Abstract
The immunogenicity immunoassay validation process ensures development of a robust, reproducible method. However, no matter how well developed, validated, and maintained a method is, in the course of running a large number of samples over time, it is not uncommon to see bad reagents, poorly calibrated equipment, personnel errors, or other unknown and unpredictable factors that have an impact in the performance of the method and quality of the sample results. The immunogenicity immunoassay thus needs to be closely monitored with an internal statistical quality control process overtime to ensure a consistent and reliable output. The statistical process control has been widely applied to monitor manufacturing processes and in clinical laboratories. Its application to immunogenicity immunoassays is relatively novel. Limited guidance is available to implement the process to monitor semiquantitative immunogenicity immunoassay performance. Here, we have performed a suitability evaluation for process control charts with actual laboratory data from three immunogenicity immunoassay methods each utilizing a different technology platform. Additionally, a panel of prepared samples designed to assess long-term method performance were periodically evaluated for over a year. Finally, we make recommendations for an internal quality control process based on the results of these evaluations.
Similar content being viewed by others
Abbreviations
- ARL:
-
average run length
- CUMSUM:
-
cumulative sum
- ECL:
-
electrochemiluminescence
- EWMA:
-
exponentially weighted moving average
- OOT:
-
out of trend
- SPR:
-
surface plasmon resonance
References
Shewhart WA. Economic control of quality of manufactured product. New York: Van Nostrand Company; 1931.
Levey S, Jennings ER. The use of control charts in the clinical laboratory. Am J Clin Pathol. 1950;20:1059–66.
Westgard J, Barry P, Hunt M, et al. A multi-rule Shewhart chart for quality control in clinical chemistry. Clin Chem. 1981;27:493–501.
Montgomery DC. Introduction to statistical quality control, 5th ed. Wiley; 2005.
Linnet K. The exponentially weighted moving average (EWMA) rule compared with traditionally used quality control rules. Clin Chem Lab Med. 2006;44:396–9.
Neubauer A. The EWMA control chart: properties and comparison with other quality-control procedures by computer simulation. Clin Chem. 1997;43:594–601.
Medicare, Medicaid, and CLIA Programs; regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Fed Regist. 1992;57:7002–7186.
Moxness M, Tatarewicz S, Weeraratne D, et al. Immunogenicity testing by electrochemiluminescent detection for antibodies directed against therapeutic human monoclonal antibodies. Clin Chem. 2005;51:1983–5.
Lofgren J, Dhandapani S, Pennucci J, et al. Comparing ELISA and surface plasmon resonance for assessing clinical immunogenicity of panitumumab. J Immunol. 2007;178:7467–72.
Mytych D, La S, Barger T, Ferbas J, Swanson S. The development and validation of a sensitive, dual-flow cell, SPR-based biosensor immunoassay for the detection, semi-quantitation, and characterization of antibodies to darbepoetin alfa and epoetin alfa in human serum. J Pharm Biomed Anal. 2009;49:415–26.
NCCLS. Evaluation of precision performance of clinical chemistry devices; approved guideline. NCCLS document EP5-A. 1999. p. 19.
Jansen R, Laeven M, Kardol W. Internal quality control system for non-stationary, non-ergodic analytical processes based upon exponentially weighted estimation of process means and process standard deviation. Clin Chem. 2002;40:616–24.
Champ C, Woodall W. Exact results for Shewhart control chart with supplementary run rules. Technometrics. 1987;29:393–401.
Champ C, Woodall W. A program to evaluate the run length distribution of a Shewhart control chart with supplementary run rules. J Qual Technol. 1990;22:68–73.
Albin S, Kang L. An X and EWMA chart for individual observations. J Qual Technol. 1997;29:41–8.
Acknowledgments
We thank PPD and the scientists at Amgen (Suzanna Tatarewicz, Geoff Houghton, Dohan Weeraratne, and Andrew Kuck) for performing the assays. This work was done at Amgen, and all authors hold company stock.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Barger, T.E., Zhou, L., Hale, M. et al. Comparing Exponentially Weighted Moving Average and Run Rules in Process Control of Semiquantitative Immunogenicity Immunoassays. AAPS J 12, 79–86 (2010). https://doi.org/10.1208/s12248-009-9166-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12248-009-9166-4