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Related Experiment Video

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In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
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A Novel Bootstrapping Test for Analytical Biosimilarity.

Thomas Zahel1

  • 1Körber Pharma Austria GmbH, Mariahilferstraße 88A, 1070, Vienna, Austria. Thomas.zahel@koerber.com.

The AAPS Journal
|October 22, 2022
PubMed
Summary
This summary is machine-generated.

A new bootstrapping test for analytical similarity in biosimilar development addresses flaws in current methods. This test controls Type I error and offers higher power, aligning with regulatory expectations for biosimilar licensing.

Keywords:
analytical similaritybiosimilarbiosimilaritybootstrappingequivalence testsrange test

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Area of Science:

  • Biopharmaceutical science
  • Statistical methodology
  • Regulatory science

Background:

  • Assessing analytical similarity is crucial for biosimilar licensing, often reducing clinical trial requirements.
  • Traditional methods like tiered approaches (equivalence and quality range tests) are evolving, with recent FDA and EMA guidelines favoring quality range tests.
  • Existing simple range tests, such as the 3SD test, have demonstrated flaws in controlling the Type I error (falsely declaring non-biosimilar as biosimilar).

Purpose of the Study:

  • To develop a novel bootstrapping test for assessing analytical similarity that overcomes limitations of current equivalence and range tests.
  • To ensure the new test meets key criteria: easily definable similarity conditions, simultaneous assessment of mean and variance differences, and controlled Type I error.
  • To demonstrate the superiority of the developed test in terms of power and compliance with regulatory standards.

Main Methods:

  • Development of a novel bootstrapping statistical test for analytical similarity assessment.
  • Evaluation of the test's ability to define similarity conditions, analyze mean and variance differences, and control Type I error.
  • Comparison of the new test's performance, including mean power values, against existing range tests.

Main Results:

  • The novel bootstrapping test allows for straightforward definition of similarity conditions.
  • It simultaneously evaluates differences in mean and variance between biosimilar and innovator products.
  • The test effectively controls the Type I error at a low level (e.g., 5%) across the similarity condition and demonstrates up to 10% higher mean power than existing range tests.

Conclusions:

  • The developed bootstrapping test offers a superior alternative to current quality range tests for analytical similarity assessment.
  • This novel method addresses identified flaws in existing tests and aligns with current regulatory expectations from agencies like the FDA and EMA.
  • The test provides a robust framework for biosimilar development, ensuring product quality and facilitating regulatory approval.