@article{Prasantha_2026, title={Risk-Based Autoclave Steam Sterilization Cycle Design and Validation for Mixed Biopharmaceutical Loads: Thermodynamic Mapping Integrated with FMEA}, volume={12}, url={http://dx.doi.org/10.22161/ijaems.122.11}, DOI={10.22161/ijaems.122.11}, abstractNote={<jats:p>The article addresses the development and validation of risk based steam sterilization cycles for mixed biopharmaceutical loads by integrating thermodynamic mapping with FMEA methodology. The relevance of the work is driven by increasingly stringent regulatory expectations and the limitations of template autoclave cycles, which do not ensure reliable air removal or the uniform attainment of sterilizing conditions in complex, porous, and combined loads. The aim of the study is to establish a scientifically justified model for cycle design that ensures not only the attainment of the required lethality and SAL levels, but also their robust defensibility before regulators. Methodologically, the work is grounded in the Quality by Design paradigm and a mixed methods research design that includes high frequency thermal mapping using wireless data loggers in typical mixed loads, lethality calculation, and a modified FMEA that directly links cycle parameters (vacuum pulses, heating rate, equilibration time) to specific failure modes. It is shown that an unsuccessful cycle is characterized by thermodynamic instability, persistent air pockets, and failure to reach the minimum temperature of 121 C at the critical point, whereas an optimized cycle with intensified vacuuming exhibits rapid equilibration less than 15 s, a narrow temperature corridor of 121 to 124 C, and excess lethality F0 approximately 29 to 32 min that substantially exceeds the overkill criterion. The scientific novelty lies in treating the mixed load as a dynamic risk object and in proposing a hierarchy of acceptance criteria, placing primary emphasis on physical indicators such as P T correlation, equilibration time, and absence of cold spots, with integral lethality used as a derived parameter. The article is intended for validation engineers, quality assurance specialists, and biopharmaceutical process developers involved in the design and defense of steam sterilization cycles.</jats:p>}, number={2}, journal={International Journal of Advanced Engineering, Management and Science}, publisher={AI Publications}, author={Prasantha, Pujari}, year={2026}, pages={80–92} }