Medicines Healthcare Products Regulatory Agency
Introduction
The MHRA is responsible for regulating nicotine-containing products (NCPs) as medicinal products in the UK. These are intended to relieve or prevent craving and nicotine withdrawal symptoms when tobacco smokers wish to quit or reduce smoking. The MHRA seeks to encourage the licensing of electronic cigarettes (e-cigarettes) and other inhaled NCPs as medicines and aims to support companies to submit marketing authorisation applications for these products. In addition to the medicines authorisation, where the E-cigarette is refillable and re-useable it will need to meet the UK Medical Device Regulations 2002 (as amended). Potential applicants who are not familiar with medicines legislation are strongly advised to contact the MHRA for regulatory and scientific advice. The MHRA commits to provide the assistance needed to ensure that potential applicants understand the process and feel able to make applications in a timely manner which are fit for purpose. For applicants with products undergoing the US FDA premarket tobacco product application (PMTA) process, the MHRA can discuss what data may be relevant for a UK marketing authorisation application.
The MHRA is also the Competent Authority for the notification scheme for e-cigarettes and refill containers in Great Britain and Northern Ireland, and is responsible for implementing the majority of provisions under Part 6 of the Tobacco and related Products Regulations (TRPR) and the Tobacco Products and Nicotine Inhaling Products (Amendment) (EU Exit) Regulations 2020. Information on the requirements for consumer e-cigarettes can be found on our consumer products guidance page. These products are not medicines and are not permitted to make medicinal claims.
To license e-cigarettes and other inhaled NCPs as medicines, the proposed products should meet standards of quality, safety and efficacy as defined under medicines regulations. The proposed medicinal products should also meet the usual quality and safety standards for consumer e-cigarettes that have been developed by national and international standards organisations, where relevant. Proposed products may also need to comply with the UK medical device regulations, depending on the design of the product.
E-cigarettes regulated as medicines may be made available in strengths and volumes greater than those permitted under the TRPR (i.e. containing more than 20 mg/ml nicotine, more than 2 ml for single use cartridge/disposable products or more than 10 ml for refill containers).
This document provides more specific guidance on the procedure for licensing e-cigarettes and other inhaled NCPs as medicines.
Applying for a marketing authorisation
The recommended starting point for information on the medicines licensing procedure is the MHRA marketing authorisations, variations and licensing guidance.
Further information can be found here:
- Applying for a licence to market a medicine in the UK
- Types of application (legal basis)
- Fees for licence applications (Note that nicotine is not a new chemical entity so it is expected that application fees would fall within the abridged complex or standard classifications)
As nicotine is not a new chemical entity, a so-called abridged application may be submitted as a generic application under Regulation 51 (previously Article 10.1 of Directive 2001/83/EC) or a hybrid application under Regulation 52 (previously Article 10.3 of Directive 2001/83/EC), of Human Medicines Regulation, as amended. These legal bases allow for submission of a dossier which is abbreviated in relation to safety and efficacy, relying on a pharmacokinetic (PK) study to compare the new product to an appropriate reference medicinal product.
Given the intended route of administration, an already-approved inhaled nicotine product such as the Nicorette 15 mg Inhalator would be a suitable reference and comparator medicinal product.
For a submission under Regulation 51, the proposed product should be bioequivalent to the reference product. This is likely to be the most appropriate approach when developing an inhalator product with reference to an established inhalator reference product, for example. For a submission under Regulation 52, the proposed product need not be bioequivalent to the reference product, but the proposed products nicotine PK profile should be justified in relation to where it sits compared to the reference product and combustible cigarettes. This is likely to be the most appropriate approach when developing an e-cigarette product with reference to an established inhalator reference product, for example. PK data should be complemented by a discussion of the proposed products safety and efficacy with reference to the literature. Please see the clinical requirements section for further information.
All marketing authorisation applications (MAAs) must be supported by a risk management plan. This must cover identified and potential risks of the product and the measures to be implemented to minimise these risks. Further information can be found in our Good Pharmacovigilance guidance (GpVP).
In assembling the dossier for an application for marketing authorisation, the guidelines relating to the quality, safety and efficacy of medicinal products need to be considered. The dossier will need to follow the format published by the European Commission in EudraLex Volume 2 - Pharmaceutical Legislation Notice to applicants and regulatory guidelines medicinal products for human use. In particular, Volume 2B Presentation and content of the dossier provides a useful overview of the data which make up a marketing authorisation and gives specific reference to many of the guidelines which should be referred to when compiling the data to support a marketing authorisation. These guidance documents can also be found on the MHRA website.
Further information on applying for a marketing authorisation can also be found in our licensing guidance. This gives relevant information in such areas as which procedure route to follow, fees, naming of the medicine and ways to make the submission. Applications should be submitted using the electronic Common Technical Document (eCTD).
There are several routes to obtain a marketing authorisation in the United Kingdom (UK), Great Britain (England, Scotland and Wales) or Northern Ireland. The national 150-Day Procedure is an accelerated procedure available for high-quality applications to market a medicine in the United Kingdom, Great Britain or Northern Ireland. Applicants are encouraged to contact the MHRA if alternate routes of submission are being considered.
Quality requirements (Module 3 of the dossier)
The quality data (Module 3) requirements are clearly defined and apply to all MAAs. Two main sets of information are needed, the first dealing with the active substance (Module 3.2.S) and the second with the finished medicinal product (Module 3.2.P).
All relevant information should be provided on the product development, the manufacturing process, characterisation and properties of the product, the quality control operations and test specification, the stability as well as a description of the composition and presentation of the finished medicinal product.
Module 3 should also include:
- information on the nicotine active substance including its synthesis and control
- details of other ingredients in the formulation of the finished medicinal product and of the container components (e.g. cartridges).
- the procedures and methods used for manufacturing and controlling the finished medicinal product. These need to be described in sufficient detail to enable them to be repeated in control tests, carried out at the request of the competent authority.
- all test procedures shall correspond to current scientific standards and need to have been validated. Results of the validation studies should be provided. In the case of test procedures included in the European or British Pharmacopoeia, the description may be replaced by the appropriate detailed reference to the monograph(s) and gene