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Chemical brand supported through new process R&D scale-up by Sigma-HSE Chemical Reaction Hazards Assessment

Client Background

The client is a Pharmaceutical CDMO brand. This brand was working to scale-up a new reaction process to produce Grignard reagents for further reactions.

Client Problem

The chemistry is well established in the literature and is known to be a difficult reaction to initiate.

Close communication between R&D teams and our laboratory staff agreed on a desired method and reagent dosage regime with greater reliability.

Client Objectives

Understand and quantify heat evolved, reaction rates and reaction initiation, and also to identify any thermal decomposition risks of reaction mixtures and products.

This was all to fully assess the intrinsic risks of the reaction process to support scale-up from laboratory scale to plant.

Testing Overview – What is Reaction Calorimetry?

Reaction Calorimetry testing is performed to assist in process development or scale-up of new chemical reactions for industrial chemical manufacture.

The testing provides information on reaction kinetics, heat evolution, gas generation, reactant accumulation and more, which all feeds into the proper design of processes and helps to optimise syntheses.

Strategy

The reaction was studied with the presence of a reaction initiator reagent after previous unsuccessful attempts without the initiator, to match the clients experience at laboratory scale trials.

The desired Grignard formation and subsequent quench steps were studied using the Power Compensated Calorimetry mode, which quantified the reaction heat against the calibrated internal heater. Reaction Calorimetry was supported by thermal screening studies with DSC and Carius tube, to assess hazard criticality of the process as a whole.

Insights and results

Sigma-HSE found that

The reaction process was assessed fully with complimentary thermal stability testing, highlighting potential exothermic decompositions in both the reaction masses and product mixtures.

Following full assessment of the process, taking account of normal process heat evolved through reaction calorimetry, and study of thermal decomposition events; the data and analysis provided to the client allowed for a proper design for the desired process with full view of the inherent risks.

The data provided allows for adequate reactor design of cooling requirements, safety devices, monitoring gauges and other process safety mitigation techniques.

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