Different regulatory agencies provide criteria for selecting a reference product for bioequivalence (BE) studies. In most cases, the criteria vary from one regulatory agency to another, and, consequently, the generic companies often have to repeat the BE studies comparing the same test product with the reference product purchased from a particular country. In addition to being a cost-intensive exercise, this practice is also unethical. The purpose of this article is to discuss the current policy of major regulatory authorities on the selection of the reference product for pharmaceutical equivalence (PE) and BE studies, the cost implications of such regulatory practices, and to also explore the opportunity to harmonize the reference product selection criteria for reducing repetitive BE studies. The regulatory guidance documents of major jurisdictions are reviewed for similarities and differences in generic product definition, BE study design and conduct, and reference product selection criteria for PE and BE studies. A case study is presented to understand how harmonisation can be achieved and how the economic benefits of this harmonisation cannot be underestimated. Harmonisation in reference product selection criteria can pave the way for a common BE study(s) that would be acceptable to the majority of regulatory agencies, and would not only significantly reduce operating costs but would also minimize the exposure of healthy human beings to drugs.