Commission Directive 2009/9/ECDangos y teitl llawn

B. Residue tests

CHAPTER I: PERFORMANCE OF TESTS

1. Introduction

For the purposes of this Annex, the definitions of Council Regulation (EEC) No 2377/90(1) shall apply.

The purpose of studying the depletion of residues from the edible tissues or of eggs, milk and honey derived from treated animals is to determine under what conditions and to what extent residues may persist in foodstuffs produced from these animals. In addition, the studies shall enable the determination of a withdrawal period.

In the case of veterinary medicinal products intended for use in food-producing animals, the residue documentation shall show:

1.

to what extent, and how long, do residues of the veterinary medicinal product or its metabolites persist in the edible tissues of the treated animal or in milk, eggs and/or honey obtained therefrom;

2.

that in order to prevent any risk to the health of the consumer of foodstuffs from treated animals, or difficulties in the industrial processing of foodstuffs, it is possible to establish realistic withdrawal periods which can be observed under practical farming conditions;

3.

that the analytical method(s) used in the residues depletion study are sufficiently validated to provide the necessary reassurance that the residues data submitted are suitable as the basis for a withdrawal period.

2. Metabolism and residue kinetics

2.1. Pharmacokinetics (absorption, distribution, metabolism, excretion)

A summary of the pharmacokinetic data shall be submitted with cross reference to the pharmacokinetic studies in target species submitted in Part 4. The full study report does not need to be submitted.

The purpose of pharmacokinetic studies with respect to residues of veterinary medicinal products is to evaluate the absorption, distribution, metabolism and excretion of the product in the target species.

The final product, or a formulation, which has comparable characteristics in terms of bioavailability as the final product, shall be administered to the target animal species at the maximum recommended dose.

Having regard to the method of administration, the extent of absorption of the veterinary medicinal product shall be fully described. If it is demonstrated that systemic absorption of products for topical application is negligible, further residue studies will not be required.

The distribution of the veterinary medicinal product in the target animal shall be described; the possibility of plasma protein binding or passage into milk or eggs and of the accumulation of lipophilic compounds shall be considered.

The pathways for the excretion of the product from the target animal shall be described. The major metabolites shall be identified and characterised.

2.2. Depletion of residues

The purpose of these studies, which measure the rate at which residues deplete in the target animal after the last administration of the medicinal product, is to permit the determination of withdrawal periods.

At a sufficient number of times after the test animal has received the final dose of the veterinary medicinal product, the quantities of residues present shall be determined by validated analytical methods; the technical procedures and the reliability and sensitivity of the methods employed shall be specified.

3. Residue analytical method

The analytical method(s) used in the residues depletion study (studies) and its (their) validation shall be described in detail.

The following characteristics shall be described:

• specificity,

• accuracy,

• precision,

• limit of detection,

• limit of quantification,

• practicability and applicability under normal laboratory conditions,

• susceptibility to interference,

• stability of incurred residues.

The suitability of the analytical method proposed shall be evaluated in the light of the state of scientific and technical knowledge at the time the application is submitted.

The analytical method shall be presented in an internationally agreed format.

CHAPTER II: PRESENTATION OF PARTICULARS AND DOCUMENTS

1. Identification of the product

An identification of the veterinary medicinal product(s) used in the testing shall be provided, including:

• composition,

• the physical and chemical (potency and purity) test results for the relevant batch(es),

• batch identification,

• relationship to the final product,

• specific activity and radio-purity of labelled substances,

• position of labelled atoms in the molecule.

The dossier of residue tests shall include:

• an index of all studies included in the dossier,

• a statement confirming that all data known by the applicant at the time of submission, whether favourable or unfavourable, are included,

• a justification for the omission of any type of study,

• an explanation of the inclusion of an alternative type of study,

• a discussion of the contribution that any study that pre-dates GLP can make to the overall risk assessment,

• a withdrawal period proposal.

Each study report shall include:

• a copy of the study plan (protocol),

• a statement of compliance with good laboratory practice, where applicable,

• a description of the methods, apparatus and materials used,

• a description of the results obtained, in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author,

• a statistical analysis of the results where appropriate,

• a discussion of the results,

• an objective discussion of the results obtained, and proposals concerning the withdrawal periods necessary to ensure that no residues which might constitute a hazard for consumers are present in foodstuffs obtained from treated animals.

(1)

OJ L 224, 18.8.1990, p. 1.