Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities

Abstract

Transition to in vitro alternative methods to in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure that vaccines of ever higher quality can reach the populations in need in the shortest possible timeframe. Advancements in the field, case studies, and experiences from Low and Middle Income Countries (LMIC) were the topics discussed by an international gathering of experts during a recent conference titled “ Animal Testing for Vaccines – Implementing Replacement, Reduction and Refinement: Challenges and Priorities ”. This conference was organized by the International Alliance for Biological Standardization (IABS), and held in Bangkok, Thailand on December 3 and 4 2019. Participants comprised stakeholders from many parts of the world, including vaccine developers, manufacturers and regulators from Asia, Europe, North America, Australia and New Zealand. In interactive workshops and vibrant panel discussions, the attendees worked together to identify the remaining barriers to validation, acceptance and implementation of alternative methods, and how harmonization could be promoted, especially for LMICs.

What Kinds of Dogs Are Used in Clinical and Experimental Research?

“…Attempts have been made to replace laboratory animals by in vitro and in silico methods [ 1 , 60 , 61 , 62 ]. For laboratory animals in most countries, the consideration and implementation of replacement, refinement, and reduction (3Rs) strategies, proposed by Russell and Burch in 1959, is mandatory [ 63 ]. For some purposes, animal testing has been forbidden by some authorities.…”

In Vitro Characterization of the Innate Immune Pathways Engaged by Live and Inactivated Tick-Borne Encephalitis Virus

“…I-TBEV, the antigen-containing fraction of the Encepur vaccine, consists of whole, formalin-inactivated TBEV in a 42% sucrose solution and thus contains virions including structural proteins and viral genomes. To produce non-conforming batches, a strategy that reduces binding by TBEV-specific antibodies [ 18 ] was followed: I-TBEV was heat-treated at 42 °C for 4 weeks in glass vials (HT I-TBEV). A 42% low-endotoxin sucrose (Sigma-Aldrich, St. Louis, MO, USA) solution in DMEM medium (Gibco, Life Technologies; Paisley, UK) was used as control (matrix), as per indications of GSK.…”

Overcoming scientific barriers in the transition fromin vivoto non-animal batch testing of human and veterinary vaccines

“…However, additional quality attributes including vaccine composition, the spatial organization of the antigen, or the presence of additional immunostimulatory molecules may be critical for specific vaccines. Importantly, it is increasingly recognized that oneto-one replacement of an in vivo test for an in vitro test will be difficult and that a combination of assays to demonstrate batch-to-batch consistency may be needed for some vaccines [11,79].…”

“…After incorporation, the methods still need to be implemented by individual manufacturers and OMCLs, which have to conduct assay validation before the conventional animal-based test can be fully replaced and eventually eliminated from pharmacopoeias. Engagement between academia, industry and regulators at an early stage of the development of in vitro alternatives is essential for getting all stakeholders acquainted with new methods, to facilitate validation studies and to achieve wide implementation of the in vitro alternatives [15,18,79].…”