Definitions
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.

CPP:  critical process parameters (ex. Freezing rate, primary & secondary frying,
pressure)

CQA:  critical quality attributes (ex. moisture, stability)

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
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