Quality by design compliant analytical method validation.

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Quality Management

Background:

• Quality by Design (QbD) is increasingly adopted for pharmaceutical process development to ensure product quality.
• Applying QbD to analytical methods is crucial for process control and reliable measurement of critical quality attributes (CQAs).
• Traditional method validation relies on checklists, necessitating a shift towards approaches ensuring high reliability for decision-making.

Purpose of the Study:

• To propose a general methodology for aligning analytical method validation with the Quality by Design (QbD) framework.
• To ensure analytical methods provide a high level of assurance for measuring drug product CQAs.
• To establish method validation criteria and decision approaches based on the intended use of analytical procedures.

Main Methods:

• Implementation of β-Expectation tolerance intervals for analytical method validation.
• Development of a general methodology to integrate QbD principles into method validation.
• Application of the methodology to quantitative impurity assays and content assays for drug substances and products.

Main Results:

• A structured methodology is presented to align method validation with QbD philosophy.
• The use of β-Expectation tolerance intervals provides a robust approach for determining method validity.
• The methodology's applicability is demonstrated through two practical case studies.

Conclusions:

• The proposed QbD-aligned methodology enhances the reliability of analytical method validation.
• This approach ensures that analytical methods are fit for their intended purpose, supporting accurate compliance decisions.
• The study provides a framework for more rigorous and scientifically sound method validation in the pharmaceutical industry.