In the biopharmaceutical industry, the characterization and optimization of chromatography processes are critical to ensure a robust manufacturing process. Quality by Design (QbD) principles are, thus, adopted to enable a thorough understanding of a product and its manufacturing process, allowing us to build quality by design, not testing quality after development. These studies are traditionally carried out in large chromatography columns, and therefore needing large amount of samples; which in turn, makes the screening of a large experimental space very expensive and in most cases impossible.<br/><br/>Over the years, high throughput screening tools have been employed to address the sample and time constraints of traditional chromatography. While these tools are widely employed in chromatography, there is limited knowledge on its application in process characterization to support quality by design efforts to ultimately determine the functional relationships that link material attributes and process parameters to product critical quality attributes (CQAs).<br/><br/>In our efforts to identify critical process parameters (CPPs) and understand their impact on a target product profile, we employed high-throughput technologies in the process characterization of a late stage monoclonal antibody. This presentation will discuss the DoE evaluation of the process operating ranges and their impact on yield and impurity clearance of the most common formats used for the development of chromatography steps to support late phase process characterization. The formats considered will include flow based systems, such as micro-columns and techniques utilizing a batch incubation principle such as microtiter plates or pipette tips pre-filled with chromatography media and will be correlated to traditional scale-down models. Aspects discussed will include identification of critical process parameters and scale-down model limitations across multiple formats.

Process characterization: A quality by design approach to scale-down studies across multiple HTPD formats

249th National Meeting (2015)

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