The UK government has again demonstrated its world-leading commitment to progressive tobacco harm reduction policy by announcing licensed e-cigarettes may soon be available for NHS clinicians to prescribe to smokers unable to quit.

The Medicines and Healthcare Regulatory Agency (MHRA) is inviting manufacturers to submit marketing authorisation applications for e-cigarette products, which upon approval, will allow clinicians to decide on an individual basis whether prescribing a patient with an e-cigarette will help them stop smoking. The licensed e-cigarette medical products would also need to be approved for use by the National Institute for Health and Care Excellence (NICE). Following guidance from the E-cigarette Expert Working Group, authorities in the field of public health advising the MHRA, updated guidance has been published on the MHRA website to enable the potential applicant to understand the new “streamlined” process and make timely applications which are fit for purpose.

The full substance of the guidance is too detailed for this blog, so we’d encourage you to check out the MHRA webpage. But to summarise the key changes, the MHRA has updated guidance relating to the quality standards requirements for the e-cigarette product. Module 3 of an applicant’s dossier should include all information on the nicotine ingredient (inc. synthesis and control), details of other ingredients in the formulation, procedures and processes for manufacturing and control, with all test procedures validated and in accordance with current CEN/BSI standards. The update includes details of how to demonstrate nicotine dose uniformity of the e-cigarette over product shelf life. This may be demonstrated employing test equipment and conditions in conformity with BS ISO 20768:2018, a standard routinely employed by Hall Analytical for the testing of consumer e-cigarette products.

For non-clinical (safety) requirements, toxicology guidance for the investigation of heating and vapourising the e-liquid formulation is provided. Levels of thermal breakdown products of concern (carbonyls) need to be investigated with validated analytical methods, and potential toxicity of these products at relevant exposure levels and routes of administration must be included. Safety review for all components of the formulation must be provided from available published research. MHRA has recognised that local inhalation toxicity of excipients and flavourings may not be available in the literature, so alternative approaches have been provided to bridge the missing information. E.g., read-across end points, PK modelling to predict local and systemic exposure, Adverse Outcome Pathways to identify intermediate markers of toxicity.

For clinical requirements of product safety and efficacy, the pharmacokinetic (PK) parameters for nicotine plasma concentration determination (applicant nicotine-containing product vs. reference product) have been defined, with guidance on appropriate study design. Criteria for justification of efficacy and safety of the nicotine-containing product against a reference product (licensed nicotine inhaler) is provided, and potential strategies to bridge clinical bioavailability studies for applicants wishing to obtain authorisation for e-cigarette products in different flavours and strengths.

We hope you’ve enjoyed this brief update on the potential for licensed e-cigarettes to be available through the NHS. Hall Analytical has significant experience in the medicinal licensing of nicotine-containing e-cigarette products. We provided analytical testing services and guidance to the team who developed the e-VOKE, the first medically approved e-cigarette. We would be delighted to assist your business through the MHRA licensing process. Please call us to arrange a free consultation.