The EMEA

The Agency is a decentralised body which is located in London, and consists of  

The mission of the European Medicines Agency is to foster scientific exceiience in the evaluation and supervision of medioines, for the benefit of public and animal health. 

Working with the Member States and the European Commission as partners in a European medioines network, the European Medicines Agency  

The executive director is appointed by the board for a term of 5 years and is, together with a secretariat of approximately 360 staff, responsible for the day-to-day operation of the Agency. As such, the secretariat provide scientific, technical and administrative support to the Scientific Committees. The organisational structure of the secretariat is shown in Eigure 2.7. 

The Scientific Committees are key to the functioning of the agency. They are the scientific decision-making component responsible for delivering opinions and advice on any issue relating to medicines. There are currently five committees, each focussed on different areas  

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An EMEA table contains a series of columns for the equipment reference number, the name of the piece of equipment, a description of the equipment type, configuration, service characteristics, etc, which may impact the fadure modes and/or effects, and aflst of the fadure modes. Table 2 provides a Hst of representative fadure modes for valves, pumps, and heat exchangers. The last column of the EMEA table is reserved for a description of the immediate and ultimate effects of each of the fadure modes on other equipment and the system. 

The EMEA begins with the selection of a subsystem or component and then documents all potential failure modes. Their effect is traced up to the system level. A documented worksheet similar to Eigure 4 is used on which the following elements are recorded. 

Figure 2.6 The EMEA mission statement and principal activities (reproduced with permission of EMEA).

Executive responsibility for the administration of regulations at national level is divested in dedicated agencies. Although distinct from government departments, the Ministers of Health are the usual political masters of these national Competent Authorities. Eor example, the authority in Ireland is known as the Irish Medicines Board (IMB) and it covers both drugs and devices. Similar to the EMEA, the authorities are scientific and technical in orientation and are guided by various advisory panels. Their main tasks include ... 

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

The procedures for obtaining a Community marketing authorisation are defined in EC Regulation No. 726/2004. The types of human-use medicinal products for which the procedure may be used are shown in Eigure 6.14. The applicant should notify the EMEA of their intention to submit an application at least 7 months... 

The applicant must submit complete copies of dossier to the EMEA, and directly to each of the rapporteurs. The EMEA are allowed 14 days to validate the application to ensure that it is complete and in accordance with the regulations, after which the rapporteurs can commence the scientific evaluation. The review process involves considerable feedback between the rapporteurs, the CHMP and the applicant, central to which can be achieving agreement on the final text of the SPC, labels and leaflet. The rapporteurs are required to deliver preliminary assessment reports to the CHMP within 80 days of the start of the review process. The applicant is also copied on the report. Over the next 40 days issues raised in... 

Applications to establish MRLs for new pharmacologically active substances must be submitted to the European Medicines Agency (EMEA) at least 6 months in advance of an application for a marketing authorisation. In order to avoid delays, manufacturers are advised to submit an application once all the necessary data are available, as a product authorisation carmot be granted unless established MRLs are in place. The EMEA should be notified of the intent to submit an application 3 to 4 months in advance of the anticipated date, so that a Rapporteur and Co-Rapporteur can be appointed from among the members of the Committee for Veterinary Medicinal Products (CVMP). 

The review of MRL applications is similar to that for centralised marketing authorisations conducted by the EMEA, in that rapporteurs are responsible for the hands-on evaluation, which is then reported back to the CVMP for consideration. If there are outstanding issues, a list of questions is forwarded to the applicant for his or her response. Otherwise, a formal opinion is prepared and presented to the Commission for legal implementation as a decision. The maximum time allowed to deliver a CVM P opinion is 120 days, excluding the time taken for an initial validation of the application and review of responses form the applicant where necessary. 

In Europe, a sponsor may request an accelerated review of a marketing authorisation by the EMEA on grounds that the product is of major interest to public health, particularly from the viewpoint of therapeutic innovation. If granted, an accelerated review must be conducted within 150 days as opposed to the 210 days allowed for a standard technical assessment. 

There is one additional general requirement included in Directive 75/318/EEC as amended, which affects all parts of the pharmaceutical section of the dossier. This is a blanket requirement that all analytical methods are to have been adequately validated and the validation data included in the submission. This applies to all analytical methods including those used in connection with preclinical and clinical parts of the dossier. Additional guidance on how to meet these requirements is included in the two notes for guidance developed on the topic of analytical validation through the ICH process, available at the EMEA web site or at the Commission s web site, mentioned earlier. 

There are three documents that give guidance on the design and conduct of in-use stability tests the EMEA/CVMP/127/95 final (adopted March 1996), CPMP/QWP/2570/98 (a concept paper adopted in November 1998) and CPMP/QWP/2934/99 draft (released for comment in December 1999). The studies undertaken may be discussed in the development pharmaceutics or the stability section of the dossier. 

This part of the chapter is based on consideration of the published EPARs at the EMEA s web site. At the time of writing there were more than 60 EPARs available. The contents of the pharmaceutical assessment section of each of these were examined, and detailed notes were made from more than 50 of those documents. The amount of information in the different EPARs varies considerably. Some have specific sections with the heading development pharmaceutics, while others include relevant information in the text without a heading. In some cases there are simple statements to the effect that satisfactory pharmaceutical development data were submitted. Therefore, an attempt has been made to glean information of a general nature, and this will be presented as a discussion of relevant topics by dosage form. 

The tenor of the two documents is similar, although certain aspects are emphasized differently or not addressed at all in one or the other. For example, transient expression systems are not addressed in the EMEA document, but they are in the FDA document.. We will concentrate on the EMEA Points to Consider and refer to the FDA Draft Guidance where appropriate. 

The risk of viral contamination in plant-based medicinal products, and requirements for strategies to ensure that the product is consistently free of contaminating viruses, is discussed in detail in the EMEA document, while it is not addressed by the FDA. In addition to contamination by insect, bird and animal excreta or carcases, organic fertilizer, production personnel and equipment, the EMEA document lists plant virus infection as a source of contamination and claims that "... freedom from contamination with all types of viruses, irrespective of natural tropism, should be demonstrated. ... 

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