Process Safety in the Pharmaceutical Industry—Part I: Thermal and Reaction Hazard Evaluation Processes and Techniques

Process safety groups in the pharmaceutical industry are important components of active pharmaceutical ingredient (API) development through its life cycle from discovery to commercial scale. The pharmaceutical process safety laboratory staff conduct a series of tests to identify chemically unstable reagents, intermediates and solvents, and mixtures to ensure that the proposed operating conditions provide a sufficient safety margin from the onset of undesired and potentially catastrophic thermal decomposition. Across several pharmaceutical companies, the methods used for these assessments and how results and conclusions are made are widespread (vide infra). A working group was created with members from several pharmaceutical companies within the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), with the goal of precompetitive collaboration and to understand each of the participating companies' procedures and assessment regarding process safety. Each company was invited to provide input using a blind survey format. This was done in the interest of making this knowledge accessible for the participating companies and the wider community of other pharma and chemical companies and even academic institutions in the US and throughout the world. This article provides the results of this in-depth survey of the members of the IQ Consortium thermal hazard working group. General issues around different tools used to assess thermal hazard risk and questions regarding staffing and tech transfer of process safety data/information from development to manufacturing were addressed. A snapshot of how various assessment strategies are employed as a function of stage of development (early, mid, and late) is also presented.