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Ligand Binding Sites02:40

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ISR: background, evolution and implementation, with specific consideration for ligand-binding assays.

John W A Findlay1, Marian M Kelley

  • 1Brevard, NC 28712, USA. jwaf115@yahoo.com.

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|January 30, 2014
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Summary

Independent Sample Retained (ISR) analysis is a key regulatory focus worldwide. This review covers ISR background, evolution, and implementation, with special attention to ligand-binding assays.

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Bioanalytical Method Validation
  • Regulatory Science

Background:

  • Independent Sample Retained (ISR) analysis gained significant attention from the US FDA in 2006.
  • Regulatory agencies globally (Europe, Asia, Latin America) have since emphasized ISR.
  • Discussions involving pharmaceutical companies, regulatory bodies, and CROs have shaped ISR implementation.

Purpose of the Study:

  • To review the background and evolution of ISR in bioanalytical studies.
  • To discuss the implementation of ISR across various regulatory landscapes.
  • To highlight specific considerations for ISR in ligand-binding assays.

Main Methods:

  • Literature review of regulatory guidelines and discussions.
  • Analysis of the historical context and development of ISR requirements.
  • Examination of current recommendations and their integration into guidelines.

Main Results:

  • ISR is now a key component of bioanalytical method validation guidelines from major regulatory agencies.
  • Recommendations for ISR conduct have been established and incorporated into guidelines by EMA, Japan (MHLW), and the FDA.
  • The review synthesizes information on ISR implementation for all assay types, including specific nuances for ligand-binding assays.

Conclusions:

  • ISR has evolved from a specific regulatory interest to a globally recognized standard in bioanalytical method validation.
  • The implementation of ISR is crucial for ensuring the reliability and reproducibility of bioanalytical data.
  • This review provides a comprehensive overview to guide the proper conduct and understanding of ISR, particularly for complex assays.