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Abstract Details
Activity Number:
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293
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Type:
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Topic Contributed
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Date/Time:
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Tuesday, August 2, 2011 : 8:30 AM to 10:20 AM
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Sponsor:
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Biopharmaceutical Section
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Abstract - #302215 |
Title:
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Regression to the Rescue: The Use of Statistical DOE to Derive a Novel Manufacturing Control Strategy for Ensuring the Quality of an Antibody-Drug Conjugate
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Author(s):
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Lisa J. Bernstein*+ and Daniel A. Coleman
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Companies:
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Genentech Inc. and Genentech Inc.
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Address:
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1 DNA Way, South San Francisco, CA, 94080, USA
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Keywords:
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antibody-drug conjugate (ADC) ;
design of experiments (DOE) ;
split-plot ;
biologic ;
manufacturing
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Abstract:
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ADC-X is an antibody-drug conjugate therapeutic candidate consisting of a monoclonal antibody linked to a potent cytotoxin by a chemical linker. The Drug-to-Antibody Ratio (DAR), the average number of toxin molecules per antibody, is a critical quality attribute related to both safety and efficacy; hence it must be controlled in manufacturing. This talk describes how a sequential experimentation strategy characterized the ADC-X manufacturing process. Multiple laboratory constraints on experimentation were managed by incorporating blocking and split-plotting into fractional-factorial designs. These characterization studies identified the important factors in each process step and provided a regression model relating those factors to the DAR and other attributes. The presentation will also show how the designed experiments uncovered a serious challenge to commercial ADC-X manufacturing and then provided a tool that met the challenge: the regression model formed the basis for a novel process control strategy involving an adjustable setpoint for the amount of linker in each batch. This control strategy has been successfully implemented in large-scale manufacturing.
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