During the commercialization of a biopharmaceutical process, formal process characterization (PC) studies are employed to examine the impact of process variability on process outcome, and constitute the backbone of stage 1 of process validation (process understanding).  An effective PC study design will not only address the input parameters posing the highest risk to process performance, but will also carefully consider how to vary those parameters in a way that most appropriately anticipates variability and control at the manufacturing scale.  In particular for purification processes, knowledge of how process buffer and in-process intermediate solution properties (e.g., pH and conductivity) will vary and are controlled in manufacturing can help to design PC studies.  Process buffer composition is typically controlled in manufacturing using mass and/or volume measurements of components and water; their properties are then often measured to a specified pH and/or conductivity range as a secondary control to ensure consistency.  In-process product intermediates, on the other hand, are commonly “conditioned” via titration to a measured pH or conductivity, allowing for the actual solution composition of the intermediate to vary.  This presentation will describe approaches taken in PC to design studies around target solution compositions, and then connecting to the pH and conductivity ranges as outcomes of the study execution.  A simple example of a critical process buffer, and a more complex example of a process intermediate as the interface between two chromatography steps, will be included.  Pros and cons of the approach and implications on the resulting definition of the control strategy will be discussed.

Addressing solution composition variability for process buffers and product intermediates in PC studies and control strategy definition

249th National Meeting (2015)

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