Adjustment for unbalanced sample size for analytical biosimilar equivalence assessment

Area of Science:

• Biopharmaceutical development
• Statistical analysis in drug regulation

Background:

• Biosimilar development often faces challenges with limited initial sample sizes for both biosimilar and reference products.
• Increasing reference product batches for variability estimation and the need for sufficient biosimilar batches can lead to significant sample size imbalances.

Purpose of the Study:

• To investigate the impact of large sample size imbalance on the power of equivalence tests in analytical biosimilarity studies.
• To propose and discuss adjustment methods for equivalence tests to mitigate the unfavorable effects of sample size imbalance.

Main Methods:

• The study analyzes the behavior of equivalence tests under conditions of substantial differences in sample sizes between biosimilar and reference products.
• Two specific adjustment methods for sample size imbalance in analytical biosimilarity equivalence tests are discussed.

Main Results:

• Large sample size imbalance can unfavorably increase the power of equivalence tests, particularly when biosimilar sample size is much smaller than the reference product's.
• This can lead to a higher likelihood of incorrectly concluding similarity for less similar products.

Conclusions:

• It is crucial to implement sample size imbalance adjustments in analytical biosimilarity studies to ensure the reliability of equivalence tests.
• Motivating sufficient sample sizes for biosimilar products is essential during the planning phase to maintain study integrity and accurate product assessment.