The use of various thermal analytical techniques as screening tools to identify process hazards during early process development has been well documented. This paper will discuss the interpretation of this thermal screening data, with respect to processing conditions, to determine the safe operating parameters/safe operating envelope for pilot plant operations. The early identification of thermal hazards associated with a process, such as large/rapid heats of reaction, exothermic decompositions and the potential for thermal runaways, facilitates process modifications before any large scale operations are undertaken. Merck has developed a three-tier safety assessment program which identifies thermal hazards and evaluates them for potential initiation during processing. The correct interpretation of this thermal data is critical in determining the risk for thermal runaway. The factors which must be evaluated are: (1) the size and rate of the heat release; (2) the size and rate of pressure generation; (3) whether gases generated during decomposition are condensable; and (4) the heat of reaction and its potential impact upon exothermic decompositions present in the reaction. Once these potential hazards are identified and evaluated, it can be determined whether a safe operating envelope exists or if the process must be modified to eliminate the potential thermal hazard. Examples will be presented where these principles have been applied.