Centralized authorization procedure

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 ... 

For all operations, activities or tasks, written procedures usually termed Safe Operating Procedures (SOPs) should be made, vetted by a Committee of Experts (COE) and approved by the Central Authority. Subsequently, no deviation/s should be made without the approval of the Central Authority. All operations or activities should be supervised by the next level of leadership, that is, supervisor or senior scientist. Thus, careful planning and strict supervision must be followed to eliminate accidents or fires. 

In the European Union, the medicinal products incorporated into feeding stuffs for prophylactic, coccidiostatic, and growth-promotion purposes are not subject to the above-mentioned authorization procedures for establishing MRLs. Being regulated under Directive 70/524/EEC (45) and its major amendments, especially 84/587/EEC (46) and 96/51/EEC (47), these products do follow, however, a centralized procedure through an EU system. Although no formal MRLs have been yet established for these products, the types of toxicity and residues data mentioned above are also required (48). 

Centralized (and to a lesser extent decentralized) authorization procedures administration of these procedures to achieve a single evaluation and marketing authorization for medicinal products... 

The incentives for orphan products are market exclusivity for 10 years after the marketing authorization even if a previously authorized product is now developed for a new orphan indication PA (scientific advice on development and dossier preparation) access to the centralized registration procedure fee reduction for all types of regulatory activities (applications review, inspections, variations, scientific advice, etc.) and provide a limited amount of EU-funded research grants for orphan products. 

Centralized procedure Under the European Union (EU) Council Regulation (EEC No. 2309/93), a Centralized Community Procedure for the authorization of medicinal products was created. The European Agency for the Evaluation of Medicinal Products (EMEA) was formed in 1995 to coordinate scientific evaluation of the safety, efficacy and quality of medicinal products under this procedure. All biologies are under the purview of EMEA evaluation, and it is optional for other conventional drug products (synthetic drugs). 

National Authorization Procedure To obtain marketing authorization in a country, the application must be submitted to the Competent Authority of that Member State in its own language. For National Authorizations in more than one country, submissions have to be sent to each country in its own language. In many ways, the National Authorization system is superseded by the Centralized and Mutual Recognition Procedures. 

Establish a pool of multinational scientific expertise (by mobilizing existing national resources) in order to achieve a single evaluation via the centralized or mutual recognition marketing authorization procedures. 

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. 

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 ... 

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). 

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. 

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 ... 

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

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

This guideline lays down the roles and responsibilities of the MAH and of the national competent authorities in respect of the products authorised through the national procedures (including the mutual recognition procedure). Also defined are the roles and responsibilities of the Reference Member States (for mutual recognition products) and of the rapporteur and EMEA for centrally approved products. The role and responsibilities of the MAH include having a named, qualified person responsible for pharmacovigilance at the EU level, and there may be a need for an additional named person at the national level when this is required. 

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