Variations AGES MEA-LCM-QUAL. Mag. Caroline Kleber. Meet the Case Manager Vienna,

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1 Mag. Caroline Kleber Meet the Case Manager Vienna, AGES MEA-LCM-QUAL

2 Regulatory Background Commission Regulation (EC) No 1234/2008, amended by No 712/2012 Guidelines of on the details of the various categories of variations, on the operation of the procedures laid down in Chapers II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 25 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted persuant to those procedures C (2013) 2804 CMDh Best Practice Guides (BPGs) for the Submission and Processing of Variations in the Mutual Recognition Procedure, CMDh/CMDv Q & A, 2

3 Classification of Variations Minor variations of type IA: Do and Tell minimal impact, or no impact at all on the quality, safety or efficacy of the medicinal product concerned Type IAin: Notification immediately after implementation Type IA: Notification within 12 months within 30 days following receipt CA takes appropriate measures ( Acknowledgement of an acceptable notification ) 3

4 Classification of Variations Major variations of type II: Tell and wait for Approval before Implementation significant impact on quality, safety or efficacy of the medicinal product concerned Prior approval necessary Extension of a marketing authorisation a Variation which is listed in Annex I 4

5 Classification of Variations Minor variation of type IB: Tell, Wait and Do neither a minor variation of type IA nor a major variation of type II nor an extension if 30 days following acknowledgement of receipt of a valid notification CA has not sent unfavourable opinion, notification is deemed accepted. 5

6 Grouping Article 7: Grouping of Variations IAs of one or more marketing authorisations owned by the same holder Several variations of the same marketing authorisation according Annex III Several Variations of the same marketing authorisation not inaccordance with Annex III but Agency agrees National: Grouped applications only in one member states, otherwise worksharing One or several variations to several purely national MAs in one MS Facilitate review and reduce administrative burden 6

7 Worksharing Article 20: Worksharing procedure Type IB, Type II, Grouping to several MA owned by the same holder National: Type IB, Type II, Grouping to one MA owned by the same holde in more than one member states Assessment report will always be prepared avoid duplication of work 7

8 Guideline of A. Administrative changes B. Quality changes I. Active Substance a) Manufacture b) Control of active substance c) Container closure system d) Stability e) Design Space and post approval change management protocol II. Finished Product a) Description and composition b) Manufacture c) Control of excipients d) Control of finished product e) Container closure system f) Stability g) Design Space and post approval change management protocol h) Adventitious Agents Safety 8

9 Guideline of III. CEP/TSE/monographs IV. Medical Devices V. Changes to a marketing authorisation resulting from other regulatory procedures a) PMF/VAMF b) Referral c) Other changes to the quality dossier requested by the competent authority C. Safety, Efficacy, Pharmacovigilance changes I. Human and Veterinary medicinal products II. Veterinary medicinal product specific changes D. PMF/VAMF 9

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11 Unforseen Variation TYPE IB unforseen a type IB variation where a z category is ticked and which has not been classified as z -category following Article 5 recommendation Article 5: Recommendation of unforseen variation holder may request a recommendation on the classification of the variation CMDh Recommendation for classification of unforeseen variations according to Article 5 of Commission Regulation (EC) No 1234/

12 Editorial changes GL: Changes to a Marketing Authorisation: Addition, Replacement, Deletion of Data Variation necessary Editorial Changes: - no separate Variation necessary - can be included in a Variation - clearly identified in the Application form - Justification as why to consider editorial 12

13 Editorial changes Q&A 3.16: Under which classification category can editorial changes be submitted? Editorial changes of the SmPC, updates in line with QRD, etc. without changing the content included in TYP IB, TYP II under Chapter C Modul 3,4,5 see EMA Guidance CMDh/CMDv: Q&A List for the submission of variations according to Commission Regulation(EC) 1234/

14 Editorial changes EMA: Human post-authorisation Q&A 4.1. What can be considered an editorial change and how can it be submitted as part of a type IA/IB/II variation? Editorial: adding headers, reordering of existing information, grammar/orthographic corrections Not considered editorial changes: removal of specification parameters or manufacturing description, update of information to bring the dossier in line with the current manufacturing process, etc. Included in sections up to the fourth level of the ectd: Variation in 3.2.S.2.1 editorial changes in 3.2.S.2.1 to 3.2.S

15 Examples for correct submissions Application Form Precise Scope and Background State changes Explanation why change is required Justificiation for Grouping Justification for Classification of Type IB if z category is ticked Present/Proposed Table Precise present and proposed content EMA/CMDh Explanatory notes on variation application form 15

16 Examples for correct submissions Q&A 3.4: Update of an ASMF/Modul 3.2.S Grouped variation according to the highest type of single change Substantial changes: B.I.z Type II Present/Proposed section filled out completely CMDh/CMDv: Q&A List for the submission of variations according to Commission Regulation(EC) 1234/

17 Examples for correct submissions Submission of Updated CEPs (Classification Category B.III.3) Each CEP Update submitted as variation scope More than one CEP version - Grouping Revisions of CEPs can be omitted Confirmation that the substance form the omitted CEP Version was not used in the FP during validity of this CEP EMA: Human post-authorisation Q&A (2.4) 17

18 Examples for correct submissions Brexit: Batch releaser New summary of Pharmacovigilance system Change in name Grouping possible CMDh/CMDv Examples of acceptable and not acceptable groupings for MRP/DCP Products 18

19 Examples for correct submissions New finished product bulk manufacturing site Changes in manufacturing process Changes in batch size Changes in in-process controls to adapt to the new manufacturing site settings Single type II under B.II.b.1 (clearly identified in the Application form) Changes in Excipients, specification parameters, container closure system Additional scopes in a grouped application CMDh/CMDv Examples of acceptable and not acceptable groupings for MRP/DCP Products 19

20 Examples for correct submissions Update Dossier in preparation of a RUP/MRP: Changes or addition of Braille, User Test, ERA, summary of pharmacovigilance system, RMP, QPs declaration, updated confirmatory stability data, updated clinical and non-clinical overviews, summaries or Expert reports based on already submitted or approved data C.I.z TYP II CMDh/CMDv: Q&A List for the submission of variations according to Commission Regulation(EC) 1234/2008 (4.12) 20

21 Examples for correct submissions QP Declarations New active substance manufacturer: QP Declarations from each finished product manufacturer and batch release sites New finished product manufacturer (no batch release): QP Declaration from the new finished product manufacturer (if located in the EU/EEA) QP Declaration from at least one batch release sites CMDh Questions & Answers QP Declaration 21

22 Questions? 22

23 Mag. Caroline Kleber MEA LCM - QUAL BASG - Austrian Federal Office for Safety in Health Care Traisengasse Vienna T : +43 (0) Caroline.Kleber@ages.at