The principle of Replacement, Reduction and Refinement of animal testing in the development of medicines (known as the 3Rs) refers to the replacement of animal studies with non-animal methods, the reduction of animal studies, and the refinement of any necessary tests through minimisation of stress of study animals (as illustrated in the graphic below). Under European law, all EU Member States must ensure that the 3Rs are systematically considered whenever animals are used for scientific purposes, including research, regulatory testing and production, education and training (see Directive 2010/63/EC on the protection of animals used for scientific purposes). On 26 February 2018, the European Medicines Agency (EMA) issued a Report summarising its activities during 2016 and 2017 in relation to the 3Rs in the regulatory testing of medicinal products.
Fig 1: 3Rs taken from EMA Report
The EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) and Committee for Medicinal Products for Human Use (CHMP) jointly operate a Working Group established for this purpose. During the reporting period, the Working Group has:
- reviewed animal tests included in product release specifications for centrally authorised veterinary vaccines and human vaccines/biologicals to ensure best practice in 3Rs is applied to the methodology for conducting any in vivo tests;
- identified opportunities for improving compliance with best practice in 3Rs and notified the relevant marketing authorisation holders accordingly (this has led to changes in practices, as one such notification resulted in the submission of a variation to amend a batch potency assay for a veterinary vaccine); and
- consulted with stakeholders on 3Rs guidance and provided expert input on 3Rs regulatory issues associated with medicinal products.
In addition to the activities above, the Working Group has prepared a number of guidance documents to promote the 3Rs. Documents prepared during the reporting period include:
- Guideline on the principles of regulatory acceptance of 3Rs testing approaches (December 2016)
- Draft reflection papers providing an overview of the current regulatory testing requirements for medicinal products for human and veterinary use and opportunities for implementation of the 3Rs (final reflection papers are scheduled for publication in Q1 2018)
- Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs (November 2017)
- CVMP position statement on the ethical use of animals in the development, manufacture and testing of veterinary medicines, which clarifies that veterinary medicines developed, manufactured and tested in third countries must conform to EU ethical and animal welfare standards when intended for supply in the EEA (December 2017)
- Draft report on the CHMP/CVMP review and update of EMA guidelines to implement best practice with regard to 3Rs in regulatory testing of medicinal products (final report is scheduled for publication in Q1 2018).
The CVMP/CHMP Working Group plans to issue a report on its activities relating to the 3Rs every two years. Its objectives for the next reporting period are largely unchanged from those of 2016/17. While the challenges associated with Brexit and the EMA’s move to Amsterdam mean that the EMA’s focus will be on core-business activities during the period of transition, the Report confirms that “the 3Rs will continue to be addressed”.