From Danger to Care – On the Challenges of a CDMO in the Field of Hazardous Chemistry

Abstract

Hazardous chemistry presents recurring challenges for contract development and manufacturing organizations (CDMOs) across the industry: highly exothermic reactions, toxic or carcinogenic and corrosive substances, unstable intermediates, high pressure/temperature processes, and stringent requirements for containment, exhaust gas purification, occupational safety, and change management. This white paper describes these challenges using key reaction classes and demonstrates which technical and organizational measures have proven effective in practice. Valsynthese SA serves as a concrete example of a Swiss CDMO whose core competence lies in handling hazardous chemicals/reactions, and which translates demanding chemical processes into robust, campaign-ready productions according to the guiding principle ‘From Danger to Care’ – with a focus on process safety, quality (ISO and GMP compliance), and reliable delivery capability. The focus is on reaction and substance classes whose industrialization is typically considered difficult or challenging: nitrations and nitrate esters,[1a] phosgenations,[1b] and hydrogenations[1c] as a common ‘bridging reaction’ in multi-step syntheses. Examples from isoprene processing[1d] and projects in the field of advanced materials for highly specific applications[1e] are also discussed. For each class, typical risk factors such as exothermicity, gas release, sensitivity, toxicity, and corrosiveness, as well as the associated countermeasures such as heat dissipation, containment, detection, automation, (emergency) quench concepts, and process window robustness, are presented in a structured manner. Where appropriate, it is also determined when batch processes are suitable and when continuous or flow technologies can contribute to intrinsic risk reduction. The latter techniques are used at Valsynthese for very specific targets, such as for example, using MgFlow^® technology[1f] for the on-site production of Grignard reagents or for continuous extractions in nitration processes.