Animal testing
Animal testing has long played an important role in the development of biological products, including biotherapeutics and vaccines, by providing critical information on mechanisms of action, safety, and efficacy. In certain cases, animal testing has continued to be used post-approval to monitor product quality and safety as part of manufacturers’ quality control processes and the lot release procedures of national control laboratories. However, the inherent variability and time-consuming nature of animal-based methods for quality control can delay the availability of life-saving products. Increasing recognition that appropriately designed in vitro tests are better suited for routine quality control of biological products has driven a shift toward alternative quality control strategies.
WHO Recommendations, Guidelines, and other guidance documents establish global norms and standards for the production, quality control, and nonclinical and clinical evaluation of biological products. These norms support countries in ensuring the quality, safety, and efficacy of biological products worldwide. WHO acknowledges the scientific limitations of many animal assays that remain in some published guidance, particularly regarding their use in post-approval quality control. As a result, WHO strongly encourages developers, manufacturers, and regulators to replace or remove animal-based quality control methods whenever scientifically justified.
This position has been reflected in both product-specific and general WHO guidance, including the WHO Guidelines on the nonclinical evaluation of vaccines and the Guidelines for independent lot release of vaccines by regulatory authorities. In 2018, the WHO Expert Committee on Biological Standardization and the Expert Committee on Specifications for Pharmaceutical Products agreed to discontinue the innocuity test in WHO Recommendations for vaccines and biological products and to remove it from the International Pharmacopoeia. More recently, in 2025, the WHO Expert Committee on Biological Standardization, at its eighty-first meeting, adopted the Guidelines on the replacement or removal of animal tests for the quality control of biological products.
These Guidelines provide guidance to biological product developers, manufacturers, and regulators on scientific and regulatory considerations related to replacing or removing animal tests used in quality control. They also include specific recommendations covering adventitious agent testing, pyrogenicity and endotoxin testing, neurovirulence testing, potency testing, specific toxicity testing, and innocuity testing. This guidance should be considered as superseding corresponding quality control recommendations in WHO Recommendations, Guidelines, and other guidance documents on biological products published prior to 2025. Product developers, manufacturers, and other stakeholders are encouraged not to wait for updates to earlier WHO documents, but instead to develop, validate, and implement non-animal-based in vitro approaches for quality control wherever possible, in close consultation with and subject to approval by the national regulatory authority (NRA).