Market Authorisation Application

Storage conditions will be used. Standard conditions to simulate normal storage are temperatures of 25 or 30 °C and relative humidity of 60 or 65%. A minimum of 12 months real-time data is required for a marketing authorisation application. Real-time data should be supported by accelerated and intermediate stress testing at higher temperature/relative humidity. Photostability should be verified using a single batch. 

Figure 5.1 Summary of clinical trials conducted as a prelude to a marketing authorisation application.

An Investigational Medicinal Product Dossier (IMPD) is intended to be more comprehensive than an IB, in that it should contain summaries of available quality data in addition to the safety and efficacy information that constitutes the main part of the IB. In total, it should provide information on the chemistry, manufacture, control and stability ofthe medicinal product, together with the results of non-clinical and clinical studies. In order to avoid repetition, the IB can be cross-referenced for non-clinical and clinical results. Ideally, the IMPD should follow the same structure as that which will be used later for the marketing authorisation application. For products with existing marketing authorisations, the Summary of Product Characteristics may replace the IMPD to varying extents (see Chapter 6). 

A Form 1572 is used for investigators to summarise their educational qualifications and experience, and to make a required formal declaration as to their commitment to conduct the study according to the protocol, GCP and the regulations. The sponsor should also collect financial disclosure information from the investigators at this stage, although formal declarations on Form 3455 are not required until the submission of a marketing authorisation application. 

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. 

Figure 6.8 Outline of information captured by an EU Marketing Authorisation Application...

Recently, similar legislation has been introduced in the European Union under regulations EC/1901/2006 and EC1902/2006. This requires that marketing authorisation applications for new drugs submitted after the 28 July 2008 must be accompanied by either the results of specific studies demonstrating safety and... 

EMEA, CHMP. Guideline on therapeutic Areas Within the Mandatory Scope of the Centralised Procedure for Evaluation for Marketing Authorisation Application, October 2005. 

The plan will eventually prescribe a likely filing date for a marketing authorisation application (MAA) (product hcence). This date is vital and when the plan becomes public information, any slippage in the date is likely to impact on the share price of the company. Accordingly, senior members of the company must be confident that the date can be met. There will always be pressure to bring the date forward but this has a cost in resources, and risks damaging credibility with investors if the accelerated timelines cannot be met. 

The full data package was submitted and assessed by assessors from each of the three disciplines. The Committee on Safety of Medicines and its sub-committees then considered their assessment report. If the decision was positive then a certificate was issued. If the decision was negative, then the applicant had the same appeal rights as those that apply to a marketing authorisation application (see Section 17.8.1). 

The position of the regulatory authorities is best illustrated by a recent Marketing Authorisation Application by Eli Lilly (www.emea.europa.eu/ humandocs/PDFs/EPAR/cymbalta/19256704en6.pdf) for their anti-depressant duloxetine. The phase III protocols specified a repeated measures ANOVA as the primary method of analysis and the regulatory submission was based on such analyses. The CPMP, however, asked for an additional simpler analysis based on change from baseline as the outcome measure and using LOCF. 

At the end of 2008, there were five NP-derived compounds in the New Drug Application (NDA) development phase in the USA and/or Market Authorisation Application (MAA) in Europe and thirty-one NP-derived compounds undergoing Phase III clinical trials (Table 11.2). Details of late stage clinical trials, mechanism of action and derivation of each compound are described in this section. 

Marketing authorisation application (MAA) files and studies used for the Transparency Commission opinion, whether or not published, can be used in a comparative advertisement on the condition that they correspond to the therapeutic indications validated by the marketing authorisation and, if applicable, the conclusions of the Transparency Commission. 

Swedish Association of the Pharmaceutical Industry Norwegian Association of Pharmaceutical Manufacturers Marketing authorisation application... 

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. 

In these documents the Marketing Authorisation Application is defined in the following sections. 

Table 3.4 Standard terms for marketing authorisation applications, Notes for Guidance in 3593/91 EN final (updated February 1998)...

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