Agencija za lekove i medicinska sredstva Srbije Pharmacovigilance System in Serbia: Current Status and Challenges Jović Ivana, M. Pharm. Medicines and Medical Devices Agency of Serbia (ALIMS) TAIEX Workshop on the Implementation of EU Pharmacovigilance Legislation Belgrade, 20 November 2015

Development of National pharmacovigilance (PV) system Legal framework Institutional framework Existing system and achieved results Future plans and challenges Collaboration between National PV Centre and WHO-UMC Overview

History of PV in former Yugoslavia National PV Centre – Clinic „Rebro“ Zagreb, Republic of Croatia - Republic PV Centre – Pharmacy Institute of Serbia (current ALIMS) Member of the WHO Programme for International Drug Monitoring

PV in Serbia National PV Centre - Clinical Centre of Serbia Member of the WHO Programme for International Drug Monitoring Medicines and Medical Devices Agency of Serbia (ALIMS) National Pharmacovigilance Centre (2005)

Law on Medicines and Medical Devices (OG RS No. 30/2010,107/2012) Section 10 Pharmacovigilance Article Rulebook on the method of reporting, collecting and monitoring adverse reactions to medicines (OG RS No. 64/2011) Legal framework Rulebook on immunisation and method of protection by drugs (OG RS, No. 11/2006, 25/2013, 63/2013, 99/2013, 118/2013, 65/2014, 32/2015) In accordance with: EU Directive 2001/83/EC, not with new Directive 2010/84/EU EU Regulation 726/2004, not with new Regulation 1235/2010 VOLUME 9A ICH guidelines

Pharmacovigilance stakeholders PatientsHealthcare professionals Agency – ALIMS (National PV Centre) Ministry of health (Inspection) Marketing authorisation holders (local PV responsible person) PHARMACOVIGILANCE STAKEHOLDERS

ALIMS – Organisation chart ALIMS Pharmacovigilance: National PV centre (12) + Coordinator of PV affairs(1)

8 Sten Olsson. Patient safety in the Balkans. Uppsala Reports 48, January 2010 (available at: “The National centre has now a staff of around ten highly qualified and dedicated professionals. A successful twinning programme with the French regulatory agency, Afssaps, has contributed to a high level of competence and confidence, making the Centre prepared to take on the challenge of joining the European Union pharmacovigilance collaboration once the political processes are completed.” National PV Centre in 2010

5 Medical doctors 7 Pharmacists 1 Technical assistant 2 PhD degree 4 Specialists (of which, 2 have PhD degree) 4 Ongoing specializations National PV Centre in 2015 (STAFF) National PV Centre staff constantly improve knowledge and competence, in order to be fully prepared to take on the challenge of joining the EU PV collaboration.

ALIMS PV ASSESSMENTS AND ACTIVITIES 10 Individual safety case reports (ICSRs) National database - VigiFlow TM ; Submisson to VigiBase ® ; Signal detection Regulatory actions Risk communication (educational programme/ material, DHPC etc) Educational campaigns continuous maintenance and improvement of the national PV system PSUR/PBRER within procedure of marketing authorisations (MA), if available; at regular intervals; within renewals RMP within procedure of MA; renewals; at any point in drug lifecycle Safety variations (changes of MA)

Reporting of adverse drug reactions (ADRs) MAH – local PV responsible person Health professionals Patients ALIMS – National PV centre ICSR assessment: seriousness expectedness causal relationship National database VigiFlow TM

PV Coordinators - PV Network 12  Coordinator for pharmacovigilance (PV coordinator) is a healthcare professional employed in a healthcare institution who performs activities related to the organization and promotion of the implementation of good practice in the collection and reporting on suspected ADRs and communication about the risks of medicinal product use in healthcare institution.  PV coordinator is the contact person of the healthcare institution for the ALIMS in the domain of pharmacovigilance and collaborates with the ALIMS.  All healthcare institution in Serbia should appoint its PV coordinator and inform ALIMS about this.  PV coordinators present our PV network for exchange of safety information.

Coordinators for pharmacovigilance 13 The National PV Network (consists of ~150 coordinators): - established during last renewed 2015 PV coordinator Healthcare professional Healthcare professional Healthcare professional

Reporting form for healthcare professionals 14 Suspected ADRs may be reported: Via Via post Via fax Individualised feedback to reporter

Reporting form for patients 15 Suspected ADRs may be reported: Via Via post Via fax Confirmation message to reporter

Online Reporting for patients and healthcare professionals 16 eReporting module released and maintained by Allows national pharmacovigilance centres to capture ICSRs directly from patients and HCPs into VigiFlow TM Gives pharmacovigilance team more time for verifying the coding and assessing ICSRs eReporting with Interface and help texts translated into Serbian available on since October 2015www.alims.gov.rs

Online Reporting for patients and healthcare professionals 17

Local PV responsible person reporting (Local MAH reporting) CIOMS I form (obligatory) 18 E2B reporting (recommendation) E2B reports uploaded into national database - VigiFlow TM manually by ALIMS PV staff No gateway

Medicines under additional monitoring Medicine contains a new active substance (authorised in the EU after 1 January 2011) Biological medicine, such as a vaccine or a medicine derived from plasma (blood) (authorised in the EU after 1 January 2011) Medicine has been given a conditional approval or approved under exceptional circumstances The company that markets the medicine is required to carry out additional studies, for instance, to provide more data on long-term use of the medicine or on a rare side effect seen during clinical trials

Regulatory actions based on pharmacovigilance data ALIMS May require from the marketing authorisation holders to conduct appropriate measures as part of their risk management system ALIMS May change the conditions of the marketing authorisation ALIMS May adopt a decision to revoke the marketing authorisation or to suspend the marketing authorisation MoH May suspend or prohibit manufacturing and/or marketing of a medicine and/or withdraw a medicine from the market

Results achieved in ICSRs 596 MA 590 Renewals 642 Variations 21 DHPCs 17 addit. risk min. measures 79 Scientific opinions 4 Restrictive actions PSURs +RMPs (administrative review)

ALIMS website Pharmacovigilance Legal framework Patients and public Human medicines Healthcare professionals Marketing authorisation holders

Newsletter 25

ALIMS website – pharmacovigilance Safety information DHPC Annual reports Reporting ADR

ALIMS publications – pharmacovigilance

FUTURE PLANS AND CHALLENGES OF THE NATIONAL PV SYSTEM Transposing and harmonization of latest aquis communitaire related to PV in the new Law on medicines and Rulebook Development of the implementation strategy for the new PV regulations (incorporated in the new Law on medicines and Rulebook) Educational campaigns for healthcare professionals – aiming to increase reporting rate and quality of ICSRs Improvement of AEFI reporting and postmarketing surveillance of vaccines (vaccinovigilance)

29 Collaboration between National PV Centre and WHO-UMC

® VigiBase ® The case reports in the WHO database do not identify the patient or reporter. Its purpose is to provide the evidence from which potential medicine safety hazards may be detected. WHO Global ICSR database; it consists of reports of adverse reactions received from member countries since 1968.

Communicating WHO signals SIGNAL is a newsletter published several times a year by UMC, based on information derived from ICSRs available in VigiBase™ Before signals are published, they are first clinically assessed by pharmacovigilance experts at UMC and then reviewed by the UMC Review Panel Articles in SIGNAL represent varying levels of suspicion resulting from this assessment Primarily intend to inform regulatory authorities

VigiAccess TM VigiAccess TM is a user-friendly interface that allows everyone to search VigiBase ® and retrieve statistical data on the suspected adverse reactions of medicines. To improve patient safety, increase transparency and encourage the reporting of adverse effects from medicinal products, the WHO launched VigiAccess TM (17/04/2015)

VigiAccess TM

Take & Tell

Take & Tell Application

CONCLUSION Continuous development of National pharmacovigilance system supported by permanent international collaboration is necessary to ensure safe and effective use of medicines. Harmonization with New EU PV Legislation and its implementation in our practice is a significant contribution to patient safety in Serbia, and small, but important step in Serbian road to the EU.

Thank you for your attention!