Division 4.2 Content: basic principles and requirementsF1

Special attention shall be paid to the following selected elements.

1. (1)

   The pharmacological and toxicological tests must show:

   1. a))

      the potential toxicity of the product and any dangerous or undesirable toxic effects that may occur under the proposed conditions of use in human beings; these should be evaluated in relation to the pathological condition concerned;

   2. b))

      the pharmacological properties of the product, in both qualitative and quantitative relationship to the proposed use in human beings. All results must be reliable and of general applicability. Whenever appropriate, mathematical and statistical procedures shall be used in designing the experimental methods and in evaluating the results.

      Additionally, it is necessary for clinicians to be given information about the therapeutic and toxicological potential of the product.

2. (2)

   For biological medicinal products such as immunological medicinal products and medicinal products derived from human blood or plasma, the requirements of this Module may have to be adapted for individual products; therefore the testing program carried out shall be justified by the applicant.

   In establishing the testing program, the following shall be taken into consideration:

   all tests requiring repeated administration of the product shall be designed to take account of the possible induction of, and interference by, antibodies;

   examination of reproductive function, of embryo/foetal and peri-natal toxicity, of mutagenic potential and of carcinogenic potential shall be considered. Where constituents other than the active substance(s) are incriminated, validation of their removal may replace the study.

3. (3)

   The toxicology and pharmaco-kinetics of an excipient used for the first time in the pharmaceutical field shall be investigated.

4. (4)

   Where there is a possibility of significant degradation during storage of the medicinal product, the toxicology of degradation products must be considered.