Oligonucleotides, short DNA or RNA molecules, are emerging as powerful tools in modern medicine. As their use in treating various diseases grows, so does the need to produce them sustainably. Below, we explore eco-friendly manufacturing matters, how they can be achieved, and the importance of choosing the right production partner.

Why is sustainability within oligonucleotide manufacturing so important?

Sustainability in oligonucleotide manufacturing is becoming more important than ever due to the expanding role of these therapeutics in treating various conditions. With the oligonucleotide and peptide therapeutics market expected to have an annual growth rate of 17.5% before 2030, the industry faces pressing challenges. These include high production costs, hazardous waste, and energy-intensive processes.

As more oligonucleotide drugs gain approval and enter development, the demand for cost-effective and environmentally friendly manufacturing solutions intensifies. 

Sustainable practices not only mitigate environmental impact but also address economic and regulatory pressures, paving the way for more efficient and responsible production methods.

How can oligonucleotide manufacturing be more sustainable?  

Making oligonucleotide production sustainable is now possible thanks to constant advancements by companies like ourselves. By focusing on waste reduction, recycling, efficiency improvements, and innovative synthesis methods, manufacturers can lower environmental impact and costs.

Cutting down waste and prioritizing recycling 

At Bachem, we’ve implemented groundbreaking continuous chromatography technology for industrial-scale oligonucleotide purification. In fact, our Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) system represents a significant leap forward in sustainable manufacturing. By continuously recycling mixed fractions, we’ve achieved over 30% reduction in solvent use compared to traditional batch methods. This 24/7 automated process not only improves sustainability but also boosts productivity, maintaining high product yield and purity while potentially reducing cycle times by up to 70%. Initially proven for peptides, we’ve now successfully scaled this cost-effective, waste-reducing technology for oligonucleotides.

Maximizing yield and quality 

Maximizing yield and quality is crucial for sustainable oligonucleotide manufacturing. Continuous chromatography processes, such as Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) typically achieve higher capacity and yield while reducing solvent consumption compared to conventional batch purification methods. Operating 24/7 through automated systems, they can substantially reduce purification cycle times. This approach not only improves efficiency but also enhances sustainability by lowering process mass intensity. Importantly, these advanced purification methods maintain or even improve API quality, demonstrating that increased productivity and sustainability can go hand-in-hand in oligonucleotide manufacturing.

Lowering PMI with methods such as one-pot liquid-phase oligonucleotide synthesis

Process Mass Intensity (PMI) is a critical sustainability metric in oligonucleotide manufacturing, measuring the total mass of materials used per mass of product. Traditional methods can result in a staggering PMI of around 4300 kg of waste per kg of API for a 20-building block oligonucleotide.

To address this challenge, innovative approaches like one-pot liquid-phase oligonucleotide synthesis are being developed. This hybrid method combines the advantages of both solution-phase and solid-phase synthesis techniques. By using liquid anchor molecules or “tags” instead of solid-phase resins, it preserves the benefits of separating products from byproducts while allowing for higher volume yields.

This approach reduces solvent consumption considerably, a major contributor to high PMI. It eliminates excessive washing steps, potentially halving the PMI contribution from solvents.

Optimizing capacity with large-scale manufacturing  

Bachem’s dedication to innovation is evident across every step of the oligonucleotide manufacturing process. Over the years, our teams have implemented unique engineering solutions to drive improvements in product quality, scalability, cost-efficiency, and sustainability.

For instance, within the synthesis stage we have set up a large-scale oligonucleotide synthesizer customized with advanced process control and crude API purity enhancements. In the cleavage and deprotection phase, our automated, large-scale system boosts both production safety and efficiency.

Leveraging our deep expertise in peptide chromatography, our teams have successfully scaled up purification processes for oligonucleotides. This includes the pioneering use of continuous chromatography technology on an industrial scale, which delivers significant advantages – improved yields and purity, reduced solvent consumption, and lower process mass intensity. Plus, our core competencies in lyophilization and clean room operations ensure a streamlined, high-quality isolation process, avoiding any bottlenecks.

Encouraging employee innovation 

Bachem’s success is rooted in its unwavering commitment to technological leadership and innovation. Our tailored approach empowers all employees to contribute ideas and make them come alive. This culture of continuous improvement enhances efficiency, optimizes business processes, and identifies advanced manufacturing technologies. 

Plus, our positive, curious, and creative corporate environment serves as the foundation for this innovative mindset, allowing our teams to set industry standards in oligonucleotide production. In fact, we adhere to the latest GMP standards set by regulatory bodies globally, with outstanding quality in all areas underpinning its top performance and new innovations. “Quality Matters” is a fundamental ethos that has guided Bachem since its founding.

By actively engaging its workforce, we have harnessed the collective ingenuity to deliver superior products and services while navigating the evolving landscape of sustainable manufacturing.

Why choose Bachem for sustainable oligonucleotide manufacturing?

Sustainability is a core priority for Bachem, deeply woven into our company’s culture and operations. We take a comprehensive approach to its environmental and social responsibilities, continuously monitoring and improving its performance through a robust Corporate Social Responsibility (CSR) management system.

Our commitment to sustainability aligns with the United Nations Sustainable Development Goals. By integrating ethical practices and integrity into our long-term success, we have demonstrated our unwavering dedication to being a responsible partner in the oligonucleotide manufacturing space.

Our team has also been awarded a platinum medal rating for sustainability by EcoVadis, placing us among the top 2% of most sustainable companies. We have also ranked among the top 1% of companies rated by EcoVadis in the manufacture of basic pharmaceutical products and pharmaceutical preparations industry.

Our focus on sustainability extends across innovative technologies, efficient processes, and stringent quality standards. As a leader in driving sustainable solutions, we offer clients the confidence to choose a manufacturing partner that prioritizes environmental stewardship, social impact, and ethical business conduct alongside world-class oligonucleotide production capabilities.

Discover how Bachem’s sustainable approaches to oligonucleotide manufacturing can benefit your business. Contact us today to learn more about our innovative solutions that prioritize waste reduction, efficiency, and environmental responsibility without compromising quality or cost-effectiveness.