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

Abstract

Introduction: Before release, vaccine batches are assessed for quality to evaluate whether they meet the product specifications. Vaccine batch tests, in particular of inactivated and toxoid vaccines, still largely rely on in vivo methods. Improved vaccine production processes, ethical concerns, and suboptimal performance of some in vivo tests have led to the development of in vitro alternatives.Areas covered: This review describes the scientific constraints that need to be overcome for replacement of in vivo batch tests, as well as potential solutions. Topics include the critical quality attributes of vaccines that require testing, the use of cell-based assays to mimic aspects of in vivo vaccine-induced immune responses, how difficulties with testing adjuvanted vaccines in vitro can be overcome, the use of altered batches to validate new in vitro test methods, and how cooperation between different stakeholders is key to moving the transition forward. Expert opinion: For safety testing, many in vitro alternatives are already available or at an advanced level of development. For potency testing, in vitro alternatives largely comprise immunochemical methods that assess several, but not all critical vaccine properties. One-to-one replacement by in vitro alternatives is not always possible and a combination of methods may be required.

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Responses from a survey of vaccines and biological therapeutics manufacturers

“…It is also important to highlight that for quality control and batch release purposes, NATs are considered superior to animal tests due to improved specificity and improved precision which makes them less variable and better suited for the purposes of batch-to-batch QC testing. These non-animal methods also bring additional advantages in terms of reduced duration for testing (which is an important factor in ensuring supply of medicines) and reduced cost [ 14 , 15 ]. For example an animal vaccine potency test may require weeks to months after administration to determine the potency and involve animal care and laboratory staff whereas a suitable NAT to confirm the vaccine antigen content and quality may take just days to conduct by a single individual.…”

Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals: Responses from a survey of National Control Laboratories and National Regulatory Authorities

“…It is widely acknowledged that for quality control and batch release purposes, NATs are considered superior to animal tests due to improved specificity and precision. These NATs have the additional advantage of reducing costs and duration of testing [ 13 , 14 ]. In addition to the robust scientific argument to transition away from animal testing paradigms there are also ethical and animal welfare concerns as the methods themselves can cause significant pain and distress to the animals [ [15] , [16] , [17] , [18] ].…”

Potency Testing of Whole-Cell Pertussis Containing Vaccines: Lesson Learned in a Multi-Laboratory Assessment of the Pertussis Serological Potency Test

“…The use of vaccine batches of sub-standard quality, i.e. decreased potency, is a must in assessing the suitability of a new method [30]. In this specific case, the level of decrease in MPT potency, after a mild heat treatment [26] was not expected to be consistent among the various vaccines, due to intrinsic differences in heat-lability among manufacturer's products and potential laboratory specific differences in the execution of the intra-laboratory alteration procedure.…”