REGULATORY AND METHODOLOGICAL ASPECTS OF STUDYING ALLERGENIC PROPERTIES OF NEW MEDICINES AT THE PRECLINICAL STAGE

Abstract

The assessment of allergic risk at the preclinical stage of drug development has been a debatable issue due to the integration of national requirements for medicines authorisation with those of the Eurasian Economic Union (EAEU). The article summarises mechanisms and factors involved in the development of drug hypersensitivity, as well as the main national and foreign regulatory requirements. It also cites the results of allergic risk assessment studies involving standard guinea pig tests, such as systemic anaphylactic reactions and active cutaneous anaphylaxis, for a number of medicines with the molecular weight of the active substance of more than 1000 Da and less than 1000 Da. Data analysis confirms that the number of positive reactions for high molecular weight compounds (>1000 Da) is significantly higher than the number of positive reactions for low molecular weight compounds (<1000 Da). There were some false-positive results detected. The results of foreign studies confirm the lack of correlation between the experimental data obtained in similar tests in guinea pigs and the clinical data. Thus, standard tests in guinea pigs cannot adequately predict the risk of immediate hypersensitivity reactions to new medicines in clinical practice. Negative or positive results should not be regarded as confirmation of potential absence or presence of anaphylactic reactions in clinical practice.

Keywords

• adverse reactions
• allergy
• allergenic properties
• medicines
• preclinical trials