Section V
Requirements for Marketing Authorisation applications for particular veterinary medicinal products.
This Section lays down specific requirements for identified veterinary medicinal products related to the nature of the active substances contained therein.
The Veterinary Medicines Regulations define a “novel therapy” as a veterinary medicinal product which is considered to be in a nascent field in veterinary medicine, including a product of a type not previously authorised in Great Britain. Novel therapies by their nature are new and innovative and may require additional data to that set out in this Manual. The Secretary of State may require applicants to provide additional supporting information in order for a thorough assessment of the benefits and risks of the product to be carried out.
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(1) Depending on the active substance and the mode of action, a novel therapy veterinary medicinal product could fall under any of the three product categories:
- (a) veterinary medicinal products other than biological veterinary medicinal products
- (b) biological veterinary medicinal products other than immunological veterinary medicinal products
- (c) immunological veterinary medicinal products
V.1.1.2
In general, marketing authorisation applications for novel therapy veterinary medicinal products, shall follow the format and data requirements described in Section II or III of this Annex depending on how the novel therapy is categorised. A full dossier containing Parts 1, 2, 3 and 4 shall normally be provided in accordance with the requirements described in Section II or III and any relevant guidance. Deviations from the requirements of this Annex may be possible when justified. Where appropriate and taking into account the specificities of novel therapy products, additional requirements may be relevant for particular types of products.
V.1.1.3
The manufacturing processes for novel therapy veterinary medicinal products shall comply with the principles of Good Manufacturing Practice (GMP) adapted where necessary, to reflect the specific nature of those products.
V.1.1.4
According to the specific nature of a novel therapy product the use of the product may potentially be associated with specific risks. Those risks shall be identified applying a risk profiling methodology to identify the risks inherent to the specific product and the risk factors contributing to those risks. In this context, risks would be any potential unfavourable effects that may be attributed to the use of the novel therapy product which are of concern to the target population and/or the user, the consumer, and/or the environment. The risk analysis may cover the entire development.
V.1.1.5
Based on the evaluation of the information on the identified risks and risk factors a specific profile of each individual risk associated with a specific product shall be established and may be used to determine and justify how the data set provided gives the necessary assurances for quality, safety and efficacy and is adequate to support a marketing authorisation application, especially for those aspects of novel therapy products that are beyond current knowledge.
V.1.1.6
To address data gaps or uncertainties at the time of product authorisation, implementation of post- authorisation measures or studies may be considered on a case-by-case basis. In order to detect early or delayed signals of adverse reactions, to prevent clinical consequences of such reactions and to ensure timely treatment and to gain information on the long-term safety and efficacy of novel therapy veterinary medicinal products a risk management plan shall detail the measures envisaged to ensure such follow up.
V.1.1.7
For any novel therapy product, in particular those considered as a nascent field in veterinary medicine, it is recommended to seek the advice of the Veterinary Medicines Directorate in a timely manner before submission of the marketing authorisation dossier in order to classify the product, determine the applicable dossier structure and to receive relevant information about the additional data set which may be necessary to support quality, safety and efficacy.
V.1.2.1
In general, description of the composition, the manufacturing method, consistency of production, controls of starting materials, controls implemented during the manufacturing process, finished product testing including implementation of an activity test or a quantification of the active substance and stability data shall be submitted.
V.1.2.2
The data requirements for manufacturing and testing for novel therapy veterinary medicinal products of biological origin and classified as a biological product or as an immunological product shall in general be in accordance with those for biological or immunological medicinal products (as described in Section III of this Annex) including the need for a relevant potency test. There may be cases where additional requirements are applicable, for particular types of product on a case by case basis and in accordance with guidance where relevant.
V.1.2.3
For novel therapy veterinary medicinal products constructed by chemical synthesis, data requirements as for veterinary medicinal products other than biological products (as described in Section II of this Annex) are generally applicable. There may be cases where additional requirements are applicable, for particular types of product on a case by case basis and in accordance with guidance where relevant.
V.1.3.1
Depending on the nature of the product and its intended use, further data to evaluate safety for the target animal, the user, the consumer or the environment could be relevant as determined by a risk analysis in each case.
The state of scientific knowledge and established guidance must be taken into account when designing safety studies and evaluating their results.
V.1.4.1
Efficacy data requirements differ primarily depending on the intended indications for use in the target species. Depending on the novel therapy product categorisation and the intended use in the target species, the efficacy requirements set out in Sections II or III may be applicable for a novel therapy veterinary medicinal product.
V.1.4.2
The indications claimed shall be supported by appropriate data in the target species.
V.1.4.3
The state of scientific knowledge and established guidance must be taken into account when designing efficacy studies and evaluating their results.
For particular immunological veterinary medicinal products and by derogation from Section IIIb, Part 2, a Vaccine Antigen Master File may be submitted with the dossier.
V.2.1.1
For the purpose of this Annex, a Vaccine Antigen Master File means a stand-alone part of the marketing authorisation application dossier for a vaccine, which contains all relevant information on quality concerning each of the active substances, which are part of the veterinary medicinal product. The stand-alone part may be common to one or more monovalent and/or combined vaccines presented by the same applicant or marketing authorisation holder.
V.2.1.2
The use of Vaccine Antigen Master Files is optional. For combined vaccines, the vaccine antigen(s) to be included in Vaccine Antigen Master File(s) shall be specified and a separate Vaccine Antigen Master File shall be required for each of them.
V.2.1.3
The submission and approval of a Vaccine Antigen Master File shall comply with the EMA Guideline on data requirements for vaccine antigen master files (VAMF)” .
The Vaccine Antigen Master File dossier shall contain the information in Parts V.2.2.1 to V.2.3.3 extracted from the relevant sections of Part 1 (Summary of the dossier) and Part 2 (Quality documentation) as set out in Section IIIb of this Annex:
V.2.2.1 Summary of the dossier (Part 1)
The name and address of the manufacturer(s) and the site(s) involved in the different stages of manufacture and control of the active substance, accompanied by copies of the corresponding manufacturing authorisations, shall be given.
V.2.2.2 Qualitative and quantitative particulars of the constituents (Part 2.A)
The complete and exact name of the active substance (for example, virus or bacteria strain, antigen) shall be provided, in the same way as mentioned in any finished product. Information on product development relevant to the active substance shall be provided.
V.2.2.3 Description of the manufacturing method (Part 2.B)
The description of the manufacturing method for the active substance shall be provided including validation of the key stages of production and justification, if relevant, of any intermediate storage proposed. For inactivated vaccines, data relevant to the inactivation of the active substance, including the validation of the inactivation process shall be provided.
V.2.2.4 Production and control of starting materials (Part 2.C)
V.2.2.4.1
The standard requirements described in Section IIIb.2C and relevant to the active substance shall apply.
V.2.2.4.2
Information on the active substance (for example, virus/bacteria strain), the substrate/s (cells, culture medium) and all the raw materials (pharmacopoeia or non-pharmacopoeia, biological or non-biological) used in the production of the active substance shall be provided.
V.2.2.4.3
The dossier shall include the specifications, information on the processes implemented and on the tests to be conducted for the quality control of all batches of starting materials and results for a batch for all components used.
V.2.2.4.4
TSE and extraneous agents (EA) risk assessment shall be provided, where applicable. It is to be noted that the target species retained for the finished products making reference to the Vaccine Antigen Master File shall be considered for the TSE and EA risk assessment. Warnings or restrictions of use may be brought in at the Vaccine Antigen Master File level depending on the information presented, which may be mitigated during the risk analysis at the level of the finished product.
V.2.2.4.5
If the active substance is obtained by recombinant techniques, all corresponding relevant data on the genetically modified virus/bacteria shall be provided.
V.2.2.5 Control tests during the manufacturing process (Part 2.D)
The standard requirements described in Section IIIb.2D shall apply for the in-process control tests carried out during the manufacture of the active substance, including validations of key control tests and, if relevant, any intermediate storage proposed (prior to blending).
V.2.2.6 Batch-to-batch consistency (Part 2.F)
The standard requirements described in Section IIIb.2F shall apply for the demonstration of consistency in the manufacture of the antigen.
V.2.2.7 Stability (Part 2.G)
The standard requirements described in Section IIIb.2G to demonstrate the stability of the antigen and, where relevant any intermediate storage, shall apply.
V.2.3.1
For vaccines containing new vaccine antigen(s) where no Vaccine Antigen Master File already exists, the applicant shall submit to the Secretary of State a full marketing authorisation application dossier including all the Vaccine Antigen Master Files corresponding to each single vaccine antigen for which the use of a Vaccine Antigen Master File is intended.
V.2.3.2
Part V.2.3.1 shall also apply to every vaccine, which consists of a novel combination of vaccine antigens, irrespective of whether or not one or more of those vaccine antigens are part of vaccines already authorised in the Great Britain.
V.2.3.3
Changes to the content of a Vaccine Antigen Master File for a vaccine authorised in the Great Britain shall be subject to a scientific and technical evaluation carried out by the Secretary of State.
V.3.1
For certain immunological veterinary medicinal products and by derogation from the provisions of Section IIIb, Part 2, a multi-strain dossier may be submitted.
V.3.2
A multi-strain dossier means a single dossier containing the relevant data for a unique and thorough scientific assessment of the different options of strains/combinations of strains permitting the authorisation of inactivated vaccines against antigenically variable viruses or bacteria for which rapid or frequent change in the composition of vaccine formulations is needed to ensure efficacy with regard to the epidemiological situation in the field. According to the epidemiological situation where the vaccine is intended to be used, a number of strains could be selected from those included in the dossier to formulate a final product.
V.3.3
Each multi-strain dossier is applicable only to one virus species, bacteria genus or vector for a given disease; mixtures of various viruses belonging to different families, genera, species or bacteria belonging to different families or genera cannot be approved in the context of a multi-strain dossier.
V.3.4
For new applications to multi-strain dossier marketing authorisations where no authorised multi-strain vaccine already exists for a particular virus/bacterium/disease, eligibility for the multi-strain dossier approach shall be confirmed by the Secretary of State before submission of the application.
V.3.5
The submission of multi-strain dossiers must be in accordance with the CVMP document titled “Guideline on Data Requirements for Multi-Strain Dossiers for Inactivated Veterinary Vaccines”
V.4.1 Principles
V.4.1.1
Vaccine platform technology is a collection of technologies that have in common the use of a “backbone” carrier or vector that is modified with a different antigen or set of antigens for each vaccine derived from the platform. This includes, but may not be limited to, protein-based platforms (virus-like particles), DNA vaccine platforms, mRNA based platforms, replicons (self-replicating RNA) and viral and bacterial vector vaccines.
V.4.1.2
Applications for marketing authorisations of immunological veterinary medicinal products manufactured based on vaccine platform technologies are considered to be eligible for reduced data requirements. A full dossier is required for the first product from a manufacturer based on a particular platform technology for a particular target species. At the time of submission of the first (full) dossier based on the platform technology, the applicant may submit in parallel a “Platform Technology Master File” comprising all data relative to the platform for which there is reasonable scientific certainty that will remain unchanged regardless of the antigen (s)/gene(s) of interest added to the platform. The nature of the data to be included in the Platform Technology Master File will depend on the type of platform.
V.4.1.3
Once a Platform Technology Master File is certified, the certificate may be used to fulfil the relevant data requirements in subsequent applications for marketing authorisations based on the same platform and intended for the same target species.
V.4.2 Evaluation and certification
V.4.2.1
The submission of Platform Technology Master Files must be in accordance with the CVMP document titled “Guideline on Data Requirements for Vaccine Platform Technology Master Files (vPTMF) A scientific and technical evaluation of a Platform Technology Master File shall be carried out by the Secretary of State
V.4.2.2
Changes to the content of a Platform Technology Master File for a vaccine authorised in Great Britain shall be subject to a scientific and technical evaluation carried out by the Secretary of State.
V.5.1 Quality (Part 2)
The provisions of Section II.2. Part 2 shall apply to marketing authorisation of homeopathic remedies not within scope of paragraph 63 of Schedule 1 with the following modifications.
V.5.2 Terminology
The Latin name of the homeopathic stock described in the marketing authorisation application dossier shall be in accordance with the Latin title of the European Pharmacopoeia or, in absence thereof, of the British Pharmacopoeia. Where relevant the traditional name(s) used shall be provided.
V.5.3 Control of starting materials
The particulars and documents on the starting materials, that is to say, all of the materials used including raw materials and intermediates up to the final dilution to be incorporated into the finished authorised homeopathic veterinary medicinal product, accompanying the application, shall be supplemented by additional data on the homeopathic stock.
The general quality requirements shall apply to all of the starting and raw materials as well as intermediate steps of the manufacturing process up to the final dilution to be incorporated into the finished homeopathic product. Where a toxic component is present, this shall be controlled, if possible, in the final dilution. If this is not possible because of the high dilution, the toxic component shall normally be controlled at an earlier stage. Every step of the manufacturing process from the starting materials up to the final dilution to be incorporated into the finished product shall be fully described.
Where dilutions are involved, those dilution steps shall be done in accordance with the homeopathic manufacturing methods laid down in the relevant monograph of the European Pharmacopoeia or, in absence thereof, the British Pharmacopoeia.
V.5.4 Control tests on the finished medicinal product
The general quality requirements shall apply to the homeopathic finished veterinary medicinal products. Any exception shall be duly justified by the applicant.
Identification and assay of all the toxicologically relevant constituents shall be carried out. If justified that identification and/or an assay on all the toxicologically relevant constituents is not possible, for example, due to their dilution in the finished medicinal product the quality shall be demonstrated by complete validation of the manufacturing and dilution process.
V.5.5 Stability tests
The stability of the finished product shall be demonstrated. Stability data from the homeopathic stocks are generally transferable to dilutions/potentisations obtained thereof. If no identification or assay of the active substance is possible due to the degree of dilution, stability data of the pharmaceutical form may be considered.
V.5.6 Safety documentation (Part 3)
Part 3 shall apply to homeopathic veterinary medicinal products with the following specification, without prejudice to the provisions of Commission Regulation (EU) No 37/2010 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin.
Any missing information shall be justified, for example, justification shall be given as to why demonstration of an acceptable level of safety may be supported, even where some studies are lacking.