Administration of Radioactive Substances Advisory Committee

In the development of most new active substances, it is required to investigate the disposition of the compound and its metabolite(s) and their rates and routes of elimination. This is generally carried out with radiolabelled compound, usually In the United Kingdom, approval of the Administration of Radioactive Substances Advisory Committee (ARSAC) is required for administration of radiolabelled compound to man. The purpose of the submission is to demonstrate that the dose of absorbed radiation is minimised by administration of the lowest dose that is consistent with meeting the objectives of the study. In general, the estimated absorbed radiation dose should be less than 500 xSv, but higher amoimts are permissible if they can be justified. The estimate is based on tissue distribution of radioactivity in animals and the pharmacokinetics in animals and man. 

In this special case, additional approval is needed from the national authorities overseeing radiation safety. For example, in the United Kingdom this is the Administration of Radioactive Substances Advisory Committee (ARSAC). Application to ARSAC only requires a summary of the study protocol, but a careful scientific justification of the amount of radiation employed and the number of subjects exposed. The EU Directive 97/43/EurATOM sets dose limits for healthy subjects and patients. 

Critical features of metabolism frequently require administration of radiolabelled material to man during ED. Such studies generally involve administration of single doses, with subsequent collection of excreta as well as blood sampling until virtually all drug has been eliminated. The clinical phase of such studies is generally not complex, but preparation for the study, with synthesis of the radioactive molecule and development of cold assays of metabolites as well as parent molecule, may take many months. Such studies also require submission of applications with detailed dosage and radioactive exposure calculations for authorisation by external bodies such as the Administration of Radioactive Substances Advisory Committee (ARSAC) in the UK. 

MBq (13.5 mCi) maximum recommended activity (Administration of Radioactive Substances Advisory Committee 1993)... 

Administration of Radioactive Substances Advisory Committee (1993) Investigations -adult patients. In Notes for guidance on the administration of radioactive substances to persons for purposes of diagnosis, treatment or research. Appendix 1, Part A. Administration of Radioactive Substances Advisory Committee - ARSAC, Oxon, UK, p 25... 

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