How Engineering Controls Protect Operators Working with High-Potency Compounds

High-potency active pharmaceutical ingredients (HPAPIs) drive breakthroughs in cancer therapies and hormonal drugs, but they also carry high risks. Tiny amounts can cause serious harm during production. To protect workers and maintain product integrity, pharmaceutical companies must use advanced containment technologies. Powder Systems Ltd. (PSL) engineers solutions that help manufacturers handle HPAPIs safely and efficiently—without compromising compliance or control.

Engineering controls are physical changes to workstations or equipment that reduce or eliminate exposure to hazardous substances. Unlike administrative controls or personal protective equipment (PPE), engineering solutions are designed to isolate the hazard from the worker. This approach aligns with the National Institute for Occupational Safety and Health (NIOSH) hierarchy of controls, which prioritises hazard elimination and substitution, followed by engineering controls as the most effective means of risk mitigation after direct elimination is not feasible (CDC, 2023).

In HPAPI manufacturing, where airborne particulates or cross-contamination pose significant concerns, engineering controls must provide airtight containment, precise airflow management, and filtration mechanisms that effectively capture hazardous materials.

PSL specialises in designing integrated containment systems tailored for HPAPI production. These systems, such as high-containment isolators and agitated Nutsche filter dryers (ANFDs), are engineered to achieve Occupational Exposure Limits (OELs) as low as 20 nanograms per cubic meter. This level of containment is vital for substances active at microgram or nanogram doses.

Key features of PSL systems include:

• Negative Pressure Operation: Maintains directional airflow to prevent particle escape.
• Safe-Change HEPA Filtration: Dual HEPA filters capture airborne contaminants before air is recirculated or exhausted.
• Clean-in-Place (CIP) and Wash-in-Place (WIP): Automated cleaning processes reduce manual handling and exposure risk.

ANFDs demonstrate how engineering controls and process equipment can be seamlessly integrated. These systems support filtration, washing, and drying within a closed environment, ensuring product purity and operator safety. PSL’s ANFDs are designed with cGMP-compliant contact surfaces, minimal retention zones, and automation features that facilitate reproducibility and cleaning validation.

By housing critical operations in a contained vessel, ANFDs eliminate the need for open transfers, a major source of exposure.

Product recovery is the central processing step, though it can be challenging with a closed process. Our strategy focuses on integrating the right containment system with solutions for ease of recovery and maximum yields. Depending on the application, this could mean integrating single-stage containment or double-chamber containment for more potent applications. These are integrated around the discharge plug which is made for ergonomic use and optimal product recovery. For example, the discharge plug is compatible with more contained funnel accessories to limit the airborne contamination inside the glovebox chamber itself. We can also offer advanced sampling solutions without breaking the contained envelope of the filter dryer, with sampling ball valves.

Every HPAPI handling scenario is unique, requiring a risk-based approach to containment. PSL collaborates with clients to perform detailed risk assessments, identifying critical control points and designing systems that match the compound’s hazard profile, batch size, and process steps. This ensures not only regulatory compliance but also operational efficiency and scalability. One such area of concern, particularly in multi-product applications, is inspecting or removing the filtration mesh. In these cases, we make it so the filter dryer’s entire base is enclosed within a containment chamber, allowing inspection/removal tasks to be performed behind physical barriers.

Both the U.S. and U.K. regulatory frameworks underscore the necessity of engineering controls in HPAPI environments. The Occupational Safety and Health Administration (OSHA) mandates the use of engineering solutions to minimise occupational exposure to hazardous drugs (OSHA, 2023). Similarly, the UK’s Control of Substances Hazardous to Health (COSHH) regulations require employers to implement the best available technology to control exposure.

PSL systems are designed to comply with these standards, providing traceability, documentation, and validation support necessary for inspection-readiness. The cGMP features of our ANFDs also consider cleaning and product residuals. End-users have successfully achieved cleaning validations down to the parts per million (ppm) range.

Beyond hardware, PSL offers training, simulation, and process optimisation services to ensure clients can operate safely and efficiently. Our containment strategy extends across the product lifecycle, from R&D-scale systems to full-scale production units. As HPAPI use continues to grow in therapeutic development, the demand for robust containment will only intensify.

PSL remains committed to advancing engineering controls that not only protect operators but also streamline pharmaceutical manufacturing. By embedding safety into the design and operation of every system, PSL empowers manufacturers to innovate confidently and responsibly.

Powder Systems Ltd. builds containment systems that stop high-potency active pharmaceutical ingredients (HPAPIs) from endangering operators. Our designs integrate strict engineering controls with deep regulatory know-how.

By focusing on real-world performance and customer needs, PSL helps pharmaceutical manufacturers meet the toughest safety standards—without compromising productivity.

Contact us for more information.