Science-based Ethnic Bridging in Drug Development; Review of Recent Precedence and Suggested Steps Forward

Area of Science:

• Pharmacogenomics
• Drug Development
• Regulatory Science

Background:

• Drug exposure, safety, and efficacy may differ across racial and ethnic groups.
• Regulatory bodies acknowledge these potential differences in guidance and drug labels.

Purpose of the Study:

• To review recent regulatory precedents for drug use in specific racial or ethnic groups.
• To identify opportunities for enhancing the informative value of clinical ethnic or racial bridging in drug development.

Main Methods:

• Analysis of Food and Drug Administration (FDA)-approved drug product labels and approval packages from January 2014 to July 2018.
• Review focused on claims, comments, and data related to specific ethnic or racial groups.

Main Results:

• None of the 266 reviewed FDA-approved products had explicit race- or ethnicity-specific dosing instructions.
• 55% of products included race or ethnicity information, primarily based on population pharmacokinetic data (87%).
• Justifications for no clinically relevant exposure differences often cited exposure ratios exceeding the 0.80-1.25 no-effect boundary.

Conclusions:

• Current regulatory practices reflect a pragmatic approach to racial/ethnic bridging, meeting expectations without providing strict prescriber guidance.
• Recommendations include defining objectives, design criteria, and data analysis methods for bridging studies.
• Investigating prospectively defined similarity tests with follow-up analysis is suggested for failed tests.