Sam Brogan , head of R & D at Sterling Pharma Solutions , looks at the challenges of safely scaling up reactions with hazardous materials
Commercial-scale diazomethane reactions : A case study
Sterling ’ s headquarters site at Cramlington , UK
Sam Brogan , head of R & D at Sterling Pharma Solutions , looks at the challenges of safely scaling up reactions with hazardous materials
Safely undertaking hazardous chemical reactions at scale is highly complex , and requires dedicated equipment and purpose-built facilities . Such reactions typically include hydrogenation , those that run at high temperature or pressure , and ones that involve potentially explosive reagents or intermediates . The high potential hazard consequences and associated capital expenditure that carrying out these processes entails has led to extensive outsourcing of these steps in small molecule API development and manufacturing .
For companies that specialise in this work , a strong , multi-disciplinary approach is necessary , combining highly skilled teams with extensive knowledge of chemical development , analytical testing , engineering and hazard evaluation . This breadth of dedicated expertise is essential to ensuring the safety of both operators and the equipment , as well as maintaining the optimum productivity and cost-efficiency of such a process .
Prioritising safety
Hazard evaluation is a critical initial step in any API development project , but safe production requires continual , proactive risk mitigation and reassessment . While early-stage laboratory work carried out using hazardous reagents and intermediates may not necessarily carry a high risk because of the limited scale of the reactions as the volumes increase up to pilot- or large-scale , some new safety precautions require consideration . With the average chemical manufacturing process involving between 20 and 40 individual steps , the greater the potential for additional hazards . 1
For a CDMO taking on a new manufacturing project , the first steps will be familiarisation itself with the chemistry and initial laboratoryscale work in order to confirm the reproducibility of the process as presented by the customer . A hazard evaluation study will also be carried out at this stage to ensure process safety at every step , regardless of the eventual projected scale .
Assessing potential hazards early helps to proactively anticipate and address hazard-related issues that might arise at a later stage in the project , while maximising efficiency . Hazard testing will usually include thermal stability studies , reaction calorimetry , explosion risk projections , and calculation of probable ignition and heat release , as well as mitigating all possible contingencies .
18 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981