Overview of the new process for Signal Detection and Managem ent - PowerPoint PPT Presentation

Overview of the new process for Signal Detection and Managem ent PCW P and HCPW P joint m eeting 2 5 February 2 0 1 4 Presented by: Georgy Genov EMA/ Inspections & Human Medicines Pharmacovigilance Division An agency of the European Union

Agenda for presentation • EU Pharmacovigilance Legislation • Overview of Signal Management Process • Pharmacovigilance Risk Assessment Committee • Trends in requests for access to information/ documents • Transparency • Summary 1 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Main pillars of the new EU PV Legislation Proactive and proportionate risk m anagem ent Higher quality of safety data Strengthened transparency, com m unication and patient involvem ent Stronger link betw een safety assessm ents and regulatory action Clear tasks and responsibilities for all parties ( m arketing authorisation holders, com petent authorities, EMA) I m proved EU decision-m aking procedures ( harm onised decisions and efficient use of resources) Establishm ent of the Pharm acovigilance Risk Assessm ent Com m ittee 2 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

New EU PV Legislation: four topic areas 1 . Collection of key inform ation on m edicines: 2 . Better analysis and understanding of • Risk Management Plans (RMPs) data and inform ation: • Periodic Safety Update Reports (PSURs) • EudraVigilance and signal detection • Post-authorisation safety and efficacy studies • Additional Monitoring (PASS/ PAES) • IT systems to support processing and • Electronic submission of core medicine analysis of data information by pharmaceutical industry • Reporting by patients 3 . Regulatory Action to safeguard public 4 . Com m unication w ith stakeholders: health: • Online publishing of information • Scientific committees and decision-making • Coordination of safety messages • Strengthening referral procedures • Public hearings 3 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Those directly involved in Pharm acovigilance Pharmaceutical companies and companies Healthcare professionals importing and/ or working with medicines distributing the medicines Patients who use the medicines European Medicines Agency coordinating the Regulatory Authorities and Member States EU's safety-monitoring and responsible for monitoring the medicines Pharmacovigilance for medicines 4 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Definition of a Signal “Information that arises from one or multiple sources (including observations and experiments), which suggest a new potentially causal association , or a new aspect of a know n association , between an intervention and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action ” Report of Council for International Organisations of Medical Sciences WG VIII Practical Aspects of Signal Detection in Pharmacovigilance (CIOMS, Geneva 2010) 5 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Sources of inform ation Spontaneous ADR reporting systems Clinical trials data Pharm acovigilance Pharmacoepidemiological studies Scientific literature Non clinical trial data e.g non- interventional studies 6

I CSR reporting pre- and post new PV legislation 7 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Proportion of I CSR reporting pre- and post new PV legislation Pre Leg After Leg 8 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Signal Detection, Validation & Confirm ation How do we review EudraVigilance data? Statistical analysis Validation Signal m eeting Confirm ation • Clinical relevance: exposure, temporal Clinical review association, plausible mechanism, de/ re- of individual challenge, severity of reaction and outcome; case safety novelty of reaction reports • Previous awareness (SmPCs/ PL; PSURs) • Other relevant sources (literature, experimental findings) 9 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

European Pharm acovigilance I ssues Tracking Tool ( EPI TT) • All validated signals are entered into EPITT by the authority who detected and validated it • Validated signals undergo further analysis and are either: CONFI RMED NOT CONFI RMED Added to agenda for the Justification to be provided as to Pharmacovigilance Risk why signal is not confirmed Assessment Committee (PRAC) 10 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Signal Managem ent Process Exchange of inform ation Signal Signal Exchange of Signal Signal Signal Signal Analysis and Recom m endation inform ation and Assessm ent Confirm ation Detection Validation Prioritisation for action im plem entation EMA EMA PRAC All stakeholders MAHs MSs MSs 11 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Trends in Adverse • Update SmPC/ PIL (# signals discussed • Referral at PRAC; 43 detected • PASS Event reports and by EMA) • MA varied, suspended… 100 signals in 2 0 1 3 (# of signal evaluated and ( Jan – Dec) discussed yearly at 2,449 P-PH-SMA team level) (# of medical terms reviewed 980,000 yearly by P-PH-SMA) (# of ICSRs received per year in EV – European database of 1,200,000 suspected adverse drug reaction reports) Adverse Reactions reported by: Patients, HCPs, Pharmaceutical companies 12 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Source of all signals evaluated by EMA in 2 0 1 3 ( n= 2 4 4 9 ) 13 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Therapeutic area of all 2 0 1 3 PRAC signals ( n= 1 0 0 ) 14 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

EMA shall make public on the European medicines web-portal a list of active substances/ medicinal products and the authority (lead Member State, co-lead Member State or the Agency) responsible for their monitoring in EudraVigilance 15

Pharm acovigilance Risk Assessm ent Com m ittee ( PRAC) Responsible for assessing and monitoring safety issues for human medicines 16 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

HCP and patient representatives 17 Presentation title (to edit, click View > Header and Footer)

PRAC recom m endations for action  No need for further evaluation or action at this point in time  Request for additional data to be submitted: • Monitor any relevant emerging information on the signal as it becomes available • Address the signal in the following PSUR or submit an ad-hoc PSUR • Submit additional data (such as cumulative review) • Collect further information or perform additional analyses in EudraVigilance or other data sources • Conduct a post-authorisation safety study  Need for regulatory action: • The product information and/ or RMP should be updated through a variation • The Member States or the Commission, should initiate a referral procedure • Urgent safety restrictions should be imposed  A Pharmacovigilance inspection should take place 18 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Outcom es of signals validated by EMA in 2 0 1 3 ( n= 4 3 ) 19 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Exam ple of signal analysis, prioritisation and assessm ent of recent signal discussed at PRAC 4 . Signals assessm ent and prioritisation 4 .1 . New signals detected from EU spontaneous reporting system s 4.1.9. Sunitinib - SUTENT (CAP) • Signal of cholecystitis Labelling Status: for initial discussion change w ith Sections 4 .4 Regulatory details: and 4 .8 of PRAC Rapporteur: Carmela Macchiarulo (IT) Sm PC updated Recom m endation( s) : 20 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Som e exam ples of signals discussed at PRAC Adalimumab - Missed dose due to m alfunction of the pre-filled pen device Leuprorelin - Medication errors (wrong technique in drug usage process) Clopidogrel - Eosinophilic pneum onia * Docetaxel - Serious/ fatal drug interactions * Bevacizumab - Anaphylactic shock Roxithromycin - Hearing disorders * Temozolomide - Hepatic failure * Ticagrelor - I nteraction with grapefruit juice * Cinacalcet - QT prolongation/ ventricular arrhythm ias * * Represents those resulting in labelling changes 21 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Requests for EudraVigilance data analyses: Type of requester ( 2 0 1 1 - 2 0 1 3 ) 22 EMA Human Scientific Committees' Working Party with PCWP & HCPWP

Transparency • Publication of data on ADRs • Currently only for CAPs • Aim to extend to NAP 23

Highlights Highlights Agenda PRAC CHMP PRAC wk1 wk2 wk3 wk4 wk1 CHMP PRAC Minutes from Publication of PRAC previous PRAC recommendations 24

Publication of PRAC agendas and m inutes 25

Publication of PRAC recom m endations – first publication October 2 0 1 3 26 EMA Human Scientific Committees' Working Party with PCWP & HCPWP