The impact of COVID-19 provided a pressing backdrop for this exercise, as the ongoing pandemic has highlighted weaknesses in the international architecture for preventing, detecting, and responding to pandemic threats. This is an urgent concern because future pandemics could match or exceed COVID-19’s devastating impact in lost lives and shattered economies. Even more concerning is that there are critical gaps in biotechnology oversight that create opportunities for accidental or deliberate misuse with potentially catastrophic global consequences. This was illustrated in the exercise scenario: a localized bioweapons attack with a genetically engineered monkeypox virus begins in the fictional country of Brinia. Over 18 months, the scenario evolves into a globally catastrophic pandemic, leaving 40% of the world’s population infected and over a quarter billion people dead.