Q2: Analytical Validation

🧪 ICH Q2: Analytical Validation

🔹 Full Title:

ICH Q2(R2) – Validation of Analytical Procedures

🔹 Objective:

To provide guidance on the validation of analytical methods used to test drug substances and products — ensuring that the methods are accurate, reliable, and reproducible for their intended use.

📘 Purpose of Analytical Validation

Analytical validation demonstrates that an analytical procedure is suitable for its intended purpose — such as identifying, quantifying, or testing impurities in a product.

It ensures:

Accuracy of results
Reproducibility between laboratories
Consistency of product quality over time

⚗️ Types of Analytical Procedures

Identification Tests – Confirm identity of a compound.
Quantitative Tests for Impurities – Measure impurity levels.
Limit Tests for Impurities – Check impurities are below limits.
Quantitative Tests for Active Ingredient (Assay) – Determine the active content.

🧩 Analytical Method Validation Parameters

Parameter	Purpose / Description
1. Accuracy	Closeness of test results to true value or reference standard.
2. Precision	Reproducibility of results. Includes: • Repeatability • Intermediate precision • Reproducibility
3. Specificity	Ability to measure analyte in presence of impurities, excipients, or degradation products.
4. Detection Limit (LOD)	Lowest amount of analyte that can be detected but not necessarily quantified.
5. Quantitation Limit (LOQ)	Lowest amount of analyte that can be quantitatively measured with acceptable precision and accuracy.
6. Linearity	Ability to produce results directly proportional to concentration.
7. Range	Interval between upper and lower concentration values showing acceptable precision, accuracy, and linearity.
8. Robustness	Ability to remain unaffected by small deliberate variations in method parameters.
9. System Suitability	Ensures system performance before analysis (e.g., resolution, theoretical plates, tailing factor).

🔍 When Validation is Required

New analytical method development.
Transfer of method between labs.
After major method or instrument change.
As part of periodic revalidation (per SOP or regulatory requirement).

🧾 Typical Documentation

Method validation protocol.
Raw data and chromatograms.
Calculations and statistical analysis.
Validation summary report with conclusion.

🏭 Regulatory Importance

Required by ICH, WHO, FDA, EMA, and CDSCO.
Supports NDA, ANDA, and DMF submissions.
Ensures data integrity and product release reliability.