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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Office-led project

Review of animal use requirements in WHO biologics guidelines

At a glance

In progress
Current contacts

R

  • Replacement
Syringe removing liquid from vial

Project overview

Biologicals such as vaccines, cytokines, enzymes, and hormones are tested extensively post-licensure as part of routine quality control and batch release testing to ensure the safety and potency of products. The World Health Organization (WHO) is mandated to establish international standards for this purpose and as such their guidelines and recommendations carry significant influence, being adopted by most global regulatory authorities. However, a review of the animal testing requirements within these guidelines has never been conducted and there may be opportunities to adopt the latest non-animal technologies that are being missed as a result.

We have been tasked by the WHO and funded by the Bill & Melinda Gates Foundation to carry out an independent and comprehensive review of WHO guidelines for biologics to determine:

  1. Which animal tests are recommended for the batch release testing of biologics and vaccines.
     
  2. What 3Rs principles are already encouraged, what opportunities exist for better implementation of 3Rs principles and alternative test methods within those guidelines, and to make recommendations to WHO on how this could be best achieved.
     
  3. What barriers exist in different regions which may hinder the adoption of 3Rs approaches by manufacturers, national regulatory authorities, and control laboratories that are responsible for the testing and release of biologicals.

It has been estimated that more than 10 million animals a year are used worldwide in biologics development and that 80% of these animals are used for routine quality control and batch release tests of licensed products. The use of such a large number of animals puts a significant financial burden on manufacturers and national control laboratories, is time and resource intensive, and the methods themselves can cause significant pain and distress to the animals. 

The project was presented to WHO ECBS in October 2019 and was formally recognised and approved: WHO Technical Report Series. 2020; 1024: Section 2.2.2 (p8).

The project is being overseen by an expert international working group to support the review of the guidelines and develop the recommendations that will be submitted to the WHO Expert Committee on Biological Standardization (ECBS) for their approval and implementation.

Surveys

Help us understand the opportunities and barriers for implementing the 3Rs in quality control, batch and lot release testing of biologicals.

Are you a regulator or a scientist within a national regulatory authority or national control laboratory responsible for approving or testing of biological therapeutics?

If this is the case for you, please complete our survey to gather information on how the 3Rs are implemented in quality control, batch and lot release testing of biologicals. We would like to learn about the 3Rs impacts you have achieved, future opportunities for implementing the 3Rs and any barriers you have experienced that make such implementation challenging.

Your responses will be used to inform the recommendations we make to WHO’s Expert Committee on Biological Standardization (ECBS) on the wider integration of 3Rs approaches within their guidelines. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing and help support faster access to cheaper products by the global communities who need them most urgently.

The survey should take no more than 30 minutes to complete. It is now closed but we are accepting further responses until Friday 15 April.

This follows on from a previous survey directed towards biologicals manufacturers, This survey is now closed but we would be interested in additional responses. If you would like more information, please email elliot.lilley@nc3rs.org.uk.

Regional workshops

Implementing the 3Rs in WHO guidelines – understanding the impact on quality control and batch release testing of biologicals

We are hosting a series of regional workshops to better understand the potential impact of these changes on manufacturers and regulators globally. The output from these workshops will inform the recommendations we make to WHO and reduce the barriers for their implementation by ECBS.

Two workshops are currently scheduled for the following regions:

Additional workshops are being developed for Africa and Pan-America.

Working group members

Name Affiliation

Ian Ragan (Chair)

Independent consultant, UK

Cynthia Allen Health Canada

Dave Allen

Integrated Laboratory Systems, LLC

Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)

Uzma Alam African region consultant

Patricia Aprea

National Administration of Drugs, Foods and Medical Devices (ANMAT), Argentina

Cristina Barbirato

Merck, Italy

Martijn Bruysters

National Institute for Public Health and the Environment, The Netherlands

Gilles Chenard

Janssen Vaccines and Prevention, The Netherlands

Emmanuelle Coppens

Sanofi Pasteur

Wlamir Correa de Moura FIOCRUZ / INCQS
Pradip Das Biological E, India
Francis Galaway Medicines and Healthcare products Regulatory Agency, UK

Simeon Gill

Medicines and Healthcare products Regulatory Agency, UK

Sunil Goel

Serum Institute of India, India

Richard Isbrucker

World Health Organisation, Switzerland

Masaaki Iwaki

National Institute of Infectious Diseases (NIID); Japan

David Jones

Medicines and Healthcare products Regulatory Agency, UK

Carmen Jungbäck International Alliance for Biological Standardization, Switzerland
Mario Landys Finlay Vaccine Institute, Cuba

Robin Levis

US Food and Drug Administration, USA

Laurent Mallet European Directorate for the Quality of Medicines and Healthcare, France
Sylvie Morgeaux National Agency for the Safety of Medicines and Health Products, France
Zebun Nahar Incepta Vaccine Ltd, Bangladesh

Volker Oeppling

Paul Ehrlich Institut, Germany

Supaporn Phumiamorn

Institute of Bilogical Products, Ministry of Public Health, Thailand

Jean-Marie Preaud International Alliance for Biological Standardization, Switzerland
Mitsutoshi Senoh National Institute of Infectious Diseases, Japan
Shahjahan Shaid GSK Vaccines, Belgium
Sarah Sheridan Merck, UK
Dean Smith Health Canada
Yeowon Sohn Seoul National University, South Korea

Paul Stickings

National Institute for Biological Standards and Control, UK

Youchun Wang National Institutes for Food and Drug Control, China

Publications