The pharmaceutical industry faces significant environmental challenges as the demand for peptide-based drugs skyrockets. Companies like Novo Nordisk and Eli Lilly and Company are expanding their production capabilities to meet this growing demand, investing billions in the process. However, the manufacturing practices for these drugs, particularly peptides, are under scrutiny for their sustainability.
In Kalundborg, Denmark, Novo Nordisk is investing approximately $6 billion to enhance its active pharmaceutical ingredients (APIs) production, focusing on peptides used in weight-loss and anti-diabetic medications. Similarly, Eli Lilly has established a peptide synthesis plant in Kinsale, Ireland, underscoring a significant shift in pharmaceutical manufacturing geared towards these advanced treatments.
The peptides in drugs like Novo Nordisk’s Wegovy and Lilly’s Zepbound mimic natural hormones which are crucial in regulating blood sugar and reducing appetite, and are beneficial for weight loss and diabetes management. The approval of these drugs by the U.S. Food and Drug Administration has led to a surge in demand, with Novo Nordisk and Lilly reporting substantial sales figures in recent years.
Despite the medical benefits, the production of peptides could be environmentally costly. Peptide synthesis, mainly through solid-phase peptide synthesis (SPPS) , involves substantial quantities of organic solvents, leading to significant industrial waste.
Since the 1960s, solid-phase peptide synthesis (SPPS) has been the preferred method for producing peptides after its introduction by Bruce Merrifield, who earned a Nobel Prize in Chemistry for this innovation. Before SPPS, the liquid-phase synthesis was commonly used for creating shorter peptides, typically up to 20 amino acids in length. However, this method proved inefficient for longer peptides like semaglutide and tirzepatide due to complex purification issues.
Experts like Rodney Lax, a former business development manager at PolyPeptide, and Matteo Villain, a vice president at Piramal Pharma Solutions, express concerns about the sustainability of current production methods. The large-scale use of harmful solvents such as N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone, and dichloromethane poses health risks and environmental challenges, raising questions about the long-term viability of these practices.
Even brief exposure to these solvents can lead to health issues such as stomach pain, nausea, vomiting, skin rashes, jaundice, and even cancer in both humans and animals. To safeguard workers, the European Union set new safety limits in 2021 on how much of the solvent DMF people can be exposed to through the air or skin contact.
These solvents are commonly used across various industries like paint, adhesive, and drug manufacturing. However, the peptide industry requires particularly large amounts of these chemicals. For instance, according to a study, producing just one kilogram of a specific type of peptide (GLP-1 receptor agonist) might need up to 14 metric tons of solvent, a stark contrast to the roughly 0.3 metric tons needed for most other synthetic chemicals, as highlighted in a recent study.
In response to these challenges, the industry is exploring alternative methods to lessen its environmental impact. For example, Novo Nordisk uses a yeast-based fermentation process for its semaglutide production, which is considered more environmentally friendly. On the other hand, companies like CordenPharma and PolyPeptide are investing in new technologies and processes that reduce solvent use and increase the use of green solvents.
Despite these efforts, the demand for peptides is expected to continue growing, driven by the global increase in conditions such as obesity and diabetes. This demand pressures the industry to innovate and adopt more sustainable manufacturing practices swiftly.
As the industry moves forward, the need for sustainable manufacturing processes becomes more urgent. Innovations in peptide synthesis, such as enzyme-based coupling methods and continuous manufacturing processes, offer promising alternatives to traditional methods. However, the widespread adoption of these greener techniques is still in progress, and the industry must intensify its efforts to shift away from environmentally harmful practices.
