ON-LINE PROCESS CONTROL: Automating the Control of Process-Scale Purification Columns Using On-Line Liquid Chromatography - Using on-line HPLC to monitor the eluent from process-scale columns allows t

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ON-LINE PROCESS CONTROL: Automating the Control of Process-Scale Purification Columns Using On-Line Liquid Chromatography
Using on-line HPLC to monitor the eluent from process-scale columns allows the process decision—when to start and stop collection—to be based on a critical quality attribute rather than on a surrogate measurement.


BioPharm International


Conclusions

Using on-line HPLC to monitor the eluent from process-scale chromatography columns allows a critical quality attribute (product purity) to be measured on-line in near–real time. The product purity data generated from an on-line HPLC analyzer can be used to automate the collection of product pools. Using the measurement of the critical quality attribute to adjust the mainstream pool collection points allows the process to vary as needed to compensate for variability in the process scale separation. This flexible process endpoint allows this variability to be accommodated by varying the timing of mainstream pool collection rather than have it show up as increased variability in the mainstream pool purity.

In addition to reducing product variability, using on-line HPLC also increases product yield; enables the use of increased levels of automation; reduces opportunities for errors; and reduces overall cycle time.

Obtaining product purity data in near–real time can enable unique approaches to product purification to be implemented. For example, two process-purification column steps can be combined and their sequencing can be fully automated. When this combination of column operations was carried out at Eli Lilly and Company process throughput was significantly increased, primarily as a result of cycle time reduction, allowing the production area to increase its throughput for the process step tenfold.

Acknowledgements

The author thanks Eli Lilly and Company for allowing the use of its process example to demonstrate the value of on-line HPLC in process scale chromatography operations.

The author would like to particularly acknowledge the invaluable contributions of several scientists, engineers, and technicians who were involved in the development, implementation, and support of this pioneering work at Eli Lilly and Company: Charles Stevenson, Danny Johnson, David Crozier, Richard Moss, Michael Hilgert, Robert Wilken, Jim Owens, Jerry Shrake, and Mearl Gibson. In addition, without the challenging questions of the late Dr. Leroy Baker, the development and use of on-line HPLC probably would not have been initiated at Eli Lilly and Company in 1980.

RICK E. COOLEY is the manager of process analytics center of excellence at Dionex Corporation, 765.349.6002,

References

1. Cooley RE. Utilizing PAT to monitor and control bulk biotech processes Presentation at University of Michigan Pharmaceutical Engineering Seminar, 2003 Mar 4. Available from: http://www.fda.gov/cder/OPS/cooley/index.htm


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