The MHRA operates a system of licensing before the marketing of medicines. Medicines which meet the standards of safety, quality and efficacy are granted a marketing authorisation (previously a product licence), which is normally necessary before they can be prescribed or sold. This authorisation covers all the main activities associated with the marketing of a medicinal product. This section gives an overview of the process for obtaining a marketing authorisation in the United Kingdom.
In this section...
Who can apply?
Applications are generally submitted by the pharmaceutical industry, but anyone with the necessary supporting data may apply for a licence.
The legal framework
Applicants need to be aware of the relevant EC and UK primary legislation and subsidiary documentation.
The life cycle of a new medicine begins with discovery and laboratory studies carried out by the pharmaceutical company. During this period, studies will be conducted on the mode of action of the drug, how it moves around the body and its safety. The MHRA has no interest in these early stages of development until the company wants to start clinical trials in patients. It is at this stage of development that the company will have sufficient evidence to indicate whether the product is going to be a licensable medicine.
Purpose of the application
The applicant will be hoping to obtain a marketing authorisation as quickly as possible. To minimise delays, it is important that adequate information is provided to demonstrate that the product is of adequate quality for its intended use, that it is sufficiently safe and that it is effective. No other factors are considered when assessing the application (for example, comparative efficacy or cost benefit).
Types of application
There are a number of different types of application, depending on the nature of the active ingredient of the product. These vary from applications for products containing new active substances, those whose active ingredients have previously been evaluated before, known as abridged applications, to those biological and biotechnology products manufactured by recombinant DNA technology, products where genetic manipulation of cells is required, or a monoclonal antibodies.
Submitting the application
All applications must follow the common technical dossier (CTD) format which has been a requirement since 2003. The preferred format for new marketing authorisation (MA) applications is the electronic Common Technical Dossier (eCTD). However, we accept that many companies are not yet ready to submit applications in that format. Therefore, we will accept applications in PDF-only format. The Summary of Product Characteristics (SmPC) will need to be prepared using the Word template. You also need to use the MHRA Adobe Application form which is available via the MHRA Portal. This will produce an XML file that we will be able to upload directly into our database. eCTD applications must be created according to the current specifications: eCTD specification v 3.2, EU Module 1 specification v 1.0, eCTD EU application v 1.0.
The table on the page below provides the details of the fees payable for licence applications:
|Marketing authorisation application forms|
|Marketing authorisation application form (486Kb)|
|Marketing authorisation - application for renewal (206Kb)|
|Marketing authorisation - application for variation (1064Kb)|
|Marketing authorisation - application for change of ownership (MLA 201 (COA)) (53Kb)|
|Marketing authorisation - parallel importing (45Kb)|
|Marketing authorisation - parallel importing (variation) (41Kb)|
|Sample for a product licence appliation (98Kb)|
|NSAID Diclofenac Variation Form (113Kb)|
|NSAID Ibuprofen Variation Form (112Kb)|
|NSAID Naproxen Form (107Kb)|
|NSAID Others Variation Form (113Kb)|
In April 2012, following consultation with medicines trade associations and member companies we announced some procedural changes concerning the requirement to submit full-colour mock-ups of labels and patient leaflets. For more details on these changes please see our mock-ups section.
Before assessment of the application can begin, validation takes place. The forms are checked for completeness and appropriate signatures. The dossier is checked for pagination and the inclusion of English summaries.
The data requirements for applications are laid down in the 'Notice to Applicants' published by the European Commission's Committee for Medicinal Products for Human Use (CHMP) , available from the Commission or The Stationery Office. The full text is also available on The European Commission - Enterprise DG - Pharmaceuticals website. To summarise, for new active substances, full toxicological, pharmacological and clinical data would be expected. For other applications, adequate chemistry and pharmacy data together with appropriate toxicological and clinical bridging data should be provided, except where an authorised cross-reference is given to another granted marketing authorisation.
The Expert Reports are checked for valid signatures and the dossier will be checked against the requirements of 'Notice to Applicants' for completeness. If any omissions are spotted, the applicant has a brief window of opportunity to correct them or the application is returned as invalid. Any manufacturing sites and other companies named in the application are checked to confirm their acceptability and the product's proposed name is checked for any possible trade mark infringement or confusion with other medicines. If the application is considered valid, it is now referred for professional assessment by the appropriate assessment group, depending on the type of application.
Guidance on the MHRA's handling of the requirement in the Paediatric Regulation to undertake a ‘compliance check’ during validation - July 2008
We have published guidance outlining to companies how the MHRA intends to handle the impact of the requirements of the Paediatric Regulation on the validation of applications for marketing authorisations (MAs). In summary, where an application is submitted to the MHRA and no previous compliance check has been undertaken by the Paediatric Committee, the MHRA will, in all cases which are purely national applications or where we are Reference Member State, request an opinion from the Paediatric Committee as to whether the studies conducted by an applicant are in compliance with the agreed Paediatric Investigation Plan (PIP).
Guidance on the MHRA’s handling of the requirement in the Paediatric Regulation to undertake a ‘compliance check’ during validation
When an application has been validated it is placed in a queue for professional assessment. There are a number of different queues depending on the type of product and whether the application was made via the European route or direct to the MHRA.
The role of the assessor is to determine whether, in their professional opinion, the applicant has provided adequate information to determine the product's quality, safety and efficacy, taking into account the claims made in the application forms. Before reaching an opinion they may need to discuss the data with the applicant or request additional information.
Applications for new active substances, novel delivery systems, the first generic version of an existing product and those applications where the assessor(s) are not satisfied with the information provided must be referred to the advisory bodies.
The main advisory body for the evaluation of human medicines is the Commission on Human Medicines (CHM). A number of specialist subcommittees have been established to assist the CHM in its work.
If an advisory committee advises the Licensing Authority to refuse an application, the applicant has the right to a hearing (written or oral) before the committee. If, after this, the committee still advises against granting a licence, the applicant has the right to appeal to the ‘Person Appointed’ by the Licensing Authority.
Renewals and variations to licences
Marketing authorisations are granted for periods up to five years and have to be renewed at the end of this time. On renewal each marketing authorisation must reflect all the up to date knowledge about the product including any necessary action from the most recent periodic safety update report (PSUR).
Variations to marketing authorisations are necessary to introduce changes to take account of technical and scientific progress, introduce additional safeguards, or reflect evolving therapeutic indications. It is common practice for new products to be varied many times, particularly in their first couple of years on the market.
Contact for further information
For further information on this part of our site, please contact our Regulatory Information Service, 4.T, 151 Buckingham Palace Road, London SW1W 9SZ, telephone 020 3080 7400.