RFID solutions will improve the traceability of biological samples stored at low temperature (77 K) in biobanks. To achieve this goal, the reliability of RFID tags is essential. In this paper, we focus on the reliability aspect of RFID tags in harsh environment and more specifically to assembly design optimization through numerical simulations and accelerated life tests. A package-dimensioned model and a wire-interconnect centered model have been used to assess stress distribution in the package and wire bonds. We also develop a specific versatile test bench to apply thermal cycling while monitoring the functionality of the tags. We investigate three different tag configurations and demonstrate that the main failure mode is related to wire breaks. The occurrence of this failure depends mainly on the nature and thickness of the encapsulant resin which induce compressive and tensile stresses during thermal cycling. FEM results are in good agreement with observed failures.