Pharmacovigilance System - EU

Transcription

1 Pharmacovigilance System - EU Rechtsanwalt Prof. Burkhard Sträter Sträter Rechtsanwälte Kronprinzenstraße 20 Fon: +49 (0) mail@straeterlawyers.de D Bonn Fax: +49 (0)

2 Pharmacovigilance Legal framework Reg. 726/2004/EC Community MA as amended by Dir. 2001/83 EC other MA and Com. MA Regulation (EC) 1235/2010 Directive 2010/84/EU 2

3 Pharmacovigilance GVP PV System Art. 104 MA shall operate PV System Performance of good vigilance practice ( 63a AMG 15. Novelle) ~ Art. 104 para 1, Art. 104 para 3 Content of PVS Art. 1 para. 28 d Definition of PV System Art. 8 para. 3 (ia) Summary of PVS - short version of PVS Masterfile for the MA application 3

4 Pharmacovigilance System (PVS) Art. 104 MA operates a PVS Content para. 3 - QPPV - PVS Masterfile - RMS for each product - monitor outcome of measures - RMP - permanent assessment of risk benefit 4

5 Pharmacovigilance system (PVS) Art. 1 para. 28 d - Definition of PV System: Pharmacovigilance system: a system utilized by marketing authorisation holders and by Member States to fulfil the tasks and responsibilities listed in Title IX and designed to monitor the safety of authorised medicinal products and detect any change to their riskbenefit balance. 5

6 PV System Masterfile (PVS-MF) Art. 1 para. 28 e - Definition of PVS-MF: Pharmacovigilance system masterfile: A detailed description of the pharmacovigilance system utilized by the marketing authorisation holder with respect to one or more authorised medicinal products. It s company related!! MF has to be at the disposal of the MAH and will be checked in case of inspections. 6

7 Transitional Provisions Masterfile PVS MS Art. 2 No. 1 MA granted before after renewal or Expiry of 3 years starting which ever is earlier 7

8 Risk Management System (RMS) Art. 104 para. 3 lit c As part of the PVS, the MAH shall be required to: (c) operate a risk management system for each medicinal product; It s product related!! Art. 104 a defined exceptions 8

9 Risk Management System (RMS) Art. 1 para. 28 b: Risk management system: a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including the assessment of the effectiveness of those interventions. 9

10 Risk Management System (RMS) Art. 104 a para. 1 RMS mandatory para. 2 Exceptions para. 3,4 further requirements of NCA 10

11 Risk Management Plan (RMP) Art. 104 para. 3 lit d As part of the PVS, the MAH shall be required to: (d) monitor the outcome of risk minimization measures which are contained in the risk management plan or which are laid down as conditions or requirements in the marketing authorisation pursuant to Articles 21a, 22 or 22a; 11

12 Risk Management Plan (RMP) Art. 1 para. 28 c Definition: Risk Management Plan: a detailed description of the RMS 12

13 RMP RMS PVS RMP is part of the RMS, which is part of the PVS!! The PVS is company related! The RMS and RMP are product related! 13

14 Pharmacovigilance - GVP - in DRA-Procedures: RMP clear legal base Art. 21 a Conditions: PASS Special ADR-Reporting any other conditions or restrictions with regard to safety Deadlines for fulfilment No Commitment required any longer! 14

15 PA Safety Efficacy - Study after MA is granted PASS Art. 22 a para. 1 a PAES Art. 22 a para. 1 b NCA or EMA impose obligation in writing when duly justified If the same concern applies to more than one MP Encouragement of joined PASS 15

16 Art. 1 para. 15 PASS Definition PASS: Any study relating to an authorised MP conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the MP or of measuring the effectiveness of risk management measures No definition of PAES! 16

17 PASS Supervision Chap. 4 PASS: Initiated by MAH Chap. 4 Art. 107 m, n, o, p 107 m General requirements, payments, etc. 107 n Written endorsement of PRAC or NCA para 3 within 60 days before commencement! 17

18 PASS Supervision Chap o Endorsement by PRAC or NCA of substantial amendments 107 p Final study report 12 months after end of data collection 107 q Consequences Measures of PRAC or NCA Publication PV-WEB 18

19 PV Additional monitoring Art. 23 Reg. (EC) 726/2004 EMA publishes list of MPs concerned Five years duration of monitoring Link to SmPC + RMP Black symbol referred to in Art. 23 Art. 106 d - published on Web Portal EMA 19

20 PV Labelling Art Art. 23 para 5 Reg. (EC) 726/2004 This MP is under additional monitoring preceded by the black symbol referred to in Art. 23 Reg. (EC) 726/2004 Triangle Proposal PRAC not yet available 20

21 PV Labelling Art. 59 No black box! Description of ADRs and measures Additional monitoring Asking patients to communicate ADRs Jan 2013 Report on shortcomings and improvements of SmPC + PIL 21

22 PV Web portal - EMA Art. 26 Reg. 726/2004/EC Content for example: - Members of Comittees - Minutes of the meetings - RMPs - MPs under additional monitoring - EU-AMIS - Templates for reporting - Outcome of PASS s - PV-Procedures Art. 107i ff. - Assessments and Decisions Art. 106 Directive 2001/83/EC Web portals of NCA linked to EMA Web portal 22

23 PV ADR-Reporting Art. 107 para. 3, Art. 28 Reg. (EC) 726/2004 Adressee: EMA Eudravigilance Database not NCA but Gateway to NCAs Cave: Transitional provisions! Deadlines: all serious 15 days all non serious 90 days Occurence: EU + 3rd countries all serious! EU only all non serious - irrespective of expectance! 23

24 PV ADR-Reporting Literature: EMA-Assessment for listed MPs pursuant to Art. 27 Reg. 726/2004 EMA Art. 107 para. 3 so far no reporting obligation All other MPs + journals MAH 24

25 Transitional Provisions ADR-Reporting Art. 2 No. 3 Dir. 2010/84/EC 107 (3) as amended shall apply 6 months after Functionalities of the database are established and have been announced by the Agency via Art. 28 Reg. (EC) 1235/2010 ~ CMA?! 25

26 Transitional Provisions ADR-Reporting Until Agency can ensure functionalities: All serious, even expected ADRs NCA on whose territory the case occured Art. 2 No. 4 All non serious, even expected ADRs as usual up till now to NCA However, NCA may require 90 days reports Art. 2 No. 5 NCAs report to EMA Art. 2 No. 6 26

27 Eudravigilance database EMA Art. 24 Reg. 726/2004/EC: Content: para. 2 ADRs, overdose, misuse, medication errors, studies Access: para. 2,3 NCA MAH limited? Healthcare professionals and public limited! to what extent? Publicly accessible in aggregated format?! 27

28 PSUR Assessment Art 107 d + e National CA more than one MA a single assessment Com. MA PRAC Rapporteur National + Decentral CMD(h) RMS Art. 28 Com. MA PRAC Art. 107 b + c analogue Art. 107h EMA Monitoring ADRs 28

29 Transitional Provisions PSUR Report to EMA Single Assessment by PRAC or RMS Until Agency can ensure the functionalities agreed for the repository of PSURs MAH shall submit to NCA, where the MP is authorised via Art. 28 Reg. (EC) 1235/2010 ~ CMA!? 29

30 Urgent Union Procedure - UUP Art. 107 i - l RL 2001/83/EC Art. 107i para. 1 Art. 107j para. 1 para. 2 Art. 107k Start Info Agency Preliminary national measures requested by EU-Commission Announcement in Web Portal Assessments 30

31 Urgent Union Procedure UUP Art. 107 k Procedure PRAC para. 1 public announcement request information of stake holders para. 2 public hearing possible para days PRAC procedure 31

32 Urgent Union Procedure UUP Art. 107 l PRAC Opinion nat. / decentral para. 1 CMD(h) Central (at least one) para. 3 CHMP 32

33 Urgent Union Procedure UUP Art. 107 l nat. / decentral Para. 2 CMD(h) central Para. 4 CHMP Consensus: if fails (-) Commission decision (+) Nat. Transformation EMA Publication of assessment Art. 107 m 33

34 Vielen Dank für Ihre Aufmerksamkeit. Rechtsanwalt Prof. Burkhard Sträter Sträter Rechtsanwälte Kronprinzenstraße 20 Fon: +49 (0) D Bonn Fax: +49 (0)