As human subjects research becomes more complex and distributed—through sIRB models, contract research organizations (CROs), clinical research associates (CRAs), sponsor-controlled systems, and third-party vendors—IRBs are increasingly confronted with potential noncompliance and unanticipated events that stem from structural or external failures rather than investigator actions. This session examines how distributed responsibility and limited local control complicate IRB determinations related to noncompliance, unanticipated problems, corrective actions, and reporting obligations. Speakers will explore how HRPPs and IRBs can assess responsibility and regulatory requirements when issues arise across institutional and external boundaries—and how to respond when the source of the issue lies outside the investigator or IRB’s direct authority. Attendees will leave with practical approaches to evaluating reportability, assigning responsibility, and developing consistent, defensible responses in complex, multi-entity research environments.