ASTM_E_2891_-_13.pdf

Designation:E289113Standard Guide forMultivariate Data Analysis in Pharmaceutical Developmentand Manufacturing Applications1This standard is issued under the fixed designation E2891;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.Asuperscript epsilon()indicates an editorial change since the last revision or reapproval.1.Scope1.1 This guide covers the applications of multivariate dataanalysis(MVDA)to support pharmaceutical development andmanufacturing activities.MVDA is one of the key enablers forprocess understanding and decision making in pharmaceuticaldevelopment,and for the release of intermediate and finalproducts.1.2 The scope of this guide is to provide general guidelineson the application of MVDA in the pharmaceutical industry.While MVDA refers to typical empirical data analysis,thescope is limited to providing a high level guidance and notintended to provide application-specific data analysis proce-dures.This guide provides considerations on the followingaspects:1.2.1 Use of a risk-based approach(understanding theobjective requirements and assessing the fit-for-use status),1.2.2 Considerations on the data collection and diagnosticsused for MVDA(including data preprocessing and outliers),1.2.3 Considerations on the different types of data analysisand model validation,1.2.4 Qualified and competent personnel,and1.2.5 Life-cycle management of MVDA.1.3 This standard does not purport to address all of thesafety concerns,if any,associated with its use.It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2.Referenced Documents2.1 ASTM Standards:2C1174 Practice for Prediction of the Long-Term Behavior ofMaterials,Including Waste Forms,Used in EngineeredBarrier Systems(EBS)for Geological Disposal of High-Level Radioactive WasteE178 Practice for Dealing With Outlying ObservationsE1355 Guide for Evaluating the Predictive Capability ofDeterministic Fire ModelsE1655 Practices for Infrared Multivariate QuantitativeAnalysisE1790 Practice for Near Infrared Qualitative AnalysisE2363 Terminology Relating to Process Analytical Technol-ogy in the Pharmaceutical IndustryE2474 Practice for Pharmaceutical Process Design UtilizingProcess Analytical TechnologyE2476 Guide for Risk Assessment and Risk Control as itImpacts the Design,Development,and Operation of PATProcesses for Pharmaceutical ManufactureE2617 Practice for Validation of Empirically Derived Mul-tivariate Calibrations2.2 ICH Standards:3ICH-Endorsed Guide for ICH Q8/Q9/Q10 Implementa-tion ICH Quality Implementation Working Group Pointsto Consider(R2)ICH Q2(R1)Validation of Analytical Procedures:Text andMethodology3.Terminology3.1 DefinitionsCommon term definitions can be found inTerminology E2363 for pharmaceutical applications and someterms can be found in other standards and are cited when theyare mentioned.4.Significance and Use4.1 A significant amount of data is being generated duringpharmaceutical development and manufacturing activities.Theinterpretation of such data is becoming increasingly difficult.Individual examination of the univariate process variables isrelevant but can be significantly complemented by multivariatedata analysis(MVDA).Such methodology has been shown tobe particularly efficient at handling large amounts of data from1This guide is under the jurisdiction of ASTM Committee E55 on Manufactureof Pharmaceutical Products and is the direct responsibility of Subcommittee E55.01on PAT System Management,Implementation and Practice.Current edition approved Nov.1,2013.Published November 2013.DOI:10.1520/E2891-13.2For referenced ASTM standards,visit the ASTM website,www.astm.org,orcontact ASTM Customer Service at serviceastm.org.For Annual Book of ASTMStandards volume information,refer to the standards Document Summary page onthe ASTM website.3Available from International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human Use(ICH),ICHSecretariat,c/o IFPMA,15 ch.Louis-Dunant,P.O.Box 195,1211 Geneva 20,Switzerland,http:/www.ich.org.Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959.United States1 multiple sources,summarizing complex information intomeaningful low dimensional graphical representations,identi-fying intricate correlations between multivariate datasets tak-ing into account variable interactions.The output from MVDAwill generate useful information that can be used to enhanceprocessunderstanding,decisionmakinginprocessdevelopment,process monitoring and control(including prod-uct release),product life-cycle management and continualimprovement.4.2 MVDA is a widely used tool in various industriesincluding the pharmaceutical industry.To generate a validoutcome,MVDA should contai