Regulatory frameworks and filing discrepancies in generic drug approvals: A cross-regional study with analysis of FDA ANDA deficiencies.

Objectives: This research aims to analyse the regulatory frameworks for generic drug applications in the U.S., EU, India, Japan, and China comparing their filing requirements to identify gaps and areas for harmonization. Additionally, it focuses on examining common deficiencies in ANDA from FDA submissions in 2014-2023 to address issues, facilitating more efficient approvals and minimizing delays.

Material and methods: The research involved analysing regulatory documents available on official websites, including the FDA, EMA, CDSCO, PMDA, and NMPA to achieve first objective. For second objective, a recurring common deficiency across key review disciplines such as bioequivalence, labelling and chemistry was identified through a detailed analysis of deficiency letters available on the FDA website. A targeted analysis was conducted on ANDA submissions filed between 2014 and 2024.

Results: A total of 172 deficiencies were identified, with bioequivalence (35%), chemistry (34%), and labelling (31%). Method validation had the most deficiencies, especially non-compliance with FDA guidelines. In the labelling discipline, the most common deficiency was non-compliance with reference listed drug (RLD) labelling. Comparisons with EMA and WHOPQTm revealed similarities in common deficiencies.

Conclusion: This descriptive study highlights regulatory frameworks for generics share significant differences in practical requirements. A harmonized approach could enhance efficiency and standardized submissions. Bioequivalence issues were the most prevalent, with chemistry-related deficiencies, while labelling issues were the least common seen in ANDA applications. This offer concerns to manufacturers for dossier compilation, aiming to accelerate generic drug registration.