Launch of Veterinary Vaccine Development Process Map

Target Product Profile (TPP)

The first step in any vaccine development project with a commercial target in mind should be the creation of a Target Product Profile (TPP). As with human vaccines, the TPP for a veterinary vaccine is a strategic planning document used to guide vaccine development process from the earliest stages. It sets out clear parameters for the characteristics of the desired end product, and ensures that various disciplines are aligned on desired outcomes, product characteristics and measures of success. A well-crafted TPP generally presents optimistic, realistic, and minimal goals, and helps all stakeholders focus on the same aims. The TPP also guides the design, conduct and analysis of safety and efficacy trials, as it allows the development team to focus on the desired characteristics of the vaccine and to ensure that the proposed regulatory trials generate rigorous data, which may eventually support product label claims.

Discovery/Feasibility Phase

For veterinary vaccines a Discovery/Feasibility Phase replaces the human Pre-clinical Discovery Phase. Early Discovery work may be carried out in laboratory animals in order to screen a number of potential vaccine candidates and select promising formulations and the appropriate dose. However, such laboratory animal models are often poor indicators of a vaccine’s safety and protective efficacy within the target species. Therefore, preliminary studies within the target species are often used in veterinary vaccine research in order to identify promising vaccines and reach an early demonstration of efficacy for the intended product. Although many of the steps are essentially the same for human and veterinary vaccines and both targeted at discovering a lead candidate, the veterinary feasibility process will include proof-of-concept safety and efficacy studies within the target species for the vaccine. Thus, with a veterinary vaccine there is generally a greater degree of confidence for successful licensure based on clinical trials within the relevant host before the vaccine enters the more costly Product Development Phase.

Early-Phase Development

Once there is confidence that the experimental vaccine candidate elicits an immune response that correlates with protection then this lead vaccine can be taken into Early-Phase Development. At this stage it is wise to ensure that that you have freedom to operate with regards to any pre-existing intellectual property and to file for patent protection of your vaccine, if it is sufficiently novel. This phase replaces the human Pre-Development Phase and it is focussed on addressing the three key elements of a Regulatory Dossier, which within the UK/EU are defined as Quality, Safety and Efficacy. The Quality data will address the purity and consistence of the final product and ensure that each batch of vaccine is fit for purpose. An important element of this is the Potency Test. This can be either an in vitro or in vivo assay and it will guarantee the efficacy of the finished vaccine over its product shelf-life. Other elements of the Quality data include information on all the product starting materials, a detailed description of the manufacturing process, in process quality control assays and final product release testing. The Early-Phase Safety Testing data should be carried out according to the principals of Good Laboratory Practice (GLP) and will be dependent on the nature of the vaccine (live attenuated, inactivated, sub-unit, etc). This will generally include single, repeat and possibly overdose studies carried out with maximum titre/potency product in minimum age animals. Additional studies will also be required for animals in pregnancy or birds in lay and further data is needed for live vaccines. Finally, the Efficacy data within this Early-Phase of development will include onset and duration of immunity studies conducted with minimum titre/potency product in minimum aged animals. It may also involve efficacy in the face of maternally derived antibodies, a study of the requirement for booster doses and an investigation into the immune mechanisms involved in the hosts response to the vaccine.

Late-Phase Development

Data from Early-Phase Development will be used to apply for permission to conduct field trials as part of Late-Phase Development in order to ensure that the vaccine is both safe and efficacious under field conditions designed to mimic its “everyday” use. To obtain the necessary permission you will need to apply for Animal Test Certificate (ATC). This application should generally include analytical information such as qualitative and quantitative particulars relating to the product and details of any information relevant to the safety of the product. It may also include preliminary laboratory efficacy data from Early-Phase Development or justification as to why such data cannot be generated within a laboratory environment and thus field efficacy testing is required. Field Trials should generally be conducted according to the VICH Guideline (GL9) on Good Clinical Practice (GCP). Depending on the regulatory requirements, these field trials are often conducted on multiple sites and in different international locations.

The Registration Phase, which forms part of the Late-Phase Development, will be dependent on the regulatory strategy and intended markets for the product. If it is just intended for the UK Market then the regulatory authority would be the UK Veterinary Medicines Directorate (VMD). If intended for wider use in Europe then the European Medicines Agency (EMA) should be involved. Other markets in North America, South America, Africa, Asia and Australasia will have their own regulatory agencies and associated specific requirements.

Please note, these Process Maps are intended to be overall guides and the UK Vaccine Network takes no responsibility for how they may be used in individual vaccine R&D projects.