We describe a method developed for making <i>in situ</i> measurements of protein concentration in frozen drug substance. This technique is based on the measurement of the signal from a fluorescently labelled protein and a CCD camera. Data collected using this method in laboratory small-scale experiments was demonstrated to be in good agreement with traditional ice coring method developed for measuring the localized protein concentration. The technique allows for the visualization of the freezing process with good resolution on the local details from ice crystal growth to the last point to freeze. The whole freezing process can be mapped in 2D and 3D heat maps through the various stages of freezing.  The ability to measure localized protein concentration in the frozen state allows for mapping of the “cryo-concentration” occurring as a consequence of progression of the freezing front. This helps to establish the bracketing conditions for the protein concentration in a storage container and will provide insight for the development of simulation tools and scaled down models. A better understanding of the morphology of the frozen protein solutions offers the potential to improve stability of protein in long-term frozen storage.

Non-destructive in-situ method for measuring protein concentration in frozen drug substance

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.