The veterinary dossier
A veterinary marketing-authorisation dossier brings together administrative information and evidence of quality, safety and efficacy. Its safety documentation considers people handling the medicine, consumers of food from treated animals and environmental exposure.
Structure and format
Eudralex Volume 6 describes registration procedures and the presentation and content of the dossier.
The Notice to Applicants format described in Volume 6B has four parts, with the same general structure for pharmaceutical and immunological veterinary products:
- Administrative information and summary of the dossier.
- Quality documentation.
- Safety documentation, including residues documentation for pharmaceutical products.
- Efficacy documentation.
The detailed content differs between pharmaceutical and immunological products, and immunological products have additional requirements.
In the 2014 account of this format, a Common Technical Document (CTD) dossier was generally acceptable with a correlation table to the Notice to Applicants structure. A hybrid dossier was also possible, with most parts following the Notice to Applicants format and, for example, a CTD module for quality documentation. The exact format should be discussed in a pre-submission meeting with the competent authority.
Parts 2, 3 and 4 may each have a written introduction, but the 2014 account states that this was not mandatory for electronic submissions: these parts could consist only of individual study reports or literature references.
Part 1: administrative information and summaries
Part 1 contains administrative information and product information, including the summary of product characteristics, labelling and package leaflets. It also contains detailed and critical summaries of the quality, safety and efficacy documentation. These summaries and product-information texts are documents for which regulatory affairs departments may seek a medical writer’s help. The 2015 version of Eudralex Volume 6B replaced the older term “expert reports” with “critical summaries”.
A centralised authorisation produces common product-information text that must be translated into the national languages of the countries where market access is gained. Veterinary product-information templates differ from human templates, and veterinary product information does not require readability testing.
Part 2: quality
Part 2 corresponds roughly to CTD Module 3 and covers composition, pharmaceutical development and manufacturing methods. It contains physicochemical, biological or microbiological documentation for the individual components and the finished product. This is usually the part containing the most sensitive information for protecting intellectual property.
Part 3: safety and residues
Part 3 addresses potential risks to people and the environment arising from use of the product. Human safety includes people using the product and people consuming food derived from treated animals. The user may be a veterinarian, farmer, someone administering treatment at home or a worker in a feed mill. Adverse effects in the target species enter this part insofar as they inform the risk assessment for people and the environment; target-species safety is considered in detail in Part 4.
For pharmaceutical products, Part 3 covers safety to the user, the consumer of food from treated animals and the environment. It contains mainly toxicological studies in laboratory animals, particularly no-observed-effect levels, from which a user risk assessment is performed and, for food-producing animals, an acceptable daily intake of potential residues in edible tissues is calculated. For food-producing animals, Part 3A contains safety documentation, including environmental safety, and Part 3B contains residues documentation.
For immunological products, Part 3 focuses on potential risks from human exposure, for example during administration to an animal. For products consisting of live organisms, especially organisms that vaccinated animals could shed, the potential risk to unvaccinated animals must be evaluated.
Part 4: efficacy in the target species
Part 4 contains preclinical and clinical trials demonstrating efficacy, and every claim about the product’s properties, effects and use must be supported by results of trials conducted for the application. Preclinical studies are usually required to establish pharmacological activity and tolerance. Clinical trials demonstrate the effect at the proposed dosage regimen and route of administration and specify indications and contraindications according to species, age, breed and sex. Where a product is intended for several species, such as pigs, sheep or horses, the trials and documentation must cover those species and substantiate each claim.
For pharmaceutical and immunological products, the focus is confirming the clinical dose through laboratory studies and field trials in the target species, which may include dogs, cats, cattle, pigs, horses or poultry. For pharmaceutical products, Part 4 also includes mode of action, potential resistance of antimicrobial or antiparasitic substances, pharmacokinetic particulars, tolerance in the target species and determination of the clinical dose.
Generic applications
Bioequivalence studies provide pivotal data for generic veterinary marketing-authorisation applications by allowing the reference product’s safety and efficacy data to be bridged to the generic. A common situation is development of a generic version of an approved product whose data-protection period has expired.
Reduced data requirements
In 2016, the minor use, minor species/limited market (MUMS) classification brought reduced data requirements that were considered during assessment. The policy aimed to stimulate development for minor species and for diseases in major species with limited markets, where products would otherwise not be developed under prevailing market conditions.
VarroMed, a fixed combination of oxalic acid dihydrate and formic acid for Varroa mites in honey-bee colonies, was classified as MUMS when the Committee for Medicinal Products for Veterinary Use recommended marketing authorisation in October 2016. Laboratory and field studies in different European climates showed that it killed more than 80% of mites, below the 90% effectiveness level recommended by the committee’s Varroa guideline. The committee accepted a lower level of 80% when integrated Varroa control techniques were in place, and the product was intended for a programme including non-chemical techniques such as queen trapping or drone brood removal.