Downstream processing of monoclonal antibodies - Application of platform approaches

被引:672
作者
Shukla, Abhinav A.
Hubbard, Brian
Tressel, Tim
Guhan, Sam
Low, Duncan
机构
[1] Amgen Inc, Prod Dev, Thousand Oaks, CA 91320 USA
[2] Amgen Inc, Proc Dev, Seattle, WA 98119 USA
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2007年 / 848卷 / 01期
关键词
monoclonal antibodies; fc fusion proteins; cell culture harvest; protein a chromatography; viral inactivation; viral filtration; ultrafiltration/diafiltration; process characterization; process validation;
D O I
10.1016/j.jchromb.2006.09.026
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
This paper presents an overview of large-scale downstream processing of monoclonal antibodies and Fc fusion proteins (mAbs). This therapeutic modality has become increasingly important with the recent approval of several drugs from this product class for a range of critical illnesses. Taking advantage of the biochemical similarities in this product class, several templated purification schemes have emerged in the literature. In our experience, significant biochemical differences and the variety of challenges to downstream purification make the use of a completely generic downstream process impractical. Here, we describe the key elements of a flexible, generic downstream process platform for mAbs that we have adopted at Amgen. This platform consists of a well-defined sequence of unit operations with most operating parameters being pre-defined and a small subset of parameters requiring development effort. The platform hinges on the successful use of Protein A chromatography as a highly selective capture step for the process. Key elements of each type of unit operation are discussed along with data from 14 mAbs that have undergone process development. Aspects that can be readily templated as well as those that require focused development effort are identified for each unit operation. A brief description of process characterization and validation activities for these molecules is also provided. Finally, future directions in mAb processing are summarized. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:28 / 39
页数:12
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