Analytical Validation Strategy: Acceptance Criteria (Analytical Target Profile)

Overview:

Validation of analytical procedures, i.e. the demonstration of suitability for the intended purpose is an essential GMP and regulatory requirement. The new revision of the ICH guideline Q2(R2) “Analytical procedure validation” published end of 2023 provides recommendations to address the relevant performance characteristics. Some of the gaps and deficiencies of the old guideline have been addressed, for example the exclusive focus on chromatographic methods, new lifecycle aspects were considered (in combination with the new guideline Q14 “Analytical Procedure Development”), and some new requirements were adopted. Acceptance criteria for the performance characteristics should be defined in the validation protocol. However, the Q2 guideline - and even the “illustrative” examples in Annex 2 - do not provide orientation how such acceptance criteria can be derived. Only the Q14 guideline gives some examples, but with not much background. Unfortunately, the topic of acceptance criteria is also neglected (even intentionally!) in the ICH Q2(R2)/Q14 Training Materials (July 2025).

Why you should Attend:

A rational, efficient, and science-based validation is important to ensure an appropriate performance of analytical procedures as well as to obtain a marketing authorization of a pharmaceutical product. Therefore, a comprehensive understanding of the performance parameters and their requirements (Analytical Target Profile, ATP) is key. Participants will learn how to derive performance and validation acceptance criteria to demonstrate the suitability of the analytical procedure. Appropriate acceptance can be based on the capability of the respective analytical technique (empirical acceptance criteria), but have to be primarily compatible to the specification limits (as representation of the Quality Attribute requirements). Participants will learn to derive acceptance criteria for precision from specification limits (USP <1033>, USP <1225> Rev.), and how such acceptable variability is related to the other performance characteristics, such as accuracy(bias), or calibration model.

Areas Covered in the Session:

• Required analytical performance (Analytical Target Profile)
• Empirical approach (analytical state-of-the art)
• Requirement-based derivation of precision from specification limits (Bioassay (USP <1033>, USP <1225> Rev.), from normal distribution probability, using tolerance factors)
• Bottom-up approach: Establishment of specification limits from precision
• Acceptable bias (accuracy)
• Acceptance criteria for impurities (concentration dependence of precision)

Who Will Benefit:

• Analysts
• Lab Supervisors and Managers in Analytical Development and Quality Control responsible for method development
• Optimization, and Validation
• Quality Assurance and Regulatory Affairs representatives responsible to approve or evaluate analytical procedure validation