Marketing authorization application submitted

The draft guidelines give considerable information on how an applicant can submit relevant data to request parametric release. However, since this is unlikely to be accepted until considerable manufacturing experience of the product concerned has been gained, it is probable that this will be submitted as a later variation application rather than in an initial marketing authorization application. 

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 ... 

Figure 11.1 An example of the activities that are likely to form the critical path for the development of a drug. MAA is the market authorization application that a company has to submit in Britain in order to produce and market a drug...

If the herbal medicinal product contains a preparation, rather than merely the herbal substance itself, the comprehensive specification for the herbal substance must be followed by a description and validation of the manufacturing process for the herbal preparation. The information may be supplied either as part of the marketing authorization application or by using the European Active Substance Master File procedure. If the latter route is chosen, the documentation should be submitted in accordance with the Guideline on active substance master file procedure" (EMEA/CPMP/QWP/227/02 and EMEA/CVMP/134/02). 

At the completion of the sponsor s clinical development program a marketing authorization application (MAA) is submitted. An MAA is used for both small molecule drugs and biologies. There are two submission routes for the sponsor to choose from ... 

Before process validation can be started, manufacturing equipment and control instruments, as well as the formulation, must be qualified. The formulation of a pharmaceutical product should be studied in detail and qualified at the development stage, i.e., before the application for the marketing authorization is submitted. This involves preformulation studies, studies on the compatibility of active ingredients and excipients, and of final drug product and packaging material, stability studies, etc. 

Under the centralized route, marketing authorization applications (dossiers) are submitted directly to the EMEA. Before evaluation begins, the EMEA staff first validate the application, by scanning through it to ensure that all necessary information is present and presented in the correct format. This procedure usually takes one to two working weeks to complete. Biotech-based dossiers are termed part A applications , whereas new chemical entities are termed part B applications . 

The directive lays down the principles and guidelines of good manufacturing practice to be followed in the production of medicines, and requirements to ensure that manufacturers and member states adhere to its provisions. Manufacturers must ensure that production occurs in accordance with GMP and the manufacturing authorization. Imports from non-EC countries must have been produced to standards at least equivalent to those in the EC, and the importer must ensure this. All manufacturing processes should be consistent with information provided in the marketing authorization application, as accepted by the authorities. Methods shall be updated in the light of scientific advances, and modifications must be submitted for approval. 

It is worthwhile to note that, in the US, where the applicant will just be dealing with a single authority, there is no need to re-submit data that was previously submitted as part of an IN D application to conduct clinical trials. Instead, the applicant can cross-reference the IND file. This does not apply in Europe, because clinical trial applications will have been submitted to individual Competent Authorities, whereas marketing authorisation applications are usually submitted either centrally to the European Medicines Agency (EMEA) or collectively to a number of Competent Authorities. Thus, the files need to be self-supporting. 

An application is submitted to the European Medicines Agency (EMEA). The EMEA evaluates the application and forwards its opinion (positive or negative for granting of a marketing authorization) to the European Commis-... 

Identical applications are submitted to those member states where marketing authorizations are sought. The first member state that reviews the application is called the Reference Member State. It notifies other states, called Concerned Member States. Concerned Member States may suspend their own evaluations to await assessment by the Reference Member State. The decision of the Reference Member State is forwarded to the Concerned Member States. If the Concerned Member States reject mutual recognition, the matter is referred to the CHMP of the EMEA for arbitration. The EMEA forwards its opinion to the European Commission, which makes the final deci-... 

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

Since it is essential that only valid manufacturing processes be used, it is increasingly expected that data should be submitted in the application for marketing authorization demonstrating the validity of a given process.. .. ... 

In the past, pesticides were optimized for efficacy, but sometimes with harmful side effects to man or the environment. Today, modern pesticides have high selectivity for the target organism, and testing programs are mandatory to minimize risks and maximize benefits. Before a pesticide can be sold, the supplier must ask the competent authorities of the respective countries for a permit, the marketing authorization. The applicant must submit a dossier containing all information... 

The U.S.-based pharmaceutical company William S. Merrell, Inc., licensed thalidomide from its German manufacturer, Chemie Griinenthal, in 1958. After carrying out laboratory, animal, and initial human tests, the company submitted an application to the FDA for marketing authorization. Frances Kelsey, the medical officer assigned to review the application, found deficiencies in the animal studies and criticized the company s testing methods.20 She then requested additional toxicity tests, putting the application on hold. 

To obtain a national marketing authorization, an application is submitted to the competent authority of the MS. The documentation is the same as required for the MRP and the technical assessment should be completed within 210 days. Since... 

A product dossier, which should be submitted for multisource (generic) products, for innovator products which have been on the market for less than five years, and for products containing substances that have specific properties that may have explicit impact on the safety, efficacy or quality of the product. The Model application form for new marketing authorizations, periodic reviews and variations, with notes to the applicant (7) may also provide a helpful example of guidelines for this type of submission. 

All manufacturing processes should be consistent with information provided in the marketing authorisation application, as accepted by the authorities. Methods shall be updated in the light of scientific advances, and modifications must be submitted for approval. 

Once the clinical and safely evaluation studies for a new medicinal product have shown it to be safe, effective and of acceptable quality, the pharmaceutical company will usually want to submit a Marketing Authorisation Application (MAA) or New Drug Application (NDA) to the regulatory authorities. The chemistry, manufacturing and controls (CMC) section will form a major part of the application. For an MAA in Europe, a development pharmaceutics section is required to describe how the product was developed, and to explain the rationale for the selection of the formulation, pack, manufacturing process and specifications. Also required for Europe are expert reports for each of the pharmaceutical, safety and clinical parts of the application. These have to be written by experienced scientists nominated by the pharmaceutical company who have to critically appraise the development programme for the product. The pharmaceutical expert must acknowledge the acceptability of the CMC part of the application. 

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. 

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