Nanosimilars in the U.S. Healthcare Landscape: Learning from Challenges to Move Forward

Follow-on versions of nanomedicines (“nanosimilars”) can lower costs but face U.S. regulatory, legal, and manufacturing challenges. They enter via the Abbreviated New Drug Application (ANDA, 505(j)) or 505(b)(2) pathways. Therapeutic equivalence (TE) codes are not automatic for the latter, and delays can block pharmacy substitution. Patent linkage through the U.S. FDA’s Orange Book can further postpone final approvals, as listed patents may extend timelines, even if later ruled invalid. Specialized manufacturing and global supply chains face inconsistent inspections and shifting trade policy. Nab-paclitaxel (Abraxane) illustrates how minor formulation differences among comparable follow-ons determine regulatory pathways, TE coding, and patient access. These examples highlight the regulation–IP–supply nexus. We propose uniform TE assessments, independent Orange Book patent reviews, and adaptive tariffs to strengthen the nanosimilar framework.