The Missing Element: Dr. Warner on Green Chemistry and the Future of Drug Discovery

Driven by changing consumer preferences and overall market trends, the pharmaceutical industry has begun to embrace more sustainable materials and processes. Leading this charge is renowned chemist Dr. John Warner, a member of the GL CHEMTEC Scientific Advisory Board. 

Dr. Warner’s prolific career spans over 350 patents and over 100 publications across various fields, including non-covalent derivatization, polymer photochemistry, metal oxide semiconductors, and more. His accolades include the Perkin Medal and the Presidential Award for Excellence in Science Mentoring.

As a co-founder of green chemistry, Dr. Warner has championed its widespread adoption, helping to redefine pharmaceutical processes and innovation. For his efforts, he was recognized as one of “25 visionaries changing the world.”

We recently met with Dr. Warner to learn more about green chemistry, and why embracing greener, safer chemical practices isn't just the ethical choice; it's also a strategic business move.

What is Green Chemistry?

Green chemistry is an approach to chemistry that focuses on the design, development, and implementation of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Unlike traditional chemistry, which often overlooks environmental impacts in favor of functionality, green chemistry integrates sustainability into every stage of a product's lifecycle, from inception to disposal.

At its core, green chemistry is about providing actionable strategies and tangible solutions. With this in mind, Dr. Warner and Paul Anastas outlined 12 guiding principles in their book “Green Chemistry: Theory and Practice,” which provide a framework that can be applied to all aspects of chemistry.

The 12 principles of green chemistry include:

1. Preventing waste: Preventing the creation of waste rather than treating or cleaning it up after it has been produced.
2. Maximizing atom economy: Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
3. Designing less hazardous chemical syntheses: Wherever possible, synthetic methods should be designed to use and generate substances with little or no toxicity to human health and the environment.
4. Designing safer chemicals: Chemical products should be designed to achieve their desired function while minimizing their toxicity.
5. Using safer solvents and auxiliaries: The use of auxiliary substances, such as solvents, should be made unnecessary wherever possible, and any use should be as innocuous as possible.
6. Increasing energy efficiency: The energy requirements of chemical processes should be recognized for their environmental and economic impacts, and processes should be designed to minimize energy use.
7. Using renewable feedstocks: Raw materials or feedstocks should be renewable rather than depleting, whenever feasible.
8. Avoiding chemical derivatives: Unnecessary derivatization should be minimized or avoided if possible.
9. Using catalysts: Catalytic reagents are superior to stoichiometric reagents.
10. Designing for degradation: Chemical products should be designed so that they break down into innocuous degradation products and do not persist in the environment.
11. Implementing real-time analysis for pollution prevention: Analytical methodologies should be developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
12. Minimize the risk of accidents: Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.

The Benefits of Adopting Green Chemistry Principles

In the last 20 years, many large pharmaceutical companies, including Amgen, Merck, Pfizer, Abbott, Johnson & Johnson, and Roche, have started implementing green chemistry practices for drug discovery, development, and manufacturing. While these changes may have been made for ethical reasons, a green chemistry approach also provides significant benefits, including:

• Dramatic cost savings
  Adopting green chemistry practices can reduce waste and lead to significant cost savings. Traditional cost analysis often overlooks the high costs associated with waste disposal for hazardous materials, which can include monitoring, transportation, disposal, treatment, and special training, along with additional costs covering the supply chain, legal considerations, and environmental impact.
  
  “Often, those making the products don't see the full cost, only the inputs; there's a disconnect between the cost of acquiring materials and the cost of disposal, which can be three to five times more expensive. A pharmaceutical company, for instance, can save millions annually by reducing waste even by a small percentage,” Dr. Warner said.
  
  For a real-world example, consider the case of the diabetes drug Januvia. Merck and Codexis developed a green synthesis of sitagliptin, the active ingredient in the drug, which eliminated the need for a metal catalyst, reduced waste by 19%, and increased yield by 10-13%.
  
  In another example, Amgen developed a greener synthesis process for its lung cancer drug LUMAKRAS, which involved eliminating a purification step that generated significant solvent waste. This resulted in improved drug yield and an estimated annual savings of £3.17 million.
• A culture of innovation
  For Dr. Warner, companies and CDMOs like GL CHEMTEC that have embraced green chemistry principles have a unique advantage: a culture of innovation.
  
  “We all take the same classes and go to the same conferences, we all read the same journals; we’re all doing the same thing. There's a certain normalization happening because of that. But interestingly, when you try to do things greener, it makes you think differently. It makes you break away from the pack. And that, by definition, is the core of competitiveness and innovation,” he said.
  
  By seeking out sustainable solutions, companies are forced to explore new avenues, potentially leading to the discovery of novel processes or materials with unforeseen benefits.
• Enhanced productivity
  Embracing green chemistry and its focus on creative problem-solving can also improve efficiency and productivity, and identify areas of improvement.
  
  "Organizations tend to be more productive when they embrace innovation, but there needs to be the will to do it," Dr. Warner noted. “The key is in the culture. GL CHEMTEC, for example, embraces the concepts of green chemistry at its core values. It has great leadership and amazing skills, but it's that culture that is going to change the world and make people successful."
  
  Many companies cite a lack of time as a barrier to embracing innovative approaches, but those that do have demonstrated that prioritizing sustainability doesn't slow down progress; instead, it drives improvement across business operations.
  
  Amgen, for instance, created a green chemistry team to define and implement green chemistry expectations. This, in turn, fostered investment in technology, tools, and reporting processes, and a new focus on the "triple bottom line" of environmental, social, and economic performance. Leveraging this approach, the company has reduced materials during the synthetic process, which in one instance led to an improved yield, an 82% decrease in the E (environmental) factor, and an 83% reduction in costs.
  
  Merck also used a green chemistry focus to enhance the manufacturing process for its COVID-19 antiviral drug molnupiravir, reducing solvent consumption, increasing yield by over 50%, and streamlining synthesis from 5 steps to just 3.

The Future of Green Chemistry

For Dr. Warner, articulating the 12 principles of green chemistry was just a starting point. He believes that education is the key to shaping the future, a conviction forged through two life-altering experiences.

The first occurred during his tenure at the Polaroid Corporation, where he developed the theory of non-covalent derivatization. This innovative approach resulted in numerous patents, accolades, and products, but also exposed the challenges of the regulatory system and the need for support and protocols for novel ideas.

The second experience was deeply personal and tragic: the loss of his 2 year-old son to a birth defect.

“Lying in bed the night of my son’s funeral, I wondered if something I touched in the lab had caused my son's birth defect. I wondered if something I got an award for caused his disease and death. I didn't feel like some amazing chemist. I felt that there was something fundamentally missing, and that's when I had this epiphany. From that point on, I was on a mission to change the way we teach chemistry,” he said.

In traditional chemistry education, students follow a reductionist approach, studying various branches like analytical chemistry, organic chemistry, and physical chemistry. This fragments the understanding of chemistry into separate areas and makes it easier to miss the holistic perspective needed to address environmental concerns.

“Adding green chemistry to the mix adds a piece that's been missing. I always refer to it as the missing element of chemistry,” Dr. Warner said.

To help fill that gap, Dr. Warner co-founded Beyond Benign, a non-profit that encourages universities to incorporate green chemistry principles into their core curriculum. 170 universities have signed on so far, but Dr. Warner believes the work has just begun.

“My goal is not for every university to sign the green chemistry commitment, but for it to become irrelevant because everyone's doing it. When we put ourselves out of business, that's when we've succeeded.” 

GLC: Your Trusted Green Chemistry CDMO Partner

GL CHEMTEC is passionate about your success and committed to solving your most complex chemistry challenges. With our expertise in small molecule API development and tailored polymers, we offer fast, flexible, cutting-edge solutions. Our commitment to a collaborative partnership means we scale and adapt precisely to meet your evolving needs.

GL CHEMTEC provides: 

• A unique combination of expertise in small molecule and bespoke polymers tailored to the target.
• Integrated solutions that accelerate early-stage API development and innovative drug delivery solutions, with seamless continuity from R&D to manufacturing.
• Strong organic polymer expertise and advanced materials applied to medical devices, drug delivery, and ophthalmic applications. 
• Unmatched expertise in polymer design and development, including tailored polymers, hydrogels, films, and emulsions/nano-emulsions.
• North American facilities, offering a reliable alternative to overseas supply chains and partners.
• A highly customer-centric culture and a 22-year track record of success. 
• ISO 9001:2015 and ISO 13485:2016 certifications.