SUPAC.docx
- 文档编号:24206927
- 上传时间:2023-05-25
- 格式:DOCX
- 页数:14
- 大小:25.06KB
SUPAC.docx
《SUPAC.docx》由会员分享,可在线阅读,更多相关《SUPAC.docx(14页珍藏版)》请在冰豆网上搜索。
SUPAC
SUPAC-IRQuestionsandAnswersaboutSUPAC-IRGuidance
(February18,1997)
AllNDA,ANDA,andAADAHolders
DearSponsors:
OnNovember30,1995,theScale-upandPost-ApprovalChangesGuidanceforImmediateReleaseProducts(SUPAC-IR)waspublished.SincethenanumberofquestionshavearisenininterpretingtheGuidanceasitappliestospecificsituationsencounteredorthatcouldbeencounteredinthepharmaceuticalindustry.Thepurposeofthisletterisprimarilytosharewithyouthequestionsthathavebeenaskedmostfrequentlyorthatweconsiderthemostsignificant.AlsoincludedaretheCenter'sresponsestothesequestions.TheresponsesweredevelopedandconcurredwithbytheOfficeofNewDrugChemistryandOfficeofGenericDrugs,CenterforDrugEvaluationandResearch(CDER).WebelievethesharingoftheinformationwillresultinfurtheringtheuseoftheGuidancetoincreaseregulatoryflexibilityforindustry.
Inaddition,theCenter'sChemistryandManufacturingControlsCoordinatingCommittee(CMCCC)hasmetandreconsideredtwoSUPAC-IRissueswhichhavebeenofgreatconcernandinteresttoindustry.Thefollowinginformationonstandalonepackagingoperationsitechangesandstandaloneanalyticalsitechangesrepresentsare-assessmentofhowSUPAC-IRshouldbeinterpretedontheseissues.
STANDALONEPACKAGINGOPERATIONSSITECHANGES
Forimmediatereleasesolidoraldosageforms,astandalonepackagingoperationssitechange,utilizingcontainer(s)/closure(s)intheapprovedapplication,maybesubmittedasaChangesBeingEffectedsupplement.ThefacilityshouldalsohaveacurrentandsatisfactorycGMPcomplianceprofilewithFDAforthetypeofpackagingoperationinquestionbeforesubmittingthesupplement.ThesupplementshouldcontainwrittencertificationfromthepackagingfacilitystatingthatitisinconformancewithcGMP's.IfthefacilityhasnotreceivedasatisfactorycGMPinspectionwithintheprevioustwoyearsforthetypeofpackagingoperationinvolved,aprior-approvalsupplementwiththesamecommitmentforstabilityisrecommended.
Thesupplementshouldalsocontainacommitmenttoplacethefirstproductionbatchoftheproductonlong-termstabilitystudiesusingtheapprovedprotocolintheapplicationandtosubmittheresultingdatainannualreports.Wheretheproductisavailableinmorethanonestrength,size,orcontainer/closuresystem,onebatchofeachcombinationshouldbeplacedonlong-termstabilitystudies.BracketingormatrixingisallowedonlyifithasbeenapprovedpreviouslybyFDA.Anychangestoanapprovedstabilityprotocolshouldhaveasupplementalapprovalpriortotheinitiationofthestabilitystudy.Batchesshouldbetestedannuallyasperthestabilitycommitmentsintheapprovedapplication.
STANDALONEANALYTICALTESTINGLABSITECHANGES
Forimmediatereleasesolidoraldosageforms,astandaloneanalyticaltestinglaboratorysitechangemaybesubmittedasaChangesBeingEffectedsupplement,ifthenewfacilityhasacurrentandsatisfactorycGMPcomplianceprofilewithFDAforthetypeoftestingoperationinquestion.ThesupplementshouldcontainacommitmenttousethesameSOP'sandtestmethodsemployedintheapprovedapplication,writtencertificationfromthetestinglaboratorystatingthattheyareinconformancewithcGMP's,andafulldescriptionofthetestingtobeperformedbythetestinglab.IfthefacilityhasnotreceivedasatisfactoryGMPinspectionwithintheprevious2yearsforthetypeoftestinginvolved,aprior-approvalsupplementisrecommended.
TheCMCCCandtheCenterintendthattheSUPAC-IRGuidancewillberevisedtofurtherclarifyandupdateitsrecommendationsandtoassuregoodcorrespondencebetweentheserecommendationsandthoseofotherSUPACdocumentsinpreparation.Inthemeantime,wehopethesequestionsandanswerswillhelpclarifytheapplicationoftheGuidance.
Sincerelyyours,
/s/
RogerL.Williams,M.D.
DeputyCenterDirectorforPharmaceuticalScience
CenterforDrugEvaluationandResearch
Enclosure
SUPAC-IR:
QUESTIONSANDANSWERS
(Totheextentthesequestionsandanswersprovideguidance,thatguidancewaspreparedbytheChemistry,Manufacturing,andControlsCoordinatingCommitteeintheCenterforDrugEvaluationandResearch(CDER)attheFoodandDrugAdministration.AlthoughthisguidancedoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindtheFDAortheindustry,itdoesrepresenttheAgency'scurrentthinkingonquestionsrelatedtotheScale-UpandPost-ApprovalChangesGuidanceforImmediateReleaseProducts(SUPAC-IR).AnelectronicversionofthesequestionsandanswersarealsoavailableviaInternetusingtheWorldWideWeb(WWW).ToaccessthedocumentontheWWW,connecttotheCDERHomePageathttp:
//www.fda.gov/cder1andgotothe"RegulatoryGuidance2"section.)
COMPONENTANDCOMPOSITIONCHANGES
1.Q:
Mayonecolorbereplacedwithanotherbyplacingthebatchonconcurrentstabilityandreportingitintheannualreport?
A:
Achangefromonecolortoanothershouldbesubmittedasapriorapprovalsupplement.2.Q:
CancolorbechangedunderSUPAC-IR?
A:
Yes.Achangeincolor,eitherinamountorfromonecolortoanother,isalevel3componentandcompositionchangewhichcallsforapriorapprovalsupplement.However,ifthecolorismerelybeingremoved,itisalevel1changeandcanbereportedinthenextannualreport.3.Q:
Whatisthefulldefinitionofachangein'technicalgrade"ofanexcipient?
Doesthisonlymeanachangeinexcipientspecificationsthatmayimpactfunctionalityordoesitincludeachangeinsupplierevenifallapplicablespecificationsremainthesame?
A:
Technicalgradesofexcipientsdifferintheirspecificationsandintendeduse.Technicalgradesmaydifferin:
1)specificationsand/orfunctionality;2)impurities;and3)impurityprofiles.IfasupplierofanexcipientchangesbutitstechnicalgradeANDspecificationsremainthesame,theagencyshouldbenotifiedinanannualreport.4.Q:
HowdoesoneapplySUPAC-IRtomultifunctionalexcipients,e.g.,starch?
A:
SUPAC-IRcompositionchangesarebasedonbeingabletodefinetheuseoractionoftheparticularexcipientintheproduct.Thisrationaleshouldbeincludedbytheapplicantsaspartoftheiroriginalapplications.Notallmultifunctionalexcipientsarelistedintheguidance.However,ifanexcipientwasutilizedtoprovidemultiplefunctionssuchaspregelatinizedstarchasafiller,starchasadisintegrant,starchpasteasabinder,thenthemostconservativerecommendedchangeshouldbefollowed(e.g.,foranexcipientthatisafiller,disintegrantandbinder,therecommendedlimitforaLevel2changeis"0.5percent,seepage7,SUPAC-IR).Anapplicantmaywishtoaddanexplanationofhowthechangewillaffectotherfunctionsoftheexcipientintheproduct.Ifthisinformationwasnotincludedintheoriginalapplication,thereviewdivisionshouldbeconsultedbeforefilingsuchaSUPACchange,eitherthroughaCBEorannualreport.
5.Q:
Whatisthereferencesourcefordefiningtheactionofaninactiveingredient,forexample,lubricantversusglidant?
Whatiftheactionisdefineddifferentlyintwosources?
A:
Anapplicantshouldbeabletojustifythechoiceandthebasisfortheselectionofaparticularexcipient,i.e.,itsexpectedfunctioninthedrugproduct.Itmaybeusefultociteasource.Theactionmaydependonthespecificproduct.6.Q:
DoesSUPAC-IRcoverchangesingranulatingsolutionvolumeoutsidetherangeinanapplication?
A:
ChangesingranulatingsolutionvolumearenotcoveredunderSUPAC-IR.Minorchangesareconsideredasnormaloperatingprocedureandshouldbeincludedintheexecutedbatchrecord.However,ifthisrepresentsapermanentchange,suchachangemaybedescribedintheannualreportalongwiththedatatojustifythattheformulationqualityandperformance(i.e.,drugproductiswithintheapprovedspecifications)wasnotaltered.7.Q:
Towhatcategorydoesachangeingranulationsolventinawetgranulationprocessbelong?
A:
Achangeingranulatingsolvent(e.g.,alcoholtowater)wouldalterthecompositionofthedrugproduct,bothqualitativelyandquantitatively,eventhoughitmayberemovedduringmanufactureofthedrugproduct.Becausesuchachangemayhavesignificantimpactonformulationqualityandperformance,itisalevel3compositionchangethatneedsapriorapprovalsupplement.8.Q:
TheNDAincludesvalidated/approvedrangesforexcipientsintheformulation.Wewouldliketomovethetargetformulaamountofoneofthefillerstotheuppervalueintherange.Willthisbealevel1changeincomposition?
A:
Allchangesarepredicatedonthetargetapprovedintheoriginalapplicationorthroughapriorapprovalsupplementforaformulationchange.Forproductsapprovedwithonlyarangeforanexcipient,thetargetmaybeassumedtobethemid-pointoftheapprovedrange.Ifthenewtargetiswithinthevalidatedrange,thechangewillbealevel1or2changedependingonthespecificexcipientchangedandthepercentchange(seetheSUPAC-IRguidancedocument).Thetargetoriginallyapprovedremainsthetargetofrecord;i.e.,Level1orLevel2componentchangesmadeunderSUPAC-IRdonotchangethetarget.Ifthenewtargetisnotwithinthevalidatedrange,theproposedtargetwillneedapriorapprovalsupplement.9.Q:
Whenmicrocrystallinecelluloseisincreasedby5%,thetabletweightincreases.Canthisstillbealevel1change?
A:
AftertheSUPAC-IRchange,ifthenewtargetweightisstillwithintherangeintheapprovedoriginalapplication,itisalevel1change.Otherwise,itisaLevel2or3change,bothofwhicharetobesubmittedasapriorapprovalsupplement.10.Q:
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- SUPAC