PMID- 20589669
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20100705
IS  - 1097-0290 (Electronic)
IS  - 0006-3592 (Linking)
VI  - 106
IP  - 6
DP  - 2010 Aug 15
TI  - Defining process design space for monoclonal antibody cell culture.
PG  - 894-905
LID - 10.1002/bit.22764 [doi]
AB  - The concept of design space has been taking root as a foundation of in-process 
      control strategies for biopharmaceutical manufacturing processes. During mapping 
      of the process design space, the multidimensional combination of operational 
      variables is studied to quantify the impact on process performance in terms of 
      productivity and product quality. An efficient methodology to map the design 
      space for a monoclonal antibody cell culture process is described. A failure 
      modes and effects analysis (FMEA) was used as the basis for the process 
      characterization exercise. This was followed by an integrated study of the 
      inoculum stage of the process which includes progressive shake flask and seed 
      bioreactor steps. The operating conditions for the seed bioreactor were studied 
      in an integrated fashion with the production bioreactor using a two stage design 
      of experiments (DOE) methodology to enable optimization of operating conditions. 
      A two level Resolution IV design was followed by a central composite design 
      (CCD). These experiments enabled identification of the edge of failure and 
      classification of the operational parameters as non-key, key or critical. In 
      addition, the models generated from the data provide further insight into 
      balancing productivity of the cell culture process with product quality 
      considerations. Finally, process and product-related impurity clearance was 
      evaluated by studies linking the upstream process with downstream purification. 
      Production bioreactor parameters that directly influence antibody charge variants 
      and glycosylation in CHO systems were identified.
FAU - Abu-Absi, Susan Fugett
AU  - Abu-Absi SF
AD  - Manufacturing Sciences & Technology, Bristol-Myers Squibb Co., 6000 Thompson 
      Road, East Syracuse, New York 13057, USA.
FAU - Yang, LiYing
AU  - Yang L
FAU - Thompson, Patrick
AU  - Thompson P
FAU - Jiang, Canping
AU  - Jiang C
FAU - Kandula, Sunitha
AU  - Kandula S
FAU - Schilling, Bernhard
AU  - Schilling B
FAU - Shukla, Abhinav A
AU  - Shukla AA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biotechnol Bioeng
JT  - Biotechnology and bioengineering
JID - 7502021
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*biosynthesis
MH  - Bioreactors
MH  - Biotechnology/*methods
MH  - CHO Cells
MH  - Cell Culture Techniques/methods
MH  - Cricetinae
MH  - Cricetulus
MH  - Drug Industry/*methods
MH  - Recombinant Proteins/biosynthesis
EDAT- 2010/07/01 06:00
MHDA- 2010/11/05 06:00
CRDT- 2010/07/01 06:00
PHST- 2010/07/01 06:00 [entrez]
PHST- 2010/07/01 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
AID - 10.1002/bit.22764 [doi]
PST - ppublish
SO  - Biotechnol Bioeng. 2010 Aug 15;106(6):894-905. doi: 10.1002/bit.22764.