Improved iGAL 2.0 Metric Empowers Pharmaceutical Scientists to Make Meaningful Contributions to United Nations Sustainable Development Goal 12

Roschangar, Frank; Li, Jun; Zhou, YanYan; Aelterman, Wim; Borovika, Alina; Colberg, Juan; Dickson, David P.; Gallou, Fabrice; Sheldon, Roger A.

doi:10.1021/acssuschemeng.1c01940

Cited by 44 publications

(41 citation statements)

References 32 publications

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“…The product was deemed to be free of residual protein as none was detected by the Bradford assay. In terms of green chemistry metrics, the Complete Environmental Impact Factor (cEF) of this enzymatic process is 65 kg·kg –1 (176 kg·kg –1 , including substrate synthesis), which leads to a relative process greenness (RPG) of 31%. , …”

Section: Resultsmentioning

confidence: 99%

Discovery and Process Development of a Scalable Biocatalytic Kinetic Resolution toward Synthesis of a Sterically Hindered Chiral Ketone

Wamser

Buono

et al. 2022

Org. Process Res. Dev.

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Sterically hindered chiral ketones are useful intermediates in the synthesis of active pharmaceutical ingredients. Here, we report a scalable and highly enantioselective synthesis through a kinetic resolution process promoted by a wild-type ketoreductase (KRED) enzyme. The process was investigated thoroughly, including DoE optimizations and a kinetic study. Scale-up demonstrations on up to 0.8 kg revealed an enzyme aggregation/deactivation challenge, and solutions were provided to obtain the desired enantiomer in high yields and enantiomeric excesses with relatively low enzyme loadings (2−4 wt %).

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Section: Resultsmentioning

confidence: 99%

Discovery and Process Development of a Scalable Biocatalytic Kinetic Resolution toward Synthesis of a Sterically Hindered Chiral Ketone

Wamser

Buono

et al. 2022

Org. Process Res. Dev.

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“…The iGAL can be represented employing eqs and , where mGAL defines the average coproduced waste per unit of average commercial drug FMW. The FMW describes the salt-free MW of API excluding salt, cocrystal, or solvate components. Based on iGAL, the calculation of RPG will be as per the following equation: Roschangar et al proposed an improved model for the metric named iGAL 2.0 to overcome current obstacles related to iGAL. It can serve the purpose of the United Nations Sustainable Development Goal 12, which aims at significantly reducing production waste by 2030 with a vision to catalyze greener API manufacturing around the world.…”

Section: Green Chemistry (Gc)mentioning

confidence: 99%

Green Chemistry in the Synthesis of Pharmaceuticals

et al. 2021

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The principles of green chemistry (GC) can be comprehensively implemented in green synthesis of pharmaceuticals by choosing no solvents or green solvents (preferably water), alternative reaction media, and consideration of one-pot synthesis, multicomponent reactions (MCRs), continuous processing, and process intensification approaches for atom economy and final waste reduction. The GC's execution in green synthesis can be performed using a holistic design of the active pharmaceutical ingredient's (API) life cycle, minimizing hazards and pollution, and capitalizing the resource efficiency in the synthesis technique. Thus, the presented review accounts for the comprehensive exploration of GC's principles and metrics, an appropriate implication of those ideas in each step of the reaction schemes, from raw material to an intermediate to the final product's synthesis, and the final execution of the synthesis into scalable industry-based production. For real-life examples, we have discussed the synthesis of a series of established generic pharmaceuticals, starting with the raw materials, and the intermediates of the corresponding pharmaceuticals. Researchers and industries have thoughtfully instigated a green synthesis process to control the atom economy and waste reduction to protect the environment. We have extensively discussed significant reactions relevant for green synthesis, one-pot cascade synthesis, MCRs, continuous processing, and process intensification, which may contribute to the future of green and sustainable synthesis of APIs. CONTENTS1. Introduction 3638 2. Green Chemistry (GC) 3639 2.1. Definition 3639 2.2. The Principles of GC 3641 2.3. The Metrics of GC 3641 2.3.1. Standardization of the E Factor Concept 3641 2.3.2. Baran's Process Ideality Metric 3641 2.3.3. Identification of Process Complexity 3641 2.3.4. The Green Aspiration Level Concept 3642 2.3.5. Innovation Green Aspiration Level (iGAL) 3642 3. The Choice of Solvents in the Green Synthesis of APIs 3642 4. The Reaction with Green Solvents 3643 4.1. The No-Solvent Process 3644 4.

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“…The recently introduced iGAL 2.0 model represents a valuable extension to PMI for API manufacturing by putting this efficiency measure into perspective by accounting for molecular complexity and development phases of the APIs . iGAL 2.0 thereby enables quantitative assessment of a Relative Process Greenness (RPG) score to identify potentially underperforming and environmentally concerning processes early in their development cycle and thereby deliver environmental and economic values.…”

Section: Igal 20 Calculatormentioning

confidence: 99%

“…6 ■ IGAL 2.0 CALCULATOR The recently introduced iGAL 2.0 model represents a valuable extension to PMI for API manufacturing by putting this efficiency measure into perspective by accounting for molecular complexity and development phases of the APIs. 7 iGAL 2.0 thereby enables quantitative assessment of a Relative Process Greenness (RPG) score to identify potentially underperforming and environmentally concerning processes early in their development cycle and thereby deliver environmental and economic values. The metric is complemented by its Scorecard Calculator companion 8 to highlight the impact of innovation on reductions of API manufacturing waste, which enables scientists to readily communicate the value of their work, thereby empowering and inspiring them to make meaningful and significant contributions to global sustainability.…”

Section: ■ Pmi Calculatorsmentioning

confidence: 99%

Making Sustainability Assessment Accessible: Tools Developed by the ACS Green Chemistry Institute Pharmaceutical Roundtable

Diorazio¹,

Richardson²,

Sneddon³

et al. 2021

ACS Sustainable Chem. Eng.

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Improved iGAL 2.0 Metric Empowers Pharmaceutical Scientists to Make Meaningful Contributions to United Nations Sustainable Development Goal 12

Cited by 44 publications

References 32 publications

Discovery and Process Development of a Scalable Biocatalytic Kinetic Resolution toward Synthesis of a Sterically Hindered Chiral Ketone

Discovery and Process Development of a Scalable Biocatalytic Kinetic Resolution toward Synthesis of a Sterically Hindered Chiral Ketone

Green Chemistry in the Synthesis of Pharmaceuticals

Making Sustainability Assessment Accessible: Tools Developed by the ACS Green Chemistry Institute Pharmaceutical Roundtable

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