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NASA’s Goddard Space Flight Center is investigating the use of small, commercial off the shelf (COTS) spacecraft to enable breakthrough astrophysics research at radically reduced cost over previous generations of missions. This paper will focus on the Mission Systems perspective of this investigation. It will cover the spacecraft to instrument interface, and lessons learned in early concept payload development. Low-cost COTS spacecraft have proliferated in the last ~5 years. They represent an order of magnitude reduction in the cost of spacecraft bus development and acquisition. They are enabled by the advent of low-cost smallsat launch options in the immediately preceding years, and are seeded by recent distributed and disaggregated missions in other sectors such as telecommunications megaconstellations (e.g. Starlink, OneWeb, Project Kuiper) and ongoing Space Development Agency (SDA) developments. Our study was tasked with developing a standardized, mass-produceable, astrophysics payload which is reconfigurable to different wavelength bands while maintaining a single optics bench design, and a standardized mechanical, electrical, data, and thermal interface to the spacecraft bus, and which may be reconfigured to multiple COTS spacecraft offerings. In this paper we will discuss lessons learned from our case study. We will also present identified keys to mission success for performing cutting edge astrophysics observations while taking advantage of economies of scale with a disaggregated, standardized architecture.