OBJECTIVES: The objective of the study was to review and evaluate the policies and procedures of orphan drug programs in the US (FDA) and Australian (TGA). The availability of orphan drugs is a major global concern. It is essential to understand the dynamics and the efficiency of these policies to ensure that those who require these resources can get them. Accordance to their current polices on orphan drugs in order to ensure easy access by patients who need them. METHODS: A comprehensive Orphan Drug database was reviewed and focusing on data from the FDA and biotech pharmaceutical companies and furthermore the actual information was gathered from the experts, research articles, policy documents, regulatory framework, regulations. Multiple databases such as PubMed, Google Scholar, Springer Links, Scopus, and the Cochrane Library were searched. RESULTS: The results of this study found that the Therapeutic Goods Administration (TGA) implemented orphan drug legislation, regulations and policy after the U.S Food and Drug Administration (US-FDA) had initiated to do so in 1983. Regulations and policy tools from both agencies were reviewed with a focus on six broad categories: orphan drug designation; national orphan policies; incentives; marketing authorization; pricing and repayment plan; and marketing exclusivity. CONCLUSIONS: Patients with rare diseases have the same right to pharmaceutical products as patients that have more common diseases. The difficulty is enticing drug companies to put the expense and time into the development of orphan drugs that represent only a small portion of the market share. As a solution to the problem, several countries have developed some orphan drug policies, regulation, legislation, that provides incentives to help convince drug companies to develop drugs for the specific populations. Both countries have very nicely managed program in place. . Both agencies have similar challenges in terms of availability, affordability and accessibility of the product by patient.