E-cigarettes and other Nicotine Delivery Devices

Recent years have seen a rapid expansion in the market for non-tobacco products that deliver inhaled nicotine, most notably, electronic cigarettes. These do not involve burning processes, rather converting an “e-liquid”, containing nicotine and other excipients, into a vapour that is inhaled by the user. Thus, we provide critical e-cigarette safety evaluation, for regulatory compliance and more.

In general, in the EU, electronic cigarettes and other electronic nicotine delivery systems (ENDS) and non-tobacco nicotine delivery devices (NTNDD) will come under the revised Tobacco Products Directive (TPD2; 2014/40/EU). Article 20 states the need for manufacturers and importers of e‑cigarettes to submit a ‘notification’ six months prior to the intended placing on the EU market (or, if already on the market on 20 May 2016, the notification shall be submitted within 6 months). The notification in question must therefore include “toxicological data regarding the product’s ingredients and emissions, including when heated, thus referring in particular to their effects on the health of consumers when inhaled and taking into account, inter alia, any addictive effect”. Where Member States consider that the submitted information is incomplete, as a result they shall be entitled to request the completion of the information. In addition and especially relevant, Member States shall ensure, among other requirements, that “except for nicotine, only ingredients are used in the nicotine-containing liquid that do not pose a risk to human health in heated or unheated form”.

We provide valuable advice on toxicological issues relating to e-cigarettes, and can support your regulatory submissions within the scope of MHRA, REACH and CLP

Whereas consequently, according to the Medicines and Healthcare Products Regulatory Agency (MHRA), the relevant UK competent authority, any such product “which claims or implies that it can be used for cutting down, quitting and reducing harm is considered to be a medicinal product and must be licensed as a medicine”. Therefore as part of the license application process, a supplier must assess the safety and efficacy of the product, including a detailed safety review of all chemical components in the liquid formulation and a comprehensive e-cigarette safety evaluation of the potential extractables and leachables originating from all parts of the e-cigarette. We have good experience of the MHRA approval process, having assisted a client with obtaining a medical license for the general sale of their breath-operated product (Voke®) from the MHRA.

 

Toxicological assessments – E-cigarettes and other NTNDDs

  • Preliminary hazard screening of e-liquid ingredients to outline critical toxicology and identify substances of high concern to human health. This screening allows companies to identify at an early stage possible substances of high human health concern in their formations and to act on this (e.g. consider reformulation of the e-liquid), prior to analytical testing of their products and submission of a regulatory notification/registration.
  • Toxicity monographs including expert searches to identify existing toxicology data on the product, individual components, ingredients, impurities, emissions, metabolites and/or read-across candidates. These include the key available data for a comprehensive range of toxicological endpoints (including cardiopulmonary and Carcinogenic, Mutagenic and Reproductive (CMR) properties) as well as addictiveness data. These monographs have proved to be a key part of companies TPD2 notifications, and could form the basis for a PMTA submission.
  • Human health risk assessment on emissions, including carbonyls, VOCs, TSNAs and potentially hazardous metal impurities. This is often conducted by bibra toxicologists, following the identification and quantification of the emissions profile of the product by a trusted analytical laboratory.
  • Thorough toxicological reviews and e-cigarette safety evaluations on the product components, formulation ingredients, emissions, and extractables and leachables.
  • Application of read-across and (Q)SAR to fill data gaps, where identified.

 

Electronic cigarettes and other ENDS may also fall within the scope of both REACH and CLP, due to being regarded as containers of chemical substances. Most noteworthy, for substances imported at one tonne or more per year per legal entity, it is required that they are registered under REACH and are notified to the Classification and Labelling Inventory. Our internationally renowned team of scientific experts can guide you through your REACH registration process and classification and labelling requirements.

Get in touch if you need help, for example, in the preparation of a ‘notification’ for submission under TPD2, in the preparation of a medicine license application (e.g. for the MHRA), a thorough toxicological evaluation for a PMTA in the US, or assistance with your REACH or CLP obligations.

 

Continue reading about our previous work in the e-cigarette industry:

Find out more about our work on “Extractables and Leachables in the ENDS (electronic nicotine delivery system) sector

Read our recent interview regarding e-cigarette safety evaluation with ECigIntelligence on “TPD test requirements criticised as vague: what can manufacturers do?

Read Charlie’s e-cigarette series of blogs, on our dedicated webpage.

Pete and Richard recently gave an interview to Smithers Rapra, about the e-cigarette safety evaluation and ongoing safety assessment obligations for e-liquids and e-cigarette hardware…click here to read more!

 

Recent work in this field

More about our company Meet the team Our recent work