Transcription of fDA Guidance for Industry Dissolution Testing of …
1 ' Vorking Group Members: II.. f lui, - lnme. j . IIsII, jll III, IIllsell"- jlllS bllll'Slll,* HelrY MIIiIIWsli, fDA Guidance for Industry 1. 111111 Millry, Ilrry 1lllrllrl, 1m lIy,* ""Iu, 11111, elr jll hi 111,1, Dissolution Testing of Immediate 11.,1 1111111,* 111111,111. IlIlr I. WIIIIIIS. Release solid Oral dosage forms 'Tb(l' IIIJ/(;IfiIIIl/s OflTTrntJy HI u:ttb lIN FDA.."'/; ;;.'/:"'", fl11"Tf1pfltttktu:t Jh~uM he IIdtirrsud 7iJis gllidl/I/ce is df'lleloped jar immedil/Ie "lease (lR) dosl/ge j017I1S I/Ild is illtrnded 10 prrruide (/) gel/eml 1'(!)))
2 R0711111/!Iftintiol1S for dissolmiol1 Testing ; (2) approaches for settillg tlisso/lllion specifications feinted to the Deparnncnt of J-Iealth and hiop/Jfl17mlccllfic rvn11lcterist;rs oftbe drug substallce; (3) stnlisriclI/1I1efbods for comparing disso/llfioll profiles; Human Services ({ud (J) (/ prOCeII' to belp determine when din"olution Testing is SfljJide1lt to grant (J woiver for 011 ill vivo Food and Drug Administration CClltt.!r for Dmg E\'aluatiol1 and bim:qllit'lllcl1ct! st/ld). This t/ocumf!11f "Iso p1 TJvides recommendations for dissolutiol1 tests to be/p eJlSflrc c011till- Research (CDER).))}
3 IIOliS drug prodfll1 fjllflliry IIl1d pnfo17 JlfUlCe ofter m1ni1l portuppITJVol1ll0nllfnctliring chonges. SU1II1I10ry August 1997. il/fort/wlio" 01/ dissoillt iOlllllt'fbodology) IPP"ratlls) IIlId operllting conditiollS for Dissolution Testing of IR pmd- BPI. lIffS is provided ill SIlIllIllIll)1 forlll ill Appelldix A. Tbis guidonce is ime1lded to comple1llelll tbe SUPAC - IR. TABLE OF. gl/idnllce jar il/ill/slly: 1 III111eililllr RelellS" solid 01'111 dosage FOl7l1s: Scilie-llp nlld Post-Appmvnl Challges: CONTENTS PAGE.
4 Cbe1llistly, {\fulIlIjiltturiJlg IIlId COIlf1 J/S, In Vitro Disso/llfiol1 Testing , IIlld 111 VIVO Bioequiullience BACKGROU":'JD .. 15. Dommen/alio/1, 11 1i//; jpeciji( IY'ji'l"f!Jl(e to the gel1f!f{lIioll ofdisso/mioll profilesfor CfJwpllmtive pmposes, BlOPIIARMACEUTICS. CL\SSLFICA'rI ON .. 16. SE1~rI1" G Dissolution . SPFCiF1 CATION$ ,.. 16. A. Approaches for Setting BACKGROUND Specifications for a New Chemical I!:mil), ..16. D. rug absorption from a solid dosage New drug applications (NDAs) submitted to G. Approaches for Selring form afte r oral administration the Food and Drug Administration (FDA) con- D is'iolution SllCcifications for Generic productS.)}}
5 17. depends on the release of the drug tain bioavailability data and in vitro Dissolution C. Special Cases .. 17. subst:1t1ce from the drug product, data, that, together with chemistry, manufactur- D ..\bpping or Response Surface the Dissolution or solubilization of the drug ing, and controls (CMC) data, characteri ze the \ Iethoooiogy .. ,..17. under physiological conditions, and the penne- quality and perfonnance of the drug prodUCT. In E. In \,,,o ln Vitro Correiations ..I8. ability ,lcross the gastrointestinal tract.
6 Because vitro Dissolution data are generall), obmined from E \~1 lid:ltion and \ 'crification of of the critical nature of the first nYo of these batches that have been used in pil'Oml clinical SI>ccifications .18. steps, in vitro Dissolution Illay be reJevanr to the andlor bioavailability srudies and from other DlSSOLUTI O~ PROHLE. CO" IPARI SO~S ..18. prediction of in vivo performance. Based on this human studies conducted during product devel- A. '-todcllndepellden t Approach general consideration, in vitro Dissolution tests opment.
7 Acceptable bioequivalence data and Usillg ~ Similarity Factor .. 18. for immediate release solid oral dosage fonns, comparable in \;tro Dissolution and CMC data n. \1odel Indel>endent Multi\'lIri3le such as tablets and capsules, are used to (I) assess are required for appro",,1 of abbreviated new Confidence Rc ~,'ion Procedure .. 19. d,e lot-to-Iot quality of a drug product; (2) guide drug applications (ANDAs) (2 1 CFR ) ). C. Modd Depcndcl11 Approaches .19. development of new fomlUlationsj and (3) ensure The in \;tro specifications for generic products DISSOLlJT'ION AND SUPAC IR 19.
8 Continuing product quality and performance should be established based on a Dissolution pro- BIOWMVERS .. , .. 20. after certain changes, such as changes in the for- file. For new dmg applications, as well as generic Apl>endix A .. 20. mulation, the manufacturing process, the site of drug applications, the Dissolution specifications RFFFR E1'lCES ..12. manufacture, and the scale-up of the manufacrur- should be based on acceptable clinical, bioavail- 'Th,s gllidn"rr hIlS bUll prtparrd by fht ing process, ability, and/or bioequivalencc batches.
9 Rdfllst &''f!C1 t WorkiNg Group oftht BiophonNoctuti($. Current knowledge about the solubili ty, Once the specifications are esmblished in an Cf)()rtlil1lJrillg C"mmltttt In tht Cmu,. permeability, Dissolution , and pharmacokinetics NDI\, the Dissolution specifications for batch-to- for Ot'lIg eVlJllIIllirm and Rtstllrch of a drug product should be considered in defin- (COER) lit the Food 11111/ Drug batch quality assurance are published in the Ad",i/l;Strllt101l. This guitumu document ing Dissolution test specifications for the drug United States Pharmacopeia (USP) as compendi- l"fprtmm tht Agrngr OIrTnlf thillking Oil the Dissolution tmlllg of "",ntdiate approval process.
10 This know ledge should also al standards, which become the official specific-a- nlellst sQ/ill uml dosRgt fflnns. It dots I/ot be used to ensure continued equivalence of the tions for all subsequent IR products wid, the CI"tIlIC or (/Jllfn lilly rights for ( "" 011 fmy perso" (md d()t$ lIot opn-ntt to product, as well as to ensure the product's same- same active ingredients. In general, these com- himl FDA or tht public. All ness under certain scale-up and postapproval pendial Dissolution standards are single-point Illttrndriw approach mllJ ht lIstd If SItCh ftppronch JarisjitJ.)))
