Clinical data, Marketing Authorisation

Ultimately, the non-clinical data will form a substantial part of the regulatory submission that is required for marketing authorisation. 

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). 

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. 

Data on safety, efficacy and other important clinical results with respect to marketed products must be truthfully published on the internet, irrespective of the outcome of the trial within the year after the marketing authorisation has been granted. 

Irrespective of patent law, the holder of a marketing authorisation may be afforded a period of marketing exclusivity under the European regulatory provisions, i.e. a period of freedom from competition from competitors who do not themselves propose to generate and submit their own full data set in order to obtain an AlA. A company that applies for an AlA will be required to produce the results of pharmacological and toxicological tests and the results of clinical trials at the cost of considerable time and expense, unless ... 

Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001, on the approximation of the laws, regulations and administrative provisions of the member states, relates to the implementation of GCP in the conduct of clinical trials on medicinal products for human use. The commimity code relating to medicinal products for human use (2001/83/EC) was amended in 2003 (2003/63/EC), stipulating that clinical trials data used for marketing authorisation applications in the EU are required to be conducted in accordance with GCP. 

Toxicity studies are expected to be performed in compliance with Good Laboratory Practice (GLP) however, it is recognised that some studies employing specialised test systems which are often needed for biopharmaceuticals, may not be able to comply fully with GLP. Areas of non-compUance should be identified and their significance evaluated relative to the overall safety assessment. In some cases, lack of full GLP compliance does not necessarily mean that the data from these studies cannot be used to support clinical trials and marketing authorisations. 

Theoretically, the time from application to authorisation in the RMS should be less than 210 days. In fact, according to recent figures, it may vary from about 150 to almost 400 days for novel products. This is not surprising as the complexity of the data submitted can vary enormously and applicants take time to reply to questions posed. In the case of products which have been on the market of a particular MS for several years, new developments in science or in clinical practice may have taken place and a review of the existing and new data is appropriate, together with a re-evaluation of the risk benefit balance. This review should lead to updated expert reports and to an updated assessment report in the MS and is known as updating the dossier. ... 

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