Animal studies minimising

In vivo studies are preferably carried out using unrestrained, imanaesthetised animals. Animals can be fitted with transmitters that allow data to be collected by telemetry. As for all animal studies, avoidance or minimisation of pain and discomfort is an important consideration. Information from the toxicological battery of studies, if they have been adequately designed to address safety pharmacology endpoints, can... 

In the future, it is possible that the need for animal studies will be further minimised by... 

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. 

Chemical manufacturers often supply their products in many markets, and consequently various national chemical control systems have to be complied with. It is prudent to obtain advice on these requirements early in the develc ment stage, to enable infixmed business decisions to be made and to ensure full regulatory compliance. For a new chemical substance, notifications in different countries may be necessary, and it is essential to design the testing programme to fulfil all the various requirements to ensure timely regulatory approvals, and also to minimise the total cost of the studies and the use of animals. 

The information required for a notification is the chemical identity, amount manufactured or imported, use, physico-chemical properties, ecotoxicity studies, available mutagenicity studies and animal toxicity, indir t long-term effects on humans and recommendations for disposal and labelling. The data requirements for the notification of new substances are based on the OECD MPD and arc very similar to those in the EC. The minimum information required is listed in Table 34.1. There are no official reduced data requirements for notification of substances to be supplied only in low amounts, although FOEFL will negotiate on a case-by-case basis for certain of the standard tests to be omitted, especially if the substance is to be used in special applications or has special disposal methods which minimise environmental contamination. Studies are to be conducted in compliance with GLP to OECD guidelines or their equivalent. 

Clinical observations A careful clinical observation of each animal should be made at least once a day. Additional observations should be made daily with appropriate actions taken to minimise loss of animals to the study, e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals. All toxicological and pharmacological signs should be recorded including time of onset, intensity, and duration. The time of death should also be noted. Individual records should be maintained for each animal. 

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