上海CMC培训 Post Approval Changes for Finished Product.ppt

AAPS/CPA Workshop, June 28-29, 2010,1,Post Approval Changes for Finished Product,Lin Hong,AAPS/CPA Workshop, June 28-29, 2010,2,Disclaimer,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 organization with which the presenter is employed or affiliated.,AAPS/CPA Workshop, June 28-29, 2010,3,Post Approval Changes Guideline Documents,US: SUPAC: IR (1995), MR (1997) SUPAC: IR/MR Equipment Guidance (1999) SUPAC: Extended release Oral Solid Dosage Forms, Development, Evaluation and Application of In-Vitro/In-Vivo Correlation (1997) Changes to an Approved NDA or ANDA (2004),AAPS/CPA Workshop, June 28-29, 2010,4,Post Approval Changes Guideline Documents,EU: Commission Regulation (EC) No 726/2004 Commission Regulation (EC) No 1234/2008 Commission Regulation (EC) No 1084(5)/2003 Modified Release Oral and Transdermal Dosage Forms: Sections I and II CPMP/QWP/604/96, CPMP/EWP/280/96 Guideline on the Investigation of Bioequivalence CPMP/EWP/QWP/1401/98,AAPS/CPA Workshop, June 28-29, 2010,5,United States,The guidelines provide details of the Type of change Levels of change CMC documentation required to support the change (dissolution and /or bioequivalence tests, analytical testing.) Filing requirements,AAPS/CPA Workshop, June 28-29, 2010,6,United States,Minor Change (Level 1): Minimal potential to have an adverse effect Annual report (AR) Moderate Change (Level 2): Moderate potential to have an adverse effect Changes Being Effected (CBE) Changes Being Effected 30 days (CBE-30) Major Change (Level 3): Substantial potential to have an adverse effect Prior Approval Supplement (PAS),AAPS/CPA Workshop, June 28-29, 2010,7,United States,To Industry: Responsibility to classify change moved from FDA to industry Allows more changes without prior FDA approval Use of new technologies Manufacturing cost reduction Adequacy of the studies may be questioned months or years later even if the changes are predicted or approved If the validity of AR/CBE/CBE-30 changes is challenged the sponsor may be required to track the affected lots/batches and provide additional data, quarantine or recall product if it is needed Greater liability if the change is not adequately supported,AAPS/CPA Workshop, June 28-29, 2010,8,European Union,The guidelines provide details of the classification of variations into the following 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 documented.,AAPS/CPA Workshop, June 28-29, 2010,9,European Union,From 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 January 1, 2010 according to the new variations system. Marketing authorizations under the Centralized System (CP) Marketing authorizations granted under the Mutual Recognition Procedure (MRP) Decentralized Procedures (DCP) Authorizations granted following a referral,AAPS/CPA Workshop, June 28-29, 2010,10,European Union,National 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,AAPS/CPA Workshop, June 28-29, 2010,11,European Union,National mandatory to follow new guidance January 1, 2010: Belgium, Bulgaria, Denmark, Estonia, Finland, Iceland, Ireland, Italy, Luxembourg, Netherlands, Norway, Slovak Repubic, Slovenia, Spain, Sweden, UK March 2010: Hungary, July 2010: Lithuania, Romania July 2011: Cyprus, France,AAPS/CPA Workshop, June 28-29, 2010,12,European Union,AAPS/CPA Workshop, June 28-29, 2010,13,European Union,AAPS/CPA Workshop, June 28-29, 2010,14,European Union,The variation in question should be quoted using the structure: X.N.x.n “X” refers to the capital letter of the chapter in the Annex to the new guideline where the variation is included (e.g. A, B, C or D) “N” refers to the roman number of the section inside a chapter where the variation is included (e.g. I, II, III) “x” refers to the letter of the subsection inside a chapter where the variation is included (e.g. a, b, c) “n” refers to the number given in the Annex to this Guideline to a specific variation (e.g. 1, 2, 3),AAPS/CPA Workshop, June 28-29, 2010,15,Few Examples,Changes in Formulation,AAPS/CPA Workshop, June 28-29, 2010,16,Few Examples,Changes in Process,AAPS/CPA Workshop, June 28-