Nicotine Products
Our work
Recent years have seen a rapid expansion in the market for a wide range of nicotine-delivery devices, that aim to offer adults an alternative to the harms associated with smoking. Notably these include e-cigarettes, or ‘vapes’, which, rather than combusting tobacco, heat an “e-liquid” containing nicotine, solvents (propylene glycol and vegetable glycerin (PG/VG)), and flavourings, into a vapour that is inhaled by the consumer. We have been working on the front-line of the e-cigarette sector since its inception, providing our clients with critical safety evaluations to ensure regulatory compliance (e.g. with EU TPD, UK TRPR and/or US FDA PMTA). We have also been involved in the assessment of nicotine for EU REACH and EU CLP purposes, and in the safety assessment and preparation of regulatory data packages of a range of products including heated tobacco, nicotine inhalers, snus, nicotine pouches, and gums/lozenges.
Screening assessments
As a crucial first step we often carry out hazard screenings of product ingredients primarily to identify substances potentially of high concern to human health. For example, to flag those substances with concerns for possible sensitisation and/or CMR (mutagenic/genotoxic, carcinogenic and/or reproductive) effects. This screening exercise typically involves a brief literature review of the available toxicity data and (Q)SAR evaluation. The findings of this screen allows us to flag to our clients at an early stage which substances in their formulations might be of particular human health concern, and to take any necessary action (e.g. re-formulation) prior to carrying out further testing.
Toxicity monographs and risk assessment
Placing a product on the market requires the submission of a comprehensive toxicological evaluation, including appropriate risk assessments. We have produced hundreds of toxicity profiles summarising the critical hazard data of ingredients, including carriers like PG and VG, as well as flavourings (including natural extracts), and emission analytes (e.g. HPHCs).
We have also carried out numerous health risk assessments of nicotine-containing products, including of emissions, impurities and extractables and leachables studies. Each of these risk assessments include potential consumer exposure estimations.
If you'd like to download a poster on "Application of the Human Health Risk Assessment Process for Evaluation Electronic Cigarettes", co-authored by Charlie Johnson and Richard Young, please click here.
“The medicines route”
It is possible for e-cigarettes to be marketed with specific claims for “cutting down, quitting and reducing harm” related to tobacco smoking. In these cases, the product must be registered with the relevant regulatory authority as a medicine. We assisted with the first such marketing approval in the UK (Voke®), and continue to be involved with medicinal applications on both sides of the Atlantic.
Helpful information
The revised Tobacco Products Directive (TPD2)
Directive 2014/40/EU on the approximation of the laws, regulations and administrative provisions of the Member States concerning the manufacture, presentation and sale of tobacco and related products.
PMTA
Premarket Tobacco Product Application.
Section 910(b) of the Federal Food, Drug and Cosmetic Act.
Some of our case studies in this area
NAMs for NGRAs
Blog articles
Traditionally, toxicological risk assessment has involved identifying a point of departure (PoD) such as a NOAEL or LOAEL in a study of small creatures, adjusting it to be relevant to humans (to derive, for example, a TI or DNEL), and then calculating the margin of safety to a measured or estimated external exposure. As part of this process, toxicologists have to account for the uncertainties that arise in moving from the species, route and duration of the laboratory animal study to the real human world.
FDA memoranda: genotoxicity and carcinogenicity assessments of ENDS
Blog articles
As discussed in a previous blog post, the U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has issued several “scientific policy memoranda” that provide some great insights into the Agency’s evaluation process. In June 2024, the FDA made two new memos available that relate to the genotoxicity and carcinogenicity assessment of chemical constituents of Electronic Nicotine Delivery Systems (ENDS).
FDA memoranda: shedding light on health risk assessment of ENDS in PMTA submissions
Blog articles
In 2016, the United States (US) Food and Drug Administration (FDA) ruled that Electronic Nicotine Delivery Systems (ENDS) were to be regulated just like more traditional tobacco products, meaning that ENDS (e-cigarettes and e-liquids) are subject to premarket review requirements, despite containing no tobacco. ENDS manufacturers must therefore submit a Premarket Tobacco Product Application (PMTA) to the FDA Center for Tobacco Products (CTP) in order to have any chance of legally marketing their products in the US.
