Sample size requirement in analytical studies for similarity assessment

Area of Science:

• Biopharmaceutical Science
• Regulatory Science
• Statistical Methods in Drug Development

Background:

• The U.S. Food and Drug Administration (FDA) recommends a stepwise approach for biosimilarity assessment, emphasizing analytical studies of critical quality attributes (CQAs).
• Equivalence testing using an equivalence acceptance criterion (EAC) is required for CQAs most relevant to clinical outcomes, often facing challenges with imbalanced sample sizes of reference and test lots.

Purpose of the Study:

• To provide statistical justification for the FDA's proposed method for determining sample sizes to avoid imbalanced data in establishing EAC for biosimilar equivalence tests.
• To propose an alternative statistical method for sample size requirements in Tier 1 equivalence testing for biosimilarity assessment.

Main Methods:

• Statistical analysis and justification of existing proposals for sample size determination in biosimilar equivalence testing.
• Development and proposal of an alternative method for calculating sample size requirements for Tier 1 equivalence tests.

Main Results:

• The study offers statistical validation for methods aimed at balancing sample sizes in biosimilar equivalence testing.
• An alternative methodology for sample size determination in Tier 1 equivalence tests is presented.

Conclusions:

• The findings support robust statistical approaches for biosimilarity assessment, particularly addressing sample size imbalances in equivalence testing.
• The proposed alternative method offers a valuable tool for sponsors in planning biosimilar development studies.