X-Message-Number: 9934 Date: Tue, 23 Jun 1998 23:42:46 -0700 (PDT) From: Doug Skrecky <> Subject: storing antibodies Authors Duddu SP. Dal Monte PR. Institution Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. Sarma:P:Duddu:sbphrd.com Title Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic monoclonal antibody. Source Pharmaceutical Research. 14(5):591-5, 1997 May. Abstract PURPOSE: The purpose of this study is to highlight the importance of knowing the glass transition temperature, Tg, of a lyophilized amorphous solid composed primarily of a sugar and a protein in the interpretation of accelerated stability data. METHODS: Glass transition temperatures were measured using DSC and dielectric relaxation spectroscopy. Aggregation of protein in the solid state was monitored using size-exclusion chromatography. RESULTS: Sucrose formulation (Tg approximately 59 degrees C) when stored at 60 degrees C was found to undergo significant aggregation, while the trehalose formulation (Tg approximately 80 degrees C) was stable at 60 degrees C. The instability observed with sucrose formulation at 60 degrees C can be attributed to its Tg (approximately 59 degrees C) being close to the testing temperature. Increase in the protein/sugar ratio was found to increase the Tgs of the formulations containing sucrose or trehalose, but to different degrees. CONCLUSIONS: Since the formulations exist in glassy state during their shelf-life, accelerated stability data generated in the glassy state (40 degrees C) is perhaps a better predictor of the relative stability of formulations than the data generated at a higher temperature (60 degrees C) where one formulation is in the glassy state while the other is near or above its Tg. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=9934