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.

New approach methodologies (NAMs) refer to non-animal methods which may be incorporated in the assessment of the safety and efficacy of new medicines to replace or reduce animal use. Examples include in vitro (cell-based) systems and computer modelling.

These methods represent potential alternatives to animal testing in the non-clinical development phase of new medicines. Their use should be carefully considered.

Where animal testing is still needed, researchers should design and conduct such studies in line with the 3Rs principles.

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

• identifying how the 3Rs can be implemented in regulatory testing;
• developing scientific guidelines for medicine developers and manufacturers;
• providing developers a forum for early dialogue via its Innovation Task Force (ITF) to discuss the regulatory acceptance of so-called new approach methodologies to replace the use of animals in in the testing of medicines;
• 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).

Working parties and other groups

EMA has a dedicated 3Rs Working Party (3RsWP), which provides advice to its scientific committees on all matters concerning the use of animals in regulatory testing of medicines.

In addition, EMA's Non-Clinical and New Approach Methodologies European Specialised Expert Community provides a forum for information-sharing between regulatory and academic experts on innovative non-clinical testing methods. These include new approach methodologies.

Long-standing commitment

The Joint Expert Group (JEG3Rs) and the 3Rs Working Group (3RsWG) preceded the establishment of the 3Rs Working Party, demonstrating EMA's long-standing commitment to the 3Rs.

For more information, see:

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

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

EMA will resume its reporting on 3Rs activities in 2024. It will issue reports every two years.

This decision follows the establishment of the 3Rs Working Party in November 2022 and the end of business continuity measures in 2023. The latter ditacted the suspension or reduction of the activities of non-product-related working parties / groups.

EMA together with the support of its 3Rs Working Party (3RsWP) 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 regularly reviews and updates these guidelines to reflect developments in the field.

EMA 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

Recommendations on 3Rs in European Pharmacopeia

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

Veterinary medicine testing outside the EU

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