Process Safety and Risk Management

Process Safety and Risk Management are fundamental to mitigating hazards and ensuring the integrity of small molecule development, from early-stage discovery through to commercial-scale manufacturing. At Aragen, we prioritize these principles across every stage of the development lifecycle.

We work closely with our clients to ensure that each phase—from early-stage feasibility studies to full-scale commercial manufacturing—is executed with a focus on safety, scalability, and regulatory compliance. Our comprehensive approach includes advanced screening tools, risk assessments, and a deep understanding of safety regulations, which enables us to identify, assess, and mitigate potential risks at every stage.

With a commitment to safety and reliability, our experienced team helps facilitate a seamless transition from early-phase research to large-scale production, empowering clients to bring their small molecules to market faster, safer, and with confidence.

Process Safety: Methodology for assessing NCE development

Early Phase

Laying the Foundation for Safe and Feasible Manufacturing

In the early phase of drug development, the primary focus is on evaluating potential risks and setting up a safe, feasible synthetic route for the New Chemical Entity (NCE). As your CRDMO partner, we ensure that Process Safety is a core consideration, starting from the initial stages of feasibility.

Approach

• Desk Screening: Initial evaluations based on available data and safety studies to identify potential risks.
• Oxygen (O₂) Balance: A crucial tool to assess the safety of chemical reactions, ensuring no hazardous conditions such as runaway reactions or toxic by-products.
• CHETAH (Thermal Hazard Evaluation): A software tool used to estimate the thermal risks of chemical substances, identifying potential for overheating or runaway reactions.
• Safety Data Sheets (SDS) Review: Comprehensive review of SDS for all chemicals involved to assess toxicity, reactivity, and potential environmental impacts.
• Process Risk Assessment via Literature Survey: A survey of existing literature and historical data to assess the risks of similar reactions or chemical processes.

Risk Management Focus

• Early Identification of Risks: We ensure that safety risks are understood from the start, enabling informed decision-making about synthetic routes and the selection of safer process methodologies.

Informed Process Design: By proactively addressing potential risks, we guide our clients in choosing the best route to scale-up and commercialize their small molecule.

Advanced Risk Management for Scale-Up and Formulation

As the project progresses into the late phase, our risk management strategies become more advanced. We focus on ensuring that the synthesis, scale-up, and formulation processes are free from safety hazards and scalable for commercial manufacturing.

Approach

• Thermal Screening Studies
• TSU (Thermal Screening Unit): Used to evaluate the thermal properties of substances to predict reactivity and stability during manufacturing.
• RSD (Reaction Screening Device): Identifies risks associated with chemical reactions, especially for runaway reactions.
• DSC (Differential Scanning Calorimetry): Provides critical insights into the thermal stability of chemicals, helping us design safer processes.
• Management of Technology (MTSR) and System Risk and Adiabatic Evaluations 
  • MTSR: Assesses the thermal sensitivity of reactions, ensuring that the process remains safe during scale-up.
  • Reaction calorimetry (RC1e): Identifies potential heat accumulation and pressure risks during reactions, helping us predict and avoid runaway reactions.
• Advanced Thermal Screening (ARC): ARC tools identify thermal runaway reactions, ensuring safe thermal management during manufacturing.
• Powder Testing: Evaluates the flow properties of powdered chemicals, identifying explosion or health hazards associated with dust.

Risk Management Focus

• Inherently Safe Process Design: By using advanced screening tools, we aim to design processes that minimize thermal, chemical, and environmental hazards.
• Safe Scale-Up Protocols: We work with you to ensure that process safety is maintained during scale-up, providing safe and effective methodologies to transition to larger-scale manufacturing.

Ensuring Scalable, Safe, and Compliant Manufacturing

As the process moves into the commercial phase, ensuring that your small molecule production is safe, compliant, and scalable becomes our top priority. We perform thorough safety evaluations and risk management assessments, ensuring that your process meets regulatory requirements while maintaining high standards of safety.

Approach

• HAZOP (Hazard and Operability Study): A team-based risk assessment method used to identify potential hazards and operability issues at each step of the production process.
• Engineering and Administrative Controls: Based on the reaction characteristics (exothermic, endothermic), we implement:
• Engineering Controls: Temperature control, pressure relief systems, and other necessary mechanisms to mitigate risks.
• Administrative Controls: Standard operating procedures (SOPs), safety protocols, and personal protective equipment (PPE) for personnel safety.
• MOC (Management of Change), PSSR (Pre-Startup Safety Review), and Training:
  • MOC: Reviews and manages any changes to the process, ensuring safety is not compromised.
  • PSSR: Conducted before commissioning new plants or processes to ensure all safety measures are in place.
  • Training: Training of personnel on safety protocols and emergency procedures to ensure a high level of preparedness.
• PHA (Process Hazard Analysis) and Batch Monitoring: Ongoing batch monitoring ensures that any deviations from expected operating conditions are quickly identified and corrected.

Risk Management Focus

• Proactive Risk Mitigation: Our team works to identify and address any potential risks through a detailed hazard analysis, ensuring a safe and reliable process.
• Business Continuity: Addressing potential risks up front ensures that production can continue without interruptions, even during operational challenges or incidents.
• Supply Chain Reliability: By ensuring safety and reliability in the manufacturing process, we help our clients meet delivery timelines and maintain customer trust.

Process Safety Laboratory – Infrastructure

• Rotocone Vacuum Dryer (RCVD)
• Agitated Nutsche Filter Dryer (ANFD)
• Centrifuge (Capacity: 50 g – 500 g; Volume: 400 cc – 750 cc)
• Nauta Dryer (Capacity: 100 g – 1 kg)
• Reaction calorimetry (RC1e)
• Accelerated Reaction calorimetry (ARC)
• Rapid scanning device (RSD/HEL)
• Thermal screening unit (TSU/HEL)
• Differential scanning calorimeter (DSC)