Investigational medicinal products

Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products... 

Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

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). 

The manufacture of all investigational medicinal products (including placebo) that are intended for a clinical trial must be authorised and conducted according to Good Manufacturing Practice (GMP). This should be supervised and certified by a Qualified Person . An import authorisation is required for any product from outside the EU, which should also be manufactured to GMP standards. (See Ghapters 11 and 12 for information on GMP, manufacturing authorisations and Qualified Persons.)... 

The Competent Authorities are obliged to appoint Inspectors for checking that all activities associated with clinical trials are conducted in compliance with the regulations. The inspectors can inspect any sites concerned with the clinical trial, particularly the trial site (GCP), the manufacturing site of the investigational medicinal product (GMP), any laboratory used for analyses in the clinical trial (GLP), and/or the sponsor s premises. 

Annex 12 Use of Ionising Radiation in the Manutacture ot Medicinal Products Annex 13 Manufacture of Investigational Medicinal Products Annex 14 Manufacture of Products derived from Human Blood or Human Plasma Annex 15 Qualification and validation... 

Activities Carried out Manufacture of active substance Manufacture of finished product Manufacture of intermediate or bulk Q Packaging only Importing Laboratory testing Batch control and batch release Storage and distribution Investigational medicinal products Other ... 

Unexpected adverse drug reaction An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., investigator s brochure for an unapproved investigational medicinal product). 

Most of the information sought is similar to the FDA s IND requirements. One major difference is that a Qualihed Person has to certify that the investigational medicinal product (IMP) is manufactured according to GMP The Competent Authority has the right to inspect the manufacturing facility for GMP compliance, the preclinical facility for GLP compliance, and the clinical trial sites for GCP compliance. 

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. 

Product Liability Directive 85/374/EEC and Consumer Protection Act 1987 (UK). NB. In some EU countries, claims under the Directive and its implementing legislation can not be made in relation to investigational medicinal products. 

Boyce M, Warrington S. Analysis of 312 studies of investigational medicinal products in healthy subjects to assess the impact of European Union Clinical Trial Directive. Int J Pharm Med 2002 16 179-184. 

Investigational Medicinal Product means [ as defined in the Protocol. 

Neither the NHS Trust nor the Site Principal Investigator shall permit the Investigational Medicinal Product to be used for any purpose other than the conduct of the Clinical Trial and upon termination or expiration of this Agreement all unused Investigational Medicinal Product shall, at the Sponsor s option, either be returned to the Sponsor or disposed of in accordance with the Protocol. 

The principles of good manufacturing practice should be applied to investigational medicinal products. 

Member States shall take all appropriate measures to ensure that the manufacture or importation of investigational medicinal products is subject to the holding of authorisation. 

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