Centralised Procedure, European

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 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... 

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. 

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. 

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. 

The institution of the new European licensing systems (centralised and de-centralilsed) in 1995 hcis brought about the most profound change in European pharmaceutical regulation since its inception. The scientific skills and the standards applied have undoubtedly risen, the leveling-off effect hcis been upwards rather than downwards. This is most evident in the new systems where the assessment reports are freely available, but it is edso likely to have affected the national procedures. Skills learned in the centralised procedure will also be applied to national applications. 

As a result of Council Regulation (EEC) No. 2309/93 of July 22, 1993, which established the European Agency for the Evaluation of Medicinal Products, three types of procedures for authorising the placing of medicinal products on the market were introduced, depending on the characteristics and specific nature of the medicinal product in question centralised procedure, decentralised procedure and national procedure. 

Hoping to step up its activity in the EU approvals system, INFARMED has set up a European Support Unit to deal with the mutual recognition and centralised procedures. 

The Centralised Procedure results in a single application, a single evaluation and a single authorisation in all member states of the EU and generates a European marketing number for the product. 

In the Centralised Procedure a Rapporteur and a Co-Rapporteur, appointed from within the member states of EU, have to evaluate the product and report to the European Medicines Agency within 210 days. If the UK is selected as Rapporteur or Co-Rapporteur, the evaluation of the medicinal product is carried out by the MHRA. Occasionally, when there is particular interest in a novel medicinal product, or when a new medicinal product would have a significant affect on drug usage in the NHS, the MHRA will get involved and opinions will be sought from scientific advisory committees. A recent example of this was when the first inhaled formulation of human insulin was licensed. 

This provision allows Member States if they wish (there is no obligation to do so) to make national arrangements for the supply of unlicensed medicines for particular use, but only in the very limited circumstances specified by the Directive. As part of the 2001 review process, the European Commission recently issued proposals to regulate the compassionate use of medicinal products falling within the scope of Regulation 2309/93/EC (the centralised procedure). However, these proposals are unlikely to come into force for several years. 

National marketing authorisations were intended to be phased out from 1 January 1998. It was foreseen that beyond that date, all marketing authorisations within the European Union would have been issued under the rules governing medicinal products in the European Community through the Centralised Procedure, or the so-called Mutual Recognition or Decentralised Procedure (see below). However, national approvals for marketing have continued well beyond 1 January 1998. 

Under the mutual recognition procedure, the applicant company usually ends up receiving national marketing authorisations from some or all of the national drug regulatory authorities to whom the dossier is submitted. The centralised procedure, on the other hand, is all or none , and under it the applicant company would receive a single marketing approval from the EMEA valid in all European Union countries. Rejection of an application under the centralised procedure means that the product cannot be marketed in any Member State. 

In January 1995, Directive 75/319 of the Council of the European Communities came into force. The regulation introduced new procedures whereby a European MA may be obtained. The net effect of this has been to move work from a national to a European basis, particularly for novel chemicals. The IMB is active in both the centralized and decentralized (mutual recognition) licensing processes, having acted in the centralised process as rapporteur or co-rapporteur on 12 occasions, and having been Reference Member State (RMS) in approximately 10 decentralized applications. 

This part of Chapter 9 sets out a more detailed perspective of how legislation concerning chemicals is implemented in the UK, and it considers how developments have been influenced by traditions. In the context of this chapter, it is not the intention to provide a complete and comprehensive review but rather, by selective illustration, to show how the typical British approach based on informality and regulatory discretion has moved to the more formal and centralised control necessary within the European Union (EU). Where appropriate, reference to other international law is made to indicate where different approaches influence enforcement procedures. 

Since the introduction in 1995 of new procedures for the authorisation of products in the EU, the handling of product safety crises has become a European Community matter, handled at Community level. Under New Systems , serious concerns with regard to product safety where the product is on the market of more than one Member State, will be considered at European level centralised product issues are automatically a matter for the EMEA and therefore the CPMP (including its working parties), and in respect of products which may have been authorised... 

The different attributes of the centralised and decentralised systems make cost-benefit comparisons difficult. The European procedures have not as yet produced real dividends in terms of cost efficiencies through economies of scale and there is a need to reduce the administrative burden where this does not have public health implications (for example, in relation to minor variations to existing approvals). National authorities are under significant resource pressures and the relative funding of the centralised system by the Community and indirectly by national agencies is an increasing cause for concern in some Member States. 

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