African polyvalent antivenom can maintain pharmacological stability and ability to neutralise murine venom lethality for decades post-expiry : Evidence for increasing antivenom shelf life to aid in alleviating chronic shortages

Solano, Gabriela and Cunningham, Sinead and Edge, Rebecca J. and Duran, Gina and Sanchez, Adriana and Villalta, Mauren and Clare, Rachel H. and Wilkinson, Mark C. and Marriott, Amy E. and Abada, Camille and Menzies, Stefanie K. and Keen, Molly and Lalloo, David G. and Stienstra, Ymkje and Abouyannis, Michael and Casewell, Nicholas R. and León, Guillermo and Ainsworth, Stuart (2024) African polyvalent antivenom can maintain pharmacological stability and ability to neutralise murine venom lethality for decades post-expiry : Evidence for increasing antivenom shelf life to aid in alleviating chronic shortages. BMJ Global Health, 9 (3): e014813. ISSN 2059-7908

Abstract

Introduction Antivenom is a lifesaving medicine for treating snakebite envenoming, yet there has been a crisis in antivenom supply for many decades. Despite this, substantial quantities of antivenom stocks expire before use. This study has investigated whether expired antivenoms retain preclinical quality and efficacy, with the rationale that they could be used in emergency situations when in-date antivenom is unavailable. Methods Using WHO guidelines and industry test requirements, we examined the in vitro stability and murine in vivo efficacy of eight batches of the sub-Saharan African antivenom, South African Institute for Medical Research polyvalent, that had expired at various times over a period of 30 years. Results We demonstrate modest declines in immunochemical stability, with antivenoms older than 25 years having high levels of turbidity. In vitro preclinical analysis demonstrated all expired antivenoms retained immunological recognition of venom antigens and the ability to inhibit key toxin families. All expired antivenoms retained comparable in vivo preclinical efficacy in preventing the lethal effects of envenoming in mice versus three regionally and medically important venoms. Conclusions This study provides strong rationale for stakeholders, including manufacturers, regulators and health authorities, to explore the use of expired antivenom more broadly, to aid in alleviating critical shortages in antivenom supply in the short term and the extension of antivenom shelf life in the longer term.