Section I General principles and requirements

The documentation accompanying an application for a marketing authorisation pursuant to Schedule 1 of the Veterinary Medicines Regulations shall be presented in accordance with the requirements set out in this Annex.

1. General principles

1.1 The documentation accompanying an application for a marketing authorisation pursuant to Schedule 1 of the Veterinary Medicines Regulations shall be presented in accordance with the requirements set out in this Annex

1.2. In assembling the dossier for application for a marketing authorisation, applicants shall also take into account the most up-to-date veterinary medicinal knowledge and the scientific guidelines relating to the quality, safety and efficacy of veterinary medicinal products.

1.3. Applicants must ensure that appropriate parts of the dossier meet the standards set out in all relevant monographs of the European Pharmacopoeia or, where applicable, the British Pharmacopoeia, including general monographs and the general chapters.

1.4. The manufacturing processes for the active substance(s) and finished product shall comply with Good Manufacturing Practice (GMP).

1.5. All information which is relevant to the evaluation of the veterinary medicinal product concerned shall be included in the application, whether favourable or unfavourable to the product. In particular, all relevant details related to any incomplete or abandoned study or trial relating to the veterinary medicinal product shall be given.

1.6. Pharmacological, toxicological, residue and pre-clinical studies shall be carried out in conformity with the provisions related to Good Laboratory Practice (GLP)

1.7. All experiments on animals shall be conducted taking into account the requirements set out in the Animals (Scientific Procedures) Act 1986 notwithstanding the place of conduct of the experiments.

1.8. The environmental risk assessment connected with the release of veterinary medicinal products containing or consisting of Genetically Modified Organisms (GMOs) shall be provided in the dossier as a separate document. The information shall be presented in accordance with the provisions of the GMO deliberate Release Regulations.

1.9. The applicant shall confirm in Part 1 of the dossier for an application for marketing authorisation that all submitted data relevant to the quality, safety and efficacy of the veterinary medicinal product, including data publicly available, are not subject to protection of technical documentation.

1.2. Dossier composition requirements

Any dossier for an application for marketing authorisation for a veterinary medicinal product shall consist of the following parts:

2.1 Part 1: Summary of the dossier

Part 1 shall include administrative information as outlined in Schedule 1 para 2, as follows:

  • (a) Part 1A: Schedule 1 para 2
  • (b) Part 1B: Schedule 1 para 2 (h), (I), (J)
  • (c) Part 1C: Schedule 1 para 2 (n)

An application proposing classification of a veterinary medicinal product as POM-VPS, NFA-VPS or AVM-GSL shall include a critical review of the product characteristics in order to justify the suitability of such classification taking into consideration target and non-target animal safety, public health as well as environmental safety.

Each critical expert report shall be prepared with regard to the state of scientific knowledge at the time of submission of the application. It shall contain an evaluation of the various tests and trials which constitute the marketing authorisation dossier, and shall address all aspects relevant to the assessment of the quality, safety and efficacy of the veterinary medicinal product. It shall give detailed results of the tests and trials submitted and precise bibliographic references. Copies of the bibliographic references cited shall be provided.

The critical expert reports shall be signed and dated by the author of those reports, and information about the author’s educational background, training and occupational experience shall be attached. The professional relationship of the author with the applicant shall be declared.

The critical expert reports and the appendices shall contain precise and clear cross-references to the information contained in the technical documentation.

Where Part 2 is presented using the format of the Common Technical Document (CTD), the quality overall summary (QOS) shall be used for the critical expert report on quality.

For Parts 3 and 4 the critical expert report shall also include a tabulated summary of all technical documentation and relevant data submitted.

2.2 Part 2: Quality documentation (physicochemical, biological or microbiological information)

  1. The pharmaceutical quality (physicochemical, biological or microbiological) data shall include for the active substance(s) and for the finished veterinary medicinal product information on the manufacturing process, the characterisation and properties, the quality control procedures and requirements, the stability as well as a description of the composition, the development and presentation of the veterinary medicinal product.

  2. All monographs, including specific monographs, general monographs and general chapters of the European Pharmacopoeia are applicable. For immunological veterinary medicinal products, all monographs, including specific monographs, general monographs and general chapters of the European Pharmacopoeia are applicable, unless otherwise justified. In the absence of a European Pharmacopoeia monograph, the monograph of the British Pharmacopoeia may be applied. In cases where a substance is described neither in the European Pharmacopoeia nor in the British pharmacopoeia , compliance with the monograph of a third country pharmacopoeia may be accepted if its suitability is demonstrated; in such cases, the applicant shall submit a copy of the monograph accompanied by a translation where appropriate. Data to demonstrate the ability of the monograph to adequately control the quality of the substance shall be presented.

  3. If tests other than those mentioned in the pharmacopoeia are used, the use of such tests shall be justified by providing proof that the materials, if tested in accordance with the pharmacopoeia, would meet the quality requirements of the relevant pharmacopoeial monograph.

  4. All test procedures for analysis and quality control shall take account of established guidance and requirements. The results of the validation studies shall be provided. All the test procedure(s) shall be described in sufficient detail so as to be reproducible in control tests, carried out at the request of the competent authority and in order to be properly assessed by the competent authority. Any special apparatus and equipment, which may be used shall be described in adequate manner, accompanied by a diagram, if relevant. The formulae of the laboratory reagents shall be supplemented, if necessary, by the method of preparation. In the case of test procedures included in the European Pharmacopoeia or the British pharmacopoeia, this description may be replaced by a detailed reference to the pharmacopoeia in question. Where available, chemical and biological reference material of the European Pharmacopoeia shall be used. If other reference preparations and standards are used, they shall be identified and described in detail.

  5. The pharmaceutical quality (physicochemical, biological or microbiological) data for the active substance and/or the finished product may be included in the dossier in Common Technical Document (CTD) format.

  6. For biological veterinary medicinal products, including immunologicals, information on solvents needed for making the final product preparation shall be included in the dossier. A biological veterinary medicinal product is regarded as one product even when more than one solvent is required so that different preparations of the final product can be prepared, which may be for administration by different routes or methods of administration. Solvents supplied with biological veterinary medicinal products may be packed together with the active substance vials or separately.

  7. Tests shall be carried out in such a way as to use the minimum number of animals and to cause the least pain, suffering, distress or lasting harm. If available, an alternative in vitro test shall be used when this leads to replacement or reduction of animal use or reduction of suffering.

2.3 Part 3: Safety documentation (safety and residues tests)

  • (1.) The dossier on the safety studies shall include the following:

    • (a) synthesis of the tests which have been carried out in compliance with this Part, with detailed references to the published literature containing an objective discussion of all the results obtained. Omission of any tests or trials listed and inclusion of an alternative type of study shall be indicated and discussed;
    • (b) a statement of compliance with good laboratory practice for pre-clinical studies, where applicable, together with a discussion of the contribution that any non-GLP study may make to the overall risk assessment, and justification of non-GLP status.

  • (2.) The dossier shall include the following:

    • (a) an index of all studies and trials included in the dossier;
    • (b) a justification for the omission of any type of study and trial;
    • (c) an explanation of the inclusion of an alternative type of study or trial;
    • (d) a discussion of the contribution that any non-GLP study or trial may make to the overall risk assessment and justification of non-GLP status.

2.4 Part 4: Efficacy documentation (pre-clinical studies and clinical trial(s))

  • (1.) The dossier on efficacy shall include all pre-clinical and clinical documentation, whether favourable or unfavourable to the veterinary medicinal products, in order to enable an objective overall assessment of the benefit/risk balance of the product.

  • (2.) The dossier on the efficacy studies shall include the following:

    • (a) synthesis of the tests which have been carried out in compliance with this Part, with detailed references to the published literature containing an objective discussion of all the results obtained. Omission of any tests or trials listed and inclusion of an alternative type of study shall be indicated and discussed;
    • (b) a statement of compliance with good laboratory practice for pre-clinical studies, where applicable, together with a discussion of the contribution that any non-GLP study may make to the overall risk assessment, and justification of non-GLP status.

  • (3.) The dossier shall include the following:

    • (a) an index of all studies included in the dossier;
    • (b) a justification for the omission of any type of study;
    • (c) an explanation of the inclusion of an alternative type of study.

  • (4.) The purpose of the trials described in this Part is to demonstrate the efficacy of the veterinary medicinal product. All claims made by the applicant with regard to the properties, effects and use of the product shall be fully supported by results of specific trials contained in the application for marketing authorisation.

  • (5.) All efficacy trials shall be conducted in accordance with a fully considered detailed protocol, which shall be recorded in writing prior to commencement of the trial. The welfare of the trial animals shall be subject to veterinary supervision and shall be taken fully into consideration during the elaboration of any trial protocol and throughout the conduct of the trial.

  • (6.) Clinical trials (field trials) shall be conducted in accordance with established principles of good clinical practice, unless otherwise justified.

  • (7.) Before the commencement of any field trial, the informed consent of the owner of the animals to be used in the trial shall be obtained and documented. In particular, the animal owner shall be informed in writing of the consequences of participation in the trial for the subsequent disposal of treated animals or for the taking of foodstuffs from treated animals.

2.5 Detailed requirements for different types of veterinary medicinal products or marketing authorisation dossiers

  • (1.) These are outlined in the following Sections of this Annex:

    • (a) Section II describes the standardised requirements for applications for veterinary medicinal products other than biological veterinary medicinal products;
    • (b) Section III describes the standardised requirements for applications for biological veterinary medicinal products:
    • (i) Section IIIa describes the standardised requirements for applications for biological veterinary medicinal products other than immunological veterinary medicinal products;
    • (ii) Section IIIb describes the standardised requirements for applications for immunological veterinary medicinal products;
    • (c) Section IV describes the dossier requirements for specific types of marketing authorisation dossiers;
    • (d) Section V describes the dossier requirements for particular types of veterinary medicinal products.