Thursday, January 16, 2014

Biological Assay Qualification Using Design of Experiments

Leading up to the Biological Assays event taking place this May, we'll be teaming up to showcase some of the latest articles and news from our partners at BioProcess International.  Today we feature a piece authored by Todd Coffey, Mike Grevenkamp, Annie Wilson, Mary Hu Biological Assay Qualification Using Design of Experiments.
In 2012, the United States Pharmacopeia (USP) published a complementary set of three guidance documents on the development, analysis, and validation of biological assays (1,2,3). USP chapter <1033> recommends a novel, systematic approach for bioassay validation using design of experiments (DoE) that incorporates robustness of critical parameters (2). Use of DoE to establish robustness has been reported (4,–5), but to our knowledge its use in qualification or validation protocols for assessing assay accuracy, precision, and linearity is not described in literature. A validation approach incorporating different levels of critical assay parameters provides a more realistic representation of how an assay will perform in routine testing. 
After initial development of a cell-based bioassay to enable an investigational new drug (IND) application, we used a DoE-based approach to perform a comprehensive qualification of that bioassay to estimate its accuracy, precision, linearity, and robustness. Such an approach to qualification requires experimental and statistical effort similar to that of traditional validation for cell-based bioassays (6,7,8), but the additional insights we gained have led us to adopt this new approach as our standard method for qualifying bioassays. Here we outline our approach and describe its benefits and challenges.

Head to BioProcess International to read the methods, results and conclusions of the report.

This May at Bioassays, we'll have have experts on hand from Genentech and Eli Lilly to take a deeper look into Establishing and Qualifying Product Reference for the Relative Potency Assay.  For more information on these sessions and the rest of the program, download the agenda.  Would you like to join us in Berkeley?  As a reader of this blog, when you register to join us and mention code B14177JT, you can save 20% off the standard rate!

1 Chapter <1032> Design and Development of Biological Assays. USP 35–NF 30, 2012. 
2 Chapter <1033> Biological Assay Validation. USP 35–NF 30, 2012. 
3 Chapter <1034> Analysis of Biological Assays. USP 35–NF 30, 2012.
4 Chen XC, et al. Implementation of Design of Experiments (DOE) in the Development and Validation of a Cell-Based Bioassay for the Detection of Anti-Drug Neutralizing Antibodies in Human Serum. J. Immunol. Meth. 376 (1–2) 2012: 32–45. 
5 Kutle L, et al. Robustness Testing of Live Attenuated Rubella Vaccine Potency Assay Using Fractional Factorial Design of Experiments. Vaccine 28(33) 2010: 5497–5502.
6 Cheng Z-J, et al. Development of a Bioluminescent Cell-Based Bioassay to Measure Fc Receptor Functionality in Antibody-Dependent Cellular Cytotoxicity. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research, Mar 31–Apr 4, Chicago, IL. AACR Cancer Res. 72(8) 2012: supplement abstract #2840. 
7 Wei X, et al. Development and Validation of a Quantitative Cell-Based Bioassay for Comparing the Pharmacokinetic Profiles of Two Recombinant Erythropoietic Proteins in Serum. J. Pharm. Biomed. Anal. 43(2) 2007: 666–676.
8 Gazzano-Santoro H, et al. Validation of a Rat Pheochromocytoma (PC12)-Based Cell Survival Assay for Determining Biological Potency of Recombinant Human Nerve Growth Factor. J. Pharm. Biomed. Anal. 21(5) 1999: 945–959.

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