Sustainability by Design: Re-Imagining Amorphous Dispersion Manufacturing

The pharmaceutical industry often faces pressure to reduce its environmental impact, as it accounts for 20 to 25% of healthcare’s total greenhouse gas emissions.¹ However, focusing exclusively on ecological objectives overlooks a significant untapped area for improving sustainability: the manufacturing process.

Early design decisions determine 80% of a drug’s environmental impact, making intentional formulation strategies essential.² Pharmaceutical companies need to minimize energy demand while maintaining economically sustainable manufacturing practices over time, so they can allocate resources to products rather than production.

These considerations are especially relevant in small-molecule drug development. While pharmaceutical companies have largely directed their investments into biologics in recent years, newer data indicate that small molecules account for 45% of orphan pipeline candidates. With rare disease therapies projected to generate over $400 billion in global sales by 2032, these findings suggest a resurgence of non-biologic therapeutics.³

Many small-molecule manufacturing approaches can introduce significant operational and environmental challenges. They typically rely on amorphous solid dispersions (ASDs) to improve the bioavailability of poorly soluble drugs, using methods such as spray-dried dispersion (SDD), which employs organic solvents. This process generates significant environmental and operational burden, from solvent use to added facility and handling requirements. Sustainable pharmaceutical initiatives will have to become a key part of the development conversation, prioritizing both environmental and manufacturing factors, if pharmaceutical companies hope to make impactful changes.

The Sustainability Implications of Traditional ASD Processes

Conventional ASD technologies have long remained the standard because they effectively address poor water solubility, which affects 40% of marketed drugs.⁴ This system, however, is time-consuming and relies heavily on solvents, often complicating modern-day sustainability efforts.

Existing ASD models create 2 primary challenges:

• Environmental concerns: Solvent-based ASD technologies require large volumes of this material, most of which do not translate into the actual product. Manufacturers must then extract, retrieve, and handle this excess substance.
• Manufacturing inefficiencies: Discarded solvent and related waste streams translate into unnecessary time invested in the development pathway. They add dependencies on materials, equipment, handling, and processing, which can pull resources away from product-focused development.

While sustainability discussions often prioritize environmental impact, manufacturing decisions can have downstream effects that undermine long-term objectives. If pharmaceutical companies rely on outdated frameworks that increase the use of rare materials, extend timelines, and heighten supply chain risk, they will struggle to shift their priorities toward broader ecological goals. A small manufacturing decision can compound into severe consequences that sponsors, and biotech companies cannot afford to sustain, resulting in inefficiencies and resource losses that persist throughout commercialization. Third-party involvement further amplifies these logistical concerns.

Operational Risks Behind Solvent Reliance

Solvent evaporation and recovery often require resource-intensive steps that rely on external partners. Pharmaceutical companies usually outsource the procurement of extrinsic materials and coordinate with various supply chains to ensure they have all the required pharmaceutical ingredients for manufacturing.

Many of these supply chains are globally distributed, so sourcing key starting materials (KSMs) for APIs creates dependencies and increased coordination considerations across countries. Forty-one percent of US-approved KSMs are sole-sourced from China, and 16% from India.⁵ These dependencies create more touchpoints where workflows can fail, exposing companies to potential pipeline disruption. To limit points of failure and curb product loss, sustainability initiatives must focus on improving ASD operations.

Assessing Operational Sustainability in ASD Development

Sponsors can assess current ASD efficiency by asking several key questions:

• Solvent requirements. How does the development pathway use solvents, and does it create excess product that will have to be removed down the line?
• Waste generation and energy demand. Does the system create excess byproducts, in product or labor, that could be avoided?
• Scalability. Does scaling the system require multiple sizes of equipment? Is this avoidable if the ASD process were changed?
• Predictability. Are systems reliable? Do they remove variability, allowing for predictable outputs?
• Manufacturing efficiency. Do pharmaceutical manufacturing teams have to spend time managing products that end up in a waste stream?

Many of these operational and environmental challenges stem from the structure of solvent-based ASD systems, prompting some pharmaceutical companies to evaluate alternative manufacturing methods.

Alternative ASD Manufacturing Models

One area of interest is solvent-free, fusion-based processes that reduce the volume of material usage. Any API, polymer, or excipient that enters the ASD manufacturing process is retained in the final product, reducing manufacturing steps, eliminating secondary drying, and lessening reliance on scarce inputs.

This simplified approach may also bring advantages during scale-up. Legacy ASD manufacturing often requires changes in equipment size and workflows as volumes increase, introducing additional risk. With fusion-based approaches, drug-development companies scale production by adjusting throughput, avoiding changes in equipment sizes, and simplifying inefficient commercialization paths.

Removing these bottlenecks decreases costs, risks, and development timelines, supporting more predictable formulation pathways. This allows pharma companies to maintain ASD systems over time and connect environmental objectives with economic considerations.

The Business Value of Operational Simplicity

Reducing waste in ASD pipelines creates tangible business outcomes. Product performance alone no longer determines drug asset value; development and manufacturing efficiency now play a growing role. When companies minimize manufacturing byproducts, inefficiency, and complexity, they minimize their costs and risk exposure.

In time, these efficiencies will simplify processes and lower operational burden, allowing for greater predictability throughout the commercialization pathway and a naturally embedded, reduced environmental footprint in production environments. This approach directly links commercial and environmental sustainability to improved company margins, thereby maintaining long-term growth.

Sustainability and Simplicity Must Work Together

Long-term sustainability efforts must align with practical manufacturing practices to succeed. A comprehensive approach should prioritize simpler frameworks that not only have a positive impact on the environment but also curb costs, risks, and variability.

With smaller molecules accounting for a large share of drugs on the market and many of them being poorly water-soluble, traditional ASD processes are a practical place to improve sustainability from all angles. Removing solvents from the development environment could not only reduce material loss and energy use that harms environmental objectives but also lessen the operational burden, improve efficiency, and pave the way for scalable development.

References

1. Parker G and Miller AF. Tackling pharmaceutical pollution along the product lifecycle: roles and responsibilities for producers, regulators and prescribers. Pharmacy (Basel) 2024 12(6): 173. doi: 10.3390/pharmacy12060173. https://pmc.ncbi.nlm.nih.gov/articles/PMC11587451/.
2. Challener CA. Sustainability by design in the context of bioprocess development. Pharm. Technol. 2025 49(4) 24-27. https://www.pharmtech.com/view/sustainability-by-design-in-the-context-of-bioprocess-development.
3. Orphan drugs outlook 2032: sales, pipeline, & policy for rare diseases. Evaluate. Accessed June 17, 2026. https://www.evaluate.com/thought-leadership/orphan-drugs-outlook-2032/.
4. Zheng W, Chen H, Xue R, Wu Z, Liu Y, Chen F. Solvent-free aqueous spray drying of poorly soluble drugs enabled by hot-feed micellar solubilization and high-Tg polymer matrices. Intern. Journal of Pharmaceutics: X 2026 11. https://doi.org/10.1016/j.ijpx.2026.100541 https://www.sciencedirect.com/science/article/pii/S2590156726000617.
5. Concentrated origins, widespread risk: new USP insights on key starting materials. USP Quality Matters. USP. Accessed June 17, 2026. https://qualitymatters.usp.org/concentrated-origins-widespread-risk-new-usp-insights-key-starting-materials.

About the Author

Elizabeth Hickman is CEO of AustinPX.