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1、Post Approval Changes for Finished ProductLin Hong 1AAPS/CPA Workshop, June 28-29, 2010Disclaimer The information contained in the presentation has been compiled from various sources. The views and opinions expressed are those of the individual presenter and should not be attributed to any organizat
2、ion with which the presenter is employed or affiliated.2AAPS/CPA Workshop, June 28-29, 2010Post Approval Changes Guideline Documents US:lSUPAC: IR (1995), MR (1997)lSUPAC: IR/MR Equipment Guidance (1999)lSUPAC: Extended release Oral Solid Dosage Forms, Development, Evaluation and Application of In-V
3、itro/In- Vivo Correlation (1997)lChanges to an Approved NDA or ANDA (2004)3AAPS/CPA Workshop, June 28-29, 2010Post Approval Changes Guideline DocumentsEU:lCommission Regulation (EC) No 726/2004lCommission Regulation (EC) No 1234/2008lCommission Regulation (EC) No 1084(5)/2003lModified Release Oral a
4、nd Transdermal Dosage Forms: Sections I and II CPMP/QWP/604/96, CPMP/EWP/280/96lGuideline on the Investigation of Bioequivalence CPMP/EWP/QWP/1401/984AAPS/CPA Workshop, June 28-29, 2010United StatesThe guidelines provide details of the lType of changelLevels of changelCMC documentation required to s
5、upport the change (dissolution and /or bioequivalence tests, analytical testing.)lFiling requirements5AAPS/CPA Workshop, June 28-29, 2010United StateslMinor Change (Level 1): Minimal potential to have an adverse effect Annual report (AR)lModerate Change (Level 2): Moderate potential to have an adver
6、se effect Changes Being Effected (CBE) Changes Being Effected 30 days (CBE-30)lMajor Change (Level 3): Substantial potential to have an adverse effect Prior Approval Supplement (PAS) 6AAPS/CPA Workshop, June 28-29, 2010United StatesTo Industry:lResponsibility to classify change moved from FDA to ind
7、ustrylAllows more changes without prior FDA approvallUse of new technologieslManufacturing cost reductionlAdequacy of the studies may be questioned months or years later even if the changes are predicted or approvedlIf the validity of AR/CBE/CBE-30 changes is challenged the sponsor may be required t
8、o track the affected lots/batches and provide additional data, quarantine or recall product if it is neededlGreater liability if the change is not adequately supported 7AAPS/CPA Workshop, June 28-29, 2010European UnionThe guidelines provide details of the classification of variations into the follow
9、ing categories as defined in Article 2 of the variations regulation: Minor variations of Type IA, minor variations of Type IB and major variations of Type II and provides further details, where appropriate, on the scientific data to be submitted for specific variations and how this data should be do
10、cumented.8AAPS/CPA Workshop, June 28-29, 2010European UnionFrom January 1, 2010, the modified European system for handling variations to the terms of marketing authorizations comes into force (Commission Regulation (EC) No 1234/2008). The EMA will process variations applications received after Janua
11、ry 1, 2010 according to the new variations system.lMarketing authorizations under the Centralized System (CP)lMarketing authorizations granted under the Mutual Recognition Procedure (MRP)lDecentralized Procedures (DCP)lAuthorizations granted following a referral9AAPS/CPA Workshop, June 28-29, 2010Eu
12、ropean UnionNational authorizations will not be affected until Directive 2009/53/EC has been transposed into national law. It should be done by January 20, 2011, and the new procedure shall then be applied at least to all exclusively national authorizations granted after January 1, 1998 10AAPS/CPA W
13、orkshop, June 28-29, 2010European UnionNational mandatory to follow new guidancelJanuary 1, 2010: Belgium, Bulgaria, Denmark, Estonia, Finland, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Slovak Repubic, Slovenia, Spain, Sweden, UKlMarch 2010: Hungary, lJuly 2010: Lithuania, RomanialJu
14、ly 2011: Cyprus, France11AAPS/CPA Workshop, June 28-29, 2010European UnionNew GuidanceOld GuidanceIncludes all Types of variations (Type IA, IAIN, IB, II) and if a variation is not specified (or if one or more of the conditions for Type IA/IAIN is not met) it reverts to a Type IB. The simplest varia
15、tion Types IA and IAIN need no prior approval.Includes only Type IA and IB and if it is not specified it reverts to a Type II12AAPS/CPA Workshop, June 28-29, 2010European UnionVariationClassifiedGuideDetailsPrior approval needed Type IAminorNewIt becomes a simpler procedure in the new guidance in th
16、at it is a do and tell and will be reported in an annual reportNominorOldIt was the simplest procedure in the old systemYesType IAINminorNewIt is similar to new Type IA. There is no prior approval but it does need to be immediately notifiedNo (but immediate notification)N/AOldN/AN/A Type IBminorNew/OldSame (Specific supporting data for Type IB variations will depend on the specific nature of the change. In some cases, r
