Sustainability Challenges and Opportunities in Oligonucleotide Manufacturing.
Sustainability Challenges and Opportunities in Oligonucleotide Manufacturing.
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DOI：
10.1021/acs.joc.0c02291
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发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Watson AL
中科院分区：
文献类型：
--
作者：
Andrews BI;Antia FD;Brueggemeier SB;Diorazio LJ;Koenig SG;Kopach ME;Lee H;Olbrich M;Watson AL
随着制药行业对治疗性寡核苷酸的重新产生和日益增长的兴趣，药物开发商面临着越来越大的压力，要求他们更认真地对待这种模式的可持续性后果。到目前为止，已有12种寡核苷酸药物上市，还有数百种正在进行临床试验和临床前开发，目前的寡核苷酸生产水平给制造商带来了浪费和成本负担。传统技术使用大量的危险试剂和溶剂，以及在合成、纯化和分离过程中的能源密集型过程。2016年，美国化学学会(ACS)绿色化学研究所药物圆桌会议(GCIPR)将开发寡核苷酸活性药物成分(API)的更绿色工艺确定为一项关键的未得到满足的需求。因此，圆桌会议组成了一个重点小组，其职责是确定使寡核苷酸生产更可持续的绿色化学和工程改进。在这一视角下，我们总结了目前在寡核苷酸合成、纯化和分离方面的挑战；强调了潜在的解决方案；并鼓励学术界、合同研究、开发和制造组织以及制药行业之间的协同作用。我们评估的一个关键部分包括来自多家公司的过程质量强度(PMI)数据，以提供当前寡核苷酸制造过程的初步基线指标。
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.
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