The project platform (PP) unites the former EPAA platform on science (PoS) and platform on 3Rs in regulation (PoR). Under its supervision, EPAA partners & associates work on prioritising, promoting and implementing all the research based on the application of the 3Rs. They also work to improve the validation, acceptance and implementation of 3R alternatives, in European regulatory testing and decision making.
The project platform (PP) supervises and assesses the projects agreed upon by the EPAA. It provides valuable input for EPAA partners & associates’ work on prioritising, promoting and implementing research based on the application of the 3Rs. The platform also works to improve the validation, acceptance and implementation of 3R alternatives in European regulatory testing and decision making.
The PP identifies optimised approaches on testing and risk assessment strategies, in existing and upcoming legislation. It also optimises their implementation to avoid redundant or unnecessary testing. In this respect, the EPAA strives to share experience and evaluate consistency across all 7 EPAA sectors. It also analyses key issues and identifies policy drivers for testing.
The project platform is the link between the EPAA steering committee (SC) and the EPAA project teams. The key role of PP is to supervise the projects, by
The Commission and industry partners jointly lead the project platform. Representatives of both parties were appointed as co-chairs, with Gianni Dal Negro (GSK) for industry partners and Dr Susanne Belz (Directorate-General Joint Research Centre) for the European Commission. PP members meet quarterly, usually 15 days before the steering committee meetings, to discuss and report on respective projects and prepare SC meetings.
The EPAA partners promote better science and facilitate regulatory acceptance of alternatives. In doing so, they currently focus on 8 projects. These address different end-points and reach out to various sectors. The project platform manages all projects.
In the production of biological products, manufacturers are required to confirm potency and safety of each batch of product. This may involve the use of laboratory animals.
Directive 2010/63/EU prohibits manufacturers in the EU from using an animal test method, if an alternative, non-animal method is recognised by the European pharmacopoeia.
However, if alternatives are not internationally harmonised and accepted in other regions then excessive or unnecessary animal testing may be undertaken by manufacturers, in order to gain access to other, non-EU markets.
The biologicals project run by the EPAA aims to achieve global harmonisation in batch testing requirements for human and veterinary vaccines, as well as other biologicals. It is hoped the project will lead to better incorporation of the 3Rs in potency and safety testing strategies. Project deliverables include
European Medicines Agency, European Commission, pharmaceutical industry, animal health industry, Council of Europe - European Directorate for the Quality of Medicines and Healthcare (EDQM)
Increasing adoption of non-animal integrated testing strategies.
Skin sensitisation is an important endpoint in safety evaluation that must be assessed for chemicals under the current chemical legislation in Europe (REACH: 1907/2006). Other legislation including the EU Cosmetics Regulation (1223/2009), also require assessments of skin sensitisation potential. Furthermore, since March 2013 animal testing for this purpose for products marketed in Europe is prohibited.
3Rs added value and EPAA actions
Performing tests on humans instead of animal tests for the generation of primary skin sensitisation data without a good knowledge of sensitisation potential is considered unethical due to the risk of volunteers becoming sensitised. For reasons of good animal welfare and the animal testing ban imposed by the cosmetics regulation, substantial efforts continue to be made in the development of non-animal (alternative) methods. This change to in vitro alternatives has been enabled by a growing knowledge of the mechanisms underlying this human health effect, which led to the development of an adverse outcome pathway (AOP).
Furthermore, the combined use of a number of non-animal methods in integrated testing strategies (ITS) has been identified as much more reliable than a single in vitro method. Key questions now include
The EPAA project on skin sensitisation alternatives is addressing these questions by bringing together stakeholders from European and national regulators, and a wide range of industry stakeholders from various sectors (chemicals, cosmetics, fragrances, etc.). The EPAA has been collaborating with Cefic LRI and Cosmetics Europe to ensure optimal cross-fertilisation across sectors.
Information on this will be available shortly
The aim of this project is to identify opportunities for improving the science behind the regulatory testing of medicines and chemicals through the application of the 3Rs. Among the seven sectors involved primarily in this project are those concerned with the development of human medicines, veterinary medicines, and crop protection products.
The project team initially conducted a survey of regulatory requirements in the various sectors and then sent a questionnaire to the relevant EPAA member associations (EFPIA, IFAH-Europe and ECPA).
Respondents were asked for more detailed information on
The questionnaire was distributed to the member companies of the aforementioned organisations and the results were collated and analysed by the project team.
It was clear that there is a considerable divergence in practice within sectors, between sectors and between geographical areas, despite the existence of international harmonisation bodies such as ICH and VICH.
Moreover, the differing practice was as likely to be a result of tradition than the application of science.Following these discussions, the Project Team selected the area of carcinogenicity testing as one that offered great potential for the project. Therefore, all sectors need to consider the carcinogenic potential of their products. Sector practice is quite divergent, the scientific value of some study designs is currently being questioned and the introduction of in vitro methods offers the possibility of a more targeted and progressive approach to animal testing.
Since late 2008, the EPAA has been exploring the opportunities that stem cells could play in developing novel approaches for the potential hazard characterisation of chemicals and drugs
The risk assessment of chemicals and pharmaceuticals continues to rely on the use of in vivo assessments, although there is an international drive towards the replacement of animal testing with mechanistic, in vitro systems.
This new approach includes the in vitro measurement of concentration-response relationships to identify where prolonged or excessive perturbations of biochemical pathways are likely to cause adverse health effects.
The tool will be web based on a Peters’ model and freely available for downloading and independent use on desktops PC to ensure confidentiality of data.
A prototype was already developed in partnership with the British Health and Safety Laboratory (HSL). This project aims to develop a tool that is more tailored to industry needs. The first tasks to be undertaken included the building of the model and interface. These were completed as planned, within the allocate 6-month period.
UK Health and Safety Laboratory, GlaxoSmithKline, European Council of the Chemical Industry - Long-range initiative (CEFIC LRI), European Union Reference Laboratory - European Centre for Validation of Alternative Methods (EURL ECVAM), European Centre for Ecotoxicology and Toxicology of Chemicals (ECETC)
Information on this will be available shortly
The overall goal of this platform is to synchronise initiatives for 3R methods in safety and potency testing of vaccines in Europe.
This project aims to create a technical platform for human and veterinary vaccines. The platform
Vaccines require batch-specific quality control to ensure their quality, including safety and efficacy. Part of quality control, particularly for the final product, is based on animal tests required by legislation. Out of about 100 million animals that are used each year in laboratories throughout the world, 10 to 15 million animals are still being used for vaccine batch testing.
The vaccines consistency approach (VCA) for batch release is based on a thorough characterisation of the vaccine during manufacture, including formulation, using non-animal testing. The quality of subsequent batches is guaranteed by the strict application of quality systems and of consistent production of batches that are comparable to reference lots of known potency and safety.
The VCA is already used for recently registered vaccines, whereas many vaccines developed several decades ago, continue to rely on animal tests for confirming the quality of each batch.
Due to the potential of the VCA to significantly reduce the number of animal tests used in vaccines quality control, the EPAA initiated this project with the aim to provide a framework for resolving remaining scientific and technical issues and for fostering the regulatory adoption of VCA as a non-animal approach for quality control of established (conventional) vaccines.
The European Commission, industry (European vaccines manufacturers), European Medicines Agency (EMA), national regulators, OMCLs (Official Medicines Control Laboratory), EDQM (European Directorate for the Quality of Medicines and HealthCare), international regulators (observers from the US, Canada and India) and academia.
The project activities were organised by a project committee (PC) chaired by the coordinator (Ian Ragan, consultant to EPAA) in consultation with a technical committee (TC) composed of experts from vaccine manufacturers, EDQM, EURL ECVAM, OMCLs and regulatory authorities for both human and veterinary vaccines. The TC was chaired by Coenraad Hendriksen, academic member of the PC.
At the technical committee meeting on 30 September 2011, 4 priority vaccines were identified and progressed further by expert working groups: DTaP, human rabies, veterinary rabies, and clostridial vaccines.
January 2010: Workshop jointly organised by EPAA and EURL ECVAM in Brussels discussed the VCA and its potential to reduce the number of animal tests used in quality control of human and veterinary vaccines (De Mattia et al 2011, The consistency approach for quality control of vaccines: A strategy to improve quality control and implement 3Rs, Biologicals 39, p 59-65). As a follow-up, in late 2010 the EPAA agreed to initiate a VCA project.
7 April 2011: Kick-off meeting - Application of the 3Rs and the consistency approach for improved vaccine quality control, flash report (265 KB)
Milestones of the specific working groups
This workstream aims at replacing the current in vivo immunisation challenge test for batch release (the NIH test) by in vitro tests based on antigen quantification (ELISA).
This work stream aims at replacing in-process controls which use testing on animals, with cell-culture-based assays that have been developed by MSD animal health with support by the NC3Rs. The application of the consistency approach is feasible for clostridial vaccines but in vitro tests remain to be developed for some important strains.
The final aim is to introduce alternative methods into the Ph. Eur. relevant monograph(s).
The technical committee, where the Commission provided visibility and all parties committed to alternatives shared scientific know-how, has
The EPAA has
The EPAA partners would like to thank the members of the technical committee and project committee for their valuable contributions to the project.