關鍵工藝參數的定義指南4頁)本頁僅作為文檔封面，使用時可以刪除Thisdocumentisforreferenceonly-rar21year.MarchGuidanceindefiningcriticalprocessparameters關鍵參數的定義指南Thecriticalityofaprocessparameterisanassessmentoftheprobabilitythatitcanbeconsistentlyandreproduciblycontrolledwithintheprovenacceptablerange(PAR)duringroutinemanufacturing.工藝參數的關鍵性是指在生產中對可承受范圍的持續重復掌握的可能性的評估，Thisprobabilitydependson可能性主要取決于：therobustnessoftheprocessparameter(thewidthofthePAR)工藝參數的穩定性〔可承受范圍的寬度〕theabilitytotechnicallycontroltheparameter(technicallimitations)參數掌握的技術力量〔技術限制〕theuncertaintyofthemeasurementoftheparameter(reflectedbythestandard參數測量的不確定性〔用標準偏差來反映〕

deviationσ)Therobustnessofaprocessparameterisreflectedbythewidthoftheprovenacceptablerange.Thewidertherangewithinwhichaparametercouldbevariedduringprocessqualificationwithoutimpactingproductquality,themorerobustitis.可承受的參數范圍反映工藝參數的穩定性。在參數確認中不影響產品質量的可轉變的參數的范圍越寬，工藝越穩定。Theabilitytotechnicallycontrolaparameterisafunctionofacombinationofprocesspropertiesandequipmentcapabilities.Forexample,ahighlyexothermicreactionmightbewellcontrolledinasmallstainlesssteelvessel,butcouldproveimpossibletocontrolinalargerglass-linedvessel.參數的技術掌握力量是工藝特性和設備力量的綜合功能。例如，一個高放熱的反響可能在一個小的不銹鋼反響釜內能夠很好的被掌握，但是在一個大的塘玻璃反響釜內證明是不行能掌握的。Theuncertaintyofameasurement(σ)isthecombineduncertaintyofthecalibrationoftheprobe,thevarianceoftheprobeitself,andthevarianceofthesignaltransmissionfromtheprobetothedistributedcontrolsystem(DCS).Ifthemeasurementisnormallydistributed,3.4outofamilliondatapointswillbeoutsidearangeof+/-4.5standarddeviations.Thisisthebasisofthe‘sixsigma’theory.Thedifferenceof1.5between4.5and6isanempiricalvaluechosenbasedontheobservationthatthemeanofrealprocessestendstodriftbythisvalueovertime.donthe‘6-conceptwedefineaparameter‘critical’whentheprovenacceptablerangeisnarrowerthan±sixstandarddeviations.DCS的信號傳輸的變化的不確定因素的綜合。假設測量結果是正態分布的，3.4PPM〔百萬分之一〕將在+/-4.5標準偏差的范圍之外。這是六西格瑪理論的根底。4.561.5的差異是一個閱歷值基于觀看實際工藝趨勢相對時間數值的漂移?；诹鞲瘳敻拍町斠粋€參數的可承受的范圍比+/-六個標準偏差窄時，我們定義這個參數為關鍵參數。2figure1:criticalparametersetpoint

figure2:non-criticalparametersetpoint40° 45° 50°

55° 60°

65° 70° 40° 45° 50°

55° 60°

65° 70°6σ66σ6σ6σ6σprovenacceptablerange lower/upperedgeoffailure

provenacceptablerangelower/upperedgeoffailure3Whereasaprovenacceptablerangedependsonlyontheprocess,thevarianceofacontrolsystemisequipment-specific.Thevarianceofacontrolsystemforthesameprocessparametermightbedifferentinanotheroperationalenvironment,whichcouldresultinadifferentcriticalityassessment(e.g.acritical3processparameterinoneplantmaybejudgedtobenon-criticalinanotherplantwhichhasacontrolsystemwithalowervariance).〔比方在一個工廠的一個關鍵參數在另一個有較低變異的掌握系統的工廠就可能被判定為不關鍵〕Thefollowingtablecanbeusedforguidancetoassessthecriticalityofaprocessparameter以以下表在指南中用于評定一個工藝參數的關鍵性minimum PAR fortypeofprocessparameter工藝參數的類型

assumptionforσ

non-criticalparameter Comment(±6σ)判定不關鍵的最小(±6σ)Temperature0.6%溫度

+/-4%range)

Forthetypicalmeasurement(of measurement rangeof-20to180°C:+/-8°CAmount(quantity)byweight重量Amount(quantity)byvolume體積數量pHPressure(vacuum)

0.8%2%0.1pH-unit

(檢測范圍的)+/-5%(ofsetpoint)〔設定點的〕+/-12%(ofsetpoint)〔設定點的〕+/-0.6pH-units 1.0pH-units1)

-20~180°C，范圍為+/-8°CThelimitsofthebalancehavetobetakenintoaccount.See:稱的限度應當帶進數量Important:acertainminimalflowhastobeexceeded的最小流量ThepHistypicallymoredifficulttocontrolthantomeasure.pH是典型的掌握難于檢測Pressureistypicallymoredifficulttocontrolthanto壓力〔真空〕

0.8% +/-20%2)

measure.測ThepHistypicallymuchmoredifficulttobecontrolledthantobemeasured.Unlessasystemisinplacewhichsignificantlyreducesthecontroluncertainties(localpH,re-adjustment,etc.)aPARof+/-1.0pHunitsisrecommended.pH是典型的掌握比檢測要難得多。假設一個適當的系統能夠顯著的降低掌握的不確定性〔在線pH，重校正等〕推舉使用+/-1.0pH的可承受的范圍。Takingintoaccountthedifficultiesofcontrollingapressureunderchangingprocessconditionsasobservedduringe.g.drying,distillationoperationandreactionsunderpressure,aPARof+/-20%isrecommended.3考慮到在枯燥、蒸餾操作和壓力下反響中觀看到的工藝條件轉變時壓力掌握的難度。推舉使用+/-Examples:例子：1〕Areactiontemperatureislikelytobenotcriticaliftheprovenacceptablerange(PAR)forasetpointof50°Cisdeterminedas42°-58°Cforacalibratedtemperaturerangeof200°C(e.g.-20°Cto+180°C).42~58°C50°C200°C〔比如-20°C~180°C〕,那么一個反響溫度或許就是不關鍵的。42〕ApHhastobeadjustedto5.0(PAR:4.4–5.6)bychargingacid.ThefinalpHisrelevant;anoverchargeofacidcanbecorrectedbychargingbase.Thisparameteriswellcontrolledandnotcritical.pH5.0〔范圍：4.4~5.6〕，pH是相應的。加過量的酸可以通過加堿來校正。那么這個參數可以被很好的掌握并不關鍵。3〕DuringareactionanacidisreleasedandthepHhastobecontrolledbetween6.4and7.6bychargingbase.ThisparameterislikelytobecriticalasthelocalpHmightdiffersignificantlyfromthevaluemeasuredandasthechargeofbasehastobecontrolled.在一個反響中酸已經加了，pH6.4~7.6pH與檢測的值可能有顯著不同，堿的參加必需掌握，所以這個參數可能是關鍵的。4〕Adistillationistobecarriedoutunderapressureof<10KPa.Theset-pointshouldbedefinedas8KPa,theparameterlikelytobenotcritical.10KPa8KPa。這個參數可能就是不關鍵的。5〕Ahydrogenationhastobecarriedoutat0.8Mpa,itcanberunbetween0.6and1MPa;below0.6MPathereactionstopsandmorethan1MPacouldnotbetested.Thisparameterisverylikelytobenotcritical.0.8Mpa0.6~1MPa0.6M