Preclinical testing of expired antivenoms and its uses in real-world experience: a systematic review

Limited access to antivenoms is a global challenge in treating snakebite envenoming. In emergency situations where non-expired antivenoms are not readily available, expired antivenoms may be used to save lives with the risk of deteriorating quality, efficacy and safety. Therefore, we aimed to systematically review and summarise the sparse preclinical evidence of neutralising efficacy of expired antivenoms and real-world experience of using expired antivenoms in humans.

We searched for articles published until 1 March 2023 in PubMed, Scopus, Web of Science and Embase. Studies demonstrating the preclinical studies evaluating expired antivenoms or studies describing the real-world experience of using expired antivenoms were included. Narrative synthesis was applied to summarise the evidence of expired antivenoms.

Fifteen studies were included. Ten were preclinical studies and five were real-world experiences of using expired antivenoms in humans. The expired duration of antivenoms in the included studies ranged from 2 months to 20 years. The quality of expired antivenoms was evaluated in one study, and they met the standard quality tests. Five studies demonstrated that the expired antivenoms' immunological concentration and venom-binding activity were comparable to non-expired ones but could gradually deteriorate after expiration. Studies consistently exhibited that expired antivenoms, compared with non-expired antivenoms, were effective when stored in proper storage conditions. The safety profile of using expired antivenoms was reported in two included studies. However, it was inconclusive due to limited information.

Even though the quality and efficacy of expired antivenoms are comparable to non-expired antivenoms in preclinical studies, the information is limited in terms of real-world experiences of using expired antivenoms and their safety. Therefore, the use of expired antivenoms may be generally inconclusive due to scarce data. Further investigations may be needed to support the extension of antivenoms' expiration date according to their potential efficacy after expiration.