HGB(1)T-1GUIDELINENo.:TechnicalGuidelineforMakingPostApprovalChangestoChemicalDrugProducts1April20082TableofcontentsI.Overview...........................................................................................................................2II.Basicprinciplesforperformingstudiespost-approvalchangestochemicaldrugproducts...............................................................................................................................3III.ChangestoDrugSubstanceManufacturingProcess.....................................................6IV.Changestoexcipientsinadrugformulation...............................................................14V.Changestothemanufacturingprocessforadrugproduct.........................................22VI.Changestodrugproductstrengthandpackagingsize..............................................30VII.Change............................................................todrugprodcugtspecificication36VIII.Changestothedrugprodcutshelf-life(expirationdatingperiod)and/orstorageconditions...........................................................................................................................41IX.Changestodrugproductpackagingmaterialsandthecontainerclosuresyatem...37X.Changestothemanufacturingsiteofanimporteddrugproduct...............................51XI.ChangetothemanufacturingsiteofAPIusedinanimporteddrugproductandchangetothemanufacturingsiteofanimportedAPI......................................................48XII.ChangesinthesiteofManufactureforAPIusedinadomesticdrugproduct.....Error!Bookmarknotdefined.AppendixIBasicmethodsforcomparisoninvestigationofdrugdissolution/release.....36AppendixIIGeneralconsiderationsforexemptionofinvivobioequivalence(BEwaiver)............................................................................................................................................72AppendixIIIApartiallistofofmedicineswithnarrowtherapeuticwindows............Error!Bookmarknotdefined.References.........................................................................................................................77Glossary.............................................................................................................................79Authors...............................................................................................................................801I.OverviewThisguidelineisprimarilyusedtoguidepharmaceuticalmanufacturerstocarryoutstudiesforpost-approvalchanges(orchanges)tochemicaldrugproducts.Changeshererefertothechangesthatinvolvesource,methods,controlconditionswithrespecttothemanufacture,quality-controlanduseconditionandrelatedareasforadrugproductthathasbeenapprovedformarketing.Thesechangesmayaffecttheproduct’ssafety,efficacyandqualitycontrollability.Thechangestudyherereferstothestudyandqualificationworktosupportaproposedchange.Atpresent,thechangesandchangestudiescoveredinthisguideline’sincludethefollowingareas:thechangestoAPI/drugsubstance(DS)manufacturingprocess,excipientforpharmaceuticaluseinformulationanditsmanufacturingprocess,registeredspecifications,strengths,shelflife(expirationdatingperiod),storageconditions,drugproductpackagingmaterialsandcontainerclosuresystem,theimporteddrugproductmanufacturingsite,manufacturingsiteofimportedAPI/DSorAPI/DSusedinimportdrugproduct...
