Final Analytical Procedures Guidance Published

On March 7, 2024, FDA published two final guidance documents regarding analytical procedures in order to facilitate regulatory evaluations and flexibility in postapproval change management of analytical procedures. The documents were developed in collaboration with the International Council for Harmonisation (ICH). Q2(R2) Validation of Analytical Procedures outlines principles of analytical procedure validation, including the analytical use of spectroscopic data. Q14 Analytical Procedure Development harmonizes scientific approaches for analytical procedure development and provides principals for risk-based postapproval change management.

The Q2(R2) document is directed to common uses of analytical procedures and applies to analytical procedures used for release and stability testing of commercial drug substances and products. It includes information on validation studies, validation during the life cycle of an analytical procedure, reportable ranges, stability-indicating procedures, and multivariate analytical procedures. Specifically, it covers specificity/selectivity, ranges, accuracy and precision, and robustness. The document has two annexes: one provides a selection of validation tests; the other provides illustrative examples of analytical techniques.

“This guidance presents elements for consideration during the validation of analytical procedures included as part of registration applications. Analytical procedure validation forms a part of the analytical procedure life cycle, as described within [ICH] guidance for industry Q14 Analytical Procedure Development (March 2024) (ICH Q14). This ICH guidance for industry, Q2(R2) Validation of Analytical Procedures (ICH Q2), provides guidance on selection and evaluation of the various validation tests for analytical procedures. This guidance includes a collection of terms and their definitions, which are meant to bridge the differences that often exist between various compendia and documents of the ICH member regulatory authorities. The objective of validation of an analytical procedure is to demonstrate that the analytical procedure is fit for the intended purpose. Further general guidance is provided on validation studies for analytical procedures,” the guidance states. “Approaches other than those set forth in this guidance may be applicable and acceptable with appropriate science-based justification. The applicant is responsible for designing the validation studies and protocol most suitable for their product,” it further stresses.

The Q14 document discusses minimal versus enhanced approaches to analytical procedure development. Specifically, it addresses analytical target profiles, risk management, parameter ranges, procedure control strategies, multivariate analytical procedures, and real-time release testing. It also provides guidance on submission of analytical procedure information. The documents Annex gives examples of application of ICH Q14 principals and an example of multivariate model life cycle components.

“Using the tools described in the ICH guidance for industry Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (May 2021) (ICH Q12), the guidance describes principles to support change management of analytical procedures based on risk management, comprehensive understanding of the analytical procedure, and adherence to predefined criteria for performance characteristics. Knowledge gained from application of an enhanced approach to analytical procedure development can provide better assurance of the performance of the procedure, can serve as a basis for the analytical procedure control strategy and can provide an opportunity for more efficient regulatory approaches to related postapproval changes,” the guidance states.

The two final guidance documents replace draft guidance documents published in August 2022.

Source: FDA