Validation of analytical methods for drugs: Guide to validation under ICH Q2(R2) and Q14
The quality, safety and effectiveness of a pharmaceutical product depends to a large extent on the reliability of the analytical methods with which it is evaluated. The more accurately the amount of active ingredient, the contaminant profile or the dissolution rate of a drug is measured, the more well-founded the product decisions are. For this reason , the validation of analytical methods (Method Validation) is the cornerstone of the pharmaceutical quality control.
In the context of international harmonization, the guidelines I Q2(R2) and the newly published I Q14 determine how analytical methods must be validated and developed. In this article, we will cover the basic parameters of analytical method validation, the current approaches of the ICH guidelines and the GLP-compliant services of Nano-Test in this area.
What is the validation of analytical methods and why is it required?
The validation of analytical methods is the totality of the systematic work that is carried out to demonstrate the suitability of an analytical procedure for the specified purpose. A method is only considered "valid" when the validation has been completed and the performance parameters meet the acceptance criteria.
The need for validation arises in the following cases:
- Development of new methods: When a new analytical procedure is applied for the first time,
- Method transfer: When transferring one method from one laboratory to another,
- Method change: If changes are made to an existing method,
- Pharmacopoeia conformity: For methods to be used in the application for authorization,
- Routine Quality Control: If continuous verification of the method's performance is required.
Results obtained with an unvalidated method are not accepted by the licensing authorities and can lead to the rejection of the application for admission.
Validation parameters within the framework of Ich Q2(R2)
I Q2(R2) defines the basic parameters to be evaluated in the validation of analytical methods. Which parameters are required depends on the purpose of the method (identification, quantification, determination of impurities).
1. Accuracy
Denotes the proximity of the measured value to the actual value. is usually evaluated using recovery studies (recovery) and should be in the range of 98-102%.
2. Precision (Precision)
It is evaluated on three levels: repeatability (repeatability), intermediate precision, and reproducibility (reproducibility). The RSD value (relative standard deviation) should usually be below 2%.
3. Specificity (Specificity)
The ability of the method to correctly measure the analytes despite the presence of impurities, matrix components and degradation products. It is evaluated on the basis of forced degradation experiments.
4. Limit of detection (LOD) and limit of determination (LOQ)
The LOD is the lowest concentration that can be detected with the method; The LOQ is the lowest concentration that can be reliably quantified. They are determined based on the signal-to-noise ratio (S/N) or the standard deviation.
5. Linearity (Linearity) and Measuring Range (Range)
Specifies the concentration range in which the method reacts linearly. The correlation coefficient (R²) should generally be above 0.999.
6. Robustness (robustness)
Specifies the resistance of the method to small experimental fluctuations (pH, temperature, flow rate, column batch).
Need for the validation parameters depending on the purpose of the method
The following table summarizes which validation parameters within the framework of I Q2(R2) are required for which method of use of the method:
| Validation Parameters | Identification | Quantitative determination (assay) | Determination of impurities | Resolution speed |
|---|---|---|---|---|
| Accuracy | — | ✓ | ✓ | ✓ |
| Precision | — | ✓ | ✓ | ✓ |
| Specificity | ✓ | ✓ | ✓ | ✓ |
| Lod / Loq | — | — | ✓ | — |
| Linearity | — | ✓ | ✓ | ✓ |
| Area | — | ✓ | ✓ | ✓ |
| Stability | — | ✓ | ✓ | ✓ |
Q14: "Quality by Design" (QBD) in the development of analytical methods
I Q14, which came into force in 2023, introduced the “Quality by Design (QBD)” approach to the process of analytical method development. This guide provides new concepts that complement and reinforce the traditional validation approach:
- Analytical Target Profile (ATP - Analytical Target Profile): Pre-definition of the performance requirements for the method.
- Critical Method Parameters (CMP): Determination of the factors affecting method performance.
- Operational design area of the method (MODR): Definition of the parameter range in which the method works reliably.
- Risk assessment: Systematic assessment of the influence of method variables on the results.
I Q14 emphasizes that validation is not just a "checklist" but a process that requires a scientific understanding of the method. This approach ensures that the method is more robust in routine use and unexpected problems can be recognized in advance.
GLP compliant services for validation of analytical methods with nano-test
The analytical methods for your pharmaceutical products form the basis for your application for approval and your routine quality control. Nano-Test is a reliable solution partner for the pharmaceutical industry with its GLP-compliant validation services within the framework of ICH Q2(R2) and Q14.
Nano-Test – Performance Description
NANO-TEST offers Analytical Method Validation Services for the pharmaceutical industry. Work is carried out in our GLP and ISO/IEC 17025 accredited laboratories that fully comply with the ICH guidelines Q2(R2) and Q14.
Our service portfolio:
- Method development: I Q14-compliant, systematic method development including ATP and MODR definitions.
- Validation studies: Assessment of all parameters in terms of accuracy, accuracy, specificity, LOD/LOQ, linearity, measuring range and robustness.
- Forced degradation (Forced Degradation): Investigations under acid, base, oxidation, heat and light stress conditions to assess specificity.
- Method transfer: Cross-labor method transfer and comparative validation.
- Methodverification (verification): Verification of pharmacopoeia methods before routine use.
- Report: Validation reports in CTD format, with inspection approval and acceptable for the approval authorities.
Our analyses use state-of-the-art devices such as HPLC-DAD, LC-MS/MS, GC-MS/MS and ICP-MS.
The advantages of nano-test in analytical validation:
- Management of current guidelines: Complete compliance with the requirements of ICH Q2(R2) and Q14.
- GLP Certified Infrastructure: All work is carried out in accordance with GLP principles and Alcoa+ requirements.
- Multiple technical competence: HPLC, GC, LC-MS/MS, ICP-MS and spectroscopic methods under one roof.
- CTD-compliant reporting: Full validation dossiers as per module 3 requirements.
- Quick feedback: Reporting within 10-15 working days for standard validation work.
- Specialist team: A team of experienced chemists in the fields of analytical chemistry and validation.
The validation of analytical methods forms the basis for all data that prove the quality and safety of pharmaceutical products. Validation work carried out within the framework of ICH Q2(R2) scientifically proves the suitability of the method for its purpose, while the quality design approach introduced by I Q14 enables a deeper understanding of the method and its robustness in routine use.
With its infrastructure, advanced analytical technologies, and GLP-certified processes fully tailored to the current ICH guidelines, NANO-TEST fully meets the requirements of the pharmaceutical manufacturers for analytical validation. Collaborate with Nano-Test to speed up your application for admission and document the reliability of your analytical methods.