Dr John J Borg Post-Licensing Director 10 th October, 2011

1. Medicines Authority 203,Level 3, Rue D’Argens, Gzira,GZR 1368 Tel: (+356) 2343 9000 Fax: (+356) 2343 9161 Email: info.medicinesauthority@gov.mt Pharmacovigilance Directive Information Seminar Dr John J Borg Post-Licensing Director 10th October, 2011

2. The new EU Pharmacovigilance legislation Why the need for change? •European Commission Assessment Report estimated that: - 5% of all hospital admissions are due to adverse drug reactions - 5% of all hospital patients experience an adverse drug reaction - Adverse drug reactions are the 5th most common cause of hospital death - The legislation is estimated to save 5910 lives per year (Commission document SEC(2008) 2671) €237 Million of public health burden saved per year across the EU and overall cost savings of €145 Million per year to the EU industry sector. (Commission document SEC(2008) 2671) The new EU Pharmacovigilance legislation 2

3. The new EU Pharmacovigilance legislation What is new? • • Clear roles, responsibilities and obligations for the key responsible parties (National Agencies, EMEA, Companies) • • Rationalisation of EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products across the Community with a view in preventing unnecessary patient exposure to risks; • Pharmacovigilance Risk Assessment Committee (PRAC) central to decision making • •Building on the strengths of Risk Management Plans • •Simplification of PSUR reporting The new EU Pharmacovigilance legislation 3

4. The new EU Pharmacovigilance legislation What is new? • Strengthening medicines safety transparency and communication so that the understanding and trust of patients and health professionals in the safety of medicines will improve as well as the penetration of key warnings Greater transparency - medicines web-portals (EU and national) Products subject to ‘additional monitoring’ •Rationalisation of reporting/introduction of patient reporting across EU •Reduction in administration burden/increased work-sharing The new EU Pharmacovigilance legislation 4

5. The new EU Pharmacovigilance legislation What is new? • Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; • Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of Post Authorisation Safety Studies (PASS), together with rationalised single case and periodic reporting of suspected adverse drug reactions (ADRs); • Involvement of stakeholders in pharmacovigilance through direct patient reporting of suspected ADRs and inclusion of patients and heath-care professionals in decisionmaking. • Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 5 The new EU Pharmacovigilance legislation

6. The new EU Pharmacovigilance legislation The EU Pharmacovigilance framework REF: Mcarthy D, http://www.topra.org/sites/default/files/assets/pdf/pharmacovigilance.pdf The new EU Pharmacovigilance legislation 6

7. The new EU Pharmacovigilance legislation Spontaneous Reporting of ADRs • • New Definition of ADRs • A response to a medicinal product which is noxious and unintended. • Now includes: • • Medication errors that result in an ADR • •Uses outside the terms of the marketing authorisation including the misuse and abuse of the medicinal product. • Direct Patient Reporting • For Suspected ARs in Literature the burden for industry has decreased if the product is listed in the EMAs list of monitored products • -Not be required to report the suspected ARs for medicinal products containing the active substances referred to in the list of publications monitored by the EMA. The new EU Pharmacovigilance legislation 7

8. The new EU Pharmacovigilance legislation Spontaneous Reporting of ADRs • • ADR reporting • MAHs and National Agency to report ADRs to Eudravigilance • - serious within 15 days • non-serious within 90 days • –Data from MAHs forwarded to MS where ADR occurred by Eudravigilance • –MS, MAHs and public to have access to EV data The new EU Pharmacovigilance legislation 8

9. The new EU Pharmacovigilance legislation Detailed Description of Pharmacovigilance • • The Detailed Description of Pharmacovigilance in dossiers will now be replaced with a summary of the Pharmacovigilance system. • Replaced by the Pharmacovigilance Master file held at the Head Quarters where the Marketing Authorisation Holders carry out Pharmacovigilance activities. • The impact will be of less type II variations submitted to Agencies for approval. This should decrease costs to industry. • However the Master file will be subject to a PhV Inspection and issue of a certificate (still under discussion at EU level) The new EU Pharmacovigilance legislation 9

10. The new EU Pharmacovigilance legislation Risk Management Plans • Risk Management Plans a pillar in new legislation • All new products to have RMP – clear legal basis. Commission Decisions (following referrals or initial authorisation stage) will specify Conditions of Marketing authorisations that will be legally enforceable (eg Pregnancy Prevention Plans, Post-Authorisation Safety Studies, Post Authorisation Efficacy Studies) • Safety Risks will be identified and listed in Commission decisions • Obligation to monitor effectiveness of risk minimisation – EMA / MS / Company. Commission Consultation: http://ec.europa.eu/health/human-use/pharmacovigilance/developments/index_en.htm The new EU Pharmacovigilance legislation 10

11. The new EU Pharmacovigilance legislation Periodic Safety Update Reports •No longer required for many generic and traditional herbal medicinal products (can be requested on the basis of p’vigilance concerns) •Periodicity of Data Lock Point will be established by EMA (already published on the Heads of Agencies Website). •Will be submitted electronically to EMA •Emphasis on risk-benefit evaluation with line listings no longer required routinely •Worksharing principles will apply for procedures and One common assessment report and decision will be issued •EMA will send PSUR assessment reports to MAH (once repository is established) Commission Consultation: http://ec.europa.eu/health/human-use/pharmacovigilance/developments/index_en.htm The new EU Pharmacovigilance legislation 11

12. The new EU Pharmacovigilance legislation More Transparent Information Member States to make following available through web-portals •PARs, SPCs and PILs - www.maltamedicineslist.com •Summary of national RMPs •‘Additional monitoring’ list •Information/forms for ADR reporting MAHs obliged to transmit information on authorised medicinal products in all EU Member States to Eudravigilance Medicinal Products Dictionary in line with Article 57, paragraph 2, second sub-paragraph of Regulation (EC) No 726/2004 Ref: EMA/505633/2011 : Legal notice on the implementation of Article 57(2), second subparagraph of Regulation (EC) No. 726/2004 http://www.ema.europa.eu/docs/en_GB/document_library/Other/2011/07/WC500108212.pdf The new EU Pharmacovigilance legislation 12

13. The new EU Pharmacovigilance legislation What does the new legislation mean for industry Decreased PSUR submissions for generics and well established used medicinal products Single assessment report issued on safety issues Electronic reporting only once to the EMA for Post authorisation studies and PSURs instead of multiple reports sent to all MSs Replecement of Detailed description of Pharmacovigilance with a system master file; decreasing type II variations being submitted. ADRs need to be transmitted electronically to Eudravigilance and the scope has extended. RMPs transmitted to EMA electronically only once. MAHs to transmit information on authorised medicinal products in all EU Member States to Eudravigilance Medicinal Products Dictionary The new EU Pharmacovigilance legislation 13

14. The new EU Pharmacovigilance legislation Further Information Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use. (Official Journal L 348, 31/12/2010, p. 74 - 99). http://ec.europa.eu/health/files/eudralex/vol-1/dir_2010_84/dir_2010_84_en.pdf Commission Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance of medicinal products for human use, Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products. (Official Journal L 348, 31/12/2010 p. 1 - 16). http://ec.europa.eu/health/files/eudralex/vol-1/reg_2010_1235/reg_2010_1235_en.pdf Commission Consultation: Implementing measures in order to harmonise the performance of the pharmacovigilance activities provided in Directive 2001/83/EC and Regulation 726/2004/EC http://ec.europa.eu/health/human-use/pharmacovigilance/developments/index_en.htm The new EU Pharmacovigilance legislation 14

15. Thank You