Regulatory sandboxes for drug development: from uncertainty to structured evidence generation.

Regulatory sandboxes for drug development offer a framework to address regulatory and legal uncertainty associated with novel sciences and technologies without compromising efficacy, safety, or quality. Here, we explore how regulatory sandboxes support structured evidence generation when existing regulatory and legal mechanisms are insufficient to address innovation. We synthesize concepts about when a sandbox is warranted, what evidence should be generated in a controlled setting, and how governance should be structured to protect patients and data while enabling responsible innovation. Our analysis highlights that sandbox value depends on explicitly managing uncertainty, conducting controlled experimentation, maintaining safeguards and oversight, and defining clear exit criteria linked to regulatory learning. A practical governance model is presented, together with a readiness framework covering regulatory knowability, value trade-offs, institutional capacity, infrastructure, and responsibility. When appropriately designed, regulatory sandboxes enable responsible innovation, credible learning, and better-informed regulatory decision-making while preserving regulatory standards.