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.

It is not clear what kind of preferences parents in China would have for vaccines that could be added to a future immunization schedule. This study\'s aim was to assess Chinese parents\' preferences for attributes of vaccines. We surveyed parents of young infants ≤3 months of age at immunization clinics in Shanghai, China, in 2017. We used a discrete choice experiment (DCE) to present parents with choices between two hypothetical profiles of vaccines which were described using the following attributes: cost, risk of side effect, location of vaccine manufacturer, vaccine testing, vaccine effectiveness, severity of disease, disease prevalence. A logistic regression output estimates of preference utilities. In total, 599 caregivers completed the DCE. Parents expressed lower preference for vaccines with a 30% chance of fever as an adverse event vs a 10% chance (OR: 0.53, 95% CI: 0.44, 0.64), for vaccines only 85% effective vs those 95% effective (OR: 0.55, 95% CI: 0.48, 0.62), and for imported vaccines (OR: 0.74, 95% CI: 0.60, 0.92) and those not tested in Chinese children (OR: 0.45, 95% CI: 0.37, 0.53) compared to domestic vaccines. More affluent groups preferred more expensive vaccines whereas less affluent groups did not express cost-based preferences. Promotion of vaccines in China should focus on parents\' stated preferences, which include past testing done in Chinese children - which is, in fact, required of all licensed vaccines in China. Information about these trials could emphasize low risk of adverse events and high effectiveness.

The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi\'s current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices.