National authorization procedure

National Authorization Procedure To obtain marketing authorization in a country, the application must be submitted to the Competent Authority of that... 

Abridged National Authorization Procedure This procedure is for generics, and there is no necessity to provide preclinical or clinical results. However, evidence of bioavailability and bioequivalence and GMP manufacturing compliance has to be submitted. If the applicant has an abridged approval from a member state, the Mutual Recognition Procedure can be used. 

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 In many ways, the National Authorization system is superseded by the Centralized and Mutual Recognition Procedures. 

Where conformity assessment involves intervention of third party, that task is normally carried out by the notified body. The pressure equipment directive enables in addition the national authorities to authorise in their territory user inspectorates for the carrying out of conformity assessment procedures which relate to product verification. These inspectorates shall act exclusively on behalf of the group of which they are part. The placing on the market and putting into service of equipment which has undergone such assessment is however limited to the territory of the authorising Member State and to those Member States which have also proceeded to such authorisation. The equipment concerned shall therefore not bear the CE-marking. 

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

The mutual recognition procedure is an alternative means by which a marketing authorization may be sought. It is open to all drug types except products of biotechnology. Briefly, if this procedure is adopted by a sponsor, then the sponsor applies for a marketing licence not to the EMEA, but to a specific national regulatory authority (chosen by the sponsor). The national authority then has 210 days to assess the application. 

The European system is based on cooperation between the national health authorities of the member states and the EMEA. The latter aets as a focal point of a network whieh eoordinates the seientific resources made available by the member states. This partnership between the EMEA, national health authorities, and the European Union institutions is erueial to the functioning of the European authorization procedures. 

Similarly, where there are public health concerns as a result of pharmacovigilance data, nationally authorized products or products authorized by the mutual recognition procedure may be referred rmder Articles 12 or 15 of Directive 75/319/EEC. The CPMP/CVMP gives an opinion on variation, suspension, or withdrawal of the marketing authorization in such cases. 

Applications through mutual recognition or decentralised procedure are submitted to national authorities. The applications for community... 

Apart from differences in the establishment of the MRL/tolerance values, different procedures are also used for the calculation of the withdrawal period. Even in countries where similar MRLs have been established, similar drugs may differ greatly with respect to the withdrawal periods established by the national authorities. A greater degree of harmonization would be possible if a standard approach for calculating the withdrawal period was adopted throughout the world. 

Even when Community MRLs have been established, similar products in various member states may differ greatly with respect to the withdrawal times established by national authorities. Most member states employ a simple method by which the withdrawal time is set at the time when residues in all tissues in all the animals have depleted to below the respective MRL values. In addition, some member states then add an additional safety period if, for example, there are large variations in the depletion data set or other shortcomings are found in the studies. On the other hand, some other member states use statistical methods to establish withdrawal times. A greater degree of harmonization would be possible if a standard approach for calculating the withdrawal time was adopted throughout the European Union. Moreover, this would aid both the centralized and the decentralized procedures. 

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. 

The decentralized procedure, applying to a majority of conventional medicinal products, is based on the principle of mutual recognition of national authorizations. It provides for the extension of a marketing authorization granted by one member state to one or more other member states identified by the applicant. 

Prior informed consent procedures should include the national authority and the indigenous group providing the genetic resources or the traditional knowledge. At the same time, those requesting access to genetic resources and... 

In the EEC, applications or notifications for clinical trials have to be lodged with the individual national authorities. A common procedure or even mutual recognition of clinical trial certificates does not exist. A list of the different national requirements is provided in "The Rules Governing Medicinal Products in the European Communities" Volume III, Annex 1. A discussion paper (III/ 3044/91) released in 1991 by the EEC Division for Pharmaceuticals (DG III) addresses various issues on the harmonization of approval of clinical trials and may eventually lead to common, non-binding recommendations. 

Until the end of 1992, the multistate procedure, which also relied on a mutual recognition of national approvals, operated on a very similar basis and has been very disappointing. Objections against the initial assessment and approval as well as against CPMP opinions were not exceptions, but the rule. The introduction of time limits for the evaluation and responses by the national authorities must also be considered as illusory. The average period to grant or refuse a national licence, after the CPMP opinion was formulated, varied between six months in Luxembourg and 26 months in Italy (Charlesworth, 1992). The limitation for this step was initially 30 days and was subsequently extended to 60 days ... 

A similar system, the "concertation procedure" is already in place and is obligatory for products from biotechnological processes. The CPMP becomes involved as soon as the first application in any member state is lodged. One country s agency acts as rapporteur and prepares a full evaluation report, other countries provide "monitoring reports". Based on these reports and the expert reports in the dossier, the CPMP summarizes its assessment in an opinion report which is considered by the national authorities, before they make their decision. 

Scientific advice from individual national authorities is also available. Applicants contact the national authority prior to sending the formal request for scientific advice, and the rest of the procedure, in most MS, is similar to that in the EMEA procedure. With less administrative effort and more frequent presence of key members at the national authorities, scientific advice at the... 

If the multisource product under consideration contains excipients that have been used before in similar amounts in other formulations of the same API, it can be reasonably concluded that these excipients will have no unexpected consequences for the bioavailability of the product. If, however, the formulation contains different excipients, or amounts of the same excipients that are very different from usual, the national authority may choose to declare the biowaiver procedure inapplicable. 

This directive required that products covered by Annex A of the classification had to be referred to the CPMP for an opinion before a marketing authorisation (MA) could be granted in any Member State. This process became known as the Concertation Procedure, or Centralised Procedure. Products covered by Annex B could, at the request of the manufacturer, be dealt with by the Concertation Procedure or by an individual national authority and then achieve entry into other EU Member States markets if requested by means of the multistate or mutual recognition procedure. 

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