Residual Moisture in Freeze-Dried Vaccines and Biological Products: Specification and Measurement

Residual Moisture in Freeze-Dried Vaccines and Biological Products: Specification and Measurement
Fall 2003
Joan C. May, Ph.D.
Center for Biologics Evaluation and Research, FDA
APR
Keywords: Karl Fischer, residual moisture; thermogravimetry, vapor pressure moisture measurement.
Abstract
Karl Fischer, loss-on-drying, TG, and TG/MS are used to provide accurate residual moisture results for freeze-dried biological products regulated by the United States Food and Drug Administration. Residual moisture specifications must be met in order to ensure freeze-dried biological product potency and stability throughout the product?s licensed shelf life. Residual moisture results are compared for experimental lots of single dose Yellow Fever Vaccine and lots of Yellow Fever Vaccine meeting license requirements. Correlations are made between residual moisture data and vapor pressure moisture determinations which measure the moisture content in the space above the freeze-dried cake in the final container. The vapor pressure moisture methodology is able to detect 0.8 ?g increases in vial head space moisture between vials from the same lots stored at refrigerated (2 to 8?C) and room temperature (22?C).
Introduction
This paper describes correlations between Karl Fischer and thermogravimetric (TG) residual moisture results for the freeze-dried cake and moisture results for the space above the cake in the vial determined by vapor pressure moisture (VPM) measurements. The samples in this study include freeze-dried Yellow Fever Vaccine, a- Interferon and BCG Vaccine. The accurate determination of residual moisture in these products is necessary to meet regulatory limits [1]. An established residual moisture level in freeze-dried products is necessary to ensure the potency and stability of the product throughout its shelf-life [2]. Yellow Fever Vaccine is a live, attenuated virus preparation made from 17 D yellow fever virus strain [3]. The vaccine is a freeze-dried supernate of centrifuged chick embryo homogenate. a-Interferon is used to treat hairy cell leukemia and AIDS-related Kaposi?s sarcoma and other conditions. BCG Vaccine is made from a culture of an attenuated strain (Bacillus Calmette- Guerin) of living bacillus Mycobacterium bovis [4]. The bacilli are freeze-dried and viable upon reconstitution. BCG has been used to vaccinate against tuberculosis (TB) since 1921.
Procedure
Samples and Control Materials
Samples of single dose Yellow Fever Vaccine were from experimental lots and product licensed by the United States Food and Drug Administration.
Samples of BCG Vaccine were obtained from Aventis Pasteur Limited (Toronto, Canada).
Samples of a-Interferon (Interferon Alfa-2b, Recombinant) were obtained form Schering Corporation, (Kenilworth, New Jersey, USA).
Sodium tartrate dihydrate was used as a control material for the TG and Karl Fischer residual moisture methods.
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