PMID- 35429152
OWN - NLM
STAT- MEDLINE
DCOM- 20220819
LR  - 20220902
IS  - 1520-6033 (Electronic)
IS  - 1520-6033 (Linking)
VI  - 38
IP  - 4
DP  - 2022 Jul
TI  - An innovative strategy to recycle permeate in biologics continuous manufacturing 
      process to improve material efficiency and sustainability.
PG  - e3262
LID - 10.1002/btpr.3262 [doi]
AB  - Intensified perfusion processes are an integral part of continuous manufacturing 
      for biopharmaceuticals which enable agile operations and significant reduction in 
      cost of goods. However, they require large volumes of media to support robust 
      cell growth and maintain high productivity, posing substantial challenges to 
      operations, logistics, and process sustainability. This study explores a novel 
      strategy for reprocessing and reusing permeate from perfusion cultures for mAb 
      production. The concept was initially evaluated by recycling permeate, Protein A 
      flow-through (ProA FT) and CEX processed ProA FT in deep-well plate mock 
      perfusion and ambr(R) 250 perfusion formats. Further processing of ProA FT through 
      a cation exchange depth filter before recycling reduced process impurities such 
      as host cell proteins (HCPs) and DNA. However, a direct replacement of fresh 
      media with spent media reduces nutrient depth which results in a concomitant 
      reduction in productivity. In ambr(R) 250 bioreactors, recycling of ProA FT at 
      25%-50% replacement rates (defined as the fraction of recycled material in media) 
      resulted in a 13%-30% reduction in cumulative productivity while maintaining 
      product quality. To mitigate this, we used media concentrates which allowed 
      independent modulation of media depth by replacing a portion of diluent WFI with 
      recycled material. Results from deep-well mock perfusion studies demonstrated 
      that comparable or higher productivities relative to control can be achieved with 
      this approach. Taken together, our study demonstrates the feasibility of 
      recycling permeate in perfusion cultures. Process mass intensity (PMI) 
      calculations reveal that this approach can meaningfully improve material 
      efficiency by reducing water consumption, thereby enhancing overall bioprocess 
      sustainability.
CI  - (c) 2022 American Institute of Chemical Engineers.
FAU - Madabhushi, Sri Ranganayaki
AU  - Madabhushi SR
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Huang, Chung-Jr
AU  - Huang CJ
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Wang, Xiaowen
AU  - Wang X
AUID- ORCID: 0000-0003-3922-0126
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Bui, Ashley
AU  - Bui A
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Atieh, Tariq Bassam
AU  - Atieh TB
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Rayfield, William J
AU  - Rayfield WJ
AD  - Biologics Downstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Jayapal, Karthik P
AU  - Jayapal KP
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
FAU - Lin, Henry
AU  - Lin H
AD  - Biologics Upstream Process Development, Merck & Co., Inc., Kenilworth, New 
      Jersey, USA.
LA  - eng
PT  - Journal Article
DEP - 20220502
PL  - United States
TA  - Biotechnol Prog
JT  - Biotechnology progress
JID - 8506292
RN  - 0 (Biological Products)
RN  - 0 (Staphylococcal Protein A)
SB  - IM
MH  - Animals
MH  - *Biological Products
MH  - Bioreactors
MH  - Cell Proliferation
MH  - Cricetinae
MH  - Cricetulus
MH  - Perfusion
MH  - Staphylococcal Protein A
OTO - NOTNLM
OT  - Protein A flow-through
OT  - continuous bioprocessing
OT  - permeate recycling
OT  - process intensification
OT  - process mass intensity
EDAT- 2022/04/17 06:00
MHDA- 2022/08/20 06:00
CRDT- 2022/04/16 05:29
PHST- 2022/04/04 00:00 [revised]
PHST- 2022/02/10 00:00 [received]
PHST- 2022/04/07 00:00 [accepted]
PHST- 2022/04/17 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
PHST- 2022/04/16 05:29 [entrez]
AID - 10.1002/btpr.3262 [doi]
PST - ppublish
SO  - Biotechnol Prog. 2022 Jul;38(4):e3262. doi: 10.1002/btpr.3262. Epub 2022 May 2.