Replacement, reduction and refinement alternatives to animal use in vaccine potency measurement

Abstract

Models to measure potency in vaccine research and development and preclinical testing are frequently based on an immunization-challenge procedure in laboratory animals. These models have proven to be very instrumental in scientifically underpinning the correlation of protection of selected vaccine antigens and their efficacy. In vivo models in vaccine research and development are, for the time being, irreplaceable, although significant progress has been made in using in vitro prescreening tests to evaluate particular immunological parameters. For a long time, in vivo potency tests have been similarly relevant for routine vaccine lot-release testing. The design of a potency test, defined in most pharmacopeias, relied on a direct or indirect-challenge procedure in laboratory animals. For various reasons, there now is an increased interest in the development of alternatives to the current in vivo potency tests. Animal models have their limitations, with respect to their relevance, reliability, costs and moral acceptability. All alternative approaches have in common that they ultimately result in a refinement, reduction or replacement in the use of animals. The new models range from modifications of the existing in vivo test procedure (e.g., use of humane end points or serology instead of challenge) to in vitro antigen-quantification tests. A new paradigm in quality control of vaccines is the consistency approach. This approach is state-of-the-art in quality control of the new-generation vaccines and it is now finding its way into the quality control of traditional vaccines. The consistency approach implies the use of a set of parameters to constitute a product profile, which is monitored throughout production, and which guarantees that each lot released is similar to a manufacturer-specific vaccine of proven clinical efficacy and safety. Consistency relies heavily on the implementation of quality systems, such as good manufacturing practice and quality assurance, and on the use of in vitro analytical tools, such as immunochemical and physicochemical tests.

Comparative evaluation for safety & potency of inactivated Cell Culture Rabies Vaccines from four Indian manufacturers

“…The extensive quality control (QC) and independent testing of each lot of rabies vaccine by National Control Laboratory (NCL) is essential and mandatory as vaccine characteristics might vary for every batch produced under complex manufacturing procedures [20]. One of the major parameter of QC of inactivated rabies vaccine is potency which measures the product strength.…”

Ethical Issues Associated with the Use of Animal Experimentation in Behavioral Neuroscience Research

“…Although, the search for animal-free methods is complex in any research field (Doktorova et al 2012;Hendriksen 2009;Huggins 2003;Manciocco et al 2009;Penza et al 2009), in Behavioral Neuroscience in particular, the modeling of complex systems such as executive processes of the brain or the central nervous system (CNS) may indeed limit the possibility of finding alternatives and may thus demand use of animal models; at least at present, available in vitro methods, and computer models seem unable to display the complexity of CNS-generated, behavioral-cognitive processes. It may be of note, however, that the declared goal of one of the current EU flagship programs (the Human Brain Project) is: "to build a completely new ICT infrastructure for neuroscience, and for brain-related research in medicine and computing, catalyzing a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities."…”

A pilot study on potency determination of human follicle-stimulating hormone: A comparison between reversed-phase high-performance liquid chromatography method and the in vivo bioassay

“…In agreement with the "consistency approach" [29,31,32], which implies the use of specific tests to demonstrate equivalence of a product with another of proven efficacy, there is a tendency to accept alternative assays that could complement the classical in vivo bioassay. These can be used in routine determinations, after the initial validation of the process development in which a classical in vivo bioassay is recommended.…”