Inside the Changing HPAPI Manufacturing Landscape

Editor’s Take: Highly potent active pharmaceutical ingredients are no longer a niche manufacturing challenge reserved for a limited set of oncology products.

According to a recent report by Grand View Research, the global high potency active pharmaceutical ingredients market size was valued at $29.9 billion in 2025 and is projected to grow from $31.6 billion in 2026 to $48.3 billion by 2033 at a CAGR of 6.2%¹, primarily driven by the rising prevalence of cancer and other chronic diseases, increasing adoption of targeted therapies and oncology drugs, and the expanding pipeline of highly potent molecules such as antibody drug conjugates and cytotoxic compounds.

As drug pipelines shift toward targeted therapies, antibody-drug conjugates, protein degraders, radioligands, potent peptides and other precision medicines, more compounds are entering development with very low occupational exposure limits and increasingly complex handling requirements. This is changing what sponsors expect from development and manufacturing partners—and what CDMOs must be prepared to deliver.

This article explores how HPAPI development and containment strategies are evolving. Drawing on insights from experts across the CDMO and pharmaceutical services sector, it examines the therapeutic and modality trends driving demand, changing customer expectations, the importance of early risk assessment and containment verification, and the capabilities manufacturers will need as highly potent pipelines become more diverse, more global and more technically demanding.

Current State of the HPAPI Market

“The HPAPI landscape continues to be driven by the rapid expansion of precision medicine, particularly in oncology,” explains Hongfeng Chen, EVP of Process Chemistry, Wilmington PharmaTech.

He says, “The growing pipeline of targeted therapies, antibody-drug conjugates (ADCs), peptide therapeutics, and other highly potent compounds is increasing demand for specialized development and manufacturing partners with expertise in high-containment operations.”

John Jacobsen, Ph.D., Head of R&D Small Molecule North America, SK Pharmteco, says, “High-potency development and manufacturing are becoming increasingly important as drug pipelines shift toward more targeted therapies requiring specialized containment, complex chemistry, advanced purification, and sensitive analytical methods.”

“Oncology remains the largest opportunity, particularly for ADCs, which combine an antibody, linker, and highly potent payload with distinct development and manufacturing requirements,” Jacobsen explains.

“Protein degraders and molecular glues are creating additional demand and may require significantly larger volumes,” he adds. Furthermore, he says, “Beyond oncology, highly potent compounds are expanding into autoimmune and inflammatory diseases, rare diseases, CNS conditions, antivirals, ophthalmology, and metabolic disorders—reflecting a broader shift toward highly targeted medicines designed to achieve specific biological effects at increasingly low doses.”

According to Mario Di Giacomo, President, Farmabios, “More than 40% of new molecular entities currently in development carry a high-potency classification.”

He says, “This creates a growing need for specialist partners that can combine potent chemistry expertise with the containment infrastructure, analytical capabilities and regulatory understanding required to manufacture these compounds safely and at scale.”

Furthermore, he explains, “Building and maintaining these capabilities in-house is often neither practical nor economically rational, driving greater reliance on specialist CDMOs and putting a premium on choosing a partner with the right combination of expertise and infrastructure.”

Frank Sorce, Chief Commercial Officer, UPM Pharmaceuticals also observes a greater reliance on CDMOs. He says, “Outsourcing is increasing because building and maintaining dedicated HPAPI infrastructure requires substantial capital investment, specialized personnel and rigorous environmental, health and safety systems.”  

“For many emerging and even established pharmaceutical companies, working with an experienced CDMO is more practical than developing these capabilities internally,” Sorce remarks.

“Almost no smaller biotech has the in-house infrastructure to handle a compound active in the nanogram range, so for most sponsors, outsourcing isn’t a preference. It’s the only option,” adds Hibreniguss Terefe, Director of Product Development, Ardena.

Evolving Customer Expectations

UPM’s Frank Sorce says customer expectations regarding containment, safety, speed and overall project executions have evolved substantially. He explains, “In the past, sponsors often focused on whether a CDMO had a potent-compound suite and could meet a specified occupational exposure limit. Today, they expect the CDMO to demonstrate a comprehensive, science-based containment strategy supported by toxicological assessment, industrial-hygiene data, engineering controls, cleaning validation and documented containment performance.”

“Simply stating that a facility can handle a particular OEB is no longer sufficient,” Sorce claims. “Sponsors want evidence that the controls are appropriate for the specific molecule, process and scale.”

Masashi Takahashi, CTO, AGC Pharma Chemicals, observes, “Pipelines are becoming more fragmented, with a higher number of clinical programs requiring smaller, more specialized batches rather than traditional high-volume production.”

This is changing the type of capacity customers require. According to Takahashi, “Demand is moving toward flexible, multi-purpose facilities capable of managing a broad range of batch sizes and occupational exposure bands, while maintaining robust segregation and cross-contamination controls.”

Furthermore, he says, “Customers are seeking integrated partners that can support the complete pathway from route scouting and analytical development through GMP scale-up and commercial manufacture. The need is therefore not simply for high-containment capacity, but for scientific, engineering and manufacturing continuity throughout the project.”

“Responsiveness, transparent communication, and the ability to adapt to changing project requirements have become essential, particularly as development timelines continue to accelerate,” adds Taylor Henderson, EH&S Manager, Alcami.

He says, “Manufacturing flexibility is especially critical during preclinical and clinical development. As molecule characteristics, batch sizes, and timelines evolve, sponsors expect CDMOs to quickly adjust processes and manufacturing strategies while maintaining quality, safety, and schedule commitments.”

The importance of flexibility is cited by SK Pharmteco’s John Jacobsen, as well. He argues that customers need more than equipment and capacity. “They want experienced partners with proven containment capabilities, flexible scale, strong regulatory systems, and teams that understand how potency affects every stage of development and manufacturing.”

“Customer expectations have evolved well beyond simply finding a CDMO capable of safely handling highly potent compounds,” adds Wilmington PharmaTech’s Hongfeng Chen.

“Speed and flexibility have become critical,” he says. “Companies are looking for partners that can rapidly move projects from development to GMP manufacturing, adapt to changing timelines, and seamlessly scale processes as programs advance. Early collaboration, proactive communication, and transparent project management are now essential expectations.”

Overall, UMP’s Sorce says the expectation has shifted from “Can you contain and manufacture this compound?” to “Can you safely, flexibly and predictably manage the entire program?”

According to Sorce, “The most valued HPAPI partners are therefore those that combine demonstrated containment with formulation and analytical expertise, scalable manufacturing, transparent project management and a strong record of reliable execution from development through commercialization.”

Addressing the Challenge of Scaling Up

Alcami’s Taylor Henderson calls maintaining flexibility as a program scales “one of the biggest challenges” associated with moving and HPAPI from development through commercial-scale manufacturing.

“During early development, small batch sizes and pilot-scale equipment allow manufacturers to adapt quickly to process changes. As products move toward commercialization, however, the potency of the compound often requires specialized equipment, production lines, or even dedicated facilities to ensure appropriate containment and prevent cross-contamination,” Henderson explains.

“A procedure that performs well with a few kilograms in development may behave very differently when material quantities, processing times, equipment size and operator interactions increase,” UPM’s Frank Sorce adds. “Dust generation, powder flow, transfer losses, cleaning difficulty and potential exposure points can all become more significant at commercial scale.”

“Operations that appear straightforward in the laboratory, such as solids charging, sampling, filtration or discharge, may present significantly greater exposure risks at larger scale,” says AGC Pharma Chemical’s Masahi Takahashi. “Heat transfer, mixing, crystallization, particle formation and drying behavior can also change, affecting both product quality and containment performance.”

The solution to the challenges of scale-up? Takahashi says, “The most effective way to balance speed and safety is to develop the process and containment strategy together.”

“Containment planning should begin early and run alongside process development, analytical development, and reaction-safety evaluation,” says SK Pharmteco’s John Jacobsen. “Waiting until the GMP campaign is scheduled can reveal facility-fit problems when there is very little time to resolve them.”

Wilmington PharmaTech’s Hongfeng Chen says, “Balancing speed-to-clinic with containment starts with early planning and close collaboration between process development, engineering, manufacturing, and quality teams.”

This includes, “conducting thorough risk assessments, selecting scalable chemistries, and leveraging existing high-containment infrastructure help minimize delays while maintaining compliance.”

Mark Vlasic, Business Development Manager, Douglas CDMO, says there are three key considerations when developing an effective containment strategy for highly potent compounds: “First, understand the compound. The physical and toxicological properties should determine the level of containment required. Second, integrate containment into development rather than treating it as a separate activity later in the program. Finally, consider future commercial manufacture early so the containment strategy can support the product throughout its lifecycle.”

Updated High Containment Facilities

With evolving demand and expectations, facilities also need to be updated to support increasingly potent compounds.

“High-containment facilities look pretty different than they did even five years ago,” says Ardena’s Hibreniguss Terefe, “and that shift has been observed happening in real time, mostly because the compounds coming through the door are more potent and more complicated.”

He says, “Isolators and closed systems now come with automated sampling, robotics, and real-time particulate and vapor monitoring built in. Those used to be premium options; now they’re close to standard.”

Furthermore, he observes facilities built for classic small-molecule work at exposure limits below 10 µg/m³ being redesigned or retrofitted to handle bioconjugation too, because ADC programs need potent small-molecule containment and biologics-grade handling within a few doors of each other.

“Analytics have also kept pace,” he adds. “Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and other ultra-trace methods are now designed into facilities from the start, not bolted on as a separate lab service.”

“High-containment facilities are becoming more closed, modular, and better suited to the smaller, changing batch sizes common in HPAPI development,” adds SK Pharmteco’s John Jacobsen. “Reactor volume alone is no longer the best measure of capability. The ability to safely handle different scales, physical forms, and potency levels is increasingly important.”

“Modern facilities increasingly use isolators, contained transfer systems, split butterfly valves, sealed charging and discharging, local exhaust ventilation and equipment designed to minimize manual intervention,” UMP’s Frank Sorce says. “This approach provides greater protection for operators while also reducing cross contamination risk and improving process consistency.”

Automation and digital monitoring represent another “major area of investment,” according to Sorce. He claims, “Automated material handling, electronic batch records, continuous environmental monitoring and remote equipment operation can reduce the number of times employees must interact directly with potent materials. These technologies also provide better process data, improve deviation investigations and support more consistent execution across clinical and commercial campaigns.”

“Containment is not just about equipment,” Wilmington PharmTech’s Hongfeng Chen stresses. “It depends on people and processes.”

He emphasizes, “Well-trained personnel, standardized procedures, and a strong culture of safety are essential to maintaining consistent performance. The most effective containment strategies integrate scientific understanding, engineering controls, operational discipline, and quality systems to protect both employees and product integrity throughout the product lifecycle.”

“None of this works without the people side: training, gowning discipline, and cleaning validation protocols all have to match the specific exposure limit and the specific operations involved,” adds Ardena’s Hibreniguss Terefe. “Put a poorly trained operator in front of a beautifully engineered isolator, and the isolator won’t save you.”

Future Outlook

Over the next five years, AGC Pharma Chemicals’ Masashi Takahashi expects continued growth in both the number and diversity of highly potent development programs. He predicts, “Oncology and ADC payloads will remain major drivers, but the manufacturing landscape will become increasingly varied as new targeted small molecules and conjugate formats progress through clinical pipelines.”

“The central trend will be integration,” Takahashi forecasts. “The strongest HPAPI platforms will connect toxicology, process development, analytical science, engineering, industrial hygiene and GMP manufacturing from the earliest project stages. That integration will be essential to deliver faster development without compromising employee safety, product quality or regulatory compliance.”

“Capacity will probably stay tight for a while,” predicts Ardena’s Hibreniguss Terefe. “New high-containment suites take two-plus years to build. The bigger constraint, according to several industry observers, isn’t the buildings at all — it’s a shortage of specialized people, particularly occupational toxicologists and containment engineers.”

“Combine that with reshoring pressure in North America and the capacity race underway in Asia-Pacific, and manufacturing looks set to keep spreading out geographically rather than consolidating around any one region,” he says. “And as regulators in the U.S., Europe, and Asia keep tightening standards and edging toward convergence, sponsors will keep raising the bar on proof: not just that a containment system passed qualification once, but that it will keep working across a molecule’s entire life, from the first clinical batch to full commercial scale.”

SK Pharmteco’s John Jacobsen foresees, “Automation and remote operations will be used more widely in containment suites to reduce manual handling and improve consistency, while modular designs will help manufacturers respond to smaller batch sizes and more varied pipelines.”

UPM’s Frank Sorce believes supply chain resilience will continue to influence sourcing decisions. He says, “Sponsors will place greater value on regional capacity, alternate sources and partners that can integrate formulation, analytical development, clinical manufacturing, validation, packaging and commercial supply. The objective will be to reduce handoffs, avoid late-stage transfers and maintain better control over critical products.”

Overall, Sorce predicts the most competitive HPAPI facilities five years from now will be “closed, flexible, automated and supported by strong scientific expertise.” “The greatest opportunity will not belong simply to manufacturers that can claim a particular containment band,” Sorce says. “It will belong to organizations that can demonstrate containment performance, solve formulation and analytical challenges, accommodate changing volumes and move potent products reliably from development through commercial supply.”