PMID- 33253568
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20210623
IS  - 1520-6904 (Electronic)
IS  - 0022-3263 (Print)
IS  - 0022-3263 (Linking)
VI  - 86
IP  - 1
DP  - 2021 Jan 1
TI  - Sustainability Challenges and Opportunities in Oligonucleotide Manufacturing.
PG  - 49-61
LID - 10.1021/acs.joc.0c02291 [doi]
AB  - With a renewed and growing interest in therapeutic oligonucleotides across the 
      pharmaceutical industry, pressure is increasing on drug developers to take more 
      seriously the sustainability ramifications of this modality. With 12 
      oligonucleotide drugs reaching the market to date and hundreds more in clinical 
      trials and preclinical development, the current state of the art in 
      oligonucleotide production poses a waste and cost burden to manufacturers. Legacy 
      technologies make use of large volumes of hazardous reagents and solvents, as 
      well as energy-intensive processes in synthesis, purification, and isolation. In 
      2016, the American Chemical Society (ACS) Green Chemistry Institute 
      Pharmaceutical Roundtable (GCIPR) identified the development of greener processes 
      for oligonucleotide Active Pharmaceutical Ingredients (APIs) as a critical unmet 
      need. As a result, the Roundtable formed a focus team with the remit of 
      identifying green chemistry and engineering improvements that would make 
      oligonucleotide production more sustainable. In this Perspective, we summarize 
      the present challenges in oligonucleotide synthesis, purification, and isolation; 
      highlight potential solutions; and encourage synergies between academia; contract 
      research, development and manufacturing organizations; and the pharmaceutical 
      industry. A critical part of our assessment includes Process Mass Intensity (PMI) 
      data from multiple companies to provide preliminary baseline metrics for current 
      oligonucleotide manufacturing processes.
FAU - Andrews, Benjamin I
AU  - Andrews BI
AUID- ORCID: 0000-0002-7852-3675
AD  - Chemical Development, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom.
FAU - Antia, Firoz D
AU  - Antia FD
AD  - Biogen, Inc., Cambridge, Massachusetts 02142, United States.
FAU - Brueggemeier, Shawn B
AU  - Brueggemeier SB
AD  - Bristol-Myers Squibb, New Brunswick, New Jersey 08901, United States.
FAU - Diorazio, Louis J
AU  - Diorazio LJ
AD  - Chemical Development, Pharmaceutical Technology & Development, Operations, 
      AstraZeneca, Macclesfield SK10 4TF, United Kingdom.
FAU - Koenig, Stefan G
AU  - Koenig SG
AUID- ORCID: 0000-0002-1878-614X
AD  - Genentech, Inc., A Member of the Roche Group, South San Francisco, California 
      94080, United States.
FAU - Kopach, Michael E
AU  - Kopach ME
AD  - Eli Lilly and Company, 1400 West Raymond Street, Indianapolis, Indiana 46285, 
      United States.
FAU - Lee, Heewon
AU  - Lee H
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, United 
      States.
FAU - Olbrich, Martin
AU  - Olbrich M
AD  - F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
FAU - Watson, Anna L
AU  - Watson AL
AD  - Chemical Development, Pharmaceutical Technology & Development, Operations, 
      AstraZeneca, Macclesfield SK10 4TF, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20201130
PL  - United States
TA  - J Org Chem
JT  - The Journal of organic chemistry
JID - 2985193R
RN  - 0 (Oligonucleotides)
RN  - 0 (Solvents)
SB  - IM
MH  - *Drug Industry
MH  - *Oligonucleotides
MH  - Solvents
PMC - PMC8154579
COIS- The authors declare no competing financial interest.
EDAT- 2020/12/01 06:00
MHDA- 2021/06/24 06:00
PMCR- 2021/05/27
CRDT- 2020/11/30 20:09
PHST- 2020/12/01 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2020/11/30 20:09 [entrez]
PHST- 2021/05/27 00:00 [pmc-release]
AID - 10.1021/acs.joc.0c02291 [doi]
PST - ppublish
SO  - J Org Chem. 2021 Jan 1;86(1):49-61. doi: 10.1021/acs.joc.0c02291. Epub 2020 Nov 
      30.