The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is reviewing World Health Organization (WHO) manuals, guidelines and recommendations for vaccines and biotherapeutics to identify the extent to which animal-based testing methods are described. The aim is to recommend where updates to these documents can lead to an increased and more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction and Refinement of animal tests) in the quality control and batch release testing requirements for vaccines and biotherapeutics. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing. Developing recommendations that are widely applicable by both the manufacturers and national regulatory authorities for vaccines and biological therapeutics globally requires a detailed understanding of how different organisations view the opportunities and barriers to better integration of the 3Rs. To facilitate this, we developed and distributed a survey aimed at individuals who work for national regulatory authorities (NRAs) and/or national control laboratories (NCLs). In this paper, we present the key findings from this survey and how these will help inform the recommendations for wider integration of 3Rs approaches by WHO in their guidance documents applicable to the quality control and batch release testing of vaccines and biotherapeutics.

Substandard or spurious drugs are a global problem with respect to Health and Economic burden. The impact is higher when medicines are from the category of life-saving drugs, essential medicines or high cost targeted medical treatment. Biopharmaceuticals are one such class of drugs where Quality testing plays a pivotal role to stop substandard drugs from reaching the patient. This study of 17,451 samples has highlighted the trend of occurrence of substandard biologicals (2.34%) over a decade (2011-2021) and the importance of continuous and complete evaluation of such Biopharmaceuticals. More such National Control Laboratories (NCL) should be involved in cross-checking the quality of the increasing number of biopharmaceuticals present in the market which are released only on the basis of the onsite inspection and dossier reviews. This will help the Regulators to ensure the readiness for testing the newer biologicals, devise effective policies for better health care initiatives and keep the substandard biopharmaceuticals at bay.