SynthesisThe AAPS journal2025
Regulatory Divergence in Narrow Therapeutic Index Drugs: A Comparative Review of the US, EU, Japan, Canada, and South Korea.
Synthesis in The AAPS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Drug Brand Switching: A Regulatory Perspective.Drug safety · 2026Review
- Narrow Therapeutic Index Drugs: Regulatory Frameworks, Bioequivalence, and Model-Informed Precision Dosing.Pharmaceutics · 2026Review
- Importance of Single Global Regulatory Standards for the Assessment of Generic and Biosimilar Medicines to Advance Patient Access.The AAPS journal · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generic drugs offer cost-effective alternatives to brand-name medications while ensuring comparable safety and efficacy. However, narrow therapeutic index drugs (NTIDs), which require precise dosing due to narrow margins between therapeutic and toxic concentrations, present additional regulatory challenges. Concerns regarding the interchangeability of generic NTIDs are amplified by international variation in definitions, bioequivalence (BE) standards, and regulatory approaches. This systematic review compares NTID-related regulatory frameworks across major authorities to inform the development of the ICH M13C guideline and foster global harmonization of evaluation standards for generic NTIDs. A comprehensive comparative analysis was conducted of NTID-related regulatory frameworks in five ICH member countries (United States [US], European Union [EU], Japan, Canada, and South Korea), with Egypt, Jordan, and Saudi Arabia included as reference countries. Data were obtained from literature searches and official regulatory sources, focusing on NTID definitions, BE standards, and NTID lists. Marked regulatory divergence was observed. South Korea uniquely incorporates quantitative pharmacological and toxicological criteria into NTID definitions. The US employs the most stringent NTID BE standards, utilizing a fully replicated design, reference-scaled average bioequivalence (RSABE), and variability assessment. Only cyclosporine and tacrolimus are classified as NTIDs by all five core countries. Variability in NTID lists and evaluation criteria complicates global harmonization efforts. Achieving consistent evaluation and safe international use of generic NTIDs requires global alignment on definitions, BE criteria, and NTID lists. This review supports integrating real-world data into regulatory decision-making and advances the ICH M13C guideline.
Indexed as
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.