Regulatory Science: Original Research Analysis of Review Times for Recent 505(b)(2) Applications Sharon Sakai, PhD, RAC 1 , Joseph A. DiMasi, PhD 2 , and Kenneth A. Getz, MBA 2 Abstract Background: Annual review statistics released by the Food and Drug Administration (FDA) and a number of studies indicate that the review process improvements introduced under various versions of the Prescription Drug Use Fee Act (PDUFA) have been successful in decreasing average times for marketing approval of new molecular entities (NMEs). Similar statistics are not available, however, for non-NME new drug applications. These application types, such as those covered under section 505(b)(2) of the Food and Drug and Cosmetic Act, represent more than half of all new drug application (NDA) submissions annually and they are primarily based on previously approved drugs. To our knowledge, this is the first study to gather review statistics on 505(b)(2) designations. Methods: For this study, we analyzed total review times and review designations for 284 505(b)(2) NDA approvals between 2009 and 2015. Results: Our results show that overall, the 505(b)(2) regulatory pathway results in longer review time than for NMEs despite the intent of the 505(b)(2) designation to simplify and streamline the review process. Several illustrative examples and the implications are discussed. Conclusions: For drug developers, the important take home message is that—as for any program at the FDA—shorter review times and fewer FDA requirements under a 505(b)(2) designation should not be anticipated or expected. The study results serve as benchmark data providing insights into regulatory submission strategy and planning. Keywords FDA, 505(b)(2), NDA review Background Reviewing divisions at the Food and Drug Administration (FDA) are responsible for the review of 2 primary new drug application types i : (1) applications that contain full reports of investigations of safety and effectiveness (section 505(b)(1)); and (2) applications that contain full reports of investigations of safety and effectiveness but where at least some of the infor- mation required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference (section 505(b)(2)). The approved drug that supplies information to support a 505(b)(2) new drug application (NDA) is defined as the listed drug for that application. The FDA guidance document on 505(b)(2) applications 1 describes what changes to the listed drug may be allowed. These include  dosage form,  strength,  route of administration,  substitution of active ingredient in a combination prod- uct or new combination product,  formulation changes beyond those that are acceptable for submission as a 505(j) application,  dosing regimen,  active ingredient (e.g., a change in salt form),  indication, and  prescription to over-the-counter (OTC) switch. The 505(b)(2) pathway is generally viewed as an attractive path for drug developers as information used to support prior approvals may be leveraged and the data package required for the new drug application may be reduced considerably. Accep- table sources of data for a 505(b)(2) NDA include published literature (providing that appropriately detailed supporting information is available) as well as the Agency’s previous findings of safety and effectiveness. A 505(b)(2) application may be used to grandfather in a product that was previously marketed without an approved NDA, using either published 1 Sakai Regulatory Consulting, Berkeley, CA, USA 2 Tufts Center for the Study of Drug Development, Tufts University School of Medicine, Boston, MA, USA Submitted 10-Nov-2016; accepted 6-Mar-2017 Corresponding Author: Sakai Regulatory Consulting, 2223 Marin Ave., Berkeley, CA 94707, USA. Email: sharon@sakaireg.com Therapeutic Innovation & Regulatory Science 2017, Vol. 51(5) 651-656 ª The Author(s) 2017 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2168479017703138 tirs.sagepub.com DIA