Difference Between Validation and Verification of Analytical Methods

To ensure analytical methods perform consistently and meet regulatory expectations, laboratories must either validate or verify them, depending on method’s origin and intended use. While the two terms are often confused, validation and verification are distinct in both purpose and application.

Method validation is now recognized as part of a broader lifecycle. Validation should be aligned with a validation strategy, a structured plan that defines the performance characteristics to be assessed, the acceptance criteria, and the supporting data from analytical development.

The goal is not only to confirm the method’s accuracy, precision, and specificity, but also to demonstrate it is suitable over its full reportable range under intended operating conditions.

Verification is appropriate when an analytical method has already been validated, typically compendial methods or those from a regulatory submission. Rather than repeating all validation tests, laboratories are expected to confirm performance in their specific context by assessing critical characteristics like precision, specificity, and system suitability.

Verification activities should be documented and justified in relation to the intended use and any changes to the method, sample, or laboratory setup.

Method Validation: Confirming Performance Characteristics

Method validation is the process of establishing and documenting that an analytical method is capable of producing results that are accurate, precise, and reliable for its intended purpose. It involves assessing a set of predefined performance characteristics to demonstrate that the method consistently generates data that meets regulatory and quality requirements.

Typically applied to newly developed or significantly modified methods, validation provides the evidence that a method performs as expected across a defined range of conditions and sample types. The scope and depth of validation are determined by the nature of the method and the criticality of the results it supports.

Why Is Method Validation Important?

Method validation is a documented process that proves an analytical method is suitable for its intended use.

Validation is essential for:

• New methods developed in-house
• Significantly altered compendial methods
• Methods used for new products or formulations
• Non-compendial methods without prior validation

Common Scenarios That Require Method Validation

Below are some situations when method validation is required:

• Developing an HPLC method to quantify a new impurity
• Introducing a new matrix that may interfere with a validated method
• Adjusting the parameters of a compendial method beyond allowable limits

Method Verification: Assessing Suitability for Intended Use

Verification confirms that a previously validated analytical method performs reliably under the actual conditions of use, including the specific laboratory, instruments, personnel, and product matrix. It is not a repeat of the full validation process, but a targeted assessment to demonstrate that the method retains its expected performance when implemented in a new laboratory, on different equipment, or with varying materials. 

Why Is Method Verification Important?

All legally recognized compendial methods act as regulatory analytical procedures. However, their suitability must still be verified in the receiving laboratory.

Verification focuses on analytical performance characteristics (already proven during validation) and ensures they remain valid for:

• A specific type of sample
• The available equipment
• The environmental or matrix-specific conditions

Note: Once verified, analytical methods can be fully implemented for routine use.

Examples of When to Verify a Method

• Adopting a USP or Ph. Eur. method in a QC lab
• Using a validated method from a Marketing Authorization dossier
• Transferring a validated method from another site

Note: Method verification is especially important when excipients, impurities, or equipment may impact method performance under actual conditions​.

Method Validation vs. Method Verification

While both validation and verification aim to confirm the reliability of analytical methods, they differ in scope, application, and regulatory intent. Understanding these differences is essential for determining the appropriate approach based on the method’s origin, intended use, and the laboratory’s role. 

The following comparison outlines how these two processes diverge in terms of performance characteristics assessed and the contexts in which they are applied.

Performance Characteristics Assessed

Analytical Method Transfer

Analytical method transfer is the process of qualifying a receiving laboratory to use an existing analytical method with the same level of accuracy and reliability as the originating lab. Depending on the extent of changes involved—such as different equipment, analysts, or sample matrices—this process may require partial validation, full validation, or comparative testing. 

Partial validation is usually sufficient when minor changes are introduced, but the method remains fundamentally unchanged. Full validation is needed if significant modifications affect key performance characteristics like accuracy, specificity, or method robustness. 

When both laboratories are actively involved in assessing method performance using shared samples and protocols, comparative testing may be the preferred route.

Equivalency Testing

Equivalency testing is necessary when a laboratory develops its own analytical method but intends to claim compliance with a recognized compendial standard. In this case, it’s not enough to validate the method independently—there must be clear evidence that the in-house method performs at least as well as the official one. This means the two methods must produce statistically and practically comparable results.

One common approach is to analyze the same batch of product using both the in-house and compendial methods. The results are then compared side-by-side to ensure consistency in assay values, impurity profiles, or other critical parameters. Any significant deviation would raise concerns about the suitability of the internal method.

Another approach is to spike samples with known impurities or degradation products and test them using both methods. This helps evaluate whether the in-house method can detect and quantify impurities with the same level of sensitivity, specificity, and resolution as the compendial method. 

For example, if the compendial method can separate two closely eluting impurities with clear resolution, the internal method must do the same or better. Additionally, recovery studies should confirm that the in-house method accurately measures spiked components within acceptable limits.

When to Validate vs When to Verify Methods

Regulatory Guidance for Method Validation and Verification

• ICH Q2(R2) – Validation of Analytical Procedures
• USP <1225> – Validation of Compendial Procedures
• USP <1226> – Verification of Compendial Procedures
• USP <1224> – Transfer of Analytical Procedures
• EDQM OMCL (PA/PH/OMCL (13) 82 R5) – OMCL Guideline for Validation and Verification

Activities That Are NOT Part of Method Validation

It’s critical to distinguish method validation from other essential operational checks, such as:

Instrument Calibration

Calibration ensures instrument components work correctly, but it does not validate method performance.

Example:
HPLC detector calibration includes:

• Wavelength accuracy
• Linearity
• Signal to noise, and drift checks (baseline checks)

System Suitability Testing (SST)

SST ensures the system is ready for analysis. It’s done before sample injection to confirm the method is performing correctly.

HPLC SST Parameters:

• Resolution (R)
• Peak to Valley Ratio (P/V)
• Number of theoretical plates (N)
• Peak asymmetry
• RSD of standard replicate injections (Standard Repeatability)

These tests are an essential part of the method’s operational control. According to regulatory expectations, SST must be performed before and sometimes during sample runs, particularly in chromatographic methods (HPLC, GC) 

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