In detail
Origin and status
The guideline goes back to ICH Q2A (1994) and Q2B (1996), which were merged into Q2(R1) in 2005. The fully revised version, Q2(R2), was adopted at Step 4 on 1 November 2023. It covers more recent analytical techniques and is aligned with ICH Q14 on analytical procedure development. In the EU it has applied since 14 June 2024.
Scope
Q2(R2) applies to procedures used for release and stability testing of commercial drug substances and products, both chemical and biological. It can be applied on a risk basis to other procedures in the control strategy. During clinical development, its principles can be applied in a phase-appropriate manner.
Validation characteristics
- Specificity or selectivity
- Range, including the calibration model, linear or non-linear, and lower range limits (detection and quantitation limits)
- Accuracy
- Precision: repeatability, intermediate precision and reproducibility
Which characteristics are needed depends on the intended purpose. An identity test usually only requires specificity, whereas assay and quantitative impurity tests also require range, accuracy and precision.
What changed compared with Q2(R1)
Rather than referring only to linearity, the guideline speaks of the reportable range and also permits non-linear and multivariate calibration models. New elements include guidance on multivariate procedures such as NIR and examples for techniques such as qPCR, NMR and LC/MS. Under Q2(R2), robustness is typically evaluated during development in line with ICH Q14. A protocol stating the purpose, characteristics and acceptance criteria must be prepared before the validation study, and the results are summarised in a report. According to the guideline, the system suitability test (SST) is an integral part of the procedure and serves as a regular check of performance. Where an established platform procedure is used for a new purpose, validation testing can be abbreviated if scientifically justified.
In practice at A&O Pharma
Analytical method validation is part of our strategic GxP consulting. Our GMP-certified laboratory in Itzehoe offers, among other services, trace analysis by triple quadrupole LC-MS/MS and testing of starting materials to Ph. Eur. or an alternative monograph.
GMP & GxP Consulting & QA SupportFrequently asked questions
When did ICH Q2(R2) come into effect in the EU?
EMA gives 14 June 2024 as the date from which it applies. ICH adopted the guideline on 1 November 2023.
What is the difference between ICH Q2(R2) and ICH Q14?
ICH Q14 describes the development of analytical procedures, ICH Q2(R2) their validation. The two are aligned, and data from development can be used as part of the validation data.
Is robustness still part of validation?
Under Q2(R2), robustness is typically evaluated during development in line with ICH Q14, before the validation study itself. The results can be submitted with the development data or made available on request.
