Before performing validation studies and conformance runs, column packing is validated. Ranges for process control parameters
(e.g., flow rate, load, pH, conductivity) will be established in characterization studies. Engineering runs will be performed
at production scale. Before confirming scale up, it will be necessary to determine if any modifications resulting from scale
changes might alter the process control parameters or product critical quality attributes.
Column storage will be validated by evaluating packing integrity (e.g., frontal analysis, removal of storage agents, any
residues removed by the cleaning effect of storage, and control over bioburden.
Column cleaning will be validated by a combination of small-scale prospective studies and concurrent in-process analysis at
Experience over the last decade in developing and producing biotherapeutics has enabled the development of a structured approach
to process validation that begins in development and continues throughout the lifetime of the product. Although process analytical
technologies continue to be discussed as a means for achieving better quality and process control, the need for process validation
does not appear to be going away. Improvements in analytical methods have improved our understanding of downstream intermediates
and final purified products. These analytical tools enhance the value of process validation. Improvements in process validation
approaches have resulted in better process understanding that enables better control over variability—the intent of process
validation. The use of enhanced analysis and feedback control, process development, statistical analysis, and characterization
studies to establish robust processes have led to the ability to define a space in which the process delivers the critical
The Polymerase Chain Reaction (PCR) is covered by patents owned by Roche Molecular Systems and F. Hoffman-LaRoche. A license
to use the PCR process for certain research and development activities accompanies the purchase of certain reagents from licensed
Gustav Rodrigo and Maria Murby, GE Healthcare Life Sciences R&D, Uppsala, Sweden, are gratefully acknowledged for providing
the data from the DoE study on Capto S.
All illustrations are reproduced with the permission of GE Healthcare Bio-Sciences AB, a General Electric Company, Bjorkgatan,
Gail Sofer is director of regulatory compliance at the life sciences business unit of GE Healthcare, and a member of BioPharm International’s
Editorial Advisory Board, 732.457.8000, firstname.lastname@example.org.
Mattias Ahnfelt is senior research engineer and black belt in Six Sigma at the life sciences business unit of GE Healthcare, +46 18 612 1990,
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