Click here to view the PDF
Where Does Peptide Manufacturing Need to Go?
The peptide and oligonucleotide (TIDES) manufacturing market has been niche, with average production sizes of a few kilograms of API. However, peptide-based drugs might need to serve up to a billion people by 2030, with a forecasted global demand of 80–120 tons. This necessitates a shift towards large-scale manufacturing. The high cost of these complex molecules creates barriers for global adoption and strains healthcare systems. Capacity and capability expansions will face challenges in supply chain logistics, starting materials, and waste management.
A comprehensive assessment of synthetic peptide environmental metrics found that solid-phase peptide synthesis (SPPS) has a high process mass intensity (≈ 13,000) (4). SPPS involves excess solvents and reagents, negatively impacting the environment, highlighting the need for newer technologies to reduce the environmental footprint (4).
Peptide CDMOs need to become faster, greener, and cheaper while improving API quality and producing at an unprecedented scale. Four main areas for technological and scientific innovation are identified.
Chemical Complexity Continues to Increase
Peptide-drugs have seen increased chemical complexity to improve pharmacokinetic properties, stability, and efficacy. This trend continues with the next generation of GLP-1 based drugs, including dual and triple agonists (cagrisema, retatrutide, mazdutide, and survodutide) in phase 3 trials for obesity and metabolic complications (3, 7). Fragment- and hybrid-based approaches to synthesize these multimeric molecules require new protective group chemistries, linkers, and coupling to fatty acids or proteins. Increased complexity demands new and effective quality controls and analytics throughout manufacturing.
Capacity Expansion and Industrial Intensification of Peptide Manufacturing
Every peptide CDMO is investing in capacity expansion and building new manufacturing sites. Manufacturing complex peptide APIs requires chemical expertise, dedicated engineering teams, equipment, supply chain and risk management, processes for technology transfers, and strategic partnerships. Bachem’s planned Sisslerfeld site will use a greenfield approach for optimal design of material, information, and waste flows (5).
Platform Flexibility Will Become Essential for CDMOs
Most CDMOs that invest in a specific platform tend to stick with it, because investment requirements create a high entry barrier. However, it is crucial to stay adaptable. Reinvesting in research and innovation is key. Bachem’s trailblazing concept involves starting with multiple processes and eliminating some at certain milestones. Platform flexibility is also essential for addressing sustainability challenges.
Sustainability Challenges Need to Be Addressed Head-On
Industry leadership on sustainability is crucial. Implementing greener processes often requires customer cooperation, which has improved over the last decade. Regulatory pressure from the EU, often perceived as a disadvantage, has driven focus on ambitious climate and sustainability goals. Bachem has pioneered the commercialization of Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) (6), a continuous chromatography system that increases throughput, yields, and reduces solvent consumption and costs. This innovation has led other CDMOs to adopt continuous chromatography solutions, promoting sustainable peptide manufacturing.
Without these innovations, GLP-1 drugs cannot become widespread, affordable, and desirable for environmentally conscious customers, patients, and governments. Companies without a sustainability vision are likely to fail, so all CDMOs must respond.
CDMOs Are Enablers of the GLP-1 Healthcare Revolution
We are at the beginning of the anti-obesity healthcare revolution. These drugs blur the lines between lifestyle, nutrition, healthy living, and medicine. People will want the choice to feel better, look better, and be healthier. The industry must be ready for this possibility. Effective, fast, high-quality, and low-cost manufacturing is crucial, as is sustainability. CDMOs must make these molecules affordable, safe, and their production greener.
That is why leadership in new manufacturing technologies and innovations are necessary, and we believe there is a huge responsibility for all CDMOs to do our part as well. We at Bachem are currently enablers and that puts some pressure on us, but it also gives our employees purpose; the opportunity to be part of something bigger than ourselves.
And who would not want to be part of that?
References and notes
- Zheng, Z., Zong, Y., Ma, Y. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024). https://doi.org/10.1038/s41392-024-01931-z
- GLP-1-Analogues market forecast. (2024, July 11). Market Watch. https://www.marketwatch.com/press-release/glp-1-analogues-market-forecast-usd-471-1-billion-by-2032-with-a-33-2-cagr-marketsandmarkets-tm-30cc9b51
- Melson, E., Ashraf, U., Papamargaritis, D. et al. What is the pipeline for future medications for obesity?. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01473-y
- Kekessie, I., Wegner, K., Martinez, I., Kopach, M. E., White, T. D., Tom, J. K., Kenworthy, M. N., Gallou, F., Lopez, J., Koenig, S. G., Payne, P. R., Eissler, S., Arumugam, B., Li, C., Mukherjee, S., Isidro-Llobet, A., Ludemann-Hombourger, O., Richardson, P., Kittelmann, J., . . . van den Bos, L. J. (2024). Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis. The Journal of Organic Chemistry, 89(7), 4261-4282. https://doi.org/10.1021/acs.joc.3c01494
- Bachem. (2022, December 19). Bachem expands presence in northwestern Switzerland. New production site planned in Sisslerfeld. https://www.bachem.com/articles/news/bachem-expands-presence-in-northwestern-switzerland-new-production-site-planned-in-sisslerfeld/
- Bachem. (2024, January 24th). The era of large-scale peptide & oligo purification with MCSGP has begun. https://www.bachem.com/articles/commercial-apis/the-era-of-large-scale-peptide-oligo-purification-with-mcsgp-has-begun/#:~:text=In%20a%20recent%20webinar,%20the%20experts%20behind%20this
- Drug manufacturers work to develop the next wave of weight loss drugs. (2024, June 24). (Video). NBC News. https://www.nbcnews.com/health/health-news/beyond-ozempic-glp-1-drugs-promise-weight-loss-health-benefits-rcna157525
ABOUT THE AUTHOR
A Leading CDMO’s Perspective on New Peptide-Based Anti-Obesity Drugs
Peptide-based anti-obesity drugs (1) are projected to become significant in the pharmacological landscape, with the global GLP-1 market expected to reach $471 billion by 2032 (2). The increasing demand pressures the pharmaceutical industry to upscale production and reduce costs to ensure long-term and equal access to new obesity pharmacotherapies (3). What can peptide CDMOs do to assist drug innovators in making the next healthcare revolution a reality?
Dr. Torsten Wöhr, CCO at Bachem, highlights trends in peptide manufacturing and where the industry needs to go.
Business Collaboration:
Bachem AG
Tel +41 58 595 2020
Tel +1 888 422 2436
sales.ch@bachem.com
