High Potency FAQs
Frequently Asked Questions
Highly Potent Active Pharmaceutical Ingredients (HPAPIs) are compounds with very low Occupational Exposure Limits
(OELs), often below 1 μg/m³. Their potency requires specialized containment, engineering controls, and safety systems
to protect operators, the environment, and product integrity.
HPAPIs are banded into Occupational Exposure Bands (OEBs) based on OEL values, typically ranging from OEB1 (>100
μg/m³) to OEB5 (<0.1 μg/m). This classification drives containment strategy, facility design, and operational controls.
Key factors include:
- Proven HPAPI expertise and safety systems
- Robust potency and toxicity assessment capabilities
- State-of-the-art engineering and containment controls
- Strong cleaning validation and quality systems
- Integrated R&D, analytical, and manufacturing services
- Organizational commitment to HPAPI excellence
Hazard assessment incorporates toxicity data, structural analogs, mode of action, intermediates and raw materials,
thermal stability, dust and explosivity testing, gas flow dynamics, and electrostatic discharge risk.
Personal Protective Equipment (PPE) is considered the last line of defense. Effective HPAPI manufacturing relies
primarily on engineering controls, such as HVAC systems, pressure gradients, and closed handling, to prevent exposure
at the source.
Controls include independent HVAC systems, pressure cascades, closed material transfers, no open powder handling,
full treatment or capture of process streams, and emergency backup systems for critical utilities.
Controlled personnel flow, dedicated material pathways, and cascading room pressurization gradients minimize the
risk of cross-contamination and uncontrolled exposure during manufacturing operations.
Common technologies include rigid barrier isolators, soft-sided or disposable containment systems, split-butterfly
valves, continuous liner systems, rapid transfer ports, and specialized milling and filtration equipment.
Single-use systems can provide very low containment limits, rapid turnaround for clinical programs, reduced
cross-contamination risk, elimination of cleaning validation, and less dependence on dedicated equipment.
Cleaning approaches are selected using a risk-based matrix considering OEB, solubility, and acceptable surface
limits. Strategies may include single-use components, dedicated equipment, and advanced analytical verification
such as TOC testing.
Cross-contamination is managed through industrial hygiene calculations, defined NOEL-based cleaning limits,
highly sensitive analytical methods, and validated cleaning verification protocols.
HPAPI manufacturing requires organization-wide dedication, specialized training, certified competency programs,
regulatory success, and a strong safety culture. Corporate commitment ensures consistent execution across all
stages and sites.
HPAPIs commonly include oncology agents, hormones, steroids, antibody-drug conjugate payloads, and other
small molecules with high biological activity.
The right partner acts as a dedicated ally—reducing risk, accelerating timelines, ensuring compliance, and
supporting the product from early development through commercial supply.
Curia supports HPAPI development and manufacturing up to OEB5, including compounds with occupational exposure limits below 0.1 µg/m³, across multiple global sites.
Curia classifies compounds in five bands by OEL: OEB1 above 100 µg/m³, OEB2 from 100 to 10 µg/m³, OEB3 from 10 to 1 µg/m³, OEB4 from 1 to 0.1 µg/m³ and OEB5 below 0.1 µg/m³. OEB4 and OEB5 compounds are handled in barrier isolators that provide primary containment, supported by HVAC pressurization gradients, distributed control systems and remote monitoring to minimize operator interaction.
Four sites in the network have HPAPI capability: Buffalo (discovery scale), Albany (route scouting, process development, scale-up and analytical), Rensselaer (scale-up and commercial production) and Valladolid (process development, scale-up and commercial production of steroids and hormones).
Curia’s Rensselaer, New York site has been SafeBridge certified since 2010 and holds the SafeBridge Industry Standard designation, received in 2025. Rensselaer is Curia’s commercial-scale site for highly potent and controlled APIs in the United States.
Across the network, Curia runs an HPAPI certification program, either through SafeBridge or an internal standard, so that containment competency is consistent at every site handling potent compounds. This is backed by site-wide training and by quality, EHS, containment and industrial hygiene expertise.
Curia can handle HPAPI manufacturing at up to 1200 L reaction scale, with quantities from grams for development through to hundreds of kilograms per year at commercial scale.
Scale is matched to the site. Albany supports development quantities from grams to approximately 500 g for OEB5 and approximately 2 kg for OEB4 compounds, using Corning and tubular reactors and static mixers. Rensselaer runs three independent high potency suites producing batches from grams to more than 100 kg. Valladolid operates six stainless steel isolators with micronization and milling in isolation, producing steroid and hormone batches from grams to multi-kilogram scale.
Curia manufactures highly potent corticosteroids and hormones in a segregated high potency suite with isolator technology at its Valladolid, Spain site. The site’s steroid facilities handle compounds from OEB1 through OEB5, with isolators for OEB4 and OEB5 materials and micronization under containment.
Valladolid is Curia’s center of excellence for steroids and hormones, with four chemical plants dedicated to steroids, so potent steroid programs run on equipment and in suites built for that product family rather than in general-purpose API suites.
