{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:39:29Z","timestamp":1784659169549,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Implementing the 2009 US Tobacco Control Act established a new infrastructure for tobacco and nicotine science. At its heart is the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). A key challenge facing FDA CTP is determining whether nicotine products are \u201cappropriate to the protection of the public health,\u201d and this is the central component of the Premarket Tobacco Application (PMTA) and Modified Risk Tobacco Application (MRTP) processes. CTP has granted such marketing orders for only a few products but has been consistent in its reasoning: the applicant demonstrated that the product(s) has low levels of Harmful and Potentially Harmful Constituents (HPHCs). By doing so, FDA has equated low levels of HPHCs with public health benefit. Other factors will be increasingly important, but the regulatory history indicates that no product will be granted a marketing order unless it has low levels of HPHCs. This science\u2010driven regulatory approach has been possible due to the rapid evolution of the knowledge base and expansion of scientific human resources, including establishment of a robust CTP Office of Science to evaluate the extensive dossiers that manufacturers must submit. Companies therefore established internal regulatory science programs, and contract research organizations developed capabilities needed to support regulatory dossiers. This article focuses on the chemistry and toxicology part of the regulatory science process and also presents the industry side of the regulatory process by examining the experience of one company\u2014Swedish Match\u2014that was granted the first PMTA and MRTP marketing authorizations.<\/jats:p>","DOI":"10.1002\/dta.3369","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T08:16:32Z","timestamp":1662970592000},"page":"1198-1204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The importance of harmful and potentially harmful constituents in the implementation of the 2009 US Family Smoking Prevention and Tobacco Control Act"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-0949","authenticated-orcid":false,"given":"James","family":"Solyst","sequence":"first","affiliation":[{"name":"JMS Scientific Engagement  Severna Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Family Smoking Prevention and Tobacco Control Act Public Law 111\u201331 June 22 2009. 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Accessed 3 March 2022.https:\/\/www.fda.gov\/tobacco\u2010products\/manufacturing\/submit\u2010tobacco\u2010product\u2010applications\u2010deemed\u2010tobacco\u2010products#:~:text=To%20be%20timely%20submitted%2C%20applications efficiently%20transmit%20and%20receive%20applications"},{"key":"e_1_2_10_11_1","unstructured":"US Food and Drug Administration.FDA grants first\u2010ever modified risk orders to eight smokeless tobacco products. FDA News Release22 October2019. Accessed 3 March 2022.https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-grants-first-ever-modified-risk-orders-eight-smokeless-tobacco-products"},{"key":"e_1_2_10_12_1","unstructured":"US Food and Drug Administration.Premarket tobacco product applications and recordkeeping requirements. a rule by the Food and Drug Administration on 10\/05\/2021. Accessed 3 March 2022.https:\/\/www.federalregister.gov\/documents\/2021\/10\/05\/2021-21011\/premarket-tobacco-product-applications-and-recordkeeping-requirements"},{"key":"e_1_2_10_13_1","unstructured":"US Food and Drug Administration.Premarket Tobacco Applications for Electronic Nicotine Delivery Systems (ENDS). Guidance for Industry. June2019. Accessed 3 March 2022.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/premarket-tobacco-product-applications-electronic-nicotine-delivery-systems-ends"},{"key":"e_1_2_10_14_1","unstructured":"US FDA Center for Tobacco Products Office of Science.Premarket Tobacco Application (PMTA) Technical Project Lead (TPL) Review. March 11 2015. Accessed 3 March 2022.https:\/\/www.fda.gov\/media\/94582\/download"},{"key":"e_1_2_10_15_1","unstructured":"US Food and Drug Administration.Harmful and potentially harmful constituents in tobacco products and tobacco smoke: established list. April2012. 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