Analytical Methodologies for Anti-Infective Orphan Drugs: A Comprehensive Review of FDA Approvals (2013-2023) Part 1.

Most orphan diseases, which affect small patient populations, are chronic, incurable and often lead to early death. Due to small market size, orphan drugs developed to address these diseases receive little attention from the pharmaceutical industry. This lack of interest also applies to the development of analytical methods, which are crucial for drug analysis and quality control. Analysis of orphan drugs faces challenges, including a lack of reference standard and an inadequate number of samples for testing. In addition, constant adjustment of analytical techniques is demanded due to the lengthy development process. Financial constraints further hinder the advancement of analytical techniques since orphan drugs represents a narrow niche market and the pharmaceutical industry often focuses on research with greater impact, causing orphan drugs to be deprioritized. This review summarizes the analytical methods developed for US FDA-approved anti-infective orphan drugs (except antivirals) in the period between 2013 to 2023, covering in depth small molecules and broadly biologics in numerous dosage forms and biological samples. It covers the most common reported analytical methods, such as liquid chromatography, TLC, spectroscopy, and electrochemical analysis. This review highlights the crucial need for the continuous development of new analytical techniques to support the development and quality control of orphan drugs.