Analytical Method Validation Requirements: A Comparative Review of ICH, USP, Chinese Pharmacopeia, and ANVISA (Brazil) Regulatory Guidelines

Shaileshkumar Bhingaradiya; Mahesh Vahini; Elumalai Selvaraja

doi:10.37022/jis.v9i2.164

Shaileshkumar Bhingaradiya Associate Director, Quality Control,Granules Pharmaceutical Inc., Chantilly, VA-20151, USA.
Vahini Mahesh Master’s degree in Biomedical Engineering, Drexel University, Philadelphia, USA
Selvaraja Elumalai Department of Chemistry, Neemrana, District Kotputli-Behror (Alwar), Rajasthan 301705, India

DOI https://doi.org/10.37022/jis.v9i2.164

Abstract

Analytical method validation is an essential component of pharmaceutical quality assurance, ensuring that analytical procedures are suitable for their intended purposes and consistently generate reliable results. Regulatory authorities and pharmacopoeial organizations have established validation requirements to support pharmaceutical development, manufacturing, quality control, and regulatory submissions. However, differences in validation terminology, experimental design, acceptance criteria, and documentation practices may complicate global regulatory compliance. This review critically compares the analytical method validation requirements described in the International Council for Harmonization (ICH) Q2(R2) guideline, United States Pharmacopeia (USP) General Chapter ⟨1225⟩, Chinese Pharmacopeia (ChP), and Brazilian Health Regulatory Agency (ANVISA) Resolution RDC No. 166/2017. This review focuses on specificity/selectivity, accuracy, precision, linearity, range, detection limit, quantitation limit, robustness, and system suitability. The review also examines how analytical quality by design, risk-based validation, lifecycle management, and statistical evaluation are integrated into contemporary analytical practice. Although the four frameworks share the fundamental objective of establishing analytical procedure fitness for purpose, they differ in regulatory status, procedural prescription, and how they interpret validation evidence. ICH Q2(R2) provides an internationally harmonized scientific framework, USP ⟨1225⟩ establishes compendial validation principles, the Chinese Pharmacopeia addresses validation within China's pharmacopoeial system, and ANVISA RDC 166/2017 specifies detailed requirements for analytical methods used in Brazilian pharmaceutical regulatory activities. A scientifically justified validation strategy that considers these differences can reduce redundant experimentation, facilitate international submissions, and improve analytical reliability. Future harmonization should emphasize performance-based acceptance criteria, analytical procedure lifecycle management, and transparent documentation.

Keywords: Analytical method validation, ICH Q2(R2), USP ⟨1225⟩, Chinese Pharmacopeia, ANVISA, Regulatory harmonization, Analytical quality by design

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