Separation processes, both old and new, depend on mixture physical properties. Accurate and practical physical property models are required to accurately model and compare separation processes. Data from bio-relevant compounds and mixtures are often scant, unreliable, or unavailable. In general, reliance on property estimation methods, which may not be relevant to bio-relevant compounds and mixtures, result in low confidence process analysis results. Developing adequate thermodynamic models requires an understanding of the process, the mixtures involved, and the sensitivity of the process to uncertainty in physical properties. Developing adequate thermodynamic models begins with determining whether sufficient data exists; and if insufficient data exists, evaluating the impact the lack of data on the analysis. If sufficient data exists, the next question is determining whether existing models can adequately represent the data. If not, the existing models must be modified or new models developed. The final step in the process is fitting the model to the available data.