Assay Validation Guidelines

While method validation is a requirement of pharmaceutical test methods, the specifics of the validation process vary depending on the purpose of the method and the regulatory bodies governing drug development and production. Government regulations, written primarily with the goal of consumer protection, tend to avoid dictating specifics when it comes to the science of analysis. This approach allows for evolution and incorporation of new technologies and techniques without requiring specific legislation for each advance. Being thusly non-restrictive, however, can leave regulated companies with questions about the expectations of official compliance auditors, as well as what constitutes sufficient scientific rigor in method validation.

To clarify expectations, several government and regulatory bodies (e.g., FDA, ICH, IUPAC) have issued guidances that reflect current thinking and practices regarding method validation. While these guidances are largely non-binding, they do correspond with regulatory requirements and accepted industry standards for developing and producing safe and effective products. For this reason, the pharmaceutical industry tends to follow these guidances closely, deviating from them only when scientifically justified.

The following documents represent some of the more widely-used guidances and standards from various authorities. Note the “Draft” status of two of the FDA Guidances. These documents are unofficial and have been released to the public to allow for comments and suggestions prior to official publication. This draft status historically has not precluded them from use as official references; some guidances remain in draft status for years, yet are cited in various publications and used in developing validation programs.

FDA

• Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics (Draft Guidance), 2014
• Guidance for Industry: Bioanalytical Method Validation (Draft Guidance), 2013
• Guidance for Industry: Bioanalytical Method Validation, 2001

ICH

• Q2(R1), Validation of Analytical Procedures: Text and Methodology (Current Step 4 version), 2005

IUPAC

• Harmonized Guidelines for Single-Laboratory Validation of Methods of Analysis, 2002

USP 36

• <1225> Validation of Compendial Procedures

External Links

• Eurachem – The Fitness for Purpose of Analytical Methods: A Laboratory Guide to Method Validation and Related Topics
• ISO – 17025:2005 (available for purchase from www.iso.org)
  Related information: AOAC: How to Meet ISO 17025 Requirements for Method Verification