中英文 關(guān)鍵工藝參數(shù)的定義指南

Guidanceindefiningcriticalprocessparameters關(guān)鍵參數(shù)的定義指南Thecriticalityofaprocessparameterisanassessmentoftheprobabilitythatitcanbeconsistentlyandreproduciblycontrolledwithintheprovenacceptablerange(PAR)duringroutinemanufacturing.工藝參數(shù)的關(guān)鍵性是指在生產(chǎn)中對可接受范圍的持續(xù)重復(fù)控制的可能性的評估，Thisprobabilitydependson可能性主要取決于：therobustnessoftheprocessparameter(thewidthofthePAR)工藝參數(shù)的穩(wěn)定性(可接受范圍的寬度)theabilitytotechnicallycontroltheparameter(technicallimitations)參數(shù)控制的技術(shù)能力(技術(shù)限制)theuncertaintyofthemeasurementoftheparameter(reflectedbythestandarddeviationo)參數(shù)測量的不確定性(用標(biāo)準(zhǔn)偏差來反映)Therobustnessofaprocessparameterisreflectedbythewidthoftheprovenacceptablerange.Thewidertherangewithinwhichaparametercouldbevariedduringprocessqualificationwithoutimpactingproductquality,themorerobustitis.可接受的參數(shù)范圍反映工藝參數(shù)的穩(wěn)定性。在參數(shù)確認(rèn)中不影響產(chǎn)品質(zhì)量的可改變的參數(shù)的范圍越寬，工藝越穩(wěn)定。Theabilitytotechnicallycontrolaparameterisafunctionofacombinationofprocesspropertiesandequipmentcapabilities.Forexample,ahighlyexothermicreactionmightbewellcontrolledinasmallstainlesssteelvessel,butcouldproveimpossibletocontrolinalargerglass-linedvessel.參數(shù)的技術(shù)控制能力是工藝特性和設(shè)備能力的綜合功能。例如，一個高放熱的反應(yīng)可能在一個小的不銹鋼反應(yīng)釜內(nèi)能夠很好的被控制，但是在一個大的塘玻璃反應(yīng)釜內(nèi)證明是不可能控制的。Theuncertaintyofameasurement(o)isthecombineduncertaintyofthecalibrationoftheprobe,thevarianceoftheprobeitself,andthevarianceofthesignaltransmissionfromtheprobetothedistributedcontrolsystem(DCS).Ifthemeasurementisnormallydistributed,3.4outofamilliondatapointswillbeoutsidearangeof+/-4.5standarddeviations.Thisisthebasisofthe‘sixsigma’theory.Thedifferenceof1.5between4.5and6isanempiricalvaluechosenbasedontheobservationthatthemeanofrealprocessestendstodriftbythisvalueovertime.Basedonthe‘6cf-conceptwedefineaparameteras‘critical’whentheprovenacceptablerangeisnarrowerthan士sixstandarddeviations.測量的不確定性是探頭或檢測器的校驗(yàn)，監(jiān)測器本身的變化和從探頭到DCS的信號傳輸?shù)淖兓牟淮_定因素的綜合。如果測量結(jié)果是正態(tài)分布的，3.4PPM(百萬分之一)將在+/-4.5標(biāo)準(zhǔn)偏差的范圍之外。這是六西格瑪理論的基礎(chǔ)。4.5和6之間1.5的差異是一個經(jīng)驗(yàn)值基于觀察實(shí)際工藝趨勢相對時間數(shù)值的漂移?；诹鞲瘳敻拍町?dāng)一個參數(shù)的可接受的范圍比+/-六個標(biāo)準(zhǔn)偏差窄時，我們定義這個參數(shù)為關(guān)鍵參數(shù)。figure1:criticalparameterfigure2:non-criticalparametersetfigure1:criticalparametersetpointsetpoint40°45°50°55°60°65°7040°45°50°55°60°65°70°provenacceptablerangelower/upperedgeprovenacceptablerangelower/upperedgeoffailureprovenacceptablerangelower/upperedgeoffailureWhereasaprovenacceptablerangedependsonlyontheprocess,thevarianceofacontrolsystemisequipment-specific.Thevarianceofacontrolsystemforthesameprocessparametermightbedifferentinanotheroperationalenvironment,whichcouldresultinadifferentcriticalityassessment(e.g.acriticalprocessparameterinoneplantmaybejudgedtobenon-criticalinanotherplantwhichhasacontrolsystemwithalowervariance).如果一個可接受的參數(shù)范圍僅僅依賴于工藝，控制系統(tǒng)的變異是設(shè)備屬性。對同樣的工藝參數(shù)的控制系統(tǒng)的變異可能在另一個操作環(huán)境下不同，這個可能導(dǎo)致一個不同的關(guān)鍵性評估(比如在一個工廠的一個關(guān)鍵參數(shù)在另一個有較低變異的控制系統(tǒng)的工廠就可能被判定為不關(guān)鍵)Thefollowingtablecanbeusedforguidancetoassessthecriticalityofaprocessparameter以下列表在指南中用于評定一個工藝參數(shù)的關(guān)鍵性typeofprocessparameter工藝參數(shù)的類型assumptionforominimumPARfornon-criticalparameter(±6o)判定不關(guān)鍵的最小可接受范圍Comment備注Temperature溫度0.6%+/-4%(ofmeasurementrange)(檢測范圍的)Forthetypicalmeasurementrangeof-20to180°C:+/-8°C對于典型的測量范圍-20?180°C，范圍為+/-8°CAmount(quantity)byweight重量0.8%+/-5%(ofsetpoint)(設(shè)定點(diǎn)的)Thelimitsofthebalancehavetobetakenintoaccount.See:稱的限度應(yīng)該帶進(jìn)數(shù)量Amount(quantity)byvolume體積數(shù)量2%+/-12%(ofsetpoint)(設(shè)定點(diǎn)的)Important:acertainminimalflowhastobeexceeded重要提示：必須超過確定的最小流量pH0.1pH-unit+/-0.6pH-units+/-1.0pH-units1)ThepHistypicallymoredifficulttocontrolthantomeasure.pH是典型的控制難于檢測Pressure(vacuum)壓力(真空)0.8%+/-20%2)Pressureistypicallymoredifficulttocontrolthantomeasure.壓力是典型的控制難于檢測ThepHistypicallymuchmoredifficulttobecontrolledthantobemeasured.Unlessasystemisinplacewhichsignificantlyreducesthecontroluncertainties(localpH,re-adjustment,etc.)aPARof+/-1.0pHunitsisrecommended.pH是典型的控制比檢測要難得多。如果一個適當(dāng)?shù)南到y(tǒng)能夠顯著的降低控制的不確定性(在線pH，重新校正等)推薦使用+/-1.0pH的可接受的范圍。Takingintoaccountthedifficultiesofcontrollingapressureunderchangingprocessconditionsasobservedduringe.g.drying,distillationoperationandreactionsunderpressure,aPARof+/-20%isrecommended.考慮到在干燥、蒸餾操作和壓力下反應(yīng)中觀察到的工藝條件改變時壓力控制的難度。推薦使用+/-20%的可接受的參數(shù)范圍Examples:例子：Areactiontemperatureislikelytobenotcriticaliftheprovenacceptablerange(PAR)forasetpointof50°Cisdeterminedas42°-58°Cforacalibratedtemperaturerangeof200°C(e.g.-20°Cto+180°C).如果一個可接受參數(shù)范圍是溫度范圍是42?58°C，設(shè)定點(diǎn)是50°C，而校驗(yàn)過的溫度為200°C(比如-20°C?180°C),那么一個反應(yīng)溫度或許就是不關(guān)鍵的。ApHhastobeadjustedto5.0(PAR:4.456)bychargingacid.ThefinalpHisrelevant;anoverchargeofacidcanbecorrectedbychargingbase.Thisparameteriswellcontrolledandnotcritical.一個pH必須通過加酸調(diào)節(jié)至5.0(范圍：4.4?5.6)，最終pH是相應(yīng)的。加過量的酸可以通過加堿來校正。那么這個參數(shù)可以被很好的控制并不關(guān)鍵。DuringareactionanacidisreleasedandthepHhastobecontrolledbetween6.4and7.6bychargingbase.ThisparameterislikelytobecriticalasthelocalpHmightdiffersignificantlyfromthevaluemeasuredandasthechargeofbasehastobecontrolled.在一個反應(yīng)中酸已經(jīng)加了，pH必須通過加堿控制在6.4?7.6,因?yàn)楝F(xiàn)場的pH與檢測的值可能有顯著不同，堿的加入必須控制，所以這個參數(shù)可能是關(guān)鍵的。Adistillationistobecarriedoutunderapressureof<10KPa.Theset-pointshouldbedefinedas8KPa,theparameterlikelytobenotcritical.一個蒸餾在壓力小于10KPa的條件下進(jìn)行。這個設(shè)定點(diǎn)應(yīng)該定義為8KPa。這個參數(shù)可能就是不關(guān)鍵的。Ahydrogenationhastobecarriedoutat0.8Mpa,itcanberunbetween0.6and1MPa;below0.6MPathereactionstopsandmorethan1MPacouldnotbetested.Thisparameterisverylikelytobenotcritical.一個氫化反應(yīng)必須在0.8Mpa下進(jìn)行。它可能在在0.6?1MP