Requirements of EU pharmacovigilance legislation for distributors Julia Sipos Quality Management Director Pharmacovigilance coordinator Version 03

Pharmacovigilance Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem (Guideline on good pharmacovigilance practices –GVP - Annex I – Definitions) Version 01

Objectives Today’s work supports tomorrow’s safety Pharmacovigilance activities provide more information on the pharmaceuticals as during clinical investigations limited information can be gained some impacts may become known in long term only real environment of use may be different from that of the clinical investigation free flow of and access to information on pharmaceutical safety room for necessary measures to be taken by MAH useful information to required risk assessment Version 01

Tools and scope Tools to achieve the objectives Scope continuous collection all available information share the information gained: report adverse events to the EU database (according to law) Scope Distributed pharmaceuticals where Institute of Isotopes is the MAH (however other MAHs can have similar requirements) Version 01

Definitions Signal Adverse event (AE) Science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem Adverse event (AE) Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment Version 01

Definitions Adverse (drug) reaction (ADR) A response to a medicinal product which is noxious and unintended Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility Adverse reactions may arise from use of the product within or outside the terms of the marketing authorisation or from occupational exposure. Conditions of use outside the marketing authorisation include off-label use, overdose, misuse, abuse and medication errors. Version 01

Definitions Serious adverse event (SAE) An adverse reaction which results in death, is life-threatening, requires in-patient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly/birth defect. Life-threatening in this context refers to a reaction in which the patient was at risk of death at the time of the reaction; it does not refer to a reaction that hypothetically might have caused death if more severe. Version 01

Abbreviations MAH: Marketing Authorization Holder – in this case: Institute of Isotopes QPPV: Qualified person for pharmacovigilance SDEA: Safety Data Exchange Agreement CIOMS (form): Council for International Organizations of Medical Sciences - form for Suspect adverse event report Version 01

Types of adverse events Diagram shows the relationships of adverse events, serious adverse events that can be unexpected and drug related Yellow part shows cases to be reported to the EU database Version 01

The legal framework of pharmacovigilance for medicines marketed within the EU/1. Basic Regulation (EC) No 726/2004 with respect to centrally authorised medicinal products (laying down own Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency) Directive 2001/83/EC with respect to nationally authorised medicinal products (including those authorised through the mutual recognition and decentralised systems) (on the Community code relating to medicinal products for human use) Version 01

The legal framework of pharmacovigilance for medicines marketed within the EU/2. Additional Commission Implementing Regulation (EU) No 520/2012 includes details in relation to certain aspects of pharmacovigilance to be respected by marketing authorisation holders, national competent authorities and EMA (on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council) Good pharmacovigilance practice guidelines(GVP) released by EMA in order to facilitate the performance of pharmacovigilance activities. (These GVP modules replace Volume 9A) Version 01

The legal framework of pharmacovigilance for medicines marketed in 3rd country. -2001/83 The MAH shall strive to collect any safety information from 3rd countires (out of EU Community Territory and inform the relevant Agencies, stakeholders accordingly. Legal background: EC. (Art 104, paragraph 1 and 4) - (EC) No 726/2004 Good pharmacovigilance practice guidelines(GVP) released by EMA in order to facilitate the performance of pharmacovigilance activities. (These GVP modules replace Volume 9A) If regional or local regulations conflict with international guidelines, the stakeholders should follow a conservative approach (i.e., the aim is to be able to comply with the strictest regulation). Version 01

Requirements for distributors/1. To be familiar with relevant requirements of EU legislation on pharmacovigilance To be familiar with their national legislation on pharmacovigilance Share with MAHs the following information as a minimum: national requirements for pharmacovigilance access data of person responsible for receiving all incoming information on drug safety (adverse reactions): name, e-mail, phone number, address. Any changes in these data shall be reported immediately to the MAH’s QPPV. Version 01

Requirements for distributors/2 Conclude a SDEA with the MAHs – covering in detail all co-operation activities tasks and responsibilities of the parties in terms of pharmacovigilance Continuous screening of domestic professional literature for any safety issues of the distributed pharmaceuticals – report any signals to MAHs Version 01

Requirements for distributors/3 Encourage their partners (health institutions and/or health care professionals and/or patients as applicable) to report all information on drug safety For this purpose: share contact data with their partners provide information on the 4 necessary (minimum) data to MAH – see next slide forward all information arriving from the MAH to their partners in this issue in due time inform their partners on further fate of their reported signals or adverse/pregnancy events Version 01

Requirements for distributors/4 Information may arrive from patients/their relatives or healthcare professionals Collect and provide all follow-up information if required by MAH additional data related to the reported case answer on authorities’ requests Meet time frames required by MAH for Pharmacovigilance information must not be made public Version 01

Reporting to MAH Report At least four basic data shall be included signals, adverse or pregnancy event information to the MAH’s QPPV immediately via e-mail or fax using free text or phone or using CIOMS form (Can be downloaded from: http://www.cioms.ch/) At least four basic data shall be included data of the reporter (name, address, access data, e.g. e-mail address or phone number) patient data (monogram or identification code, date of birth or age, sex) at least one suspected pharmaceutical at least one suspected adverse event Version 01

Special cases Institute of Isotopes (IoI) is distributor of a product of another MAH In case of incoming event report the same information should be sent to that MAH as in case of IoI’s product and please send to IoI as well for information if no contact is available to the MAH, send the information to IoI Version 01

Contacts at IoI Pharmacovigilance Coordinator (connection to QPPV) Sipos, Julia e-mail: gyogyszerbiztonsag@izotop.hu phone: +36-1- 391-0900 mobile: +36-30-991-0468 (available 24 hours/day) Version 01

Contact us in case of any questions! THANK YOU FOR YOUR ATTENTION! Version 01