Creating Process Safety Data Sheets for Safe Scale-Up in Pharma/API Production

Table of Contents

• Introduction
• Why Process Safety Testing is Critical?
• Process Safety Testing Techniques
• Data Utilization of Process Safety
• Practical Implications for API Manufacturing
• Conclusion

Introduction

The pharmaceutical industry faces unique challenges as it progresses from R&D bench-scale to plant production, moving from milligram quantities to tons. High-quality active pharmaceutical ingredients (APIs) must be produced in a cost-effective fashion while complying with regulatory requirements for safety and consistency. As such, process safety remains a fundamental pillar to meet these demands and mitigate potential hazards linked to industrial production. In this article, we explore best practices and state-of-the-art tools that can be used to produce Process Safety Date Sheets (PSDS).

Why Process Safety Testing is Critical?

Identifying and managing hazards that might occur at all stages of the industrial process is essential. A proactive approach to Process Safety avoids potential incidents with potentially catastrophic consequences, as we have witnessed in well-known industrial accidents. Among the causes that resulted in this type of accident, thermal runaway-derived explosions, dust explosions, or unanticipated chemical reactivity are common. Comprehensive safety testing is a powerful tool that helps companies understand the behavior of their material under different conditions. The compiled results will, in turn, guide safe production practices and ensure regulatory compliance. In practice, this process involves applying a combination of assessments at various stages, starting with basic tests, like thermal screening, using instruments such as H.E.L’s TSu. As the process moves from the R&D lab and bench-top scale towards the kilo lab, pilot plant, and full-scale manufacturing, more advanced techniques, such as isothermal calorimetry, are required. Each step adds layers of insight, from initial thermal stability to explosivity and reaction calorimetry, providing scientists with the data required to guarantee process integrity and safety.

Process Safety Testing Techniques

Companies need to use a combination of techniques to support safer scale-up. Each tool provides different information and perspectives required to gather critical safety data.

• Thermal screening: This technique evaluates changes in the thermal behavior and pressure of materials, using minuscule amounts of material. Thermal screening provides onset temperatures, thermal rise rates, and safe temperature thresholds critical for scaling reactions and material storage safely.
• Adiabatic calorimetry: This type of analysis tracks the accumulation of heat linked to a reaction, preventing heat loss to the surroundings. It allows for precisely recording temperature changes, which can lead to explosions. Adiabatic calorimetry helps to characterize materials and reactions accurately and efficiently.
• Isothermal calorimetry: Understanding the kinetics of reactions enables researchers and engineers to acquire critical safety parameters, such as the adiabatic temperature rise, maximum temperature of a synthesis reaction (MTSR), and time to the maximum rate (TMR). The accurate characterization of these values remains essential for preventing thermal runaway incidents during scale-up.