The administration of a single dose of a multivalent (DHPPiL4R) vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

AbstractFour challenge studies following vaccination of dogs with a multivalent vaccine containing canine parvovirus (CPV-2b), adenovirus (CAV-1/-2) and distemper (CDV) are described. Six week old puppies received a single vaccination while non-vaccinated control dogs received water. In each respective trial, groups of dogs were challenged 21days after vaccination with heterologous viral isolates. Clinical observations, rectal temperature measurements, and blood and swab samples for analysis were collected throughout the study.Dogs in all studies had normal temperatures and general health up to challenge. Clinical signs of infection and temperatures outside the normal range were observed in non-vaccinated dogs challenged with CDV, CPV, CAV-1 and CAV-2; vaccinated dogs remained clinically normal after challenge. All dogs were sero-negative prior to vaccination, non-vaccinated dogs remaining negative until challenge. Vaccinated dogs all sero-converted by 21days after vaccination, with further increases seen after challenge. Non-vaccinated dogs sero-converted following challenge with CPV or CAV-2; no final blood samples were taken in the CDV and CAV-1 studies. Rectal swab analysis showed prevention of CPV shedding in vaccinated compared to non-vaccinated dogs, and nasal swab analysis following CAV-2 challenge showed longer duration and higher amount of viral shedding for non-vaccinated dogs.In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV

Modern science for better quality control of medicinal products “Towards global harmonization of 3Rs in biologicals”: The report of an EPAA Workshop

This article summarizes the outcome of an international workshop organized by the European Partnership for Alternative Approaches to Animal Testing (EPAA) on Modern science for better quality control of medicinal products: Towards global harmonization of 3Rs in biologicals. As regards the safety testing of biologicals, the workshop participants agreed to actively encourage the deletion of abnormal toxicity tests and target animal batch safety tests from all relevant legal requirements and guidance documents (country-specific guidelines, pharmacopoeia monographs, WHO recommendations). To facilitate the global regulatory acceptance of non-animal methods for the potency testing of, e.g., human diphtheria and tetanus vaccines and veterinary swine erysipelas vaccines, international convergence on the scientific principles of the use of appropriately validated in vitro assays for replacing in vivo methods was recognized as a further means to unify regulatory approaches in different jurisdictions. It was recommended to include key regulators and manufacturers early in the corresponding discussions. Manufacturers and responsible expert groups, e.g. at the European Directorate for the Quality of Medicines and Health Care of the Council of Europe or the European Medicines Agency, were invited to consider leadership for international collaboration.JRC.F.3-Chemicals Safety and Alternative Method

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants

Finding Synergies for 3Rs – Toxicokinetics and Read-Across: Report from an EPAA Partners’ Forum

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners’ Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. An important hurdle to PBK modelling is a lack of toxicokinetic data. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetic parameters required for read-across; case studies exemplifying how toxicokinetics data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools; and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to create a database of toxicokinetic tools that assist risk assessment.JRC.F.3-Chemicals Safety and Alternative Method

One science-driven approach for the regulatory implementation of alternative methods: A multi-sector perspective

EU regulations call for the use of alternative methods to animal testing. During the last decade, an increasing number of alternative approaches have been formally adopted. In parallel, new 3Rs-relevant technologies and mechanistic approaches have increasingly contributed to hazard identification and risk assessment evolution. In this changing landscape, an EPAA meeting reviewed the challenges that different industry sectors face in the implementation of alternative methods following a science-driven approach. Although clear progress was acknowledged in animal testing reduction and refinement thanks to an integration of scientifically robust approaches, the following challenges were identified: i) further characterization of toxicity pathways; ii) development of assays covering current scientific gaps, iii) better characterization of links between in vitro readouts and outcome in the target species; iv) better definition of alternative method applicability domains, and v) appropriate implementation of the available approaches. For areas having regulatory adopted alternative methods (e.g., vaccine batch testing), harmonised acceptance across geographical regions was considered critical for broader application. Overall, the main constraints to the application of non-animal alternatives are the still existing gaps in scientific knowledge and technological limitations. The science-driven identification of most appropriate methods is key for furthering a multi-sectorial decrease in animal testing.JRC.F.3-Chemicals Safety and Alternative Method

Finding Synergies for 3Rs – Toxicokinetics and Read-Across: Report from an EPAA Partners’ Forum

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners’ Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. An important hurdle to PBK modelling is a lack of toxicokinetic data. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetic parameters required for read-across; case studies exemplifying how toxicokinetics data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools; and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to create a database of toxicokinetic tools that assist risk assessment.JRC.F.3-Chemicals Safety and Alternative Method