Ethical use of animals in medicine testing

This content applies to human and veterinary medicines

The European Medicines Agency (EMA) supports the implementation of the so-called 3Rs principles - replace, reduce and refine - for the ethical use of animals in medicine testing across the European Union (EU). These principles encourage alternatives to the use of animals in the testing of medicines while safeguarding scientific quality and improving animal welfare where the use of animals cannot be avoided.

Directive 2010/63/EU requires marketing authorisation holders to integrate the 3Rs and welfare standards for the treatment of animals in all aspects of the development, manufacture and testing of medicines.

The Directive aims to protect animals in scientific research, with the final aim of replacing all animal research with non-animal methods.

The 3Rs stand for:

• replacing the use of animals with non-animal methods where possible;
• reducing the number of animals used to a minimum while still obtaining scientifically valid results;
• refining practices to minimise the stress and improve the welfare of study animals used for regulatory purposes.

EMA supports the implementation of Directive 2010/63/EU and the 3Rs principles in the EU, by:

• identifying how they can be implemented in regulatory testing;
• developing guidance for medicine developers and manufacturers;
• providing information and advice to stakeholders;
• providing recommendations on 3Rs methods in the European Pharmacopoeia to help marketing authorisation holders comply with new or revised measures;
• carrying out a scientific review of batch release tests for human and veterinary vaccines and biologicals to ensure alignment with best practice in 3Rs;
• contributing to the development of harmonised guidance and requirements in Europe and globally, by working closely with relevant European and international bodies, such as the:
  • European Directorate for the Quality of Medicines and HealthCare (EDQM);
  • European Union Reference Laboratory for alternatives to animal testing (EURL-ECVAM);
  • International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH);
  • International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH).

EMA has a dedicated Joint CVMP/CHMP 3Rs Working Group (J3RsWG), which provides advice to its scientific committees on all matters concerning the use of animals in regulatory testing of medicines.

For more information, see:

• EMA position on the application of the 3Rs in the regulatory testing of human and veterinary medicinal products

EMA has published a report summarising actions carried out by its committees in 2016 and 2017 to support the implementation of the 3Rs principles.

EMA intends to publish a report on this topic every two years.

EMA develops scientific guidelines to help medicine developers comply with Directive 2010/63/EU in integrating the 3Rs and welfare standards for the treatment of animals in the testing of medicines:

• Overview of the current regulatory testing requirements for medicinal products for human use and opportunities for implementation of the 3Rs
• Overview of the current regulatory testing requirements for veterinary medicinal products and opportunities for implementation of the 3Rs
• Guideline on regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches
• Guidance for individual laboratories for transfer of quality control methods validated in collaborative trials with a view to implementing 3Rs

EMA's Joint CVMP/CHMP 3Rs Working Group also conducted a review of all EMA guidelines to ensure that they do not make reference to animal tests that are no longer considered appropriate. For more information and the guidelines that EMA has or will update as a result, see:

• Review and update of EMA guidelines to implement best practice with regard to 3Rs (replacement, reduction and refinement) in regulatory testing of medicinal products – report on actions taken

Wherever the manufacture or batch testing of veterinary medicines to be marketed in the European Economic Area (EEA) takes place, they must conform to EU ethical and animal welfare standards.

For more information, see:

• CVMP position on the ethical use of animals in the testing, development and manufacture of veterinary medicines

In the table below, EMA provides recommendations on 3Rs methods in the European Pharmacopoeia to help marketing authorisation holders comply with new or revised measures.

Document	Applies to
Recommendation highlighting the need to ensure compliance with 3R methods described in the European Pharmacopoeia	All medicinal products
Recommendation highlighting recent measures in the human field to promote 3Rs measures described in the European Pharmacopoeia	Human vaccines
Recommendation highlighting recent updates for the 3Rs methods described in the European Pharmacopoeia applicable to human vaccines against hepatitis A	Human vaccines against hepatitis A
Recommendation highlighting recent measures in the veterinary field to promote 3Rs measures described in the European Pharmacopoeia	Veterinary vaccines
Recommendation for veterinary vaccines, highlighting the need to update marketing authorisations to remove the target animal batch safety test (TABST) following removal of the requirement from the European Pharmacopoeia monographs	Veterinary vaccines