The first phase in a freeze drying process is freezing the sample to initiate formation of ice which subsequently sublimes under the low pressure applied during primary drying. Freezing can be achieved by several procedures, e.g. putting the sample into a freezer, immersing it in LN2 or cooling it directly on the shelves of a freeze dryer. Before nucleation (= the initial formation of ice crystals) starts, the sample has usually super-cooled to a greater or lesser extent. Super-cooling means that a solution is held at a temperature below its thermodynamic freezing point without nucleation occurring. The degree of super-cooling is defined as the temperature differential between the equilibrium freezing point and the temperature at which ice crystals start to form. Nucleation is a random process and the nucleation temperature (and time) may vary in a wide range, compromising batch homogeneity. The degree of super-cooling determines the ice crystal size and therefore the pore structure and pore size distribution (e.g., greater super-cooling results in smaller ice crystals and vice versa). Ice crystal size directly impacts primary drying rate and hence the time required for the primary drying phase in a freeze drying process.