Safe operation of biosafety laboratories requires directional airflow and stable pressure gradients to contain pathogenic aerosols. However, door operations between the core and buffer rooms frequently disrupt this balance, inducing transient pressure disturbances. Conventional PI control often responds inadequately to such rapid transients, which can lead to airflow reversal and compromise biosafety. This study develops a Modelicabased two-zone transient differential pressure regulation model for the core and buffer rooms and proposes a coordinated control strategy that integrates feedforward compensation with an integral-freezing mechanism. During door opening, the feedforward mechanism adjusts the exhaust airflow, rapidly increasing the doorway air mass flow rate to 0.12–0.14 kg/s. This establishes a directional airflow barrier (velocity ≥ 0.2 m/s), thereby reducing the risk of leakage during personnel transit. By freezing the PI integral term during the door-open phase and applying feedforward exhaust compensation upon closure, the proposed strategy restricts the maximum pressure undershoot during door closure to −17 Pa (against the −15 Pa design setpoint), compared to −24 Pa under conventional PI control. The pressure recovery time is also reduced from 48.3 s to 13.6 s. These findings provide a simulation-based basis for improving the dynamic containment of high-level biosafety laboratories under transient disturbances.