1、Designation:E247510Standard Guide forProcess Understanding Related to PharmaceuticalManufacture and Control1This standard is issued under the fixed designation E2475;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year of last re
2、vision.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 The purpose of this guide is to establish a frameworkand context for process understanding for pharmaceuticalmanufacturing using q
3、uality by design(QbD)(Juran,1992;2FDA/ICH Q8).The framework is applicable to both activepharmaceutical ingredient(API)and to drug product(DP)manufacturing.High(detailed)level process understandingcan be used to facilitate production of product which consis-tently meets required specifications.It can
4、 also play a key rolein continuous process improvement efforts.1.2 Process Analytical Technology(PAT)is one elementthat can be used for achieving control over those inputsdetermined to be critical to a process.It is important for thereader to recognize that PAT is defined as:“a system for designing,
5、analyzing,and controlling manufacturing throughtimely measurements(i.e.,during processing)of critical quality and performanceattributes of raw and in process materials and processes,with the goal ofensuring final product quality.It is important to note that the term analytical inPAT is viewed broadl
6、y to include chemical,physical,microbiological,mathematical,and risk analysis conducted in an integrated manner.The goal ofPAT is to enhance understanding and control the manufacturing process”(U.S.FDA PAT)1.3 This standard does not purport to address all of thesafety concerns,if any,associated with
7、 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:3E456 Terminology Relating to Quality and StatisticsE2281 Practice for
8、Process and Measurement CapabilityIndicesE2474 Practice for Pharmaceutical Process Design UtilizingProcess Analytical TechnologyE2617 Practice for Validation of Empirically Derived Mul-tivariate Calibrations2.2 U.S.Government Publications:4FDA/ICH Q8 Pharmaceutical DevelopmentFDA/ICH Q10 Pharmaceuti
9、cal Quality SystemsU.S.FDA PAT Guidance Document,Guidance for IndustryPATA Framework for Innovative PharmaceuticalManufacturing and Quality Assurance3.Terminology3.1 Definitions of Terms Specific to This Standard:3.1.1 critical inputs,ncritical process parameters andcritical raw material attributes
10、for a given process.American Society for Quality53.1.2 empirical,adjany conclusion based on experimentaldata and past experience,rather than on theory.3.1.3 expert system,nan expert system is a computerprogram that simulates the judgment and behavior of a humanor an organization that has expert know
11、ledge and experience ina particular field.3.1.3.1 DiscussionTypically,such a system contains aknowledge base containing accumulated experience and a setof rules for applying the knowledge base to each particularsituation that is described to the program.Sophisticated expertsystems can be enhanced wi
12、th additions to the knowledge baseor to the set of rules.3.1.4 first principles,na calculation is said to be from firstprinciples,or ab initio,if it starts directly at the level ofestablished laws of physics and does not make assumptionssuch as model and fitting parameters.3.1.5 mechanistic,adj(1)of
13、,or relating to,theories thatexplain phenomena in purely physical or deterministic terms:amechanistic interpretation of nature.1This guide is under the jurisdiction of ASTM Committee E55 on Manufactureof Pharmaceutical Products and is the direct responsibility of Subcommittee E55.01on Process Unders
14、tanding and PAT System Management,Implementation andPractice.Current edition approved April 15,2010.Published August 2010.DOI:10.1520/E2475-10.2Juran,J.,Juran on Quality by Design:The New Steps for Planning Quality IntoGoods and Services,Free Press,New York,N.Y.,1992.3For referenced ASTM standards,v
15、isit 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.4Available from U.S.Government Printing Office Superintendent of Documents,732 N.Capitol St.,NW,Ma
16、il Stop:SDE,Washington,DC 20401,http:/www.access.gpo.gov.5Available from American Society for Quality(ASQ),600 N.Plankinton Ave.,Milwaukee,WI 53203,http:/www.asq.org.Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959.United States1 3.1.6 process capability,nstatistical estimate of the out-come of a characteristic from a process that has been demon-strated to be in a state of statistical control.E22813.1.7 process inputs,nthe combination of all processp