New USP Chapter <1210> Statistical Tools for Procedure Validation

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

Following the draft for chapter <1210>, which was published in Pharmacopeial Forum (PF) 42(5) in September 2016, the United States Pharmacopeia (USP) adopted its new General Chapter <1210> Statistical Tools for Procedure Validation. The chapter has been published in USP 41-NF 36 and becomes official on May 1, 2018. 

The chapter describes the utilization of statistical approaches in procedure validation as described in Validation of Compendial Procedures <1225>. “Procedure validation” in this context refers to the analytical procedure qualification stage of the three stages of the analytical method life cycle, following design and development and prior to testing.

The new chapter <1210> assists General Chapter <1225> which requires analytical procedure to be validated based on the intended use of the analytical procedure. Chapter <1225> also describes common types of uses and suggests procedure categories (I, II, III, or IV) based on the collection of performance parameters appropriate for these uses. Performance parameters that may need to be established during validation include accuracy, precision, specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, and range. In some cases (e.g., biological assays), relative accuracy takes the place of accuracy. According to the USP, chapter <1210> focuses on how to establish analytical performance characteristics of accuracy, precision, and LOD. For quantitative analytical procedures, accuracy can only be assessed if a true or accepted reference value is available. In some cases, it will be necessary to assess relative accuracy. In many analytical procedures, precision (random error) can be assessed even if accuracy (systematic error ) cannot be assessed. Furthermore, the section addressing LOD can also be applied to limit tests in Category II. Other analytical performance characteristics of <1225>, e.g. specificity, robustness, and linearity, are out of scope for chapter <1210>.

In the three stages of the analytical procedure lifecycle the validation step must provide evidence of a procedure's fitness for use. The statistical hypothesis testing paradigm is commonly used to conduct validation consistent with <1225>. In chapter <1210> some statistical interval examples are provided for accuracy and precision. However, USP states "these methods are not intended to represent the only approach for data analysis, nor to imply that alternative methods are inadequate".

More information can be found in the new USP general chapter <1210> Statistical Tools for Procedure Validation published in USP 41-NF 36.