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

Abstract

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. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the second in the series, provides recommendations for current and future use of nonanimal methods and strategies for veterinary vaccine potency testing. Workshop participants recommended that future efforts to replace animal use give priority to vaccines (1) that use large numbers of animals per test and for which many serials are produced annually, (2) that involve significant animal pain and distress during procedures, (3) for which the functional protective antigen has been identified, (4) that involve foreign animal/zoonotic organisms that are dangerous to humans, and (5) that involve pathogens that can be easily spread to wildlife populations. Vaccines identified as the highest priorities were those for rabies, Leptospira spp., Clostridium spp., Erysipelas, foreign animal diseases (FAD), poultry diseases, and fish diseases. Further research on the identification, purification, and characterization of vaccine protective antigens in veterinary vaccines was also identified as a priority. critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included (1) investigations into the relative impact of various adjuvants on antigen quantification assays, (2) investigations into extraction methods that could be used for vaccines containing adjuvants that can interfere with antigen assays, and (3) review of the current status of rabies and tetanus human vaccine in vitro potency methods for their potential application to the corresponding veterinary vaccines. Workshop participants recommended enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for veterinary vaccine potency testing that will benefit animal welfare and replace animal use while ensuring continued protection of human and animal health.

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

“…Recurring themes that surfaced during the discussions included (1) the need for more open access to methods and information such as pharmacopoeial monographs; (2) increased sharing of information among regulators, manufacturers, and the scientific community; (3) international harmonization of requirements on test methods and specifications (e.g., ICH Q2 R Development and validation of potency assays); (4) recognition that the regulatory authorities should encourage the use of 3Rs approaches by various means; and (5) the need for widely available validated reference standards, antisera, and reagents. Although specific detailed recommendations from each workshop/symposium differed, these same general themes of the need for specific scientific research, the need for international harmonization of regulations and specifications, the need for sharing of information, the responsibility that regulators have for encouraging the use of alternative methods, and the need for validated reagents were evident in the output from each workshop/symposium.…”

“…This was followed by breakout sessions to discuss the state of the science and recommendations for future progress for in vitro potency tests for human and veterinary vaccines. Workshop recommendations to advance the use and development of alternative methods that can replace animals for the potency testing of human vaccines are provided in this paper, while the report on replacement of animals for veterinary vaccines is available elsewhere in these proceedings [4].…”

“…Participants developed recommendations for future progress in three major areas: (1) in vitro replacement methods for potency testing; (2) reduction and refinement methods for potency testing; and (3) reduction, refinement, and replacement methods for vaccine safety testing [2]. Reports were prepared for each of the three topics for human vaccines and for each of the three topics for veterinary vaccines [3,4,5,6,7,8]. This report addresses methods and strategies for the replacement of animal use for potency testing of human vaccines.…”

Development of a flow cytometric bead immunoassay and its assessment as a possible aid to potency evaluation of enterotoxaemia vaccines

“…Various reports have expressed the need for a reduction in the use of animals for vaccine potency testing (Hendriksen 2007;Kulpa-Eddy et al 2011). Whist there is no alternative to immunising test animals when assessing the potency of vaccines, the quantification of protective anti-epsilon toxin antibodies may be determined by in vitro methods.…”