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          <div hidden="">https://doi.org/10.1016/j.cogsc.2021.100564</div>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2452223621001206" id="S2452223621001206" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Green metrics in pharmaceutical development</span></span></a>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Concepcion “Conchita” Jimenez-Gonzalez, Claire Lund</div>
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            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100564</dd>
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                            <p>This short review presents an overview of key metrics that have been used to assess the ‘greenness’ of pharmaceutical processes in development in the larger context of environmental sustainability. The green metrics
                              cover areas of resource efficiency (mass and energy), environment, health, and safety considerations, and life cycle assessment. There is also a discussion of currently unmet needs in the area that need enhanced focus.
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          <div hidden="">https://doi.org/10.1016/j.cogsc.2021.100569</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Roger A. Sheldon, Moira L. Bode, Stephanie G. Akakios</div>
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                            <p>The increasingly apparent negative impact of human activities on the environment has heightened the urgency for the chemistry community to adopt greener and more sustainable practices. The E-factor can still be
                              considered a valuable tool in this drive, particularly because of its broad acceptance and familiarity amongst both industrial and academic chemists. An important factor in broadening the adoption of green principles is
                              ensuring that the academics responsible for training the next generation of chemists prioritise green and sustainable practices in their undergraduate and post graduate laboratories. Green metrics must be easy to use to
                              motivate the broader chemistry community to develop greener syntheses. For maximum impact to be achieved the detail of the exact green metrics applied are less important than their adoption by the broader chemical
                              community. Of growing importance is the replacement of fossil resources with renewable alternatives to reduce greenhouse gas emission that is a significant driver of climate change. The C factor is used to compare the
                              carbon footprints of different routes to a particular product.</p>
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          <div hidden="">https://doi.org/10.1016/j.cogsc.2021.100571</div>
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                            <p>Synthetic chemistry relies heavily on organic solvents which are often toxic and hazardous as well as expensive in purchase and disposal. The application of water as an alternative reaction medium is not only
                              advantageous from an environmental and safety perspective but can also offer improved selectivity and reaction rates. The exploration of this new, sustainable approach comes along with an ever-growing spectrum of
                              reaction procedures. In this current opinion, we provide an overview of a new methodology that uses a polymeric cellulose derivative, hydroxypropyl methylcellulose, to enable chemical reactions in water.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Insights into EcoScent Compass™, a holistic tool to measure a fragrance's sustainability footprint, based on its intrinsic green properties and
                environmental impact</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.cogsc.2021.100583</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Fabrice Robvieux, Jocelyn Roth, Christian Chapuis, Maud Reiter</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">February 2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100583</dd>
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                            <p>In response to demands for more transparency on the impact of its fragrance products on both people and the planet, Firmenich developed a new, holistic digital assessment tool, EcoScent Compass™, to rank both perfumery
                              ingredients and perfumery formulations in terms of green chemistry as well as environmental footprint criteria. Using knowledge gathered in the field of green and sustainable chemistry over the past 20 years,
                              multi-indicator&nbsp;clusters have been deployed and combined into a single index for green properties and environmental impact.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Defossilization of pharmaceutical manufacturing</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.cogsc.2021.100586</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Lea Wollensack, Kristi Budzinski, Jan Backmann</div>
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            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100586</dd>
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                            <p>As is true with most established industries, a significant portion of the raw materials used in the pharmaceutical industry is of fossil origin, that is, essentially can be traced back to crude oil. The present article
                              attempts to assess to which degree the modern manufacturing of pharmaceuticals depends on raw materials of fossil carbon compounds and which could be appropriate ways to increasingly switch to non-fossil sourcing to
                              eventually completely defossilize the raw-material base of the sector.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Designing for sustainability with biocatalytic and chemoenzymatic cascade processes</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.cogsc.2022.100591</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Chihui An, Kevin M. Maloney</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">April 2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100591</dd>
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                            <p>Cascade reactions have been widely recognized to cut costs, decrease solvent usage, and reduce cycle times in chemical processes. Recently, biocatalytic cascades have altered how we design synthetic routes to complex
                              molecules to achieve sustainable commercial processes for pharmaceutical, agricultural, and fine chemical industries. With advancements in protein engineering and an increase in the number of enzyme classes available to
                              chemists, industrial and academic groups alike have endeavored to expand the scope of biocatalysis from single reactions to multi-enzyme cascades to rapidly build complex molecular structures. Recent reports have drawn
                              inspiration from biosynthetic pathways and have applied engineered enzymes to <em>in&nbsp;vitro</em> enzymatic cascades. Furthermore, combining transition-metal catalysis and enzymes in one-pot chemoenzymatic cascades
                              likewise serves to broaden the scope of biocatalysis, enabling traditional chemical reactions to be performed under mild aqueous conditions. In this article, we review recent biocatalytic and chemoenzymatic cascades from
                              2019 to 2021.</p>
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          <div hidden="">https://doi.org/10.1016/j.cogsc.2022.100606</div>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2452223622000189" id="S2452223622000189" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">“The hidden power and competitive advantage of applying green chemistry metrics”</span></span></a>
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              <div class="text-s u-clr-grey8 js-article__item__authors">John L. Tucker</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">June 2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100606</dd>
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                            <p>Green chemistry (GC) metrics provide insight into the relative waste, time and cost implications of pharmaceutical chemical processes and serve to guide scientists in the strategic application of resources to develop
                              more efficient and sustainable processes. Examples of the application of GC metrics in evaluating pharmaceutical process efficiency and the subsequent development toward improvement exist in abundance from journals such
                              as <em>Organic Process Research and Development</em>, <em>Green Chemistry</em>, or as encompassed by the winning examples from the ACS GCI Pharmaceutical Roundtable's [1] Peter J. Dunn award [2] or the US EPA's Green
                              Chemistry Challenge award [3]. By their nature, GC metrics are continuously evolving but justify the necessary, unceasing investment in understanding and application as they offer unique, opportunistic insight serving to
                              guide scientific resource deployment when developing greener pharmaceutical, chemical processes.</p>
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          <div hidden="">https://doi.org/10.1016/j.cogsc.2022.100614</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Sarah Argoud, Kristi Budzinski, Daniel D'Aquila, Sri R. Madabhushi, Phillip Smith</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">June 2022</dd>
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                            <p>Biologics are the fastest growing segment of the pharmaceutical market, therefore, the environmental impact of manufacturing these drugs needs to be fully characterized. For monoclonal antibodies, in particular, several
                              metrics have been identified as the manufacturing process is quite standardized for batch processes. This paper will provide an overview of carbon footprint analysis, process mass intensity (PMI), water related impact of
                              energy (WARIEN) and life cycle assessment (LCA) as they have been applied to monoclonal antibody production. Further development and standardization of these tools will allow the industry to identify and implement new
                              technologies that significantly lower the environmental impact of not only monoclonal antibody production but other modalities as well.</p>
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          <div hidden="">https://doi.org/10.1016/j.cogsc.2022.100643</div>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Michael E. Kopach, Benjamin I. Andrews</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">October 2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100643</dd>
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                            <p>This review article highlights the need for the development of synthetic peptide and oligonucleotide manufacturing processes with improved sustainability credentials. These therapeutic classes are fast growing and have
                              the potential to deliver multiple high volume products over the next decade. While there have been significant technical innovations in the past few years there is limited evidence for adoption of these new technologies
                              in manufacturing, which still largely rely on traditional approaches that generate large quantities of waste and use many chemicals of concern. Examples of strategies that could improve the environmental footprint for
                              peptides include Tag-Assisted Liquid-Phase Peptide Synthesis, Hybrid Solid/Liquid Phase Peptide Synthesis and the implementation of continuous processes. For oligonucleotides, convergent liquid-phase synthesis and
                              enzyme-catalyzed synthesis strategies are highlighted which have potential for significant positive environmental improvement if incorporated into the development lifecycle. To guide development, the collection of
                              baseline sustainability metrics such as Process Mass Intensity is recommended.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Assessment of analytical testing: The impact of metrics for the sustainable measurement of pharmaceuticals</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.cogsc.2022.100689</div>
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            <dd class="article-info text-xs"><span class="js-article-subtype">Review article</span><span class="js-open-access"><span class="js-access-indicator u-margin-xs-hor access-indicator-no"></span>Abstract only</span></dd>
            <dt>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2452223622001018" id="S2452223622001018" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Assessment of analytical testing: The impact of metrics for the sustainable measurement of pharmaceuticals</span></span></a>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Michael B. Hicks, Sean Oriana, Yong Liu</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">December 2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100689</dd>
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                            <p>Analytical metrics allow a periodic, healthy examination of methods and how they impact the environment, while ensuring that procedures are reproducible, reliable, repeatable, transferable, and of high quality. This
                              article provides a review of current trends with analytical metrics, such as the analytical method green score (AMGS). More importantly, the AMGS impact on sample preparation, development strategy, and energy consumption
                              considerations are provided. Finally, recent uses of metrics with specific relevance to the pharmaceutical research and development area through method transfer are covered.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article National leadership and cross-sector collaboration could help overcome differences in stakeholder definitions of sustainable chemistry</span></label>
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          <div hidden="">https://doi.org/10.1016/j.crgsc.2021.100222</div>
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              </h3>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Summer Lingard Smith, Diane B. Raynes, Karen L. Howard</div>
            </dd>
            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100222</dd>
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                          <h5>Abstract</h5>
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                            <p>GAO conducted a technology assessment to explore among other things, the opportunities, challenges, and stakeholder roles in sustainable chemistry. We found that stakeholders across industry, government, and academia
                              lack agreement on how to define sustainable chemistry and how to measure or assess the sustainability of chemical processes and products. These differences hinder the development and adoption of more sustainable
                              chemistry technologies. However, based on a review of the literature and stakeholder interviews, GAO identified several common themes underlying what sustainable chemistry strives to achieve – including that standard
                              definitions and metrics for sustainability are important for stakeholders. In addition, we note that national leadership and collaboration across many sectors could enhance sustainable chemistry progress. This includes
                              the potential for sustainable chemistry to inspire new products and processes, create jobs, and enhance benefits to human health and the environment. However, we found that technological and business challenges interfere
                              with efforts to implement some of these sustainable chemistry technologies, and that the diverse set of stakeholders can lead to coordination challenges. We offer strategic approaches that may help overcome these
                              challenges.</p>
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          <div hidden="">https://doi.org/10.1016/j.crgsc.2021.100229</div>
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            <dd class="article-info text-xs"><span class="js-article-subtype">Research article</span><span class="js-open-access u-text-italic"><span class="js-access-indicator u-margin-xs-hor access-indicator-yes"></span>Open access</span></dd>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086521001764" id="S2666086521001764" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Manufacturing mass intensity: 15&nbsp;​Years of Process Mass Intensity and development of the metric into plant cleaning and beyond</span></span></a>
              </h3>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Colin H. Benison, Philippa R. Payne</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100229</dd>
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                            <p>The American Chemical Society Green Chemistry Institute (ACS GCI) Pharmaceutical Roundtable is committed to continue to expand and identify elements of small-molecule active pharmaceutical ingredient (API) manufacturing
                              that should be quantified to drive towards more sustainable practices. Process mass intensity (PMI) has been used for over 15 years to evaluate and benchmark progress towards more sustainable manufacturing and quantifies
                              process input mass (e.g. solvent, water, reagents) per mass of output produced. This manuscript introduces Manufacturing Mass Intensity (MMI), a metric that builds upon and expands the scope to account for other raw
                              materials required for API manufacturing. Examples are included to illustrate how quantification of these additional resource requirements will drive more sustainable practices.</p>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Grassroots and blue skies lead to greener landscapes</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.crgsc.2021.100242</div>
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            <dd class="article-info text-xs"><span class="js-article-subtype">Research article</span><span class="js-open-access u-text-italic"><span class="js-access-indicator u-margin-xs-hor access-indicator-yes"></span>Open access</span></dd>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086521001892" id="S2666086521001892" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Grassroots and blue skies lead to greener landscapes</span></span></a>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Kristi Budzinski, Stefan G. Koenig</div>
            </dd>
            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100242</dd>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Engaging scientists in a sustainability culture</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.crgsc.2021.100247</div>
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            <dd class="article-info text-xs"><span class="js-article-subtype">Research article</span><span class="js-open-access u-text-italic"><span class="js-access-indicator u-margin-xs-hor access-indicator-yes"></span>Open access</span></dd>
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                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086521001946" id="S2666086521001946" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Engaging scientists in a sustainability culture</span></span></a>
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              <div class="text-s u-clr-grey8 js-article__item__authors">Louis J. Diorazio, Alex Mullen</div>
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            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100247</dd>
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          <div hidden="">https://doi.org/10.1016/j.crgsc.2022.100279</div>
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            <dt>
              <h3 class="text-m u-font-serif u-display-inline">
                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086522000212" id="S2666086522000212" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Sustainability case studies on the use of continuous manufacturing in pharmaceutical production</span></span></a>
              </h3>
            </dt>
            <dd class="js-article-author-list u-clr-grey8 text-s">
              <div class="text-s u-clr-grey8 js-article__item__authors">Mark S. Kerr, Kevin P. Cole</div>
            </dd>
            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100279</dd>
            <dd class="js-article-link u-margin-xs-top u-margin-s-bottom article-item-link">
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                          <h5>Abstract</h5>
                          <div>
                            <p>Continuous processing is now commonly used in the manufacturing of fine chemicals including agrochemicals and pharmaceuticals. Datasets are now available, including some on environmental sustainability aspects, that
                              enable more direct comparison between related batch and flow processes. This article examines six continuous processes where an environmental sustainability concept or metric (e.g. process mass intensity) can be compared
                              to that from a closely-related batch process in order to assess the impact that continuous manufacturing has on that theme. Some current case studies where additional Green Chemistry concepts are exemplified are shared
                              along with how continuous processing impacts the manufacture. We illustrate situations where continuous processing can reasonably be expected to show sustainability advantages over batch, as well as a scenario where
                              increased solvent usage in flow mode worsened the environmental profile. While we believe that continuous processing can provide sustainability benefits, there are cases where its application can have a negative effect
                              on environmental metrics. Our hope is to provide impartial guidance for development and manufacturing scientists so they may best utilize continuous technologies in an environmentally responsible way.</p>
                          </div>
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          <div class="checkbox checkbox-small move-left u-show-from-md"><label class="checkbox-label" for="checkbox-S2666086522000352"><input id="checkbox-S2666086522000352" type="checkbox"
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Roche's approach to green metrics in drug development</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.crgsc.2022.100293</div>
          <dl class="js-article article-content">
            <dd class="article-info text-xs"><span class="js-article-subtype">Research article</span><span class="js-open-access u-text-italic"><span class="js-access-indicator u-margin-xs-hor access-indicator-yes"></span>Open access</span></dd>
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              <h3 class="text-m u-font-serif u-display-inline">
                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086522000352" id="S2666086522000352" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Roche's approach to green metrics in drug development</span></span></a>
              </h3>
            </dt>
            <dd class="js-article-author-list u-clr-grey8 text-s">
              <div class="text-s u-clr-grey8 js-article__item__authors">Georg Wuitschik, Martin Olbrich, Stefan Hildbrand</div>
            </dd>
            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100293</dd>
            <dd class="js-article-link u-margin-xs-top u-margin-s-bottom article-item-link">
              <a class="anchor pdf-download u-margin-l-right text-s anchor-default" href="/science/article/pii/S2666086522000352/pdfft?md5=ec305461a88a5a37e40d367e39b35ca9&amp;pid=1-s2.0-S2666086522000352-main.pdf" data-aa-name="Pdf link" target="_blank" aria-describedby="S2666086522000352"><svg role="img" focusable="false" viewBox="0 0 98 128" height="20" width="18.375" class="icon icon-download" aria-label="Download"><path d="m77.38 56.18l-6.6-7.06-16.78 17.24v-40.36h-1e1v40.34l-17.72-17.24-7.3 7.08 29.2 29.32 29.2-29.32m10.62 17.82v2e1h-78v-2e1h-1e1v3e1h98v-3e1h-1e1"></path></svg><span class="anchor-text">Download PDF</span></a>
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                          <h5>Abstract</h5>
                          <div>
                            <p>This article describes standard, often used metrics and more recent developments. Efforts and possibilities on how to apply them in drug development are shown on the example of Roche.</p>
                          </div>
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                class="checkbox-label-value checkbox-small move-left u-show-from-md">select article Green and sustainable metrics: Charting the course for green-by-design small molecule API synthesis</span></label></div>
          <div hidden="">https://doi.org/10.1016/j.crgsc.2022.100324</div>
          <dl class="js-article article-content">
            <dd class="article-info text-xs"><span class="js-article-subtype">Research article</span><span class="js-open-access u-text-italic"><span class="js-access-indicator u-margin-xs-hor access-indicator-yes"></span>Open access</span></dd>
            <dt>
              <h3 class="text-m u-font-serif u-display-inline">
                <a class="anchor article-content-title u-margin-xs-top u-margin-s-bottom anchor-default" href="/science/article/pii/S2666086522000662" id="S2666086522000662" usagezone="rslt_list_item"><span class="anchor-text"><span class="js-article-title">Green and sustainable metrics: Charting the course for green-by-design small molecule API synthesis</span></span></a>
              </h3>
            </dt>
            <dd class="js-article-author-list u-clr-grey8 text-s">
              <div class="text-s u-clr-grey8 js-article__item__authors">Harrison B. Rose, Birgit Kosjek, Brittany M. Armstrong, Sandra A. Robaire</div>
            </dd>
            <dd class="u-clr-grey8 text-s js-article-item-date">2022</dd>
            <dd class="js-article-page-range u-clr-grey8 text-s">Article 100324</dd>
            <dd class="js-article-link u-margin-xs-top u-margin-s-bottom article-item-link">
              <a class="anchor pdf-download u-margin-l-right text-s anchor-default" href="/science/article/pii/S2666086522000662/pdfft?md5=b9e1979d60a2f90c7ffec79f31050296&amp;pid=1-s2.0-S2666086522000662-main.pdf" data-aa-name="Pdf link" target="_blank" aria-describedby="S2666086522000662"><svg role="img" focusable="false" viewBox="0 0 98 128" height="20" width="18.375" class="icon icon-download" aria-label="Download"><path d="m77.38 56.18l-6.6-7.06-16.78 17.24v-40.36h-1e1v40.34l-17.72-17.24-7.3 7.08 29.2 29.32 29.2-29.32m10.62 17.82v2e1h-78v-2e1h-1e1v3e1h98v-3e1h-1e1"></path></svg><span class="anchor-text">Download PDF</span></a>
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                            <p>Sustainable small molecule Active Pharmaceutical Ingredient (API) manufacturing starts at the onset of route development by employing a Green-by-Design strategy. Reliable metrics are imperative for setting targets and
                              measuring process improvements throughout the development cycle. This article reviews some of the many tools and methods established to analyze and assess the greenness and sustainability of a process, each of which
                              highlights different aspects of process efficiency, waste formation or overall environmental impact reduction. Most calculations, such as process mass intensity (PMI), are mass-based and do not consider the types of raw
                              materials used. In contrast, a full life cycle assessment (LCA) offers detailed information about the “cradle to grave” environmental impact of a manufacturing route and its specific resources, but the high data
                              requirements and long timelines are not conducive for multiple processes or repeated assessments during process optimization. To address these challenges, we introduce a Streamlined PMI-LCA Tool, developed in
                              collaboration with the ACS Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR), that combines PMI with a “cradle to gate” approach to include the environmental footprint of the synthesis’ raw materials. The
                              frequent re-evaluation of a process continuously highlights areas for improvement and guides the prioritization of process development activities to effectively and rapidly achieve a Green-by-Design commercial synthetic
                              route. The utility of this approach to Green-by-Design is demonstrated with the reduction of PMI for MK-7264 from 366 to 88 over the course of process development.</p>
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Guide for authors


METRICS FOR GREEN CHEMISTRY (2022)

Edited by Frank Roschangar, Fabrice Gallou


LAST UPDATE 5 JANUARY 2022

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 1.  select article Green chemistry and sustainability metrics in the
     pharmaceutical manufacturing sector
     https://doi.org/10.1016/j.cogsc.2021.100562
     Review articleAbstract only
     
     
     GREEN CHEMISTRY AND SUSTAINABILITY METRICS IN THE PHARMACEUTICAL
     MANUFACTURING SECTOR
     
     Jochen Becker, Carolin Manske, Stefan Randl
     February 2022Article 100562Purchase PDF
     Article preview
      * Abstract
      * Graphical abstract
     
     
     
     GRAPHICAL ABSTRACT
     
     

 2.  select article Green metrics in pharmaceutical development
     https://doi.org/10.1016/j.cogsc.2021.100564
     Review articleAbstract only
     
     
     GREEN METRICS IN PHARMACEUTICAL DEVELOPMENT
     
     Concepcion “Conchita” Jimenez-Gonzalez, Claire Lund
     February 2022Article 100564Purchase PDF
     Article preview
      * Abstract
     
     This short review presents an overview of key metrics that have been used
     to assess the ‘greenness’ of pharmaceutical processes in development in the
     larger context of environmental sustainability. The green metrics cover
     areas of resource efficiency (mass and energy), environment, health, and
     safety considerations, and life cycle assessment. There is also a
     discussion of currently unmet needs in the area that need enhanced focus.

 3.  select article Metrics of green chemistry: Waste minimization
     https://doi.org/10.1016/j.cogsc.2021.100569
     Review articleAbstract only
     
     
     METRICS OF GREEN CHEMISTRY: WASTE MINIMIZATION
     
     Roger A. Sheldon, Moira L. Bode, Stephanie G. Akakios
     February 2022Article 100569Purchase PDF
     Article preview
      * Abstract
     
     The increasingly apparent negative impact of human activities on the
     environment has heightened the urgency for the chemistry community to adopt
     greener and more sustainable practices. The E-factor can still be
     considered a valuable tool in this drive, particularly because of its broad
     acceptance and familiarity amongst both industrial and academic chemists.
     An important factor in broadening the adoption of green principles is
     ensuring that the academics responsible for training the next generation of
     chemists prioritise green and sustainable practices in their undergraduate
     and post graduate laboratories. Green metrics must be easy to use to
     motivate the broader chemistry community to develop greener syntheses. For
     maximum impact to be achieved the detail of the exact green metrics applied
     are less important than their adoption by the broader chemical community.
     Of growing importance is the replacement of fossil resources with renewable
     alternatives to reduce greenhouse gas emission that is a significant driver
     of climate change. The C factor is used to compare the carbon footprints of
     different routes to a particular product.

 4.  select article Using polymeric hydroxypropyl methylcellulose as an
     alternative to ‘micellar catalysis’ to enable chemical reactions in water
     https://doi.org/10.1016/j.cogsc.2021.100571
     Review articleAbstract only
     
     
     USING POLYMERIC HYDROXYPROPYL METHYLCELLULOSE AS AN ALTERNATIVE TO
     ‘MICELLAR CATALYSIS’ TO ENABLE CHEMICAL REACTIONS IN WATER
     
     Niginia Borlinghaus, Valentin Wittmann, Wilfried M. Braje
     February 2022Article 100571Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Synthetic chemistry relies heavily on organic solvents which are often
     toxic and hazardous as well as expensive in purchase and disposal. The
     application of water as an alternative reaction medium is not only
     advantageous from an environmental and safety perspective but can also
     offer improved selectivity and reaction rates. The exploration of this new,
     sustainable approach comes along with an ever-growing spectrum of reaction
     procedures. In this current opinion, we provide an overview of a new
     methodology that uses a polymeric cellulose derivative, hydroxypropyl
     methylcellulose, to enable chemical reactions in water.

 5.  select article Insights into EcoScent Compass™, a holistic tool to measure
     a fragrance's sustainability footprint, based on its intrinsic green
     properties and environmental impact
     https://doi.org/10.1016/j.cogsc.2021.100583
     Review articleAbstract only
     
     
     INSIGHTS INTO ECOSCENT COMPASS™, A HOLISTIC TOOL TO MEASURE A FRAGRANCE'S
     SUSTAINABILITY FOOTPRINT, BASED ON ITS INTRINSIC GREEN PROPERTIES AND
     ENVIRONMENTAL IMPACT
     
     Fabrice Robvieux, Jocelyn Roth, Christian Chapuis, Maud Reiter
     February 2022Article 100583Purchase PDF
     Article preview
      * Abstract
     
     In response to demands for more transparency on the impact of its fragrance
     products on both people and the planet, Firmenich developed a new, holistic
     digital assessment tool, EcoScent Compass™, to rank both perfumery
     ingredients and perfumery formulations in terms of green chemistry as well
     as environmental footprint criteria. Using knowledge gathered in the field
     of green and sustainable chemistry over the past 20 years,
     multi-indicator clusters have been deployed and combined into a single
     index for green properties and environmental impact.

 6.  select article Defossilization of pharmaceutical manufacturing
     https://doi.org/10.1016/j.cogsc.2021.100586
     Review articleOpen access
     
     
     DEFOSSILIZATION OF PHARMACEUTICAL MANUFACTURING
     
     Lea Wollensack, Kristi Budzinski, Jan Backmann
     February 2022Article 100586Download PDF
     Article preview
      * Abstract
     
     As is true with most established industries, a significant portion of the
     raw materials used in the pharmaceutical industry is of fossil origin, that
     is, essentially can be traced back to crude oil. The present article
     attempts to assess to which degree the modern manufacturing of
     pharmaceuticals depends on raw materials of fossil carbon compounds and
     which could be appropriate ways to increasingly switch to non-fossil
     sourcing to eventually completely defossilize the raw-material base of the
     sector.

 7.  select article Designing for sustainability with biocatalytic and
     chemoenzymatic cascade processes
     https://doi.org/10.1016/j.cogsc.2022.100591
     Review articleAbstract only
     
     
     DESIGNING FOR SUSTAINABILITY WITH BIOCATALYTIC AND CHEMOENZYMATIC CASCADE
     PROCESSES
     
     Chihui An, Kevin M. Maloney
     April 2022Article 100591Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Cascade reactions have been widely recognized to cut costs, decrease
     solvent usage, and reduce cycle times in chemical processes. Recently,
     biocatalytic cascades have altered how we design synthetic routes to
     complex molecules to achieve sustainable commercial processes for
     pharmaceutical, agricultural, and fine chemical industries. With
     advancements in protein engineering and an increase in the number of enzyme
     classes available to chemists, industrial and academic groups alike have
     endeavored to expand the scope of biocatalysis from single reactions to
     multi-enzyme cascades to rapidly build complex molecular structures. Recent
     reports have drawn inspiration from biosynthetic pathways and have applied
     engineered enzymes to in vitro enzymatic cascades. Furthermore, combining
     transition-metal catalysis and enzymes in one-pot chemoenzymatic cascades
     likewise serves to broaden the scope of biocatalysis, enabling traditional
     chemical reactions to be performed under mild aqueous conditions. In this
     article, we review recent biocatalytic and chemoenzymatic cascades from
     2019 to 2021.

 8.  select article “The hidden power and competitive advantage of applying
     green chemistry metrics”
     https://doi.org/10.1016/j.cogsc.2022.100606
     Review articleAbstract only
     
     
     “THE HIDDEN POWER AND COMPETITIVE ADVANTAGE OF APPLYING GREEN CHEMISTRY
     METRICS”
     
     John L. Tucker
     June 2022Article 100606Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Green chemistry (GC) metrics provide insight into the relative waste, time
     and cost implications of pharmaceutical chemical processes and serve to
     guide scientists in the strategic application of resources to develop more
     efficient and sustainable processes. Examples of the application of GC
     metrics in evaluating pharmaceutical process efficiency and the subsequent
     development toward improvement exist in abundance from journals such as
     Organic Process Research and Development, Green Chemistry, or as
     encompassed by the winning examples from the ACS GCI Pharmaceutical
     Roundtable's [1] Peter J. Dunn award [2] or the US EPA's Green Chemistry
     Challenge award [3]. By their nature, GC metrics are continuously evolving
     but justify the necessary, unceasing investment in understanding and
     application as they offer unique, opportunistic insight serving to guide
     scientific resource deployment when developing greener pharmaceutical,
     chemical processes.

 9.  select article Green metrics for biologics
     https://doi.org/10.1016/j.cogsc.2022.100614
     Review articleAbstract only
     
     
     GREEN METRICS FOR BIOLOGICS
     
     Sarah Argoud, Kristi Budzinski, Daniel D'Aquila, Sri R. Madabhushi, Phillip
     Smith
     June 2022Article 100614Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Biologics are the fastest growing segment of the pharmaceutical market,
     therefore, the environmental impact of manufacturing these drugs needs to
     be fully characterized. For monoclonal antibodies, in particular, several
     metrics have been identified as the manufacturing process is quite
     standardized for batch processes. This paper will provide an overview of
     carbon footprint analysis, process mass intensity (PMI), water related
     impact of energy (WARIEN) and life cycle assessment (LCA) as they have been
     applied to monoclonal antibody production. Further development and
     standardization of these tools will allow the industry to identify and
     implement new technologies that significantly lower the environmental
     impact of not only monoclonal antibody production but other modalities as
     well.

 10. select article Trimming synthetic peptide and oligonucleotide waste-lines
     https://doi.org/10.1016/j.cogsc.2022.100643
     Review articleAbstract only
     
     
     TRIMMING SYNTHETIC PEPTIDE AND OLIGONUCLEOTIDE WASTE-LINES
     
     Michael E. Kopach, Benjamin I. Andrews
     October 2022Article 100643Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     This review article highlights the need for the development of synthetic
     peptide and oligonucleotide manufacturing processes with improved
     sustainability credentials. These therapeutic classes are fast growing and
     have the potential to deliver multiple high volume products over the next
     decade. While there have been significant technical innovations in the past
     few years there is limited evidence for adoption of these new technologies
     in manufacturing, which still largely rely on traditional approaches that
     generate large quantities of waste and use many chemicals of concern.
     Examples of strategies that could improve the environmental footprint for
     peptides include Tag-Assisted Liquid-Phase Peptide Synthesis, Hybrid
     Solid/Liquid Phase Peptide Synthesis and the implementation of continuous
     processes. For oligonucleotides, convergent liquid-phase synthesis and
     enzyme-catalyzed synthesis strategies are highlighted which have potential
     for significant positive environmental improvement if incorporated into the
     development lifecycle. To guide development, the collection of baseline
     sustainability metrics such as Process Mass Intensity is recommended.

 11. select article Assessment of analytical testing: The impact of metrics for
     the sustainable measurement of pharmaceuticals
     https://doi.org/10.1016/j.cogsc.2022.100689
     Review articleAbstract only
     
     
     ASSESSMENT OF ANALYTICAL TESTING: THE IMPACT OF METRICS FOR THE SUSTAINABLE
     MEASUREMENT OF PHARMACEUTICALS
     
     Michael B. Hicks, Sean Oriana, Yong Liu
     December 2022Article 100689Purchase PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Analytical metrics allow a periodic, healthy examination of methods and how
     they impact the environment, while ensuring that procedures are
     reproducible, reliable, repeatable, transferable, and of high quality. This
     article provides a review of current trends with analytical metrics, such
     as the analytical method green score (AMGS). More importantly, the AMGS
     impact on sample preparation, development strategy, and energy consumption
     considerations are provided. Finally, recent uses of metrics with specific
     relevance to the pharmaceutical research and development area through
     method transfer are covered.

 12. select article National leadership and cross-sector collaboration could
     help overcome differences in stakeholder definitions of sustainable
     chemistry
     https://doi.org/10.1016/j.crgsc.2021.100222
     Research articleOpen access
     
     
     NATIONAL LEADERSHIP AND CROSS-SECTOR COLLABORATION COULD HELP OVERCOME
     DIFFERENCES IN STAKEHOLDER DEFINITIONS OF SUSTAINABLE CHEMISTRY
     
     Summer Lingard Smith, Diane B. Raynes, Karen L. Howard
     2022Article 100222Download PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     GAO conducted a technology assessment to explore among other things, the
     opportunities, challenges, and stakeholder roles in sustainable chemistry.
     We found that stakeholders across industry, government, and academia lack
     agreement on how to define sustainable chemistry and how to measure or
     assess the sustainability of chemical processes and products. These
     differences hinder the development and adoption of more sustainable
     chemistry technologies. However, based on a review of the literature and
     stakeholder interviews, GAO identified several common themes underlying
     what sustainable chemistry strives to achieve – including that standard
     definitions and metrics for sustainability are important for stakeholders.
     In addition, we note that national leadership and collaboration across many
     sectors could enhance sustainable chemistry progress. This includes the
     potential for sustainable chemistry to inspire new products and processes,
     create jobs, and enhance benefits to human health and the environment.
     However, we found that technological and business challenges interfere with
     efforts to implement some of these sustainable chemistry technologies, and
     that the diverse set of stakeholders can lead to coordination challenges.
     We offer strategic approaches that may help overcome these challenges.

 13. select article Manufacturing mass intensity: 15  Years of Process Mass
     Intensity and development of the metric into plant cleaning and beyond
     https://doi.org/10.1016/j.crgsc.2021.100229
     Research articleOpen access
     
     
     MANUFACTURING MASS INTENSITY: 15  YEARS OF PROCESS MASS INTENSITY AND
     DEVELOPMENT OF THE METRIC INTO PLANT CLEANING AND BEYOND
     
     Colin H. Benison, Philippa R. Payne
     2022Article 100229Download PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     The American Chemical Society Green Chemistry Institute (ACS GCI)
     Pharmaceutical Roundtable is committed to continue to expand and identify
     elements of small-molecule active pharmaceutical ingredient (API)
     manufacturing that should be quantified to drive towards more sustainable
     practices. Process mass intensity (PMI) has been used for over 15 years to
     evaluate and benchmark progress towards more sustainable manufacturing and
     quantifies process input mass (e.g. solvent, water, reagents) per mass of
     output produced. This manuscript introduces Manufacturing Mass Intensity
     (MMI), a metric that builds upon and expands the scope to account for other
     raw materials required for API manufacturing. Examples are included to
     illustrate how quantification of these additional resource requirements
     will drive more sustainable practices.

 14. select article Grassroots and blue skies lead to greener landscapes
     https://doi.org/10.1016/j.crgsc.2021.100242
     Research articleOpen access
     
     
     GRASSROOTS AND BLUE SKIES LEAD TO GREENER LANDSCAPES
     
     Kristi Budzinski, Stefan G. Koenig
     2022Article 100242Download PDF
     Article preview
      * Abstract
      * Graphical abstract
     
     
     
     GRAPHICAL ABSTRACT
     
     

 15. select article Engaging scientists in a sustainability culture
     https://doi.org/10.1016/j.crgsc.2021.100247
     Research articleOpen access
     
     
     ENGAGING SCIENTISTS IN A SUSTAINABILITY CULTURE
     
     Louis J. Diorazio, Alex Mullen
     2022Article 100247Download PDF
     Article preview
      * Abstract
      * Graphical abstract
     
     
     
     GRAPHICAL ABSTRACT
     
     

 16. select article Sustainability case studies on the use of continuous
     manufacturing in pharmaceutical production
     https://doi.org/10.1016/j.crgsc.2022.100279
     Research articleOpen access
     
     
     SUSTAINABILITY CASE STUDIES ON THE USE OF CONTINUOUS MANUFACTURING IN
     PHARMACEUTICAL PRODUCTION
     
     Mark S. Kerr, Kevin P. Cole
     2022Article 100279Download PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Continuous processing is now commonly used in the manufacturing of fine
     chemicals including agrochemicals and pharmaceuticals. Datasets are now
     available, including some on environmental sustainability aspects, that
     enable more direct comparison between related batch and flow processes.
     This article examines six continuous processes where an environmental
     sustainability concept or metric (e.g. process mass intensity) can be
     compared to that from a closely-related batch process in order to assess
     the impact that continuous manufacturing has on that theme. Some current
     case studies where additional Green Chemistry concepts are exemplified are
     shared along with how continuous processing impacts the manufacture. We
     illustrate situations where continuous processing can reasonably be
     expected to show sustainability advantages over batch, as well as a
     scenario where increased solvent usage in flow mode worsened the
     environmental profile. While we believe that continuous processing can
     provide sustainability benefits, there are cases where its application can
     have a negative effect on environmental metrics. Our hope is to provide
     impartial guidance for development and manufacturing scientists so they may
     best utilize continuous technologies in an environmentally responsible way.

 17. select article Roche's approach to green metrics in drug development
     https://doi.org/10.1016/j.crgsc.2022.100293
     Research articleOpen access
     
     
     ROCHE'S APPROACH TO GREEN METRICS IN DRUG DEVELOPMENT
     
     Georg Wuitschik, Martin Olbrich, Stefan Hildbrand
     2022Article 100293Download PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     This article describes standard, often used metrics and more recent
     developments. Efforts and possibilities on how to apply them in drug
     development are shown on the example of Roche.

 18. select article Green and sustainable metrics: Charting the course for
     green-by-design small molecule API synthesis
     https://doi.org/10.1016/j.crgsc.2022.100324
     Research articleOpen access
     
     
     GREEN AND SUSTAINABLE METRICS: CHARTING THE COURSE FOR GREEN-BY-DESIGN
     SMALL MOLECULE API SYNTHESIS
     
     Harrison B. Rose, Birgit Kosjek, Brittany M. Armstrong, Sandra A. Robaire
     2022Article 100324Download PDF
     Article preview
      * Abstract
     
     ABSTRACT
     
     Sustainable small molecule Active Pharmaceutical Ingredient (API)
     manufacturing starts at the onset of route development by employing a
     Green-by-Design strategy. Reliable metrics are imperative for setting
     targets and measuring process improvements throughout the development
     cycle. This article reviews some of the many tools and methods established
     to analyze and assess the greenness and sustainability of a process, each
     of which highlights different aspects of process efficiency, waste
     formation or overall environmental impact reduction. Most calculations,
     such as process mass intensity (PMI), are mass-based and do not consider
     the types of raw materials used. In contrast, a full life cycle assessment
     (LCA) offers detailed information about the “cradle to grave” environmental
     impact of a manufacturing route and its specific resources, but the high
     data requirements and long timelines are not conducive for multiple
     processes or repeated assessments during process optimization. To address
     these challenges, we introduce a Streamlined PMI-LCA Tool, developed in
     collaboration with the ACS Green Chemistry Institute Pharmaceutical
     Roundtable (ACS GCIPR), that combines PMI with a “cradle to gate” approach
     to include the environmental footprint of the synthesis’ raw materials. The
     frequent re-evaluation of a process continuously highlights areas for
     improvement and guides the prioritization of process development activities
     to effectively and rapidly achieve a Green-by-Design commercial synthetic
     route. The utility of this approach to Green-by-Design is demonstrated with
     the reduction of PMI for MK-7264 from 366 to 88 over the course of process
     development.

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