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Significance and Use
4.1 This guide supports the principles of Guide E2500 and extends these principles to validation of analytical methods for PAT applications. The ongoing process of method validation is graphically represented in Fig. 1, which shows the life cycle of the validation of analytical methods for PAT applications. Prerequisites for validation are the identification of the measurement requirements and development of a method to meet those requirements.
4.2 The method risk assessment also takes into account the stage in the product life cycle at which the measurements are being made and how the resulting data will be used. The integration of these considerations in the risk assessment facilitates the determination of the level of validation necessary to ensure that the method is fit for purpose.
4.3 Changes may occur during the product life cycle necessitating identification of changes to the measurement requirements and method update and revalidation. Procedures should be established to evaluate the continued suitability of the process analytical method.
4.4 Additional informative examples can be found in Practices D3764, D6122, E1655, E1790, E2056, and E2617 that address validation of methods and models. Other useful standards include ASME BPE2009, ISO 14971, ISO 15839, and USP Acoustic Emission <1005> .
1.1 This guide provides an overview to the risk-based validation of process analytical methods under a process analytical technology (PAT) paradigm for pharmaceuticals and biopharmaceuticals and as such includes guidance on assessing risk to product quality from inappropriate method validation.
1.2 This guide builds on existing standards on the topic of validation concentrating on applying such standards to analytical methods for on-line analysis. In particular, it addresses the validation of at-line, on-line, or in-line PAT measurements and covers both API and Drug Product (DP) measurements.
1.3 The definitions of International Conference on Harmonization (ICH) validation parameters (such as specificity, precision, repeatability, etc.) apply; however, the method of demonstrating the validation parameters may vary from that described in ICH and is discussed.
1.4 As consistent with the U.S. Food and Drug Administration (FDA) process validation guidance, this document also briefly covers ongoing assurance that the method remains in a validated state during routine use.
1.5 Equipment and instrument qualification are out of the scope of this guide but will be referenced as inputs to validation of analytical methods for PAT applications.
1.6 The validation of multivariate prediction models is out of scope but will be referenced as inputs to validation of analytical methods for PAT applications.
1.7 Microbiological methods are out of scope.
1.8 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
2. Referenced Documents (purchase separately) The documents listed below are referenced within the subject standard but are not provided as part of the standard.
D3764 Practice for Validation of the Performance of Process Stream Analyzer Systems
D6122 Practice for Validation of the Performance of Multivariate Online, At-Line, and Laboratory Infrared Spectrophotometer Based Analyzer Systems
E1655 Practices for Infrared Multivariate Quantitative Analysis
E1790 Practice for Near Infrared Qualitative Analysis
E2056 Practice for Qualifying Spectrometers and Spectrophotometers for Use in Multivariate Analyses, Calibrated Using Surrogate Mixtures
E2476 Guide for Risk Assessment and Risk Control as it Impacts the Design, Development, and Operation of PAT Processes for Pharmaceutical Manufacture
E2500 Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment
E2617 Practice for Validation of Empirically Derived Multivariate Calibrations
E2629 Guide for Verification of Process Analytical Technology (PAT) Enabled Control Systems
ICS Number Code 11.120.99 (Other standards related to pharmaceutics)