? What changes would you make to this assessment of the available evidence? In particular, do you have any disagreements or concerns regarding the recommendations for further information gathering, surveillance, and research? What changes should be made to these recommendations for further information gathering and study? The TPSAC report on dissolvable tobacco products will include the above referenced summary document as well as the background materials, transcripts, presentations, and minutes from the three TPSAC meetings on dissolvable tobacco products. Would you like to provide any clarification for or dispute any information provided to the committee or resulting from the committee process (e.g., meeting transcripts) that will become part of the committee report?
MRTP	April 30, 2013	What FDA action could initiate a referral that starts the 60-day period within which TPSAC must make its recommendations to the FDA? What materials should the FDA provide in order for TPSAC to make its recommendations? In what format could TPSAC report its recommendations to the FDA?
HPHCs	August 16, 2013	How would you recommend that the FDA evaluate the relative health risks to individuals of the MRTP? How would you recommend that the FDA evaluate the increased or decreased likelihood that existing users of tobacco products who would otherwise stop using such products will switch to the MRTP? How would you recommend that the FDA evaluate the increased or decreased likelihood that persons who do not use tobacco products will start using the MRTP? How would you recommend that the FDA evaluate the risks and benefits to persons from the use of the MRTP as compared to the use of drug or device products for smoking cessation approved by the FDA to treat nicotine dependence? How might the FDA collectively evaluate the information related to topics 1–4 [the [previous topics] in order to determine the potential effects of an MRTP on the health of the population?
HPHCs	August 15, 2013	What potentially important communication objectives for the HPHC list should the FDA consider when fulfilling its statutory obligation? How could the FDA assess whether the publication of the list of HPHC in tobacco products by brand and by quantity in each brand and subbrand is in a format that is understandable and not misleading to a lay person? What additional research could the FDA conduct to inform the development of the format and assess the impact of the public display of the list of HPHCs in tobacco products by brand and by its quantity in each brand and subbrand? What strategies might the FDA use in a public education effort aimed at a deeper public understanding of HPHCs?
Addiction/dependence	April 16–18, 2014 Questions on 16th	What are your views on the differences, if any, between dependence and addiction? Have these changed over time? If so, what are the factors that influenced this change? How can current assessments of dependence/addiction be used for nontraditional products and/or nondaily users? How can current assessments be applied to individuals who use multiple products? Are new assessments necessary? On the topic of dependence/addiction, what review factors should be included in the evaluation of product submissions?
	Questions on 17th	Considering the examples of modeling approaches presenting for assessing the effects of tobacco products on population health: What are the merits and limitations of to these approaches for assessing the models? Are there other modeling approaches that may be appropriate for assessing these effects prior to allowing a product to market? Discuss the quality of the data source parameter inputs for modeling. Do you have recommendations for the process of assessing the best sources of data used for inputs? Do you have recommendations for addressing gaps in the information used to as model input parameters? Are there particular inputs that you deem critical for modeling the effects of tobacco products on populations health? Discuss the need for common terminology in defining key parameters; for example, initiation, cessation, smoking status. Do you have recommendations regarding the metrics that may be used to assess the effects of tobacco products on the population as a whole? Morbidity and mortality Quality of life Disability
	Questions on 18th	For MRTPAs seeking to market a product under Section 911(g)(1) of the FD&C Act; that is, risk modification order: What concerns, if any, do you have about the use of certain types of studies, or data, to draw inferences about the potential impact of product use on health outcomes in individuals? For MRTPAs seeking to market a product under section 911, seeking exposure modification order: What concerns do you have about certain types of studies or data to draw inferences about the potential impact of product use on exposures in individuals? What concerns do you have about the use of studies or data on exposures to individuals to infer potential health outcomes? For all MRTPAs What concerns do you have about the use of studies or data on exposures to individuals to infer potential impact of marketing of an MRTP on tobacco use behaviors? What recommendations do you have for placing greater weight on certain types of data or studies, as they relate to the assessment of tobacco use behaviors? What concerns do you have about the use of studies or data on exposures to individuals to infer potential impact of marketing of an MRTP on tobacco use behaviors? When making a determination to allow an MRTP to market, the FDA will need to assess the impact on the population as a whole: What recommendations do you have for placing greater weight on certain types of data or studies, as they relate to the assessment of health outcomes or tobacco use behaviors, when considering the impact of the population as a whole? What recommendations do you have for strategies that industry or FDA could undertake to address any areas of concern after an MRTP has been allowed to market to the U.S. population?
MRTP	April 6, 2017	How was the information provided to TPSAC prior to the 2015 meeting on the MRTPAs for the SMNA snus products helpful in preparing for the meeting? How do you anticipate preparing for upcoming application review TPSAC meetings? What information would be most useful to receive prior to an application review TPSAC meeting? What information would likely be least useful prior to an application review TPSAC meeting? How would having only an executive summary or only the sections of the application that the FDA planned to discuss, compared to having the entire application, impact your ability to prepare for an application review TPSAC meeting and give advice to the FDA? In relation to the meeting itself, how was the information provided during the presentations at the 2015 meeting on the MRTPAs for the SMNA snus products helpful in providing advice to the FDA? What information would be useful as part of the meeting presentations during an application review TPSAC meeting? What information would not be useful as part of the meeting presentations during an application review TPSAC meeting? How might the TPSAC meeting be structured so that the committee is best positioned to provide advice to the FDA?

Notes: Questions have been truncated. A more detailed description of the sub-questions is located on the FDA TPSAC website.