Directive 2001/82/EC of the European Parliament and of the CouncilDangos y teitl llawn

[F1 A. Pharmacology U.K.

A.1. Pharmacodynamics U.K.

The pharmacodynamic effects of the active substance(s) included in the veterinary medicinal product shall be characterised.

First, the mechanism of action and the pharmacological effects on which the recommended application in practice is based shall be adequately described. The results shall be expressed in quantitative terms (using, for example, dose-effect curves, time-effect curves, etc.) and, wherever possible, in comparison with a substance the activity of which is well known. Where a higher efficacy is being claimed for an active substance, the difference shall be demonstrated and shown to be statistically significant.

Secondly, an overall pharmacological assessment of the active substance shall be provided, with special reference to the possibility of secondary pharmacological effects. In general, the effects on the main body functions shall be investigated.

Any effect of the other characteristics of the products (such as the route of administration or formulation) on the pharmacological activity of the active substance shall be investigated.

The investigations shall be intensified where the recommended dose approaches a dose likely to produce adverse reactions.

The experimental techniques, unless they are standard procedures, shall be described in such detail as to allow them to be reproduced, and the investigator shall establish their validity. The experimental results shall be set out clearly and, for certain types of tests, their statistical significance quoted.

Unless good reasons are given to the contrary, any quantitative modification of responses resulting from repeated administration of the substance shall also be investigated.

Fixed combinations may be prompted either on pharmacological grounds or by clinical indications. In the first case, the pharmacodynamic and/or pharmacokinetic studies shall demonstrate those interactions, which might make the combination itself of value in clinical use. In the second case, where scientific justification for the medicinal combination is sought through clinical experimentation, the investigation shall determine whether the effects expected from the combination can be demonstrated in animals and, at least, the importance of any adverse reactions shall be checked. If a combination includes a new active substance, the latter shall have been previously studied in depth.

A.2. Development of resistance U.K.

Where relevant, data on the potential emergence of resistant organisms of clinical relevance are necessary for veterinary medicinal products. The mechanism of the development of such resistance is particularly important in this regard. Measures to limit resistance development from the intended use of the veterinary medicinal product shall be proposed by the applicant.

Where relevant, cross reference shall be made to data set out in Part 3.

A.3. Pharmacokinetics U.K.

Basic pharmacokinetic data concerning a new active substance are required in the context of assessment of the clinical safety and efficacy of the veterinary medicinal product.

The objectives of pharmacokinetic studies in the target animal species can be divided into three main areas:

(i)

descriptive pharmacokinetics leading to the determination of basic parameters.;

(ii)

use of these parameters to investigate the relationships between dosage regimen, plasma and tissue concentration over time and pharmacological, therapeutic or toxic effects;

(iii)

where appropriate, to compare the kinetics between different target species and to explore possible species differences having an impact on target animal safety and efficacy of the veterinary medicinal product.

In the target animal species, pharmacokinetic studies are, as a rule, necessary as a complement to the pharmacodynamic studies to support the establishment of effective dosage regimens (route and site of administration, dose, dosing interval, number of administrations, etc.). Additional pharmacokinetic studies may be required to establish dosage regimens according to certain population variables.

Where pharmacokinetic studies have been submitted under Part 3 cross reference to such studies may be made.

In the case of new combinations of known substances which have been investigated in accordance with the provisions of this Directive, pharmacokinetic studies of the fixed combination are not required if it can be justified that the administration of the active substances as a fixed combination does not change their pharmacokinetic properties.

Appropriate bioavailability studies shall be undertaken to establish bioequivalence:

• when comparing a reformulated veterinary medicinal product with the existing one,

• where necessary for the comparison of a new method or route of administration with an established one.]

Textual Amendments

F1 Substituted by Commission Directive 2009/9/EC of 10 February 2009 amending Directive 2001/82/EC of the European Parliament and of the Council on the Community code relating to medicinal products for veterinary use (Text with EEA relevance).