Article’s

The U.S. Food and Drug Administration (FDA) relies on two principal regulatory pathways to authorize the marketing of small-molecule drug products: the New Drug Application (NDA) pathway for innovator products and the Abbreviated New Drug Application (ANDA) pathway for generic products. Although both pathways are designed to ensure that marketed medicines meet acceptable standards of safety, quality, and performance, they differ substantially in legal basis, evidentiary burden, regulatory purpose, and commercial consequence. An NDA requires a sponsor to establish a drug’s safety and effectiveness through original evidence supported by preclinical studies, clinical investigations, and comprehensive chemistry, manufacturing, and controls (CMC) documentation. By contrast, an ANDA allows a sponsor to seek approval of a generic product by relying on the FDA’s prior finding of safety and effectiveness for a reference listed drug (RLD), provided that the applicant demonstrates pharmaceutical equivalence, bioequivalence, labeling sameness within permitted limits, and adequate manufacturing quality. This review critically examines the scientific, legal, and regulatory foundations of NDA and ANDA approval in the United States. It synthesizes research literature, FDA guidance, and statutory frameworks to compare application architecture, clinical and comparative evidence requirements, bioavailability and bioequivalence standards, CMC expectations, patent certification, exclusivity, review timelines, common causes of delay, and post-approval obligations. The review also discusses the growing importance of complex generics, the interaction between regulatory approval and market competition, and the broader public health significance of balancing pharmaceutical innovation with affordability. By examining NDA and ANDA pathways as complementary components of a single regulatory system rather than isolated approval mechanisms, this article highlights how the FDA simultaneously supports the development of new therapies and the expansion of lower-cost generic access.