On sample size requirement for analytical similarity assessment

Area of Science:

• Biopharmaceutical Sciences
• Regulatory Science
• Statistical Analysis

Background:

• The U.S. Food and Drug Administration (FDA) utilizes a stepwise approach to evaluate biosimilarity between proposed biosimilar and reference biologic products.
• Analytical similarity assessment of critical quality attributes (CQAs) is the initial step, focusing on structural, physicochemical, and functional properties.
• For Tier 1 CQAs, equivalence testing with an equivalence acceptance criterion (EAC) is recommended for similarity assessment.

Purpose of the Study:

• To discuss the FDA's proposal for selecting appropriate sample sizes in biosimilar equivalence testing.
• To analyze the impact of adjusting the equivalence acceptance criterion (EAC) margin and variability on sample size requirements.
• To conduct a numerical study comparing sample size needs under various parameter combinations.

Main Methods:

• Discussion of the FDA's proposed methodology for sample size determination in biosimilar analytical similarity testing.
• Description of sample size requirements under different scenarios, considering EAC margin and variability.
• Conducting a numerical study to compare sample size requirements across various combinations of study parameters.

Main Results:

• The study provides a thorough discussion on the FDA's proposal for sample size selection.
• Sample size requirements are described under different scenarios.
• A numerical study compares sample size requirements under various combinations of study parameters, highlighting the interplay between EAC, variability, and sample size.

Conclusions:

• Appropriate sample size selection is critical for robust biosimilar equivalence testing.
• Adjusting the equivalence acceptance criterion (EAC) margin and variability significantly influences sample size requirements.
• The findings support informed decision-making in the design of analytical similarity studies for biosimilar product development and regulatory approval.