Investigational dossier

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 comprehensive Manual for Investigation of HPV Chemicals is available (OECD 2004). The Manual describes procedures, including the use of electronic discussion groups and the online HPV database data gathering and testing SIDS, the SIDS plan, and the SIDS Dossier data evaluation initial assessment of data (guidance for assessing the hazards of chemical substances to man and the environment) preparation of the SIAR and SIAP and post-SIDS work. 

The application for a clinical trial authorisation (CTA) for the first administration of a NME to man comprises the same elements as all other CTAs but, of course, there will be no clinical data. The regulatory authority known as the competent authority (CA) of the EU member state requires receipt of confirmation of the EU clinical trials database (EUDRACT) number, a covering letter, a completed application form, the protocol with all current amendments, the IB and a full Investigational Medicinal Product Dossier (IMPD) (see below). If the study is to be conducted in more than one member state, a list of CAs should be included. If the opinion of the lEC is available, it should be provided. 

As well as GCP site inspections, an examination is imdertaken of the raw or source data and records of Chemistry Manufacturing and Control (CMC), non-clinical and clinical reports that are the basis of the application. This is to ensure that the application dossier accurately reflects the source data. The procedure issued by PMDA details that list of raw data and records must be provided. The applicant is required to bring the data and records to PMDA on the specified days and when the examination finishes they should be retrieved. Therefore, the raw data and records stored at overseas sites are usually categorised as documents not to be submitted and not subject to reliability review by PMDA. Instead, the MHLW may investigate the data from non-Japanese studies at the site of storage since submission of a photocopy of the data is not permitted. 

Pharmaceutical companies wishing to register new products must submit a dossier of data, relating to trials and investigations on the product, to MAFF. When MAFF (VMD) is satisfied that the data are complete and the research has been properly conducted to internationally accepted standards of competence (Good Laboratory Practice - GLP), the dossiers are passed to the VPC. The VPC then assesses the quality, efficacy and safety of the product. The safety assessment on the product includes the target species, human (operator, consumer) and environmental impact. If there are any substantial doubts, the licence may be refused and/or the company advised to carry out further investigations. 

Detailed guidance on the preparation of the Investigational Medicinal Product Dossier is available [11], In terms of preclinical aspects, the key considerations are ... 

The investigational medicinal product dossier can be stand-alone or be constructed by cross-reference to relevant sections of the IB (applies to preclinical and clinical data only). 

Communicate with colleagues in the Far East well in advance. Plan well ahead to investigate whether the product is of significant value to the market. Start with documentation and certificates that need legalization to save time. The index of contents should be accurate and clear. Dossier format must... 

The regulatory procedure involved is a so-called Clinical Trial Authorization appH-cation (CTA) and consists, in addition to a Clinical Trial Protocol (CTP) and Investigator s Brochure (IB), of an Investigational Medicinal Product Dossier (IMPD) in CTD format. The IMPD consists of quality data, nonclinical pharmacology and toxicology data, clinical trial and previous human experience data, and an overall risk-benefit assessment. A copy of the CTA is sent to each EU Member State where the study is conducted, as well as to the Ethics Committees for approval. These also have to be notified in case of any amendments, study termination and adverse reactions. The contents of the IMPD are case specific and may be simplified or even replaced by the... 

Rituximab represents the most important scientific achievement of the past decade. It was the first therapeutic antibody approved for the treatment of cancer and specifically for N H L. The current IWRC for N H L had their origin with the rituximab response criteria. Clinical development was completed in record time. Dossiers were filed simultaneously in the United States and in Europe. The US fihng utilized an electronic format (computer-aided product license application, CAPLA). These and many other achievements during clinical development served to provide tremendous impetus to the monoclonal antibody research area. The renewed enthusiasm in this area has yielded many new Mabs with activity in both hematologic malignancies and in autoimmune diseases. Several of these have been approved (e.g. herceptin, alemtuzumab, mylotarg, others) and many others are under active investigation. 

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