In this section...
Types of procedure
There are several alternative procedures to choose from depending on which countries the product is going to marketed in and the type of medicine.
In the European Union (EU), a company may submit a single application to the European Medicines Agency (EMA) for a marketing authorisation (licence) that is valid simultaneously in all EU Member States, plus Iceland, Liechtenstein and Norway. This is called the centralised (or community) authorisation procedure, and is mandatory for certain types of medicines and optional for others. (The precise scope is set out in Annex I of Regulation (EC) No 726/2004 (external link). Further information about European applications can be found on the EMA website (external link).
Clarification regarding Centrally Authorised Products (national notifications)
Although the EMA is the main point of contact for issues regarding EU licenses, there are occasion in which marketing authorisation holders (MAH) may need to liaise directly with National Agencies when required by the EMA (eg conditions of approval) .
One of such requirements can be to submit Education Materials. MAH needing to use education materials in the United Kingdom will need to approach the MHRA and seek our opinion on those. To ensure these types of submissions are promptly assessed, we request the MAHs to notify the MHRA by email when the education materials are dispatched. This email notification should mention product name, active substance, centralised procedure number (EMEA/H/C/….), date of the dispatch and confirm department/address to which it was sent (e.g. Area 8 - Submission Centre for CAPs). This email should be sent to the Regulatory Information Service at RIS.NA@mhra.gsi.gov.uk
Other authorisation procedures are used for medicines that do not fall within the mandatory scope of the centralised procedure, these are:
Each EU Member State has its own procedures for the authorisation of medicines that fall outside the scope of the centralised procedure. Applicants must submit an application to the competent authority of the Member State. In the UK, this is the MHRA. Applicants will receive assessment reports for major, standard and complex national initial applications. The assessment report will be sent to the applicant with the request for further information at the initial assessment stage. Following the applicant’s submission of responses, a new assessment report (containing the assessment of the responses only) will be sent to the applicant. These reports will help applicants better understand the context and basis of the comments raised by assessors.
Using the decentralised procedure, companies may apply for simultaneous authorisation in more than one EU country of products that have not yet been authorised in any EU country and that do not fall within the mandatory scope of the centralised procedure.
Mutual recognition procedure
In the mutual recognition procedure, a medicine is first authorised in one EU Member State, in accordance with the national procedures of that country. Following this, further marketing authorisations can be sought from other EU countries in a procedure whereby the countries concerned agree to recognise the validity of the original, national marketing authorisation.
Further details about the decentralised and mutual-recognition procedures can be obtained from the Coordination Group for Mutual Recognition and Decentralised Procedures – Human, CMD(h) (external link).
Types of application
Applications for new active substances are described as 'full applications'. Applications for medicines containing existing active substances are described as 'abbreviated’ or ‘abridged applications’.
- Article 8(3) of Directive 2001/83/EC (full applications)
- Article 10 of Directive 2001/83/EC, use this for generic medicines and similar biological medicinal products
- Article 10a of Directive 2001/83/EC, use this for applications relying on well established medicinal use supported by bibliographic literature
- Article 10b of Directive 2001/83/EC, use this for applications for new fixed combination products
- Article 10c of Directive 2001/83/EC, use this for applications based on informed consent from a marketing authorisation holder for an authorised medicinal product.
Full applications (under Article 8(3)) must be accompanied by a dossier of information covering:
- pharmaceutical (physico-chemical, biological or microbiological) tests
- preclinical (toxicological and pharmacological) tests
- clinical trials.
Any relevant published literature should also be included.
The applicant must decide which legal basis they are going to use. (see above). Guidance and definitions are available in ‘The Rules Governing Medicinal Products – Notice to Applicants Volume 2A(chapter 1)’.
Abridged applications do not require full preclinical or clinical dossiers. Complete guidance on the documentation required is published in ‘Notice to Applicants’. Applications for generic medicines are required to identify a ‘reference medicinal product’ from which the MHRA can determine the preclinical and clinical data. The MHRA Information Centre can provide lists of products containing a particular active ingredient from which a suitable reference product can be identified.
The approval to market a medicinal product is based on the evaluation of scientific data provided by the company to support its quality, safety and efficacy. However, most of the 'new' products which come onto the market contain drugs which have been previously well tested and approved in other forms or for other companies. In these circumstances the European Directives (in particular Directive 2001/83EC) allow for what are known as 'abridged' applications so that companies do not have to unnecessarily repeat the tests and trials on animals and humans.
Important notesThe information given in this section refers to medicinal products containing chemical active ingredients. For information on abridged applications for vaccines and other biological products see the Biological and biotechnology products section below.
In the examples described below, the relevant sub-sections of the European Directive articles are shown in brackets. Note however that the advice on these pages has no legal basis and applicants are advised to refer to the original Directives and Commission guidance for a definitive view of their particular case.
If the new product meets requirements for a generic product defined in Article 10 (2)b of the Directive (2001/83 (as amended)), then it can be authorised without its own clinical and pre-clinical testing data.
The data requirements and the assessment process aim to ensure that patients could be switched between the brand leader product and a generic version without causing any therapeutic problems.
Existing drugs with new forms, routes and indications
Sometimes, although the drug is the same, the new product has a different strength or pharmaceutical form or is used by a different route or for different clinical uses. In these cases the company can submit more pre-clinical and clinical data to supplement their abridged application. (The 'Notice to Applicants' refers to these as 'other abridged' applications. The relevant legal basis is Article 10(3) of Directive 2001/83/EC). The full text of the Notice to Applicants is available on The European Commission - Enterprise DG - Pharmaceuticals and Cosmetics website.
Existing drugs in new combinations
New combinations of existing drugs may also be proposed though they may need a full data package to support them. (Article 10b)
'Well-established' drugs and products
The new product may include a drug substance which has such a well-established medicinal use and an acceptable level of safety that the applicant company can submit published data to support the safety and efficacy aspects of their application. (Article 10a) Examples here may include some over-the-counter (OTC) remedies.
Informed consent and change of ownership applications
For commercial reasons companies may want to take over or duplicate a product licence held by another company. Where the first company agrees to this 'informed consent' approach, the second company can get an exact copy licence commonly known as a 'piggy-back' licence. (Article 10c). Alternatively, where the ownership of the company changes hands and the new owners need to take over the old product licences. These applications are called 'change of ownership' applications.
Better Regulation of Medicines Initiative (BROMI): National informed consent (Article 10c, 'simple abridged') applications
The process for approval of national informed consent (Article 10c, ‘simple abridged applications’) has been reviewed within the Better Regulation of Medicines Initiative (BROMI) and a checklist has been devised to improve the quality of applications.
Further information is available in the 'BROMI section':
New active substances
Applications for products containing new active substances (new chemical entities) can be submitted to the EMA for evaluation under the Centralised procedure or to the MHRA for a national marketing authorisation.
Applicants who have an existing authorisation another Member State can apply under the Mutual Recognition procedure.
For further information see the EMA website.
Biological and biotechnology products
The Biologicals Unit is part of the Licensing Division of the MHRA, and is responsible for the assessment of the full range of applications for biological and biotechnology products. The Unit consists of pharmacists and biochemists who assess the 'quality' , that is manufacture and formulation of the product, a toxicologist for the pre-clinical data and physicians to assess the clinical data. The Unit also provides the professional secretariat for the Biologicals Subcommittee of the Commission on Human Medicines.
What is a biotechnology product?
A biotechnology product is one manufactured by recombinant DNA technology, one where genetic manipulation of cells is required, or a monoclonal antibody. Applications for these products are required to be submitted through the European Centralised procedure (European Medicines Agency website). They comprise List A (the mandatory part) of the procedure. The UK bids for rapporteurships for these products and is a leader in the field.
What is a biological product?
Biological products are defined as so because they are more difficult to characterise or control than standard chemically synthesised pharmaceuticals. They include those where the starting material may be human or animal tissue or of microbiological origin. Also included are those where a complex bioassay system is required to monitor potency. The two largest groups of biologicals are blood products and vaccines. Other products include hormones, larger peptides and a miscellaneous group of tissue derived products.