The consistency approach for quality control of vaccines - a strategy to improve quality control and implement 3Rs.

Current batch release testing of established vaccines emphasizes quality control of the final product and is often characterized by extensive use of animals. This report summarises the discussions of a joint ECVAM/EPAA workshop on the applicability of the consistency approach for routine release of human and veterinary vaccines and its potential to reduce animal use. The consistency approach is based upon thorough characterization of the vaccine during development and the principle that the quality of subsequent batches is the consequence of the strict application of a quality system and of a consistent production of batches. The concept of consistency of production is state-of-the-art for new-generation vaccines, where batch release is mainly based on non-animal methods. There is now the opportunity to introduce the approach into established vaccine production, where it has the potential to replace in vivo tests with non-animal tests designed to demonstrate batch quality while maintaining the highest quality standards. The report indicates how this approach may be further developed for application to established human and veterinary vaccines and emphasizes the continuing need for co-ordination and harmonization. It also gives recommendations for work to be undertaken in order to encourage acceptance and implementation of the consistency approach.

Non-animal replacement methods for human vaccine potency testing: state of the science and future directions.

NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This report addresses methods and strategies identified by workshop participants for replacement of animals used for potency testing of human vaccines. Vaccines considered to have the highest priority for future efforts were (1) vaccines for which antigen quantification methods are already developed but not validated, (2) vaccines/components that require the largest number of animals, (3) vaccines that require an in vivo challenge test, and (4) vaccines with in vivo tests that are highly variable and cause a significant number of invalid tests. Vaccine potency tests identified as the highest priorities for replacement were those for diphtheria and tetanus, pertussis (whole cell and acellular), rabies, anthrax, polio vaccine (inactivated) and complex combination vaccines based on DT or DTwP/aP. Research into understanding the precise mechanism of protection afforded by vaccines and the identification of clinically relevant immunological markers are needed to facilitate the successful implementation of in vitro testing alternatives. This report also identifies several priority human vaccines and associated research objectives that are necessary to successfully implement in vitro vaccine potency testing alternatives.

The consistency approach for the quality control of vaccines.

Current lot release testing of conventional vaccines emphasizes quality control of the final product and is characterized by its extensive use of laboratory animals. This report, which is based on the outcome of an ECVAM (European Centre for Validation of Alternative Methods, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra, Italy) workshop, discusses the concept of consistency testing as an alternative approach for lot release testing. The consistency approach for the routine release of vaccines is based upon the principle that the quality of vaccines is a consequence of a quality system and of consistent production of lots with similar characteristics to those lots that have been shown to be safe and effective in humans or the target species. The report indicates why and under which circumstances this approach can be applied, the role of the different stakeholders, and the need for international harmonization. It also gives recommendations for its implementation.