Section IV

Requirements for Specific Marketing Authorisation Applications.

IV.1 Applications for generic veterinary medicinal products

  • (1) Applications based on Paragraph 10 of Schedule 1 (application for a generic veterinary medicinal product) shall contain the data referred to in Parts 1 and 2 of Section II of this Annex.

  • (2) An applicant must provide an environmental risk assessment for a generic veterinary medicinal product where:

    • (a) the marketing authorisation for the reference veterinary medicinal product was granted before 1st October 2005, and

    • (b) User safety shall be addressed in accordance with Committee for Medicinal Products for Veterinary Use (CVMP) guidelines

In addition, the dossier shall contain data demonstrating that the product has the same qualitative and quantitative composition in active substance(s) and the same pharmaceutical form as the reference medicinal product; and data, showing bioequivalence with the reference medicinal product or a justification as to why such studies were not performed with reference to established guidance. All immediate- release oral pharmaceutical forms shall be considered to be the same pharmaceutical form.

For biological (including immunological) veterinary medicinal products, the standard generic approach is in principle not considered appropriate, and a hybrid approach shall be followed (see Part IV.2.).

Applications for biological (including immunological) veterinary medicinal products cannot be made under paragraph 10 of Schedule 1.

IV.1.2

For generic veterinary medicinal products, the critical expert reports on safety and efficacy shall particularly focus on the following elements:

  • (a) the grounds for claiming bioequivalence
  • (b) a summary of impurities present in batches of the active substance(s) as well as those of the finished medicinal product (and where relevant decomposition products arising during storage) together with an evaluation of those impurities
  • (c) an evaluation of the bioequivalence studies or other information that may provide support for claiming bioequivalence in accordance with VICH GL52 and the CVMP Guideline on the Conduct of Bioequivalence Studies for Veterinary Medicinal Products”
  • (d) any additional data in order to demonstrate the equivalence of safety and efficacy properties of different salts, esters or derivatives of an authorised active substance
  • (e) a review of the user safety risk assessment focusing on differences between the generic and reference veterinary medicinal products (for example, composition in excipients)
  • (f) a review of environmental risk assessment, where relevant

IV.1.3

For applications for generic veterinary medicinal products containing antimicrobial or antiparasitic substances, the applicant must provide all available data (including published data) on the current level of resistance. [**This must include a review of available published data on the current level of resistance in target pathogens to the active substances concerned.

IV.1.4

For generic veterinary medicinal products intended to be administered by intramuscular, subcutaneous or transdermal routes, the following additional data shall be provided:

  • (a) evidence to demonstrate equivalent or differing depletion of residues from the administration site, which may be substantiated by appropriate residue depletion studies
  • (b) evidence to demonstrate target animal tolerance at the administration site, which may be substantiated by appropriate target animal tolerance studies.

IV.2 Applications for hybrid veterinary medicinal products

  • (1) Applications based on paragraph 10a of Schedule 1 (hybrid veterinary medicinal products) concern veterinary medicinal products, which are similar to a reference veterinary medicinal product, but which do not meet the conditions in the definition of generic veterinary medicinal product.

  • (2) For such applications, the following information shall be supplied:

    • (a) all the data referred to in Parts 1 and 2 of Sections II or III, as appropriate, of this Annex
    • (b) for Parts 3 and 4 of the dossier, hybrid applications may rely in part on the results of the appropriate safety, residue, pre-clinical studies and clinical trials for an already authorised reference veterinary medicinal product, and in part on new data. New data shall include a user safety risk assessment and an environmental risk assessment in accordance with Schedule 1 para 10, if applicable. In addition, for relevant products (for example, antimicrobials, antiparasitics) the risk of development of resistance shall be addressed, if applicable.

  • (3) In the case of biological (including immunological) veterinary medicinal products, the applicant must provide reasons to the secretary of state to explain why an application under paragraph 10a is appropriate..

  • (4) Where reference is made to data originating from another authorised veterinary medicinal product, a justification for the use and relevance of those data for the new product shall be provided.

  • (5) The extent of new data required to support safety and efficacy will depend on the specific characteristics of the individual new product, and its differences to the reference veterinary medicinal product, and shall be determined on a case-by-case basis. New pre-clinical and clinical data for the new product shall be presented for all aspects where the reference veterinary medicinal product does not provide relevant support.

  • (6) If new studies are conducted with batches of a reference veterinary medicinal product authorised in a third country, the applicant shall demonstrate that the reference veterinary medicinal product has been authorised in accordance with requirements equivalent to those established in Great Britain, and are so highly similar that they may substitute each other in the pre-clinical studies or clinical trials.

IV.3 Applications for combination veterinary medicinal products

  1. An application for a fixed combination product with individual active substances, which have already been the object of a marketing authorisation for a veterinary medicinal product in Great Britain, shall be submitted under paragraph 8 of schedule 1.

  2. A fixed combination product containing at least one new active substance which has not yet been authorised for a veterinary medicinal product in Great Britain, must be submitted under paragraph 2 of schedule 1.

  3. For applications submitted under paragraph 8, a full dossier containing Parts 1, 2, 3 and 4 shall be provided.

  4. A sound scientific justification based on valid therapeutic principles for the combination of active substances, including clinical data, shall be provided, which demonstrates the need for and contribution of all active substances at the moment of treatment.

  5. In general, all the data on the safety and efficacy shall be provided for the fixed combination product, and safety and efficacy data for the individual active substances alone are not required, except to clarify their individual pharmacological properties.

  6. If data on the safety and efficacy of an individual known active substance are available to the applicant with sufficient amount of detail, those data could be provided to obviate the need for some studies with the fixed combination, or contributing relevant information. In that case, possible interaction between active substances shall also be investigated.

  7. User safety assessment, environmental risk assessment, residues depletion studies, and clinical studies shall be conducted with the fixed combination product.

  8. Unless the omission is justified, a target animal safety study with the final formulation shall be provided.

IV.4 Applications based on informed consent

  1. Applications based on paragraph 9 of schedule 1 concern products with identical composition, pharmaceutical form and manufacturing process (including raw and starting materials, process parameters and manufacturing sites) as the already authorised veterinary medicinal products.

  2. The dossier for such applications shall only include data for Part 1A and 1B, as described in Annex I (points 1 to 6.4), provided that the marketing authorisation holder for the already authorised veterinary medicinal product has given the applicant his written consent to refer to the content of Parts 1C, 2, 3 and 4 of the dossier of that product. In that case, there is also no need to submit quality, safety and efficacy critical expert reports. The applicant shall provide proof of the written consent with their application.

IV.5 Applications based on bibliographic data

  • (1) For veterinary medicinal products for which the active substance(s) has or have been in well-established veterinary use as referred to in paragraph 7 of schedule 1, with recognised efficacy and an acceptable level of safety, the following specific rules shall apply.

  • (2) A full dossier (containing Parts 1, 2, 3 and 4) shall be provided. The applicant shall submit Parts 1 and 2 as described in this Annex. For Parts 3 and 4, a detailed scientific bibliography together with information demonstrating the appropriate bridging between bibliographic references and the veterinary medicinal product shall be submitted to address safety and efficacy. The bibliographic data may need to be complemented by some documentation specific to the product, for example, user safety and environmental risk assessments, or residue study data to justify any proposed withdrawal period(s).

An application based on bibliographical data cannot be made for biological (including immunological) veterinary medicinal products or novel therapies or novel therapy veterinary medicinal products

  • (3) The specific rules set out in Part IV.5.3.1 to IV.5.3.12 shall apply in order to demonstrate well-established veterinary use.

  • (4) In order to establish a well-established veterinary medicinal use of constituents of veterinary medicinal products, the following factors shall be taken into account:

    • (a) the time over which an active substance has been regularly used in the target species using the proposed route of administration and dosage regimen
    • (b) quantitative aspects of the use of the active substance(s), taking into account the extent to which the substance(s) has or have been used in practice, and the extent of use on a geographical basis
    • (c) the degree of scientific interest in the use of the active substance(s) (reflected in the published scientific literature)
    • (d) the coherence of scientific assessments

  • (5) Different periods of time may be necessary for establishing well-established use of different active substances. In any case, the period of time required for establishing a well-established veterinary use of a constituent of a medicinal product shall not be less than 10 years from the first systematic and documented use of that substance as a veterinary medicinal product in Great Britain.

  • (6) Veterinary use does not exclusively mean use as an authorised veterinary medicinal product. Well-established veterinary use refers to the use for a specific therapeutic purpose in the target species.

  • (7) If a substance in well-established use is proposed for entirely new therapeutic indications, it is not possible to solely refer to a well-established veterinary use. Additional data on the new therapeutic indication, together with appropriate safety and residue tests and preclinical and clinical data shall be provided and, in such a case, applications based on Schedule 1 para 7  is not possible.

  • (8) The published documentation submitted by the applicant shall be freely available to the public and published by a reputable source, preferably peer-reviewed.

  • (9) The documentation shall contain sufficient details to allow an independent assessment.

  • (10) The documentation shall cover all aspects of the safety and/or efficacy assessment of the product for the proposed indication in the target species using the proposed route of administration and dosage regimen. It shall include or refer to a review of the relevant literature, taking into account pre- and post-marketing studies and published scientific literature concerning experience in the form of epidemiological studies and, in particular, of comparative epidemiological studies.

  • (11) All documentation, both favourable and unfavourable, shall be communicated. With respect to the provisions on well-established veterinary use, it is in particular necessary to clarify that bibliographic reference to other sources of evidence (post-marketing studies, epidemiological studies etc.) and not just data related to tests and trials may serve as a valid proof of safety and efficacy of a product if the applicant explains and justifies the use of those sources of evidence satisfactorily.

  • (12) Public assessment reports or freedom of information summaries cannot be considered to supply sufficient information, apart from the assessment report published by the EMA following the evaluation of an application for the establishment of maximum residue limits, which may be used in an appropriate manner as literature, particularly for the safety tests.

  • (13) Particular attention shall be paid to any missing information, and justification shall be given as to why demonstration of an acceptable level of safety and/or efficacy may be supported although some information is lacking.

  • (14) The critical expert reports regarding safety and efficacy shall explain the relevance of any data submitted, which concern a product different from the product intended for marketing. A judgement shall be made whether or not the product studied in the bibliography may be satisfactorily or scientifically bridged to the product, for which the application for a marketing authorisation has been made in spite of the existing differences.

  • (15) Post-marketing experience with other products containing the same constituents is of particular importance and applicants shall put a special emphasis on this issue.

IV.6 Applications for limited markets

  1. A marketing authorisation may be granted for a veterinary medicinal product in respect of a limited market under paragraph 26(1)b of schedule 1 in the absence of comprehensive quality, safety and/or efficacy data when the applicant demonstrates that the product is intended for use in a limited market and that the benefit of availability of the new product outweighs the risk associated with the omission of some of the quality, safety or efficacy data required by this Annex.

  2. For such applications, the applicant shall submit Parts 1 as described in this Annex.

  3. For Parts 2, 3 and 4, some of the quality, safety or efficacy data required by this Annex may be omitted..

IV.7 Applications in exceptional circumstances, for a provisional Marketing Authorisation

  1. In exceptional circumstances related to animal or public health, a marketing authorisation may be granted under paragraph 26(1)a of schedule 1 subject to certain specific obligations, conditions and/or restrictions.

  2. For such applications, the applicant shall submit Part 1 as described in this Annex, together with a justification as to why the benefit of the immediate availability on the market of the veterinary medicinal product concerned outweighs the risk inherent in the fact that certain quality, safety or efficacy documentation has not been provided.

  3. For Parts 2, 3 and 4, certain quality, safety or efficacy data required by this Annex may be omitted, if the applicant justifies that those data cannot be provided at the time of submission.

  4. Post-authorisation studies may be requested as part of the conditions for marketing authorisation, and shall be designed, conducted, analysed and presented according to the general principles for quality, safety and efficacy tests set out in this Annex, and relevant guidance documents, as applicable depending on the issue to be addressed in the study.