The 505(b)(2) Drug Approval Pathway

Jonathan J. Darrow, Mengdong He & Kristina Stefanini


Codified in 1984, the Section 505(b)(2) drug approval pathway lies part-way between the regular new drug approval pathway and the generic drug approval pathway, allowing changes in characteristics such as dose or dosage form and often requiring data beyond bioavailability studies. The number of 505(b)(2) approvals has increased dramatically and now annually exceeds the number of new drug approvals. Rising 505(b)(2) approvals can be explained by accumulating exclusivities and expedited approval programs that are unavailable to generic drugs, user fee funding aimed at reducing review times, new pediatric study requirements that cannot be fulfilled under the generic drug pathway, and heightened competition in the generic drug market. Based on an examination of all 505(b)(2) approvals from 1993 through the end of 2016, we found evidence suggesting the 505(b)(2) pathway is primarily serving to increase competition, including the historical background to the pathway’s creation, the predominance of small or generic manufacturers as sponsors of 505(b)(2) applications, the frequency with which 505(b)(2) drug applicants fail to request or receive non-patent exclusivity, and the lack of identity between the 505(b)(2) applicant and the reference listed drug applicant.