TY - JOUR

T1 - African polyvalent antivenom can maintain pharmacological stability and ability to neutralise murine venom lethality for decades post-expiry

T2 - Evidence for increasing antivenom shelf life to aid in alleviating chronic shortages

AU - Solano, Gabriela

AU - Cunningham, Sinead

AU - Edge, Rebecca J.

AU - Duran, Gina

AU - Sanchez, Adriana

AU - Villalta, Mauren

AU - Clare, Rachel H.

AU - Wilkinson, Mark C.

AU - Marriott, Amy E.

AU - Abada, Camille

AU - Menzies, Stefanie K.

AU - Keen, Molly

AU - Lalloo, David G.

AU - Stienstra, Ymkje

AU - Abouyannis, Michael

AU - Casewell, Nicholas R.

AU - León, Guillermo

AU - Ainsworth, Stuart

PY - 2024/3/13

Y1 - 2024/3/13

N2 - 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.

AB - 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.

KW - Snake bite, stings and other envenoming

U2 - 10.1136/bmjgh-2023-014813

DO - 10.1136/bmjgh-2023-014813

M3 - Journal article

AN - SCOPUS:85188010483

VL - 9

JO - BMJ Global Health

JF - BMJ Global Health

SN - 2059-7908

IS - 3

M1 - e014813

ER -