Antibodies are powerful research reagents and are widely used in labs. They are essential to biomedical research, diagnostics and drug development. However, millions of animals are used globally each year to produce immunisation-dependent reagents (polyclonal and monoclonal), despite longstanding concerns regarding their specificity, reproducibility, cross-reactivity and batch variability.

The UK Government, through the Replacing Animals in Science strategy, has set a goal to stop the production of polyclonal antibody reagents using animals by 2030. While this is an important step toward reducing animal use in science, the issue is broader than polyclonal antibodies alone, because other types of antibodies (e.g. monoclonal and recombinant antibodies) can still depend on the immunisation of animals for their development and production.

Why the review is important

A paper in ATLA looked at whether current UK systems are adequate to make sure the 2030 goal leads to actual replacement of animal use, rather than simply shifting animal-based antibody production into other categories or countries. In their paper, Gray and Gough reviewed Non-Technical Summaries (which are the only publicly available source of information on licensed animal research projects) in UK project licence applications to assess how researchers explain and justify antibody production, and whether they show that non-animal alternatives have been properly searched for and considered. The study also examined the UK Home Office Annual Statistics of Scientific Procedures on Living Animals to see whether antibody-related animal use could be accurately tracked.

Gray and Gough found limited implementation of the Animals in Science Committee replacement guidance, which states that “applicants should provide a meaningful discussion of the purported scientific limitations of the animal-free methods in terms of how they relate to the objectives of the study. There should also be a robust justification of why other methods cannot be used to provide the results required, and evidence of communication with specialist providers of animal-free antibodies in order to confirm that the antibodies they seek are not available and cannot be produced using a non-animal approach”. Most licence applications did not provide a structured, evidence-based assessment of possible non-animal alternatives, evidence of the use of validated in vitro discovery platforms or strong justification for animal immunisation.

In addition, current reporting in the UK annual statistics does not provide enough detail to show exactly how many animals are being used for antibody production, especially when this work is included as part of wider commercial, basic research or translational research projects.

What should be done

Their findings indicate that, despite the UK Government’s commitment, practical, regulatory, and infrastructural reforms are not yet in place to ensure a significant reduction in animal use. In addition, the full scale or distribution of antibody reagent production procedures across different areas (i.e. research, regulatory and commercial) is not explicitly captured in the official government statistics.

Overall, their work suggests that without complementary measures addressing all immunisation-dependent antibody reagents and capacity to produce non-animal reagents, ending polyclonal production alone is unlikely to deliver the intended overall reduction in animal use. In fact, the authors highlight a few points to consider alongside possible mitigation strategies:

• If advanced non-animal antibody production methods are not readily available in the UK, researchers may outsource polyclonal antibody production to overseas facilities (with, arguably, potentially weaker welfare and transparency standards although we think that may be a bit of a straw man argument). As a result, animal use would be shifted abroad rather than eliminated, while also making it harder to monitor practices such as immunisation procedures, adjuvant use and quality control.
• If polyclonal antibody production is phased out, it could lead to increased use of other antibody formats (such as monoclonal or recombinant antibodies) that still depend on animal immunisation. Without prioritising non-animal alternatives, this shift may simply substitute one form of animal use for another, resulting in little or no overall reduction in animal use.
• Antibody production may be underreported when grouped in other broader categories for statistical and licensing purposes. This emphasises the need for consistent reporting systems that capture all immunisation-dependent antibody reagent generation, regardless of whether it is for routine production or as part of other research activities.
• The anticipated impact of increased use of non-immunisation-dependent affinity reagents will only be realised if academic and commercial antibody producers have access to well-characterised in vitro discovery platforms (i.e. without prohibitive intellectual property restrictions or excessive costs). Achieving this will require increased funding, investment, training and capacity. Without such measures, reliance on immunisation-dependent reagents is likely to continue.

The paper points out that:

“The 2030 commitment therefore creates both an opportunity and an imperative: to invest in robust non-animal infrastructure and to strengthen governance mechanisms, including those guiding service-provider workflows, to ensure that evidence-based justification is applied to any remaining immunisation-dependent antibody reagent generation. Importantly, because project licences are authorised for a five-year duration, any new authorisations permitting polyclonal immunisation beyond 2025 will extend past the 2030 deadline. If the UK is to meet its stated commitment, a transition away from polyclonal immunisation must therefore begin immediately, with revised licence expectations and shorter authorisation periods.”

What can be done?

They conclude with recommendations for a coordinated response, including:

• The adoption of consistent definitions that distinguish ‘immunisation-dependent’ from ‘non-immunisation-dependent’ in vitro This would avoid the current situation, in which terminology is being used inconsistently across scientific, commercial and policy areas.
• Clear, practicable expectations for Three Rs-aligned licence applications, to make sure existing guidance is reflected in practice.
• Improved statistical reporting to make antibody production clear regardless of the purpose.
• Targeted investment in, and wider access to, non-animal discovery infrastructure in both academic and commercial settings, to transition away from immunisation-dependent production.

The authors remark that the 2030 commitment will only deliver genuine reductions in animal use if it is supported by these measures (i.e. clearer definitions, better national reporting, stronger licensing expectations and wider access to non-animal antibody discovery technologies). Without these changes, animal use could continue in less visible ways, such as through other antibody formats or outsourcing, rather than being truly replaced.

This paper Replacing immunisation-dependent antibody reagent production: Challenges under the UK Replacing Animals in Science 2025 strategy is part of the Virtual Special Collection on Animal Friendly Affinity Reagents.

We are accepting new submissions for this collection.

If you have a paper you think may be a good fit please get in touch at rita@replacinganimalresearch.org.uk.