Marketing authorisation procedures

European legislation Directive 65/65/EEC, Directive 75/318/EEC, Directive 75/318/EEC, Commission Communication on the Community marketing authorisation procedures for medicinal products (98/C229/03) Directive 2001/20/EC, EMEA/CHMP/410869/2006. 

The final legal instrument is a Decision. A decision focuses on an individual measure and is directly binding in its entirety on the specific individuals or entities to whom it is addressed. The Commission uses Decisions to issue marketing authorisations for approval of new drugs granted under a centralised procedure (see Chapter 6). Figure 1.2 summarises the relationship between various legal instruments used in Europe. 

Evaluation of applications for drug marketing authorisations made either directly to the national authority or indirectly via the centralised procedure to the EMEA... 

The procedures for obtaining a Community marketing authorisation are defined in EC Regulation No. 726/2004. The types of human-use medicinal products for which the procedure may be used are shown in Eigure 6.14. The applicant should notify the EMEA of their intention to submit an application at least 7 months... 

The procedures and timelines for obtaining marketing authorisations for veterinary products are essentially the same as those for human medicines. Extensive guidance can be found in The Rules Governing Medicinal Products in the European Union, Volume 6 - Notice to Applicants, Veterinary Medicinal Products. The products that may follow centralised procedures and receive Community authorisations are shown in Eigure 7.5. All other products must obtain authorisations from national... 

EC) No. 1085/2003 outline the procedures for processing variations to marketing authorisations granted via National and Community procedures, respectively. The Annexes to the regulations provide criteria for categorisation of changes. 

Volume 2A Notice to applicants—Medicinal products for human use—Procedures for marketing authorisation Volume 2B Notice to applicants—Medicinal products for human use—Presentation and content of the dossier Volume 2C Notice to applicants—Medicinal products for human use—Regulatory guidelines Commission of the European Communities, Luxembourg, 1998/1998/ 1999 (and amendments)... 

EMEA, CHMP. Guideline on therapeutic Areas Within the Mandatory Scope of the Centralised Procedure for Evaluation for Marketing Authorisation Application, October 2005. 

A Procedures for Marketing Authorisation 2B Presentation and Content of the Dossier 2C Regulatory Guidelines Volume 3 Guidelines... 

However, this simplified procedure should be used only where no marketing authorisation can be obtained through procedures for t)q)ical medicinal products. In order to promote harmonisation, Member States are expected to recognise registrations of traditional herbal medicinal products granted by another Member State based... 

Where a clinical trial was proposed with a marketed product then the CTMP scheme could be used. This was a streamlined process based on the fact that there were no quality issues with a product that had already been granted a marketing authorisation. The applicant submitted a copy of the trial protocol, provided information on the investigators and, depending on whether or not the applicant was the MAH, information on the procedures for reporting adverse drug reactions. It was only possible to use this procedure for UK marketed products. It did not apply to unauthorised products manufactured specifically for trial or to products, which were licensed only in countries other than the United Kingdom. 

Marketing authorisations in the European community can be obtained at present by two main procedures - mutual recognition of a national authorisation from one Member State or a community-wide authorisation through a procedure known as the centralised procedure. In November 2005, a new procedure, known as the decentralised procedure, will be introduced under the new legislation. 

The procedures described above for UK marketing authorisations will of course change in their details when a new advisory structure is implemented. The MHRA has issued a consultation letter on its proposal to change to advisory structure (see Chapter 16). 

This procedure applies when a medicinal product has been granted a marketing authorisation by one of the Member States or when the same medicinal product is being examined by more than one Member States. Where a Member State notes that another application for the same medicinal product is being examined in another Member State, the Member State concerned shall decline to assess the application and shall advise the applicant that Articles 27 to 39 apply. 

Information on the centralised procedure can be accessed from the EC website (see end of chapter). The EMEA is required to ensure that the opinion of CHMP is given within 210 days after the receipt of a valid application. When an application is submitted for a marketing authorisation in respect of medicinal products for human use which are of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation, the applicant may request an accelerated assessment procedure. If the applicant duly substantiates the request and if the CHMP accepts... 

For applications to be processed via the centralised procedure, the CHMP appoints one of its members to act as rapporteur for the coordination of the evaluation of an application for a marketing authorisation. The CHMP may, and usually does, also appoint a second member to act as co-rapporteur. For line extensions, the CHMP will decide on the need for appointment of a corapporteur on a case-by-case basis. All members have an equal opportunity to act as the rapporteur or co-rapporteur, and therefore the CHMP members are invited to express their preference regarding rapporteurships in writing in advance of the meeting at which rapporteurs are appointed. Rapporteurs are usually appointed at every other meeting to facilitate the decision making process as regards (co)-rapporteurships. 

On receipt of a valid application via the EMEA, the rapporteur and the co-rapporteur both prepare their separate detailed assessment reports, which are circulated to the EMEA and all other Member States by day 70 from the start of the procedure. The new Regulation requires that the duration of the analysis of the scientific data in the file concerning the application for marketing authorisation must be at least 80 days, except in cases where the rapporteur and co-rapporteur declare that they have completed their assessment before that time. 

This is a new procedure introduced imder Directive 2004/27/EC. In contrast to the mutual recognition procedure, the decentrahsed procedure applies to products for which the centralised procedure is not mandatory and which are not authorised in any EU Member State. It facilitates the parallel submission to both RMS and CMSs, involvement of the CMS during the national evaluation phase, and parallel granting of national marketing authorisations after the positive finalisation of the European step of the procedure. Some of the finer details of this new procedure established under the new legislation are yet to be confirmed. 

Where an applicant wishes to market a product in more than one Member State, an identical dossier will be sent to all relevant Member States. If an authorisation has not been previously granted, one Member State will be appointed by the applicant to act as RMS who will prepare a draft assessment report with a draft SPC and a draft of the labelling and package leaflet. The CMSs will have the opportunity to review and approve the documents. Therefore, conceptually, the decentralised procedure resembles the centralised procedure without the involvement of CHMP, representing consultation between the Member States before even the first marketing authorisation is granted. 

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