PMID- 27447837
OWN - NLM
STAT- MEDLINE
DCOM- 20170119
LR  - 20170119
IS  - 1860-7314 (Electronic)
IS  - 1860-6768 (Linking)
VI  - 11
IP  - 10
DP  - 2016 Oct
TI  - Continuous precipitation of process related impurities from clarified cell 
      culture supernatant using a novel coiled flow inversion reactor (CFIR).
PG  - 1320-1331
LID - 10.1002/biot.201600271 [doi]
AB  - Coiled Flow Inverter Reactor (CFIR) has recently been explored for facilitating 
      continuous operation of several unit operations involved in downstream processing 
      of biopharmaceuticals such as viral inactivation and protein refolding. The 
      application of CFIR for continuous precipitation of clarified cell culture 
      supernatant has been explored. The pH based precipitation is optimized in the 
      batch mode and then in the continuous mode in CFIR using a design of experiments 
      (DOE) study. Improved clearance of host cell DNA (52x vs. 39x in batch), improved 
      clearance of host cell proteins (HCP) (7x vs. 6x in batch) and comparable 
      recovery (90 vs. 91.5 % in batch) are observed along with six times higher 
      productivity. To further demonstrate wider applicability of CFIR in performing 
      continuous precipitation, two more case studies involving use of two different 
      precipitation protocols (CaCl(2) based and caprylic acid based) are also 
      performed. In both cases, clearance of host cell DNA, HCP, and product recovery 
      are found to be comparable or better in CFIR than in batch operations. Moreover, 
      increase in productivity of 16 times (CaCl(2) based) and eight times (caprylic 
      acid based) is obtained for the two precipitation protocols, respectively. The 
      data clearly demonstrate that CFIR can be seamlessly integrated into a continuous 
      bioprocess train for performing continuous precipitation of clarified cell 
      culture supernatant. To our knowledge this is the first report of such use.
CI  - Copyright (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Kateja, Nikhil
AU  - Kateja N
AD  - Department of Chemical Engineering, Indian Institute of Technology Delhi, New 
      Delhi, India.
FAU - Agarwal, Harshit
AU  - Agarwal H
AD  - Department of Chemical Engineering, Indian Institute of Technology Delhi, New 
      Delhi, India.
FAU - Saraswat, Aditya
AU  - Saraswat A
AD  - Department of Chemical Engineering, Indian Institute of Technology Delhi, New 
      Delhi, India.
FAU - Bhat, Manish
AU  - Bhat M
AD  - Department of Chemical Engineering, Indian Institute of Technology Delhi, New 
      Delhi, India.
FAU - Rathore, Anurag S
AU  - Rathore AS
AD  - Department of Chemical Engineering, Indian Institute of Technology Delhi, New 
      Delhi, India. asrathore@biotechcmz.com.
LA  - eng
PT  - Journal Article
DEP - 20160811
PL  - Germany
TA  - Biotechnol J
JT  - Biotechnology journal
JID - 101265833
RN  - 0 (Caprylates)
RN  - 0 (Proteins)
RN  - 9007-49-2 (DNA)
RN  - M4I0D6VV5M (Calcium Chloride)
RN  - OBL58JN025 (octanoic acid)
SB  - IM
MH  - Animals
MH  - Bioreactors
MH  - Biotechnology/*instrumentation/methods
MH  - CHO Cells
MH  - Calcium Chloride/chemistry
MH  - Caprylates/chemistry
MH  - Cell Culture Techniques
MH  - Chemical Precipitation
MH  - Cricetulus
MH  - DNA/*analysis
MH  - Proteins/*analysis
OTO - NOTNLM
OT  - Antibody Production
OT  - Coiled flow inversion reactor
OT  - Continuous precipitation
OT  - Continuous processing
OT  - Protein A chromatography
EDAT- 2016/07/23 06:00
MHDA- 2017/01/20 06:00
CRDT- 2016/07/23 06:00
PHST- 2016/04/29 00:00 [received]
PHST- 2016/06/28 00:00 [revised]
PHST- 2016/07/08 00:00 [accepted]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2017/01/20 06:00 [medline]
PHST- 2016/07/23 06:00 [entrez]
AID - 10.1002/biot.201600271 [doi]
PST - ppublish
SO  - Biotechnol J. 2016 Oct;11(10):1320-1331. doi: 10.1002/biot.201600271. Epub 2016 
      Aug 11.