It is the goal of Moon to Mars (M2M) to establish a single consolidated set of safety requirements and a safety review process for utilization payloads that will cross program vehicle hatches or operate externally on multiple program vehicles during transport or operation that satisfies Exploration Ground Systems (EGS), Orion, EVA, and Human Surface Mobility Program (EHP), Gateway (GW), and Human Landing System (HLS) programs. This document defines the Cross Program Utilization Payload (xPUP) safety review process for mission effectivity of Artemis III and beyond. This review process will help ensure protection of the overall Moon to Mars integrated system from potential hazards created by cross program payloads that either cross a program vehicle hatch or can interface with more than one M2M lunar exploration program vehicle. The process will identify payload hazards and controls that will protect ground personnel, flight crew, the integrated vehicle, ground equipment, or facilities. This process is also applicable to samples that cross hatches between vehicles including for return to Earth. The xPUP safety review process will be led by one of the M2M programs' integration safety panels, chosen on a per-payload basis. After the lead integration safety panel is determined, the common safety process is established, based on pre-determined criteria, which includes ad-hoc members from other stakeholder programs. Stakeholder programs are those that interface with the utilization payload in any way (e.g., operating on a lunar exploration vehicle or crossing program vehicle hatches). The xPUP will execute this safety review process for flight and ground utilization payload hardware design, its ground support equipment, and landing and recovery in accordance with the applicable safety requirements as specified in M2M-30043: Moon to Mars Cross Program Utilization Payload Safety Requirements. The xPUP safety process will follow the lead integration safety panel’s safety process requirements. Formal agreements will be communicated with the payload developer using the payload integration processes documented in M2M-30037, Artemis Payload Integration Implementation Plan.