ASTM_E_2474_-_14.pdf

Designation:E247414Standard Practice forPharmaceutical Process Design Utilizing Process AnalyticalTechnology1This standard is issued under the fixed designation E2474;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.INTRODUCTIONProcess design is the systematic conversion of information about needs for a product intoknowledge about how to manufacture this product.Products and manufacturing processes should bedesigned using science-and risk-based design strategies to manage variation.To attain this goal,integration of Process Analytical Technology(PAT)principles and tools duringprocess design will enhance opportunities to build,maintain,and expand science-and risk-basedprocess understanding throughout a product lifecycle.The product lifecycle includes the period inproduction as well as development.Process understanding will be the foundation to establish manufacturing(process selection,methodology,implementation,and practice),process control(real-time control on the basis ofmeasured critical quality attributes),effective risk mitigation,and product release concepts.Process understanding will also enable regulatory strategies in that the level of regulatory scrutinymay reflect the demonstrated level of science-and risk-based process understanding.1.Scope1.1 This practice covers process design,which is integral toprocess development as well as post-development processoptimization.It is focused on practical implementation andexperimental development of process understanding.1.2 The term process design as used in this practice canmean:1.2.1 The activities to design a process(the process design),or1.2.2 The outcome of this activity(the designed process),orboth.1.3 The principles in this practice are applicable to bothdrug substance and drug product processes.For drug products,formulation development and process development are inter-related and therefore the process design will incorporateknowledge from the formulation development.1.4 The principles in this practice apply during developmentof a new process or the improvement or redesign of an existingone,or both.1.5 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:2E1325 Terminology Relating to Design of ExperimentsE2475 Guide for Process Understanding Related to Pharma-ceutical Manufacture and ControlE2476 Guide for Risk Assessment and Risk Control as itImpacts the Design,Development,and Operation of PATProcesses for Pharmaceutical ManufactureE2629 Guide for Verification of Process Analytical Technol-ogy(PAT)Enabled Control SystemsE2587 Practice for Use of Control Charts in StatisticalProcess Control2.2 FDA Standards:3FDA Guidance for Industry PATA Framework for Inno-vative Pharmaceutical Development,Manufacturing,and1This practice is under the jurisdiction of ASTM Committee E55 on Manufac-ture of Pharmaceutical Products and is the direct responsibility of SubcommitteeE55.01 on PAT System Management,Implementation and Practice.Current edition approved April 1,2014.Published April 2014.Originallyapproved in 2006.Last previous edition approved in 2006 as E2474 06.DOI:10.1520/E2474-14.2For 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 Food and Drug Administration(FDA),10903 New HampshireAve.,Silver Spring,MD 20993-0002,http:/www.fda.gov.Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959.United States1 Quality Assurance,September 2004FDA Guidance for Process Validation General Principlesand Practices,January 20112.3 ICH Guidance Standards:4ICH Q8 Pharmaceutical Development,Step 4 Document,August 2009ICH Q9 Quality Risk Management,Step 4 Document,No-vember 20053.PAT Process Design Practices3.1 Desired StateIn the desired state of a process,allsources of variation are defined and controlled,and endproduct variation is minimal.That implies that critical productattributes are controlled to target for all individual units of aproduct.As a result,processes are capable of consistentlysupplying,unit to unit and batch to batch,the desired quality.PHILOSOPHY AND PRINCIPLES3.2 Practice#1:Risk Assessment and MitigationProductsand manufacturing processes should be designed to minimizevariation.Therefore,process design is a means to mitigate therisk of having product units with varying quality.The processdesign requires the use of formal