Contributed by Juan Colberg, Green Chemistry Leader/Senior Director of Chemical Technology, Pfizer; Javier Magano, Principal Scientist, Pfizer; and John Wong, Research Fellow, Pfizer
2012 marked the 10-year anniversary of Pfizer’s Green Chemistry Program, a program that focuses on education, innovation, solvent and waste reductions, the use of safer chemistry, greener processes, cost savings, and colleague engagement. Now, five years on from the 10-year anniversary, our Green Chemistry Program continues to promote, internally and externally, the selection and use of environmentally preferable chemicals, eliminating waste and conserving energy in our chemical processes.
As Pfizer’s portfolio evolves, so does its Green Chemistry Program. Efforts are not narrowly focused on small molecules for the Pfizer Innovative Health portfolio, but broadly include Biopharma and the Essential Health portfolios as well. An important part of the program’s success has been the commitment from Pfizer to provide and support the creation of ways to share knowledge, best practices and techniques across the organization, as well as educating future chemists and engineers in colleges and universities.
As part of these efforts, we have engaged our internal and external communities with a series of educational workshops to promote the application of green chemistry principles and the use of more environmentally sustainable technologies and approaches.
Green Chemistry Workshops at Pfizer
Education is one of the key elements of Pfizer’s Green Chemistry Program. Recognizing the importance of green chemistry education, Pfizer has hosted or participated in at least one workshop annually beginning in 2003.
From 2003 to 2006, workshops were held at the Pfizer R&D site in Groton, Connecticut. These workshops, titled “Sustainable Chemistry in the Pharmaceutical Industry,” began with a reception and dinner on the first day and featured a keynote address. The second day was a full day featuring presentations and interactive breakout sessions.
John Warner was an important participant in these workshops and presented “The 12 Principles of Green Chemistry: From Philosophy to the Flask.” Pfizer colleagues gave presentations on various topics involving the application of green chemistry in the development of Pfizer drugs. The breakout sessions gave students the opportunity to apply their knowledge of green chemistry to case studies based on Pfizer drugs. For instance, the case studies presented during the breakout sessions in 2004 were based on sertraline and sildenafil, the active pharmaceutical ingredients in Zoloft® and Viagra® respectively.
Participants in the workshops were selected from colleges and universities in the Northeast. Participation in 2004 was similar to the other years in which this workshop was conducted and included 28 students from 13 institutions in six states (Connecticut: Connecticut College, UCONN, University of St. Joseph; Massachusetts: Bridgewater State, UMASS Amherst, UMASS Boston, Gordon College, Simmons College, Suffolk University, Worcester Polytechnic Institute; New Hampshire: University of New Hampshire; Rhode Island: University of Rhode Island; Vermont: University of Vermont). Overall, these workshops hosted at the Pfizer R&D site in Groton were well received based on feedback from students. Notably, two participants from the 2004 workshop became Pfizer colleagues.
Pfizer has also promoted green chemistry education outreach activities in other sites across the U.S. and Europe.
Workshop on Wheels (WOW)
With the great success of the Pfizer green chemistry workshops hosted in Groton, we decided to expand the program by engaging faculty members and reaching students from a broader range of disciplines. In 2007, the Groton Green Chemistry Team conceived the “Workshop on Wheels (WOW),”in which the workshop was set to be conducted at a college or university with a small team of Pfizer colleagues. An important element of “WOW” was the active engagement of faculty and students in organizing and conducting these workshops.
The first “WOW” was held at the University of Puerto Rico in 2007, hosted by Professor Ingrid Montes (currently Director-at-Large, ACS Board of Directors), followed by one in UCONN hosted by Professor Amy Howell. Since 2007, Pfizer has partnered with nine institutions (Boston University, Harvard University, Northeastern University, UMASS Boston, University of Rhode Island, Wesleyan Univeristy, Worcester Polytechnic, and Yale University) to bring “WOW” to their campuses. The “WOW” held at UMASS Boston in 2016 is the subject of a previous Nexus article.
Pfizer remains committed to green chemistry education and is planning a return trip to University of Rhode Island for its 2017 “WOW,” hosted by Professor Brenton DeBoef.
Workshop Focus Shifting to New, Greener Technologies
While the format of Pfizer’s green chemistry workshops has remained consistent, with presentations by Pfizer colleagues and invited speakers as well as an interactive breakout session, the focus of the topics has shifted from a basic application of the 12 Principles to applications of novel, greener technologies.
Thus, the last few years have seen the development of a number of talks by green chemistry team colleagues that cover diverse and increasingly important areas of chemistry, leading to more environmentally benign processes that have become some of the workshop attendees’ favorite topics.
- Biocatalysis: The use of enzymes in drug manufacturing has seen a resurgence in recent years thanks to enzyme engineering, resulting in highly-active and versatile biocatalysts that enable highly efficient processes. In addition, due to the chiral nature of enzymes, these catalysts are particularly well-suited for the generation of chiral centers in the products, which is of special interest in the pharmaceutical industry. A great example that is analyzed by the attendees of the “WOW”breakout sessions is a route to pregabalin (LyricaTM), in which the enzyme is used to resolve a diester. This then allows for the separation of the compound with the desired chirality leading to pregabalin, whereas the compound with undesired stereochemistry undergoes racemization and can be recycled and fed back into the process with the consequent improvements in yield and waste reduction. Another outstanding example of biocatalysis application that is presented is the synthesis of the side chain of statins, such as Lipitor, which replaced the original reduction to generate a stereocenter using toxic and pyrophoric chemicals.
- Flow chemistry: Most of the current processes under development or at the commercial stage in the pharmaceutical industry are run in batch mode. One reason for this is familiarity – process chemists are more familiar with batch processing and the large investment made over years in the existing batch process infrastructure at pharmaceutical plants. However, it is becoming increasingly evident that processes on flow have many advantages over batch mode, including improved safety when dealing with unstable reagents, smaller investments in equipment, lower solvent consumption, and efficient heat removal from exothermic reactions. Pfizer, as well as other pharmaceutical companies and academic institutions, is investing heavily in this technology as a way to manufacture drugs “on-demand” to reduce cost and improve carbon footprint.
- Catalysis using non-precious metals: Catalysis is one of the 12 Principles of Green Chemistry and is frequently used in the synthesis of drug candidates. Unfortunately, most of the metals currently used in catalysis are precious metals, such as palladium, iridium, rhodium, platinum and ruthenium. Besides cost, a concern related to the use of these metals is their toxicity, which requires extensive purification protocol to bring levels down to acceptable values with the concomitant increase in waste, as well as their long-term supply due to their scarcity in the Earth’s crust.
Pfizer, as part of an alliance with other pharmaceutical companies, has embarked in an ambitious program to replace those precious metals with more sustainable alternatives, such as iron, nickel and copper. These three metals are abundant, inexpensive, and display lower toxicity than precious metal catalysts, which contribute to turning catalysis into an even more attractive technology for the synthesis of drug candidates.
Pfizer colleagues have discussed this topic during their presentations at “WOW” by showing examples from literature and comparing advantages and drawbacks for the use of these metals. Though there is still a long way to go in replacing precious metals altogether with greener alternatives, progress is being made almost daily in both academia and industry, and theses presentations intend to inform the audience about the rewards of employing iron, nickel and copper in catalytic processes and the long-term risks of not further investing now in those technologies.
Passion for green chemistry continues to be the driver for so many Pfizer colleagues around the world to support these types of activities – passion that has continued growing across all these years since the program’s creation.
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