In recent years, the pharmaceutical industry has seen a significant increase in the development of highly potent active pharmaceutical ingredients (HPAPIs). This has been driven primarily by advances in oncology, antibody–drug conjugates (ADCs). The industry has also seen a rise in targeted therapies that require highly potent intermediates and final actives.
Advanced treatments, especially those containing highly toxic payloads, require stringent containment measures to protect workers and ensure compliance with safety standards. The Occupational Exposure Band (OEB) 6 classification has emerged as a key standard for handling this new level of highly toxic substances.
But does OEB 6 represent a lasting shift in pharmaceutical manufacturing standards, or is it simply a response to a temporary surge in highly potent drug candidates? To answer this, it is necessary to examine the molecules that fall into OEB 6, how the market for such compounds is evolving, and whether increased investment in OEB 6 capacity is justified.
Understanding OEB 6 and highly potent APIs
Occupational Exposure Bands are used to categorise pharmaceutical compounds according to the level of containment required during handling and manufacturing. OEB 6 is the highest risk category, typically associated with compounds that have an occupational exposure limit (OEL) at or below 200ng/m³. These substances can pose severe acute or chronic health risks even at extremely low levels of exposure.
Regulatory guidance from European authorities defines HPAPIs as compounds with an OEL of ≤10µg/m³, but OEB 6 molecules fall well below this threshold. Their classification is informed by toxicological assessments, including parameters such as no observed adverse effect level (NOAEL), lowest observed effect level (LOEL), permitted daily exposure (PDE), and derived OEL values.
Examples of these highly cytotoxic oncology compounds include payloads used in ADCs and peptide–drug conjugates (PDCs), which are designed to deliver extreme cytotoxicity directly to cancer cells. While several well-known anticancer agents – such as melphalan, cabazitaxel, and the maytansinoid DM4 payload – fall into OEB 5 categories, the industry trend is towards even more potent derivatives and next-generation payloads that extend into OEB 6 territory.
Is the OEB 6 APIs market growing?
The global HPAPI market is projected to grow from approximately $3.5bn in 2015 to $14.65bn by 2030. A key driver of this expansion is oncology, which accounts for roughly one-third of all drug candidates, with approximately 25% of new chemical entities classified as potent or highly potent.
In parallel, the ADC market has expanded significantly since the approval of early products such as Mylotarg and Kadcyla, with a growing number of ADCs advancing from preclinical to clinical development. These products rely heavily on ultra-potent payloads, with many approaching or exceeding traditional HPAPI containment thresholds.
According to GlobalData, there has been a surge in outsourcing in API manufacturing, with a projected 7% CAGR between 2023 and 2030 globally, suggesting a continued and strong need for specialised HPAPI manufacturing – especially as many novel therapeutics for oncology and other areas come to market.
HPAPIs are becoming increasingly diverse in their structures, synthetic routes, and manufacturing requirements, shifting from simple cytotoxics to complex, multifunctional molecules that require manufacturing facilities capable of handling a wide range of chemistries.
There are also reports that CDMOs are increasing investments in facilities dedicated to developing high potency drugs. An increase in HPAPIs activity raises the likelihood of growth of OEB 6 compounds such as pyrrolobenzodiazepine.
Beyond a trend: Why the industry should increase capacity for highly potent compounds
The increasing precision of modern therapies favours highly potent compounds that can achieve therapeutic effects at extremely low doses. Crucially, this is not a passing trend. This inherently reduces acceptable exposure limits during manufacturing, while regulatory expectations regarding operator safety and environmental protection continue to tighten, reinforcing the need for validated high-containment systems.
Manufacturing OEB 6 and highly potent API compounds requires fully integrated containment strategies covering synthesis, isolation, analysis, packaging, and waste management. The diversification of HPAPI structures further complicates containment requirements, with modern HPAPIs ranging from relatively simple alkylating agents to highly complex molecules and bioconjugates that combine small molecules with antibodies or peptides. This structural complexity frequently requires bespoke containment solutions rather than standardised production models.
This means that facilities capable of safely producing OEB 6 compounds require significant capital investment, specialised equipment, highly trained personnel, and robust health, safety, and environmental monitoring systems. As a result, capacity is likely to remain concentrated among a limited number of experienced manufacturers. Whether manufacturers should increase OEB 6 capacity depends on their ability to anticipate not just volume growth but also increasing molecular complexity.
Specialist CDMOs for high potency compounds
Indena is a specialist contract development and manufacturing organisation (CDMO) that develops and manufactures high-quality active ingredients for the global healthcare industry.
The company focuses on flexibility rather than single-product optimisation, supported by diversified capabilities including synthesis, fermentation, botanical extraction, chromatography, and lyophilisation across multiple scales.
Indena conducts a substance-specific toxicological assessment of all starting materials, intermediates, and final APIs, ensuring that each compound is assigned to an appropriate production line and that containment levels are validated through continuous monitoring. The company reports containment performance at ≤1 ng/m³, consistent with the requirements for OEB 6 substances.
Based near Milan, Italy, in Europe, Indena is fully cGMP compliant and inspected by European health authorities and the FDA, ensuring the highest industry standards for quality and safety.
One use case study is the long-term development of paclitaxel at Indena, which saw production evolve from environmentally damaging bark extraction to semi-synthetic routes and eventually to plant cell fermentation, requiring continuous investment in new technologies and containment strategies. For OEB 6 compounds, this adaptability is even more critical. As new payloads and highly potent molecules enter clinical and commercial phases, manufacturers must be able to scale safely from grams to kilograms without compromising containment performance.
OEB 6 and the future of ADCs development
The evidence would suggest that OEB 6 is not a passing trend or a marketing label used to justify incremental upgrades, but rather part of a fundamental shift in how modern medicines are designed and manufactured. The continued growth of oncology pipelines, ADCs, and other targeted therapies strongly indicates that demand for ultra-high-containment manufacturing will persist.
Beyond asking whether OEB 6 will become the new standard, the industry should ask how manufacturers will consistently meet that standard. Going forward, investment in OEB 6 capability is less about chasing a trend and more about aligning manufacturing infrastructure with the realities of next-generation drug development.
To learn more about Indena’s specialist CDMO services, download the document below.
