Amorphous: Multi-component mixtures that do not crystallize and do not have a eutectic point. They turn into a ‘glass’. For amorphous materials, freeze drying needs to be performed below the glass transition temperature.
Annealing: The process of freezing, then warming a material to allow crystals to grow.
Backstreaming: A process whereby hydrocarbon vapors from the vacuum pump can leave the pump and enter into the condenser or drying chamber.
Bound water: Water strongly bounded to the product with a relatively high bounding energy and whose presence in the product is necessary for the stability of the material. This does not take part in the freezing process.
Cake: The porous and spongy structure-like material resulting from the lyophilization process; or the solid content remaining after the freeze drying process.
Collapse: The point at which the product softens to the extent that it can no longer support its own structure.
Condenser: The component of a vacuum freeze dryer that is designed to remove solvent vapor (mainly water vapor) from the gases in the chamber to prevent them from reaching the vacuum pumping system.
Critical Temperature: During freeze drying, the maximum temperature of the product before its quality degrades by melt-back or collapse.
Crystalline: The material forms crystals when frozen. - Has a eutectic point or multiple eutectic points. -Fast freezing creates small crystals which are hard to dry. -Annealing can help form bigger crystals.
Design Qualification (DQ): The process used to verify that the freeze dryer will be constructed to reach the URS given by the customer and the functional specifications.
Desorption: Also known as secondary drying; this process involves the removal of excess moisture (bound water) by increasing the temperature of the product and reducing the partial pressure of water vapor in the container.
Eutectic Point or Eutectic Temperature: The point at which the product only exists in the solid phase, representing the minimum melting temperature. Not all products have a eutectic point, or there may be multiple eutectic points.
Factory Acceptance Test (FAT): The verification process made by the manufacturer and the customer before releasing a freeze dryer from the factory.
Foreline: Tubing fitted between the chamber or an external condenser and the vacuum pumps.
Free water: Water with a low desorption energy that has been adsorbed on a cake surface and whose presence in a final cake may cause instability of the dried formulation. It is eliminated in the secondary phase of the Lyophilization process.
Glassy state: System where there is no defined phase diagram and no latent heat associated with a transformation from both liquid to solid or solid to liquid.
GMP: good manufacturing practice promulgated by the US Food and Drug Administration
Hygroscopic: the ability of a substance to attract water molecules from the surrounding environment through either absorption or adsorption
Inspection Qualification (IQ): The process used to verify that the vacuum freeze dryer has been constructed according to the manufacturer's specifications.
Leak Rate: Unit of measurement in which the medium being measured (contained system) has a defined decay over a unit of time. Typical usage would include a loss of vacuum pressure over a time interval.
Melt-back: The total collapse of a given formulation resulting from the presence of a liquid during the primary drying phase.
Operational qualification (OQ): The process that verifies that a vacuum freeze dryer provides a safe environment for the manufacture of a material and the necessary operating parameters to conduct the Lyophilization or freeze drying process.
Real leak: A vacuum leak resulting from penetration through, in general, the vacuum system.
Site Acceptance Test (SAT): The verification process made by the manufacturer and the customer once a freeze dryer has been installed on the site plant.
Sublimation: Also known as primary drying; after the material is completely frozen, the pressure in the freeze dryer is reduced, and heat is applied to initiate the sublimation of the ice crystals, which removes the unbound moisture from the product. Less specifically, sublimation is the transition from a solid to a gas phase with no intermediate liquid stage.
Transition Glass Temperature: The interval of temperatures where the material goes from a glassy state to a rubbery state due to an increase of water mobility in the interstitial.
Vacuum pump: An engineering device designed to produce the low pressure system necessary to drive the Lyophilization or freeze drying process.
Validation Documents: documents that are utilized by the FDA for ensuring compliance to GMPs
Virtual leak: A source of gas (such as water) that is physically trapped within the chamber with only a small, very low conductance path from the trapped pocket of gas into the chamber proper. Understanding Virtual Leaks