Review of animal use requirements in WHO biologics guidelines

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 are working with the WHO, with funding from 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 biologicals 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 biologicals 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. 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 project was approved by the WHO Expert Committee on Biological Standardization (ECBS) which provides guidance to WHO on matters relating to biologicals development and testing, in October 2019: 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 ECBS for their approval and implementation.

We are hosting a series of regional workshops to better understand the potential impact that wider integration of 3Rs approaches within WHO guidelines would have on biologicals manufacturers and regulators globally. The output from these workshops will inform the recommendations we make to WHO, reduce the barriers for their implementation by ECBS and expedite their uptake by biologicals manufacturers and regulators.

We have surveyed the global biologicals manufacturing and regulatory communities to determine how extensively 3Rs approaches are already implemented in quality control, batch and lot release testing of biologicals and explore any barriers to their wider uptake. The responses to these surveys, together with the output from the regional workshops, will be used to inform the recommendations we make to WHO.

The surveys are now closed and the responses are being analysed for publication.

• Poster presented at the 11th World Congress on Alternatives and Animal Use in the Life Sciences: Review of animal testing requirements in WHO guidelines and recommendations for biologics: a proposal to implement 3Rs principles.
• Lilley E et al.(2021)Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals Biologicals 74: 24-27.doi.org/10.1016/j.biologicals.2021.10.002