Regulatory Bottlenecks in ANDA Approvals: Submission Quality and Generic Drug Shortages, Lessons from ICH-Harmonized Markets

Objectives: To examine the root causes of FDA Abbreviated New Drug Application (ANDA) approval delays through a submission quality lens, and to identify evidence-based acceleration strategies drawn from international ICH-harmonized regulatory experience. Methods: Thematic synthesis of publicly available FDA regulatory performance data, U.S. Government Accountability Office audit findings, U.S. Department of Health and Human Services supply chain reports, White House Executive Order 14017 review materials, and peer-reviewed regulatory literature published between 2018 and 2026, with failure categories identified through structured reading of the source corpus. Results: Four recurring categories of ANDA submission failure emerge from the federal evidence: CTD Module 3 Chemistry, Manufacturing, and Controls (CMC) deficiencies; pre-approval inspection failures rooted in data integrity and Good Manufacturing Practice non-compliance; pharmacovigilance planning treated as a post-approval obligation rather than a submission requirement; and cross-functional coordination failures producing internally inconsistent dossiers. None of these failures requires new science to resolve, and all are preventable before application filing. Markets that completed mandatory ICH-harmonized CTD submission transitions encountered the same failure modes under enforcement pressure and built workflows to prevent them. Conclusions: Submission quality, not scientific inadequacy, is a tractable driver of FDA ANDA approval delay and a contributor to U.S. drug shortage risk. Pre-submission readiness reviews, continuous inspection readiness, integrated pharmacovigilance frameworks, and formalized cross-functional coordination represent high-yield interventions. Documented experience from ICH-harmonized markets is a directly applicable resource that the U.S. policy conversation has largely not used.