Accomplishing near real-time HPLC for bioprocess control

Abstract

P strategies are moving toward performing large numbers of in-parallel experiments, with the collection of much real-time process and product data. Such initiatives as personalized medicine and biosimilars also drive the need to know more about entity CQA as early as possible. In PC, more near-real time CPP and even product attribute values are being considered as control parameters. This all leads to the demand for rapid and comprehensive process parameter and product attribute measurements. Modern chromatographic columns and systems now provide rapid information on aggregation by SeC, charge variants by IeX, intact mass, primary structure, many post-translational modifications by reversed-phase and cleaved glycan analysis by HIC. Finally, required HPLC validation parameters (specificity, linearity, accuracy, precision, limits of detection and quantification) are being established supporting complient, absolute quantification methods for recombinant proteins. Two recent initiatives are enabling both the development and practical application of such heightened bioprocess knowledge to process control. Commercialized validated systems support the cell-free auto sampling, flowpath and destination control of in-process bioreactor samples to any number of analytical instrumentation. And, such hardand soft-ware computer advances as Solid State Drives (SSD), cloud computing, and Big Data methods now support the processing of any number of input data through advanced statistics, mathematics or logic-enabled enterprise control algorithms.