P322: A Retrospective Analysis of Bridging Study Evaluations in Taiwan (2014–2022): Insights into Ethnically Sensitive Issues in Clinical Pharmacology
Poster Presenter
Tse-Yin Huang
Reviewer
Center for Drug Evaluation, Taiwan Taiwan
Objectives
This study investigates the potential underlying mechanism of pharmacokinetic ethnic differences between Eastern and Western populations and the impact of these differences on new drug applications in Taiwan.
Method
This study examines bridging study evaluation (BSE) cases in Taiwan in which pharmacokinetic evaluations concluded either the presence of ethnic differences between Eastern and Western populations (ethnically sensitive) or the absence/minimal presence of such differences (none to minimally ethnically sensitive). The analysis compares the distribution of pharmacokinetic characteristics between these two groups based on the eight pharmacokinetic properties recommended by ICH E5. Next, in cases where pharmacokinetic ethnic differences between Eastern and Western populations are observed, the study will further identify cases in which differences in clinical efficacy or safety are also present between these populations. It will then summarize the management or recommendations implemented at the time of market approval to address these ethnic differences.
Results
Between 2014 and 2022, TFDA (Taiwan Food and Drug Administration)/TCDE (Taiwan Center for Drug Evaluation) received a total of 391 BSE applications. After excluding 78 cases based on exclusion criteria, 313 cases remained. Based on pharmacokinetic evaluations, these cases were categorized as follows: 26 cases (8.3%) were classified as ethnically sensitive, 226 cases (72.2%) as none to minimally ethnically sensitive, and 61 cases (19.5%) as cannot be determined. Among the eight pharmacokinetic properties recommended by ICH E5, pharmacokinetic differences between East Asian and Western populations were more likely to be observed in drugs that are highly metabolized, especially through a single pathway.
Most cases classified as ethnically sensitive were ultimately recommended for a waiver or conditional waiver of bridging studies in the pharmacokinetic evaluation. The primary reason was that sufficient pharmacokinetic data had already been provided to assess differences. Notably, the waiver of bridging studies does not imply that pharmacokinetic differences between populations are clinically insignificant. Such differences may still impact drug efficacy, safety, and marketing approval, potentially leading to variations in dosage and administration, requirements for post-marketing study data, or additional precautionary statements in the labeling.
Conclusion
Drugs that are highly metabolized, especially through a single pathway, thereby increasing the potential for drug-drug interactions, are the most likely to exhibit pharmacokinetic differences between Eastern and Western populations. These differences may further impact clinical efficacy or safety, resulting in variations in dosage and administration, post-marketing data requirements, or additional precautionary statements in the labeling.
