ABSTRACT
The residual moisture content of the freeze-dried product is usually near 1.0% to 3.0% Optimum residual moisture limits are set for each freeze-dried product on a basis. Residual moisture limits for the freeze-dried are ~l1Jnn,nrtpt1 with data that demonstrate that at the recommended moisture level the purity, and of the product is maintained throughout the rw,v",r-t'c dating The Center for Biologics Evaluation and Research of the U.S. Food and Administration freeze-dried
in its section to residual moisture as publJ:she:d in Title 21 of the Code of Federal for Food and Drugs. The regulation requires that each lot of dried product be tested for residual moisture and meet and not exceed established limits as specified by an method on file in the license information about test methods and illustrative residual moisture limits for
vaccines and biological product is addressed in the Center for Biologics Evaluation and Research Guideline for the Determination of Residual Moisture in Dried Biological Products. Many recent articles report studies that have focused on residual moisture as it relates to potency, formulation, aggregation, and container closure and stopper considerations. Methods used for the measurement of residual moisture in the freeze-dried final container include the traditional loss on drying, Karl Fischer, and gas chromatographic methods as well as recent advances in coulometric Karl Fischer methods, thermogravimetry, and thermogravimetry/mass spectrometry. Special applications for near-infrared reflectance spectroscopy and tritium isotope methods are described. Recent advances in vial headspace moisture methodology (vapor pressure moisture) research have the potential to shed light on moisture and processes occurring within the freeze-dried vial over time, e.g., redistribution of moisture between container closure, container headspace, and freeze-dried cake. In addition, there is the redistribution of moisture between surface moisture and bound water in the various chemical constituents such as protein and hydrated salts in the freeze-dried cake.
