PMID- 20300882
OWN - NLM
STAT- MEDLINE
DCOM- 20100915
LR  - 20211020
IS  - 1559-0305 (Electronic)
IS  - 1073-6085 (Linking)
VI  - 45
IP  - 3
DP  - 2010 Jul
TI  - Characterization of a monoclonal antibody cell culture production process using a 
      quality by design approach.
PG  - 203-6
LID - 10.1007/s12033-010-9267-4 [doi]
AB  - The goal of quality by design (QbD) in cell culture manufacturing is to develop 
      manufacturing processes which deliver products with consistent critical quality 
      attributes (CQAs). QbD approaches can lead to better process understanding 
      through the use of process parameter risk ranking and statistical design of 
      experiments (DOE). The QbD process starts with an analysis of process parameter 
      risk with respect to CQAs and key performance indicators (KPIs). Initial DOE 
      study designs and their factor test ranges are based on the outcomes of the 
      process parameter risk ranking exercises. Initial DOE studies screen factors for 
      significant influences on CQAs as well as characterize responses for process 
      KPIs. In the case study provided here, multifactor process characterization 
      studies using a scale-down model resulted in significant variation in charge 
      heterogeneity of a monoclonal antibody (MAb) as measured by ion-exchange 
      chromatography (IEC). Iterative DOE studies, using both screening and response 
      surface designs, were used to narrow the operating parameter ranges so that 
      charge heterogeneity could be controlled to an acceptable level. The data from 
      the DOE studies were used to predict worst-case conditions, which were then 
      verified by testing at those conditions. Using the approach described here, 
      multivariate process parameter ranges were identified that yield acceptable CQA 
      levels and that still provide operational flexibility for manufacturing.
FAU - Horvath, Brian
AU  - Horvath B
AD  - Late Stage Cell Culture, BioProcess Development US, Genentech-a member of the 
      Roche Group, San Francisco, CA, USA. horvath.brian@gene.com
FAU - Mun, Melissa
AU  - Mun M
FAU - Laird, Michael W
AU  - Laird MW
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Mol Biotechnol
JT  - Molecular biotechnology
JID - 9423533
RN  - 0 (Acids)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Culture Media)
SB  - IM
MH  - Acids
MH  - Analysis of Variance
MH  - Animals
MH  - Antibodies, Monoclonal/*biosynthesis
MH  - Bioreactors
MH  - CHO Cells
MH  - Cell Culture Techniques/*methods
MH  - Chromatography, Ion Exchange
MH  - Cricetinae
MH  - Cricetulus
MH  - Culture Media
MH  - Hydrogen-Ion Concentration
MH  - Reproducibility of Results
MH  - Research Design
MH  - Temperature
EDAT- 2010/03/20 06:00
MHDA- 2010/09/16 06:00
CRDT- 2010/03/20 06:00
PHST- 2010/03/20 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2010/09/16 06:00 [medline]
AID - 10.1007/s12033-010-9267-4 [doi]
PST - ppublish
SO  - Mol Biotechnol. 2010 Jul;45(3):203-6. doi: 10.1007/s12033-010-9267-4.