Research highlighted that the biggest technical barrier to end-to-end continuous biomanufacturing is often not the lack of continuous unit operations, but interface mismatches between steady upstream harvest and cyclic downstream purification. Seoul National University’s Moo Sun Hong and colleagues reviewed batch-to-continuous transitions and focused on how residence times, throughput, and robustness can break at handoffs. In particular, perfusion-style continuous harvest produces relatively steady streams, while many downstream steps operate cyclically, creating flow-rate and residence-time mismatches. The resulting need for surge tanks or hold steps limits the operational continuity sponsors seek and introduces new vulnerabilities around measurement latency and uncertainty in residence time distribution. The authors recommend a systems-level evaluation using integrated techno-economic, sustainability, and operational performance metrics, paired with interface engineering and coordinated cycle-time synchronization plus real-time monitoring across the manufacturing train.