Taking the Green Road Towards Pharmaceutical Manufacturing

Abstract

The introduction of the Green Chemistry Principles in the late 1990s formed the basis for a transition to a greener environment. These Principles have become an integral part in the work on designing chemical processes, especially for large-scale manufacture. The ultimate target is the achievement of a sustainable production method allowing hundreds of tons of valuable materials to be prepared. For this purpose, a holistic view must be applied to the elements constituting a fully-fledged process encompassing layout of the synthetic route, defining starting materials and their origin, output of product and quality features, quantity of effluent streams and waste, recovery and recycling of chemicals involved, and energy consumption. These parameters form a complex matrix where the individual components are in a complicated relationship with each other. This short review addresses these issues and the benefits of life-cycle assessment and metrics commonly used to measure the performance of chemical manufacturing – all from a pharmaceutical industry perspective as experienced by the author.

1 Introduction: Facing Severe Challenges

2 The Historical Context: Addressing an Image Problem

3 Prospects, Drivers and Roadmap for the Green Future

4 Living by the Principles: Industrial Perspectives

5 Taking the Green Route – Catalysis Leading the Way: Case Stories

6 State of the Art: How Green Are We?

7 Sending Signals, Creating Impressions: Focus on Communication

8 Conclusions

Key words

green chemistry - sustainability - pharmaceutical manufacturing - catalysis - process design - E factor - PMI

Publication History

Received: 20 December 2021

Accepted after revision: 27 January 2022

Accepted Manuscript online:
27 January 2022

Article published online:
28 March 2022

• References

• 1 Anastas PT, Warner JC. Green Chemistry: Theory and Practice . Oxford University Press; London: 1998
• 2 Anastas PT, Kirchhoff MM. Acc. Chem. Res. 2002; 35: 686
• 3 Federsel H.-J. Green Chem. 2013; 15: 3105
• 4 Scalable Green Chemistry: Case Studies from the Pharmaceutical Industry. Koenig SG. Pan CRC Press; Boca Raton: 2013
• 5 Homberger E, Reggiani G, Sambeth J, Wipf HK. Ann. Occup. Hyg. 1979; 22: 327
• 6 Bertazzi PA. Sci. Total Environ. 1991; 106: 5
• 7 Varma R, Varma DR. Bull. Sci. Technol. Soc. 2005; 25: 37
• 8 Lapierre D, Moro J. Five Past Midnight in Bhopal: The Epic Story of the World’s Deadliest Industrial Disaster. Grand Central Publishing; New York: 2009
• 9 Broughton E. Environ. Health 2005; 4: 6
• 10 Chander J. Int. J. Occup. Environ. Health 2001; 7: 72
• 11 Federsel H.-J. Nat. Rev. Drug Discovery 2003; 2: 654
• 12a Federsel H.-J. Acc. Chem. Res. 2009; 42: 671
• 12b Federsel H.-J. Bioorg. Med. Chem. 2010; 18: 5775
• 13 Ho SV, McLaughlin JM, Cue BW, Dunn PJ. Green Chem. 2010; 12: 755
• 14 According to the United States Environmental Protection Agency (EPA).
• 15 Poliakoff M, Licence P. Nature 2007; 450: 810
• 16 United Nations Foundation: Sustainable Development Goals, see: www.un.org/sustainabledevelopment (accessed Mar 20, 2022).
• 17 Dach R, Song JJ, Roschangar F, Samstag W, Senanayake CH. Org. Process Res. Dev. 2012; 16: 1697
• 18 Sheldon RA. Chem. Ind. (London) 1992; 903
• 19 Sheldon RA. Green Chem. 2007; 9: 1273
• 20 Sheldon RA. Green Chem. 2017; 19: 18
• 21 Green Chemistry Metrics: Measuring and Monitoring Sustainable Processes . Lapkin A, Constable DJ. C. Blackwell Publishing Ltd; Chichester: 2008
• 22 Andraos J. The Algebra of Organic Synthesis: Green Metrics, Design Strategy, Route Selection, and Optimization. CRC Press; Boca Raton: 2012
• 23 Dicks AP, Hent A. Green Chemistry Metrics: A Guide to Determining and Evaluating Process Greenness. Springer; Heidelberg: 2015
• 24 Albini A, Protti S. Paradigms in Green Chemistry and Technology . Springer; Heidelberg: 2016
• 25 Sheldon RA. ACS Sustainable Chem. Eng. 2018; 6: 32
• 26 Jiménez-González C, Ponder CS, Broxterman QB, Manley JB. Org. Process Res. Dev. 2011; 15: 912
• 27 Jiménez-González C, Ollech C, Pyrz W, Hughes D, Broxterman QB, Bhathela N. Org. Process Res. Dev. 2013; 17: 239
• 28 Van Aken K, Strekowski L, Patiny L. Beilstein J. Org. Chem. 2006; 2: No. 3
• 29 Graedel T. Green Chem. 1999; 1: G126
• 30 Anastas PT, Lankey RL. Green Chem. 2000; 2: 289
• 31 Handbook on Life Cycle Assessment: Operational Guide to the ISO Standards. Guinée JB. Kluwer Academic Publishers; Dordrecht: 2002
• 32 Domènech X, Ayllon JA, Peral J, Rieradevall J. Environ. Sci. Technol. 2002; 36: 5517
• 33 Lankey RL, Anastas PT. Ind. Eng. Chem. Res. 2002; 41: 4498
• 34 Curran MA. Curr. Opin. Chem. Eng. 2013; 2: 273
• 35 Tufvesson LM, Tufvesson P, Woodley JM, Börjesson P. Int. J. Life Cycle Assess. 2013; 18: 431
• 36 Background and Future Prospects in Life Cycle Assessment. Klöpffer W. Springer; Dordrecht: 2014
• 37 Kralisch D, Ott D, Gericke D. Green Chem. 2015; 17: 123
• 38 Watson WJ. W. Green Chem. 2012; 14: 251
• 39 Roschangar F, Sheldon RA, Senanayake CH. Green Chem. 2015; 17: 752
• 40 Federsel H.-J, Sveno A. In Process Chemistry in the Pharmaceutical Industry, Volume 2: Challenges in an Ever Changing Climate. Gadamasetti K, Braish T. CRC Press; Boca Raton: 2007: 111
• 41 Sorbera LA, Leeson P, Castañer J. Drugs Future 1999; 24: 740
• 42 Hassner A, Kropp JE, Kent GJ. J. Org. Chem. 1969; 34: 2628
• 43 Paiocchi M, Belli A, Ponzini F, Villa M. WO 2002/000575, 2002
• 44 Trost BM. Science 1991; 254: 1471
• 45 Trost BM. Angew. Chem. Int. Ed. Engl. 1995; 34: 259
• 46 Trost BM. Acc. Chem. Res. 2002; 35: 695
• 47 Sheldon RA. Pure Appl. Chem. 2000; 72: 1233
• 48 Wang W, Lü J, Zhang L, Li Z. Front. Chem. Sci. Eng. 2011; 5: 349
• 49 Teasdale A, Elder D, Chang S.-J. Org. Process Res. Dev. 2013; 17: 221
• 50 Snodin DJ. Org. Process Res. Dev. 2010; 14: 960
• 51 Reddy AV. B, Jaafar J, Umar K, Majid ZA, Aris AB, Talib J, Madhavi G. J. Sep. Sci. 2015; 38: 764
• 52 Conis E. Distillations 2018; 2: 16
• 53 Davis FR. Banned: A History of Pesticides and the Science of Toxicology . Yale University Press; New Haven & London: 2014
• 54 Crystallization Technology Handbook, 2nd ed. Mersmann A. Marcel Dekker; New York: 2001
• 55 Nangia A. Acc. Chem. Res. 2008; 41: 595
• 56 Alfonsi K, Colberg J, Dunn PJ, Fevig T, Jennings S, Johnson TA, Kleine HP, Knight C, Nagy MA, Perry DA, Stefaniak M. Green Chem. 2008; 10: 31
• 57 Henderson RK, Jiménez-González C, Constable DJ. C, Alston SR, Inglis GG. A, Fisher G, Sherwood J, Binks SP, Curzons AD. Green Chem. 2011; 13: 854
• 58 Prat D, Pardigon O, Flemming H.-W, Letestu S, Ducandas V, Isnard P, Guntrum E, Senac T, Ruisseau S, Cruciani P, Hosek P. Org. Process Res. Dev. 2013; 17: 1517
• 59 Diorazio LJ, Hose DR. J, Adlington NK. Org. Process Res. Dev. 2016; 20: 760
• 60a Prat D, Hayler J, Wells A. Green Chem. 2014; 16: 4546
• 60b Prat D, Wells A, Hayler J, Sneddon H, McElroy CR, Abou-Shehada S, Dunn PJ. Green Chem. 2016; 18: 288
• 60c Clarke CJ, Tu W.-C, Levers O, Bröhl A, Hallett JP. Chem. Rev. 2018; 118: 747
• 61 Constable DJ. C, Curzons AD, Cunningham VL. Green Chem. 2002; 4: 521
• 62 Jiménez-González C, Curzons AD, Constable DJ. C, Cunningham VL. Clean Technol. Environ. Policy 2004; 7: 42
• 63 Cespi D, Beach ES, Swarr TE, Passarini F, Vassura I, Dunn PJ, Anastas PT. Green Chem. 2015; 17: 3390
• 64 Klemm D, Heublein B, Fink H.-P, Bohn A. Angew. Chem. Int. Ed. 2005; 44: 3358
• 65 Bornscheuer UT, Buchholz K. Eng. Life Sci. 2005; 5: 309
• 66 Fadlallah S, Roy PS, Garnier G, Saito K, Allais F. Green Chem. 2021; 23: 1495
• 67 Groß J, Kühlborn J, Opatz T. Green Chem. 2020; 22: 4411
• 68 Isidro-Llobet A, Álvarez M, Albericio F. Chem. Rev. 2009; 109: 2455
• 69 Greene TW, Wuts PG. M. Greene’s Protective Groups in Organic Synthesis, 5th ed. John Wiley & Sons; Hoboken: 2014
• 70 Smil V. Nature 1999; 400: 415
• 71 Federsel H.-J. Nat. Rev. Drug Discov. 2005; 4: 685
• 72 Federsel H.-J, Larsson M. An Innovative Asymmetric Sulfide Oxidation: The Process Development History Behind the New Antiulcer Agent Esomeprazole. In Asymmetric Catalysis on Industrial Scale: Challenges Approaches and Solutions. Blaser H.-U, Schmidt E. Wiley-VCH; Weinheim: 2004: 413
• 73 Blaser H.-U, Buser H.-P, Coers K, Hanreich R, Jalett H.-P, Jelsch E, Pugin B, Schneider H.-D, Spindler F, Wegmann A. Chimia 1999; 53: 275
• 74 Blaser H.-U, Hanreich R, Schneider H.-D, Spindler F, Steinacher B. The Chiral Switch of Metolachlor: The Development of a Large-Scale Enantioselective Catalytic Process. In Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions. Blaser H.-U, Schmidt E. Wiley-VCH; Weinheim: 2004: 55
• 75 Lokesh K, Ladu L, Summerton L. Sustainability 2018; 10: 1695
• 76 Lokesh K, Matharu AS, Kookos IK, Ladakis D, Koutinas A, Morone P, Clark J. Green Chem. 2020; 22: 803
• 77 Chen Z, Lovett D, Morris J. J. Process Control 2011; 21: 1467
• 78 Chen X, Zhao C. J. Process Control 2021; 107: 83
• 79 Aqlan F, Ali EM. J. Loss Prev. Process Ind. 2014; 29: 39
• 80 Lowrance WF. Of Acceptable Risk: Science and the Determination of Safety . William Kaufman, Inc; Los Altos (CA, USA): 1976
• 81 Manuele FA. Professional Safety 2010; 30
• 82 Dunn PJ, Galvin S, Hettenbach K. Green Chem. 2004; 6: 43
• 83 Dunn PJ. Chem. Soc. Rev. 2012; 41: 1452
• 84 Baumann M, Moody TS, Smyth M, Wharry S. Org. Process Res. Dev. 2020; 24: 1802
• 85 Monteith ER, Mampuys P, Summerton L, Clark JH, Maes BU. W, McElroy CR. Green Chem. 2020; 22: 123
• 86 ACS Green Chemistry Institute Pharmaceutical Roundtable website (accessed Mar 14, 2022), see: www.acsgcipr.org
• 87 Constable DJ. C, Dunn PJ, Hayler JD, Humphrey GR, Leazer JL. Jr, Linderman RJ, Lorenz K, Manley J, Pearlman BA, Wells A, Zaks A, Zhang TY. Green Chem. 2007; 9: 411
• 88 Roschangar F, Colberg J, Dunn PJ, Gallou F, Hayler JD, Koenig SG, Kopach ME, Leahy DK, Mergelsberg I, Tucker JL, Sheldon RA, Senanayake CH. Green Chem. 2017; 19: 281
• 89 Bryan MC, Dunn PJ, Entwistle D, Gallou F, Koenig SG, Hayler JD, Hickey MR, Hughes S, Kopach ME, Moine G, Richardson P, Roschangar F, Steven A, Weiberth FJ. Green Chem. 2018; 20: 5082
• 90 Green Engineering . Anastas PT, Heine L, Williamson TC. ACS Symposium Series 766; American Chemical Society; Washington DC: 2000
• 91a The 12 Principles of Green Engineering as expressed in ref. 91b: (i) Inherent Rather Than Circumstantial; (ii) Prevention Instead of Treatment; (iii) Design for Separation; (iv) Maximize Efficiency; (v) Output-Pulled Versus Input-Pushed; (vi) Conserve, Complexity; (vii) Durability Rather Than Immortality; (viii) Meet Need, Minimize Excess; (ix) Minimize Material Diversity; (x) Integrate Material and Energy Flows; (xi) Design for Commercial ‘Afterlife’; (xii) Renewable Rather Than Depleting.
• 91b Anastas PT, Zimmerman JB. Env. Sci. Technol. 2003; 37: 94A
• 92 Rosillo-Calle F. J. Chem. Technol. Biotechnol. 2016; 91: 1933
• 93 Christensen CV, Rass-Hansen J, Marsden CC, Taarning E, Egeblad K. ChemSusChem 2008; 1: 283
• 94 Sheldon RA, Sanders JP. M, Marinas A. Catal. Today 2015; 239: 1
• 95 Sheldon RA, Sanders JP. M. Catal. Today 2015; 239: 3
• 96 Yeung CS. Angew. Chem. Int. Ed. 2019; 58: 5492
• 97 Tsolakis N, Bam W, Srai JS, Kumar M. J. Cleaner Prod. 2019; 222: 802
• 98 Schilling C, Weiss S. New Biotechnol. 2021; 60: 9