Centralized procedure

There are three procedures by which pharmaceutical products may gain a marketing authorization in the EEA. These are the National, Mutual Recognition, and Centralized procedures. 

The final option is the Centralized Procedure. This is available for a defined list of product types (included in an Annex to the relevant Regulation) and for Orphan Drugs as defined by the Orphan Drug Committee. This procedure involves the appointment of... 

The Committee for Medicinal Products for Human use (CHMP). This committee is composed of 35 technical experts drawn from the various EU member countries. It is primarily responsible for formulating the EMEA s opinion on any medicinal product being considered for marketing approval under the centralized procedure. 

Unlike the FDA, the EMEA itself does not directly undertake appraisals of drug dossiers submitted to support marketing authorization applications under the centralized procedure. Instead (as discussed in detail below), they forward the dossier to selected national EU regulatory bodies, who undertake the appraisal, and the EMEA makes a recommendation to approve (or not) the application based upon the national body s report. The overall role of the EMEA is thus to coordinate and manage the new system. The EMEA s annual budget is of the order of 120 million. The key objectives of the EMEA may be summarized as ... 

Under the centralized procedure, applications are accepted with regard to (a) products of biotechnology (b) NCEs (drugs in which the active ingredient is new). Biotech products are grouped as list A and NCEs as list B . Marketing approval application for biotech products must be considered under the centralized procedure, whereas NCEs can be considered under centralized or decentralized mechanisms. 

Upon receipt of a marketing authorization application under centralized procedures, the EMEA staff carry out an initial appraisal to ensure that it is complete and has been compiled in accordance with the appropriate EU guidelines (Box 4.4). This appraisal must be completed within 10 days, at which time (if the application is in order), it is given a filing date. The sponsor also pays an appropriate fee. The EMEA then has 210 days to consider the application. In the case of human drugs, the application immediately comes before the CPMP (which convenes for 2-3 days each month). 

Centralized Procedure Under the European Community Regulation 726/2004 and Directive 2004/27/EC, the Centralized Procedure (also known as Community Authorization Procedure) is a single authorization procedure that is mandatory for medicinal products of the following categories ... 

Decentralized Procedure This is applicable where authorization has not yet been approved in any member state. The applicant may apply for simultaneous authorization in more than one ELI member state for medicines that do not fall within the mandatory scope of the centralized procedure. 

For our purposes, the committee for drug approval is the CHMP. Applications are submitted to the EMEA according to the centralized procedure. The review process is described in Section 8.3. In 2006 the CHMP provided 78 opinions (decisions) on medicinal products, of which 5 were negative (rejected). 

The CTDs were implemented in July 2003. They are format-based documents for submission to the regulatory authorities the country-specific process of review, for example, via the IND and NDA of the United States or the Centralized Procedure of the EMEA, is not affected. The harmonized CTDs help to reduce cost and accelerate approval time. Figure 7.1 shows the CTD structure five modules with Module 1 for regional administrative information specihc to each country. Module 2 on summary of quality, nonclinical and clinical. Module 3 on quality. Module 4 on nonclinical study reports, and Module 5 on clinical study reports. 

Submission Details for Centralized Procedure This procedure was effective from 1995 with further amendments effective from November 2005. Six months before submission, the pharmaceutical company wishing to apply for marketing authorization via the Centralized Procedure notifies the EMEA of its intention and expected submission date. This notification is required to be accompanied by a number of items, for example ... 

Justification for evaluation under the Centralized Procedure (refer to Parts A and B Products designation)... 

There are two stages for the Centralized Procedure. The first phase is divided into the primary evaluation phase and secondary evaluation phase. In... 

Describe the Centralized Procedure in Europe for drug approval. Compare and contrast the Centralized Procedure with NDA/BLA. 

Refer to Section 8.3.2. Note the requirement for the Qualified Person and Expert Reports in Europe. There are no separate applications in the Centralized Procedure for small and large molecule drugs. 

In Europe, inspections are conducted by member states on behalf of the European Union. For drugs approved under the centralized procedure, inspections are coordinated by the European Medicines Agency (EMEA refer to Sections 7.3 and 8.3). For countries that are members of the Pharmaceutical Inspection Cooperation Scheme (PIC/S see Section 7.13), there is mutual recognition of inspections performed by members. 

Source EMEA Inspections. Good Manufacturing Practice An Analysis of Regulatory Inspection Findings in the Centralized Procedure, Doc. Ref. EMEA/INS7GMP/23022/2007 [accessed August 28,2007]. 

Management and follow-up of marketing authorization applications under the centralized procedure,... 

The CVMP operates in a similar fashion to the CPMP and is heavily involved in the review of centralized procedures for veterinary products. It has developed a broad range of new guidelines to assist applicants in topics related to research and development for which no guidance existed previously. 

In the centralized procedure, one license to market the drug in all of the EU is issued, and in principle there is only one evaluation of the dossier. In fact, both a rapporteur and corapporteur are appointed and eaeh assesses the dossier with its own... 

Should no agreement be reached within the MRFGWMRFG, the matter is sent to the CPMP/CVMP for an opinion. Thereafter the procedure is similar to that of the centralized procedure, the end result being a commission decision after which national licenses must be issued within 30 days. 

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