Until the early 1990s, it took six separate, chemical reactions to make the painkiller and anti-inflammatory ibuprofen. Of the ingredients that went in, only about 40 percent were found in the final product.
But in 1992, the chemical producer BHC Company started using a new way to produce the drug using only three steps, utilizing about 80 percent of the initial ingredients. Today, the innovation in ibuprofen is considered a classic example of green chemistry—a set of ideas that, for the past few decades, has driven attention to sustainability in the pharmaceutical industry.
“When you practice chemistry, you’re working with materials to transform them,” Audrey Moores, professor in the Centre for Green Chemistry and Catalysis at McGill University, told The Daily Beast. “You have a lot of material and you turn it into a little material.”
Green chemistry, as Moores described it, tries to minimize the gap between the amount of material at the start of a reaction and the amount of material at the end. The ideas were formalized in the late 1990s (though practiced before then) when Paul Anastas and John Warner outlined 12 principles of green chemistry, from minimizing energy use to starting from renewable resources. The principles also stressed the importance of working with safer or non-toxic materials, when possible, and using products that minimize the potential for accidents.
Now, Moores says, the focus in the chemistry community is more toward optimizing every part of the life of a chemical product.
“You want to take a chemical and look at the whole life cycle,” Moores said. “All the aspects, from where it’s coming from, to the process to get it, to how its going to be used, to its disposal.” That includes everything from the sustainability of the source of an individual ingredient, to the emissions from the trucks driving a completed product to its final destination.
The pharmaceutical industry has embraced green chemistry more so than others, David Constable, the director of the American Chemical Society’s Green Chemistry Institute, told The Daily Beast.
“Pharma companies tend to be research-based organizations who are interested in optimizing their chemistry,” Constable said. “And, a lot of people in pharma are drawn to it because they have the idea that they’re providing things that improve the quality of people's lives. It would be a bit hypocritical to say we’re making things to improve people’s lives, but not paying attention to how they make them.”
In the 1990s, people in the industry also started to realize that pharma was a particularly inefficient chemical producer. Drugs are built through organic chemistry, which is done with molecules that contain carbon. That type of chemistry is particularly inefficient, and producing a small amount of a drug meant throwing out nearly 99 percent of the product that it started as. “But because the products were lucrative, they don't think so much about having less waste because at that price, they could afford to have to deal with it,” Moores said.
To address the issues, a number of pharmaceutical companies banded together and created a green chemistry roundtable, with a goal of identifying and troubleshooting common issues around sustainability. It had its first meeting in 2005, and today, 24 companies participate, representing all of the major novel drug producers. “The drug companies were really all in,” Constable said. The roundtable helped develop tools like lists of alternatives to highly toxic materials and scorecards for materials, and serves as an incubator for innovation.
There’s been a significant amount of progress internally at drug companies, as well. “They’re good at identifying where the pinch points are, and optimizing them over the course of development,” Constable said. Drugs go through a number of phases before they hit drugstore shelves, and at each step, the process is usually made more and more efficient. “If you look at a drug in phase 1, and then again at phase 3 or 4, the degree of optimization is pretty staggering,” he said.
Taking a green chemistry approach to creating a chemical is similar to looking at a puzzle, and trying to figure out the best way to put it together, Moores said. Because, at the end of the day, the final drug created is identential, no matter how it’s made. “It’s important to understand that the molecule is the same,” she said. “You just need to find the best process to make it.”
Cutting down on waste, and swapping toxic materials with non-toxic ones, also helps cut reduce manufacturing costs to the pharmaceutical company. Waste disposal, for one, is expensive. “If you are using a toxic metal during the process, that will end up in your material in the end. Then, companies have to clean the material, which you can do, but it costs money and generates even more waste,” Moores said. “If you replace the toxic metal with a non-toxic metal, you avoid those extra steps.”
However, Constable stressed, when those costs go down, it’s not necessarily reflected in the final price of the drug on the market. “The price of a drug is not driven by the manufacturing costs,” he said.
Though there’s been a significant progress towards sustainability in the pharmaceutical industry over the past decades, there's still a long way to go, Moores said. “They rapidly made progress because there was a lot of room for improvement,” she said. “The next steps are going to be a bit more difficult.”