Green Chemistry in Pharmaceutical Industry: Sustainable Approaches to Drug Synthesis

Recent years have seen a disheartening string of revelations in which everyday items once considered safe—food packaging, toys, clothes, furniture, electronic components, and many more products—are found to contain carcinogens, endocrine disruptors, and other harmful chemicals.1 Growing demand for healthier alternatives, already seen in food production and housing construction,2 is also happening at the building-block level of manufacturing, where so-called green chemistry represents a revolutionary change in preventing pollution and health problems starting at the chemical design stage. Many industry and government entities are beginning to espouse the principles of green chemistry on their websites and in public statements. Now comes the task of crafting policy to put those principles into action. The U.S. Environmental Protection Agency (EPA) defines green chemistry as “the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances. Green chemistry applies across the life cycle of a chemical product, including its design, manufacture, and use.”3 Green chemistry also aims to mitigate the type of uncertainty Alan Gold-berg, a professor of toxicology at the Johns Hopkins Bloomberg School of Public Health, recently described to The New York Times: “I can get [toxicity] information on only 20 percent of chemicals we interact with on a daily basis.”4 Of that 20%, he now says, he may be able to find information on overt toxicity for about half, but for details on specific effects such as developmental neurotoxicity, the figure shrinks toward zero. So what does green chemistry look like? Consider the example of pregabalin, the active ingredient in the neuropathic pain drug Lyrica®. Pfizer developed an alternative green-chemistry process that converted several steps of pregabalin synthesis from use of organic solvents to water. That reduced both health hazards and production heating requirements. With the new synthesis, waste from the process dropped from 86 kg of waste per kg product to 17 kg, and energy use dropped by 82%.5 Proponents say that’s how the field can offer a win–win–win solution: good performance, lower cost, and less environmental impact—what Richard Engler, program manager of the EPA Green Chemistry Program, calls the “triple bottom line.” For many, a standard is a logical next step. “At some point you have to go beyond a definition and principles,” says Engler. “I think that’s something the standard will enable.”

Hormones occur naturally in humans, animals, and plants, but estrogens in contraceptives and hormone replacement therapy, those given to agricultural animals, and industrial chemicals that mimic estrogen add to the enormous volume of biologically active compounds in the environment. These compounds are among the PPCP (pharmaceutical and personal care product) category of contaminants that, when excreted, make their way into surface and ground-water, wastewater treatment plants, and, eventually, back into drinking water supplies. Now scientists are looking to catalysts called Fe-TAML® (iron plus tetra-amido macrocyclic ligand) activators as a promising way to remove these contaminants from wastewater.

Conventional practices of synthesis, manufacturing, and processing have led to severe adverse consequences for living beings and the environment. Although medications cannot be replaced, the methods of synthesizing, manufacturing, and processing them can be changed and/or replaced. This paper explains the significance of green chemistry practices in the pharmaceutical industry. It emphasizes that we must replace conventional drug synthesis, processing, and manufacturing techniques with greener ones that are cost-effective, sustainable, environment-friendly, and profitable. This paper comprises five sections. Section 1 is an introduction to green chemistry and its correlation with the pharmaceutical industry. Section 2 discusses the metrics necessary to measure the greenness of a process. Section 3 is about solvents used in the pharmaceutical industry, hazards, safety status, and environmental effects, including the ozone depletion potential. Section 4 explains catalytic amidation reactions because amides are one of the most commonly occurring functional groups with pharmacological activity. Section 5 discusses successful cases of converting conventional synthesis of active pharmaceutical ingredients and/or their intermediates to greener, sustainable alternatives. A balance is necessary between profits, processes, consumers, and the environment to ensure the survival of all stakeholders and decrease the environmental burden of pharmaceuticals. Incentives such as green chemistry awards should be endorsed and encouraged, in addition to making green chemistry part of tertiary education. In addition, changes to rules and regulations for drug approval in the context of green chemistry principles are necessary in order to preserve our planet for future generations.

Chapter 18 - Current prospective of green chemistry in the pharmaceutical industry

Embedding sustainable practices into pharmaceutical R&D: what are the challenges?

Green chemistry has emerged as a central framework for addressing the environmental and health challenges associated with conventional chemical practices in the pharmaceutical industry. Rather than relying on post-production waste management and remediation, green chemistry emphasizes the design of chemical products and processes that inherently reduce or eliminate hazardous substances. This preventive approach has gained increasing relevance in the context of resource depletion, pollution, and increasing regulatory scrutiny. This article examines various aspects of green chemistry, including its conceptual foundations, guiding principles, technological strategies, and practical applications across industrial sectors. Particular attention is paid to green synthesis, catalysis, solvent selection, renewable feedstocks, and the integration of sustainability into industrial chemistry. This discussion also considers the environmental and societal implications of adopting green chemistry practices, as well as the technical and economic challenges that continue to limit widespread implementation. By synthesizing theoretical perspectives with applied examples, this article highlights green chemistry as a pragmatic and evolving discipline rather than a purely idealistic concept. The analysis suggests that continued research, policy support, and education are essential for embedding green chemistry as a standard approach in chemical science and industry, thereby contributing to long-term environmental sustainability and responsible technological development.

This chapter summarizes a large amount of work that has been carried out in Green Chemistry since the late 1990s. Green Chemistry and Engineering has been published recently and focuses on bridging the great divide between bench chemistry, process design, engineering, environment, health, safety, and life cycle considerations. The chapter focuses on the scientific and technological aspects of Green Chemistry as the means to improve the chances of sustainable development and to de-risk these developments in the broadest socio-economic and technological contexts. It also focuses on physical organic aspects of Green Chemistry and their impact on the components of life cycle analysis. The importance of evaluating the success or otherwise of new developments aimed at improving sustainable development has led to numerous metrics which emphasizes different aspects of sustainability. The management and impact of waste in the chemical and pharmaceutical industries has been extensively reviewed. Keywords: green chemistry; life cycle analysis; sustainable development

In order to protect the life of all creatures living in the environment, the toxicity arising from various hazardous chemicals must be controlled. This imposes a serious responsibility on different chemical, pharmaceutical, and other biological industries to produce less harmful chemicals. Among various international initiatives on harmful aspects of chemicals, the 'Green Chemistry' ideology appears to be one of the most highlighted concepts that focus on the use of eco-friendly chemicals. Ionic liquids are a comparatively new addition to the huge garrison of chemical compounds released from the industry. Extensive research on ionic liquids in the past decade has shown them to be highly useful chemicals with a good degree of thermal and chemical stability, appreciable task specificity and minimal environmental release resulting in a notion of 'green chemical'. However, studies have also shown that ionic liquids are not intrinsically non-toxic agents and can pose severe degree of toxicity as well as the risk of bioaccumulation depending upon their structural components. Moreover, ionic liquids possess issues of waste generation during synthesis as well as separation problems. Predictive quantitative structure-activity relationship (QSAR) models constitute a rational opportunity to explore the structural attributes of ionic liquids towards various physicochemical and toxicological endpoints and thereby leading to the design of environmentally more benevolent analogues with higher process selectivity. Such studies on ionic liquids have been less extensive compared to other industrial chemicals. The present review attempts to summarize different QSAR studies performed on these chemicals and also highlights the safety, health and environmental issues along with the application specificity on the dogma of 'green chemistry'.

Green chemistry is an interdisciplinary field that focuses on minimizing hazardous substances and promoting sustainable alternatives in chemical processes to conventional chemical processes and products. This review provides a comprehensive analysis of the fundamental principles, historical development, and practical applications of green chemistry with a particular emphasis on its role in advancing sustainable chemical synthesis, analytical methodologies, and industrial practices. Originating from the environmental activism of the 1960 s inspired by Rachel Carson's"Silent Spring,"green chemistry was formally established in the 1990 s through the 12 principles set by Paul Anastas and John C. Warner. These principles emphasize waste prevention, atomic economy, reducing hazardous chemicals, and using renewable raw materials. Green chemistry significantly impacts sectors such as pharmaceuticals, cosmetics, and education. In the pharmaceutical industry, it fosters environmentally safer analytical methods. The cosmetics sector benefits from biodegradable materials, while educational institutions implement sustainable waste management and laboratory practices. International conferences and academic publications have advanced global awareness of green chemistry, promoting sustainability goals like reducing environmental impacts, optimizing resource use, and minimizing waste. A key focus of this study is the green synthesis of nanoparticles which has emerged as a sustainable alternative to traditional synthesis methods that often rely on toxic reagents Plant-derived biomolecules serve as reducing and stabilizing agents in the synthesis of silver nanoparticles (AgNPs). These eco-friendly approaches eliminate the hazardous chemicals while yielding biocompatible nanoparticles with enhanced antimicrobial and catalytic properties, demonstrating their potential in nanotechnology and biomedical applications. Additionally, green analytical chemistry has revolutionized chemical monitoring by implementing solvent-free methodologies, real-time pollution tracking, and waste minimization techniques. The integration of green chemistry into academic and industrial settings has played a critical role in addressing global challenges such as environmental pollution, climate change, and resource depletion. This review highlights the necessity of widespread adoption of green chemistry principles to ensure economic sustainability, regulatory compliance, and scientific innovation. Future research should focus on optimizing green synthetic techniques, addressing scalability challenges, and fostering interdisciplinary collaboration to accelerate the transition toward a more sustainable future.Graphical abstract

Green approach is a novel endeavor of chemistry that attempts to minimize or eliminate the utilization of hazardous substances in chemical reactions. The implementation and adoption of green chemistry has increasingly gained importance as it minimizes risks to the environment and human health, of exposure to chemicals. It also reduces the production expenses due to reduced solvent usage, reduction in disposal expense, and less energy requirement without sacrificing the quality of product. Green chemistry finds application starting from early stages of new drug development to the production at commercial scale. The benefits of the green chemistry are also seen in chemical industry with more or less the same advantages as in pharmaceutical industry. This book chapter elaborates the advances in green chemistry, which finds applications in organic chemistry and pharmaceutical industry and has tremendous potential for growth. Researchers can use this chapter as a guide to implement the green ideas while designing new schemes. The approach has immense potential to design compounds with novel activities while simultaneously allowing for a relatively straightforward synthesis. The progress and advantages about green chemistry are of significant importance for both medicinal chemistry and bulk pharmaceutical industries.

‡ To whose memory this paper is dedicated. Joe Breen was a leading pioneer of green chemistry. Following his retirement from EPA, Office of Pollution Prevention and Toxics, where he worked on asbestos, dioxins, and pollution prevention, Joe became Executive Director of the Green Chemistry Institute, a not-for-profit organization promoting environmentally benign syntheses and processing. His premature death on 19 July 1999 created a void in the Working Party team, but encouraged all of us to continue our mission, having in mind his passion for this work and his exquisite friendship.

The ACS Green Chemistry Institute (GCI) Pharmaceutical Roundtable has launched a new award to encourage the adoption of more sustainable practices and recognize achievements in green chemistry applications at contract manufacturing organizations (CMOs) in Asia, where most of the world’s active pharmaceutical ingredients (APIs) are being produced. The CMO Excellence in Green Chemistry Award will recognize greener advances in synthetic route development for starting materials, intermediates, or APIs, including reaction conditions and chemical or manufacturing technologies. In addition, the ACS GCI Pharmaceutical Roundtable is seeking nominations for the Peter J. Dunn Award for Green Chemistry and Engineering Impact in the Pharmaceutical Industry. Applicants for both awards are being accepted through Dec. 31. A representative from the winning company or team for each award will be invited to present their innovations at the 26th Annual Green Chemistry and Engineering Conference in Reston, Virginia, June 6–8, where the awards will be given

The pharmaceutical industry plays a crucial role in advancing global sustainability objectives related to good health and well-being. In alignment with international initiatives, including the United Nations’ Race to Zero campaign and the Paris Agreement, companies are committing to environmental stewardship. The industry has adopted green chemistry (GC) principles in the production of life-saving medications, ensuring that manufacturing processes are both commercially viable and have minimal environmental impact. As such, GC emerges as a critical component of these initiatives, providing environmental and economic benefits by minimizing waste, increasing process efficiency, and reducing operational costs. Recent innovations in greener synthetic methods exemplify the practical advantages of GC in pharmaceutical manufacturing. However, the sector continues to confront challenges, particularly concerning Scope 3 emissions within the supply chain, necessitating a comprehensive approach to sustainability. The implementation of GC not only reduces environmental impacts, including waste production and water consumption, but also improves financial performance and corporate reputation. As investor interest in environmental, social, and governance (ESG) factors continue to increase, pharmaceutical companies are increasingly acknowledging the economic benefits associated with sustainable practices. This paper explores current strategies for integrating GC into active pharmaceutical ingredient manufacturing, highlighting both achievements and obstacles. It underscores the urgent need for improved communication regarding the business value of GC and the integration of environmental metrics into manufacturing practices, especially amid a shifting regulatory landscape.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBringing State-of-the-Art, Applied, Novel, Green Chemistry to the Classroom by Employing the Presidential Green Chemistry Challenge AwardsMichael C. Cann View Author Information Department of Chemistry, University of Scranton, Scranton, PA 18510Cite this: J. Chem. Educ. 1999, 76, 12, 1639Publication Date (Web):December 1, 1999Publication History Received3 August 2009Published online1 December 1999Published inissue 1 December 1999https://pubs.acs.org/doi/10.1021/ed076p1639https://doi.org/10.1021/ed076p1639research-articleACS PublicationsRequest reuse permissionsArticle Views434Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Ecology,Environmental pollution,Green chemistry,Students Get e-Alerts

Daniel Bailey of Takeda Pharmaceuticals is the recipient of the Peter J. Dunn Award for Green Chemistry and Engineering Impact in the Pharmaceutical Industry. The award, established by the ACS Green Chemistry Institute Pharmaceutical Roundtable, recognizes excellence in the research, development, and execution of new green chemistry technologies in the pharmaceutical industry. Bailey developed a technology for greener reaction conditions that reduces a six-step synthesis to four. In addition to shortening the synthetic route, Bailey and his team were able to reduce the amount of raw materials needed to make a final product. Bailey will present his technology during the 24th Green Chemistry & Engineering Conference, which will take place virtually June 15–19. Please send announcements of awards to l_wang@acs.org.