European approval procedures centralized procedure

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. 

The MA holder has to keep records on all severe ADRs that en-e reported to him by a healthcare professional in Belgium or outside the European Union. Within 15 days he or she has to report ADRs to the Minister (pharmaceutical inspection). It is recommended to use the CIOMS document to indicate the clinical data it also has to be indicated whether the ADR is already mentioned in the approved leeiflet. For products approved by the central procedure, these data have to be reported immediately to the EMEA within 15 days. 

Centralized Procedure (CP) This is the procedure of most interest for biopharmaceuticals, as this is the mandatory route for review and approval of such drugs in the European Union. In the centralized procedure a single application is submitted to the European Medicines Agency (EMEA). A variety of presubmission activities, starting six months before the intended start date of the centralized procedure, are required [8], Two initial assessments by a Rapporteur and Co-rapporteur national authorities (one from each of two member states chosen by the EMEA) are made, leading to Day 80 Critical Assessment Reports. A consolidated list of questions (LoQ) is provided to the applicant at Day 120 when there is a clock stop, normally of three months, to allow the preparation and submission of responses. Following satisfactory negotiation of other steps in the procedure, the Committee on Human Medicinal Products will recommend authorization at Day 210, with authorization by the Commission at Day 277. 

National MAs were intended to be phased out after 1 January 1998, but it is likely that national approvals for marketing will continue beyond that date. The future foresees that all MAs within the European Union (EU) will have been issued under the rules governing medicinal products in the EC by virtue of the centralized procedure or the so-called mutual recognition or decentralized procedure (vide infra). 

In the mid to later part of the 1990s, procedures were established to allow for more timely review and approval of marketing applications in the both European Union and the United States. The review process to be used and the timing for approval are defined by the local regulations, and are dependent upon the immediate therapeutic need for the product. The EU mutual recognition and centralized procedures and the U.S. Prescription Drug User Fee Act (PDUFA) will be discussed in more detail later in this chapter. 

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