Trends and Challenges Impacting Highly Potent API Development

Demand for highly potent active pharmaceutical ingredients (HPAPIs) remains high in the face of a continued focus by the pharmaceutical industry on the oncology space, targeted therapies, and precision medicine. Consequently, HPAPIs account for a growing percentage of pipeline candidates. Advances in synthetic chemistry, bioproduction, continuous manufacturing, and containment technologies are increasing the feasibility of bringing these ever more-potent therapeutics to the market.

The value of the global HPAPI market is estimated to be expanding at a compound annual growth rate (CAGR) of approximately 9% to surpass $60 billion by 2034 (1,2). Given the specialized nature of HPAPI manufacturing, this strong demand growth is also driving healthy growth for the HPAPI contract manufacturing market. One estimate pegs the global value for this sector at $8.15 billion in 2024 and expanding at a CAGR of 10.93% to reach $23 billion by 2023 (3).

How is the HPAPI landscape evolving?

A distinguishing feature of the HPAPI market is the rapid rate of change it has been experiencing over the past decade-plus. The fast pace of evolution can be attributed to several factors, according to Ester Masllorens, senior vice president of global R&D with Olon. “The HPAPI landscape is rapidly evolving, driven by breakthroughs in oncology, rare diseases, and advanced delivery platforms such as antibody-drug conjugates (ADCs) and peptides. The growing complexity and potency of these molecules requires sophisticated containment capabilities and manufacturing strategies,” she says.

At the same time, Alessandro Agosti, director of Olon’s R&D Rodano Hub, notes that regulatory scrutiny and environmental, safety, and governance (ESG) expectations are compelling contract development and manufacturing organizations (CDMOs) to operate in a cleaner, safer, and more sustainable manner.

Technological innovations are helping to both reshape HPAPI development and scale-up and addressing evolving challenges. “For example, technologies such as flow chemistry, continuous manufacturing, and advanced membrane technologies reduce operator exposure while enhancing efficiency and consistency,” comments Agosti. He also highlights the increasing importance of automation, predictive modeling, and artificial intelligence-driven design-of-experiments (DoE), particularly for high-potency compounds requiring stringent containment.

What are some technical, operational, and regulatory challenges?

Development and production of HPAPIs have always been challenging given the need for specialized expertise to ensure their safe handling with respect to both operators and the environment. The unique combination of technical, operational, and regulatory challenges faced by HPAPIs continues to increase as the diversity and higher complexity of HPAPI candidates under development today continues to widen, according to Masllorens.

“In addition to the need for robust containment, validated cleaning procedures, and strict protection of operators, HPAPI CDMOs must also be able to implement highly specialized synthesis and purification capabilities, often under extreme containment, to generate molecules from ADCs and peptides to newer types of bioconjugates,” observes Masllorens. She adds that ease of formulation, bioavailability, and supply chain security remain persistent issues as well and are further complicated by fluctuating raw material markets and global economic pressures.

Why is a multipronged approach essential?

To overcome these many challenges, HPAPI manufacturers are pursuing strategies that involve numerous independent tactics. “To address the complexity of HPAPI development, the industry is increasingly adopting modular containment systems, green chemistry approaches, and digitalization,” states Masllorens. Regardless of the specific approach taken, she emphasizes that a strong commitment to innovation, safety, and sustainability is a fundamental requirement.

Olon has found that co-locating its high-containment R&D, quality control, and good manufacturing practice (GMP)-compliant production units has streamlined tech transfer activities and enabled rapid scale-up as client candidates progress through clinical development, according to Masllorens. In a similar vein, the company has connected its global network of 14 sites through a centralized R&D hub, which has supported harmonization of processes and facilitated best-practice sharing across all technologies.

Developing processes using DoE and quality-by-design approaches and advanced modeling tools, meanwhile, ensures safety, robustness, and reliable transfer throughout the entire lifecycle of highly potent compounds, notes Agosti.

Finally, Olon believes that its integration of biological capabilities—microbial fermentation for semisynthetic APIs and bioconjugation to ADCs—with its chemical HPAPI expertise positions the company to meet evolving scientific and sustainability demands of next-generation HPAPI development, according to Agosti. He notes this integrated approach is particularly advantageous for payloads that require both biological and chemical steps such as maytansinoids and camptothecins. In addition, Masllorens believes that the vertical integration of chemical and biological capabilities allows Olon to support clients across a wide range of production volumes and modalities, from early-phase clinical batches to late-stage commercialization.

Managing the move from small- to large-scale manufacturing

Tech transfer is one of the most critical and sensitive steps in HPAPI development, particularly when moving from small-scale R&D settings to full-scale GMP manufacturing. “Key challenges include validating cleaning procedures for ultra-potent compounds, maintaining consistent containment integrity, and ensuring personnel are fully trained to handle these materials safely,” Agosti observes. He adds that for biologically derived HPAPIs, such as bioconjugates, variability in biological systems and complex purification and downstream further complicate scale-up. Here again, integration of R&D, analytical development, and GMP production in the same location ensures that R&D teams stay involved through validation and even first commercial batches, ensuring continuity of knowledge.

What are some continued CDMO investments?

The HPAPI sector is set for sustained growth, driven by a strong pipeline in oncology, rare diseases, and immune-modulating therapies, according to Masllorens. Many of these molecules, such as ADCs and peptide therapeutics, require ultra-high containment, highly specialized synthesis or fermentation, and strict regulatory compliance, which is driving demand for services from CDMOs with advanced and demonstrated capabilities, she adds.

In addition, Agosti notes that clients are increasingly prioritizing ESG performance, supply chain resilience, and digital integration; therefore, CDMOs must be positioned to address these needs as well.

In response to these evolving expectations and the healthy growth of the HPAPI market, a high level of investment by CDMOs has been observed over the past several years, including a few notable moves in the United States in 2024 and 2025.

Olon added new occupational exposure band (OEB) 5 production lines and a state-of-the-art OEB6 facility dedicated to ultra-potent compounds such as ADC payloads and payload-linkers, according to Masllorens. “The OEB6 facility integrates analytical labs, pilot units, and GMP manufacturing and leverages technologies such as flow chemistry, photochemistry, biocatalysis, and tangential flow filtration to enable safer, greener, and more scalable operations and support of the development and production of ADCs,” she says. Plans are in place to expand the OEB6 facility to meet rising demand for ultra-potent payloads and biological intermediates by 2026 and scale Olon’s bioconjugation capabilities. With respect to implementation of newer technologies, Olon has incorporated both upstream and downstream innovations including antibiotic-free processes and codon-optimized microbial expression.

In June 2025, Piramal Pharma Solutions announced it will spend $90 million to expand ADC manufacturing capability at two facilities in the US, including HPAPI production (payload-linkers) in Michigan and ADC fill/finish capacity in Kentucky (4). SK pharmteco, meanwhile, launched a new CGMP analytical testing laboratory dedicated to HPAPIs at its Rancho Cordova, California site in February 2025 (5).

AGC Pharma Chemicals announced in January 2025 the expansion of its HPAPI capabilities in Barcelona, Spain with the goal of achieving “seamless scale-up from grams to tons within a single integrated ecosystem” (6). Once completed, the company’s entire development and manufacturing chain from its new R&D facility through laboratory to commercial production will be adapted to OEB5 standards.

Sterling Pharma Solutions announced in May 2024 that it would be investing $3 million to expand its integrated ADC development and manufacturing capabilities in Wisconsin. A dedicated GMP suite including a modular isolator with containment capabilities down to less than 1 nanogram per cubic meter will be added that will enable toxin linker manufacturing up to the kilogram scale (7).

References

1. Grand View Research. High Potency Active Pharmaceutical Ingredients Market–By Product, By Drug Type, By Manufacturer Type, By Application–Global Forecast, 2025–2034. February 2025. https://www.gminsights.com/industry-analysis/high-potency-active-pharmaceutical-ingredients-market
2. Mordor Intelligence. High Potency APIs Market Size & Share Analysis–Growth Trends & Forecasts (2025–2030). https://www.mordorintelligence.com/industry-reports/highpotencyapis%.
3. Nova One Advisor. High Potency API Contract Manufacturing Market Size to Hit USD 23.00 Bn by 2034. Nov. 7, 2024. https://www.biospace.com/press-releases/high-potency-api-contract-manufacturing-market-size-to-hit-usd-23-00-bn-by-2034
4. Piramal Pharma Solutions. Piramal Pharma Solutions Breaks Ground on $90M Expansion Plan. Press Release, June 25, 2025. https://www.prnewswire.com/news-releases/piramal-pharma-solutions-breaks-ground-on-90m-expansion-plan-302494239.html
5. SK pharmteco. SK pharmteco Launches State-of-the-Art HPAPI Laboratory. Press Release. Feb. 12, 2025. https://www.skpharmteco.com/news-insights/news/sk-pharmteco-launches-state-of-the-art-hpapi-laboratory/
6. AGC Pharma Chemicals. AGC Pharma Chemicals Announces Expansion of HPAPI Capabilities in Barcelona. Press Release, Jan. 29, 2025. https://www.agcpharmachemicals.com/en/news/agc-pharma-chemicals-announces-expansion-of-hpapi-capabilities-in-barcelona/
7. Sterling Pharma Solutions. Sterling Expands HPAPI Capabilities to Further Strengthen Integrated ADC Services. Press Release, May 30, 2024. https://www.sterlingpharmasolutions.com/knowledge-hub/news/sterling-pharma-solutions-expands-hpapi-capabilities-in-germantown/

About the author

Cynthia A. Challener, PhD, is a contributing editor to Pharmaceutical Technology®.

Article details

Pharmaceutical Technology®
Vol. 49, No. 9
November/December 2025
Pages: 13–14, 21

Citation

When referring to this article, please cite it as Challener, C.A. Trends and Challenges Impacting Highly Potent API Development. Pharmaceutical Technology 2025 49 (9).