PMID- 30267619
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1520-6033 (Electronic)
IS  - 1520-6033 (Linking)
VI  - 34
IP  - 6
DP  - 2018 Nov
TI  - Quantitative assessment of environmental impact of biologics manufacturing using 
      process mass intensity analysis.
PG  - 1566-1573
LID - 10.1002/btpr.2702 [doi]
AB  - Process mass intensity (PMI) is a benchmarking metric to evaluate the efficiency 
      of a manufacturing process, which is indicative of the environmental impact of 
      the process. Although this metric is commonly applied for small molecule 
      manufacturing processes, it is less commonly applied to biologics. In this study, 
      an Excel based tool developed by the ACS GCI Pharmaceutical Roundtable was used 
      to calculate PMI of different manufacturing processes for a monoclonal antibody 
      (mAb). For the upstream process, three different versions were compared: 
      fed-batch, fed-batch with N-1 perfusion, and perfusion in the N-stage bioreactor. 
      For each upstream process version, an appropriate downstream operational mode was 
      evaluated from the following: a column chromatography process utilizing Protein A 
      and anion exchange (AEX) resin, a Protein A column and an AEX membrane, and a 
      three-column periodic counter-current (3C PCC) chromatography process for Protein 
      A and an AEX membrane. The impact of these different process variations on PMI 
      was evaluated. Of all the process inputs, water contributes about 92-94% of the 
      overall PMI. Additionally, the upstream processes and the chromatography steps 
      account for 32-47 and 34-54% of the overall PMI, respectively. Sensitivity 
      analysis was performed to identify opportunities for further reducing PMI. These 
      data indicate that a semicontinuous manufacturing process (perfusion, 3C PCC, and 
      AEX membrane) is the most efficient process, resulting in a 23% reduction of PMI 
      when compared with the fed batch and two-column chromatography process. Together, 
      PMI can be used to guide the development of efficient and environmentally 
      sustainable mAb manufacturing processes. (c) 2018 American Institute of Chemical 
      Engineers Biotechnol. Prog., 34:1566-1573, 2018.
CI  - (c) 2018 American Institute of Chemical Engineers.
FAU - Madabhushi, Sri R
AU  - Madabhushi SR
AUID- ORCID: 0000-0003-3847-3084
AD  - Upstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Gavin, John
AU  - Gavin J
AD  - Environmental Sustainability COE, Merck & Co., Inc., 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Xu, Sen
AU  - Xu S
AUID- ORCID: 0000-0001-7185-6779
AD  - Upstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Cutler, Collette
AU  - Cutler C
AD  - Downstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Chmielowski, Rebecca
AU  - Chmielowski R
AD  - Downstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Rayfield, William
AU  - Rayfield W
AD  - Downstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Tugcu, Nihal
AU  - Tugcu N
AD  - Downstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
FAU - Chen, Hao
AU  - Chen H
AD  - Upstream Process Development and Engineering, Biologics Process Development and 
      Clinical Manufacturing, Merck & Co., Inc. (USA), 2000 Galloping Hill Road, 
      Kenilworth, New Jersey, 07033.
LA  - eng
PT  - Journal Article
DEP - 20180929
PL  - United States
TA  - Biotechnol Prog
JT  - Biotechnology progress
JID - 8506292
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Staphylococcal Protein A)
SB  - IM
MH  - Antibodies, Monoclonal/chemistry
MH  - Bioreactors
MH  - Chromatography/*methods
MH  - Staphylococcal Protein A/*chemistry
OTO - NOTNLM
OT  - environmental
OT  - mAb
OT  - manufacturing process
OT  - process mass intensity
OT  - sustainability
EDAT- 2018/09/30 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/09/30 06:00
PHST- 2018/04/01 00:00 [received]
PHST- 2018/07/11 00:00 [revised]
PHST- 2018/09/30 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/09/30 06:00 [entrez]
AID - 10.1002/btpr.2702 [doi]
PST - ppublish
SO  - Biotechnol Prog. 2018 Nov;34(6):1566-1573. doi: 10.1002/btpr.2702. Epub 2018 Sep 
      29.