Some reagents used in the initial small-scale synthesis of a drug are too expensive to be used in large-scale reactions, and it may be necessary to replace an expensive reagent with something cheaper. The commercial availability of reagents also has to be taken into account. If the reagent has to be prepared ‘in-house’, it will add to the cost of the process. Some reagents are unsuitable for large-scale synthesis on safety grounds. Highly toxic, carcinogenic or explosive reagents should be avoided if possible. The nature and quantity of the solvent used in a reaction is one of the most common issues that needs to be addressed in chemical development. During chemical development, it is important to study all the parameters that are likely to have an effect on a reaction. However, there are some parameters that are unique to the scale-up process and cannot be effectively modeled with smaller scale experiments in the laboratory.