3R - A Global Approach with Implications for the Pharmaceutical Industry

Background

On Monday, July 7, the National Institutes of Health (NIH) announced at an NIH and FDA workshop on reducing animal testing, that the biomedical agency will no longer award grants for new funding applications that rely exclusively on animal testing. Dr. Nicole Kleinstreuer, Acting NIH Deputy Director for Program Coordination, Planning, and Strategic Initiatives, is quoted in the press as saying: “I'm delighted to announce today that all new NIH funding opportunities moving forward should incorporate language on consideration of NAMS. NIH will no longer seek proposals exclusively for animal models.”
This statement is also in line with the FDA's announcement of the gradual abolition of mandatory animal testing for monoclonal antibodies and other drugs.This current development is also evident worldwide, as shown in the following overview:

The principle behind it

The 3R principle – replacement, reduction, and refinement – was formulated by Russell and Burch in 1959. Today, it forms the ethical and scientific basis for the responsible use of animal testing. Governments, scientific institutions, industries, and animal welfare organizations around the world are committed to implementing these principles.

1. International organizations and frameworks

OECD (Organization for Economic Cooperation and Development)

• Develops and validates standardized test methods for chemicals.
• Promotes the recognition of alternative methods that do not involve animal testing in test guidelines (e.g., OECD TG 431 for skin corrosion without animal testing).

EU (European Union)

• Directive 2010/63/EU strictly regulates animal testing and requires the use of alternative methods when available.
• EURL ECVAM (European Reference Laboratory) coordinates the validation of alternative methods.
• Funding through the EU research framework program Horizon Europe (e.g., projects such as ToxRisk, PARC).

ICCVAM (USA) & NICEATM

• The Interagency Coordinating Committee on the Validation of Alternative Methods coordinates US activities for the validation of animal-free methods.
• Cooperation with OECD and international partners.

WHO & ICH

• WHO promotes animal-free vaccine testing (e.g., consistency-based batch release).
• The International Council for Harmonisation (ICH) integrates 3Rs into regulatory guidelines for human medicines.

2. Regional and national initiatives

Germany

• BfR and ZEBET promote alternative methods and their recognition.
• 3R centers at universities (e.g., Charité 3R, CAAT-Europe).
• Greater integration of 3Rs into funding programs (e.g., through the BMBF).

United Kingdom

• Leading the way with the NC3Rs (National Centre for the Replacement, Refinement & Reduction of Animals in Research).
• Close cooperation with industry, universities, and regulatory authorities.

USA

• In addition to ICCVAM, the FDA and EPA are also active in integrating alternative methods.
• Programs such as Tox21 and ToxCast use high-throughput methods and computer models.
• The NIH has announced that it will no longer fund pure animal testing arrangements.

China, Japan, South Korea

• Growing acceptance of alternative methods in regulatory processes.
• Expansion of validation centers and international cooperation with the OECD and EU.

3. Method development and technological advances

In the US in particular, the use of alternative technologies and methods has been given a name that is becoming increasingly common: NAMS (New Approach Methodologies). This refers to:

• In vitro models, e.g., 3D cell cultures, organ-on-a-chip, human stem cell models.
• In silico models, e.g., computer-aided predictions of toxicity and efficacy (QSAR, machine learning).
• Combination of databases, AI, and simulation models.
• Ex vivo approaches, e.g., use of human tissue samples (e.g., skin, liver).

All of these reduce the need for animal models in certain test areas, including pharmaceuticals, whether it be endotoxin and pyrogen testing, toxicity testing, and much more.

Conclusion

Global activities related to the 3Rs principles show significant progress in reducing animal testing. Nevertheless, further investment in research, education, regulatory recognition, and international cooperation is necessary to replace animal testing with reliable alternatives in the long term. The development of innovative technologies and political pressure toward ethical research provide a solid foundation for this.

Relevant topics such as alternative testing methods for microbiological testing, potency assays, and recombinant factors will be discussed in detail at PharmaLab 2025 on November 24-26 in Neuss.