Centralised procedure

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. 

The pharmaceutical unit is the more active of the units as there is much greater use of EU-centralised procedures in drug regulation compared to devices. However, the activities of both units can be broken down under four main headings legislation support and guidance external relations and information technology. 

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

Figure 6.14 Human medicinal products that may be authorised via the centralised procedure.

The decentralised procedure can be used in cases where the product has never been authorised in any of the Member States, and the applicant wishes to obtain a license in a number of states simultaneously. The applicant must submit applications with the complete dossier to the Competent Authorities of each of the Member States where authorisation is desired. A single Member State should be chosen as the reference state to undertake the scientific assessment ofthe complete dossier, while the other states are designated as concerned states. The review process has many parallels vhth the centralised procedure, in that similar time lines exist, the reference State plays the role ofthe rapporteur, and the concerned States replace the CHMP. Once all States have validated that the dossiers are complete, the reference State is allowed 70 days to review the dossier and prepare a preliminary assessment report, which is circulated to the concerned Member States and the applicant. Comments from the concerned Member States and applicant responses are collected so that by day 120 the reference State may issue a draft assessment report together vhth draft SPC, label and leaflet texts. The clock may be stopped until requested responses from the applicant are received. The application then enters the second step in the assessment process, during which all the concerned Member States consider the... 

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... 

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

In early 2007, the EMEA reported the analysis of GMP deficiencies in its document entitled Good Manufacturing Practice An Analysis of Regulatory Inspection Findings in the Centralised Procedure. It detailed the deficiencies reported in 435 inspections of manufacturers of medicinal products and starting materials in the European Union and third countries in the period 1995 to 2005. Altogether there were 9465 deficiencies, of which 193 were critical (2%), 989 major (10%), and 8283 (88%) others. The top 20 deficiencies are presented in Table 10.1. 

Article 83.1 states that Member States may make a medicinal product falling within the scope of the centralised procedure available for compassionate use. 

However, the provisions with regard to labelling do allow for differences to arise between labels for products destined for different Member States. The variation in material is intended to be located in one place on a product label, which has come to be known as the blue box. Within the blue box. Member States are allowed to require information about the price of the product, reimbursement conditions, legal status and other information that goes to product identification and authenticit). This permissive aspect of the Directive is notable, as it means that even in relation to products that have been authorised through the centralised procedure, where the authorisation is in all other respects identical, it is rarely possible to produce one label that (when translated) is acceptable and appropriate for every Member State in which the product will... 

The new Regulation allows Member States to supply, on compassionate use grounds to certain groups of patients, unauthorised human medicinal products that are required to use the centralised procedure. This wiU allow patient access to certain imauthorised products, provided there are adequate public health and safety grounds. In addition, for centrally authorised products, a new provision will be introduced that allows the conditional authorisation of medicinal products in defined circumstances, provided there are justified reasons (such as the products of public health interest). The conditions imder which the authorisation is made would be reassessed on an annual basis. The EC has also agreed to estabhsh the circumstances in which small and medium-sized companies may pay reduced fees, defer pa)nnent of fees or receive administrative assistance. 

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. 

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... 

Conceptually, this procedure for Community authorisations (also known as the centralised procedure) resembles a hybrid of the national procedure and the mutual recognition procedure, with the differences that first, the application is submitted to EMEA second, the dossier supporting the application undergoes a detailed assessment by the CHMP before approval in any Member State of the EU third, the applicant is provided with an opportunity to clarify any issues raised by any of the EU Member States fourth, the procedure naturally has an extended time frame but stUl with predetermined deadlines and finally, the applicant ends up with an approval or a refusal to market the product in all or any Member States of the EU. The centralised procedure is shown in Figure 17.2. 

The types of product that fell within the scope of Council Regulation (EEC) No. 2309/93 as amended, were set out in the Annex to that Regulation. Eor medicinal products falling within the scope of Part A of the Annex, applicants were obliged to use the centralised procedure and send their application to the EMEA. Eor those falling within the scope of Part B of the Annex, applicants may, at their discretion, also use the centralised procedure. Unlike the previous concertation procedure (Council Directive... 

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. 

Once a product goes through the centralised procedure, all its post-approval activities are undertaken by the same rapporteur and go through this procedure. 

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. 

Information regarding each of the products approved through the centralised procedure (European PubUc Assessment Report - EPAR) http //www.emea.eu. int/htms/human/epar/epar.htm... 

The centralised procedure allows applications to be made directly to the EMEA, which are then allocated for assessment to one member state (the rapporteur) assisted by a second member state (co-rapporteur). This approach is mandatory for biotechnology products and optional for new medicinal products. 

National Requirements for Registration of Medicinal Products Following EU Centralised Procedure ... 

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