1. PharmacoVigilance: Development of PhV systems and processes

2. 2  Systematic surveillance of all authorised veterinary medicinal products  Ensure safe and effective products on the market  Fast and proportional action on signals from data analysis  Active crisis management with good and open communication The goal of pharmacovigilance:

3. 3 Estimate the need and expectation depending on Existing PhV system or starting new Financial and personnel resources Size of country or region Husbandry production and medicinal use Cooperation with other authorities Legislation Different levels of PhV systems

4. 4 Steps 1.Draft legislation framework for PhV (avoid details) 2.Plan PhV-system in competent authority: responsibility, level of ambition, cooperation in region, practical work, etc 3.Define responsibilities and obligations of companies 4.Consult draft plans with stakeholders – companies and vets 5.Establish necessary documentation and systems Reporting form for adverse events (AE) Filing system for AE-reports: Paper  small electronic system  database Tools for analysis of data; signal detection; trend analysis; trigger thresholds Operating procedures Feedback communication Developing the PhV system

5. 5 Communication and awareness plan Training? Make companies and vets aware of their obligations Set deadline for companies to implement in-house systems and procedures (compliance) Spread the PhV-understanding to vets/users/owners Standard reporting form available on website, paper, by telephone, on conferences, etc Start analysing across substances, products, species Consider using a risk-based approach, where the surveillance intensity is proportional with the expected risk level Implementing the PhV system

6. 6 Definitions of adverse events, scope of PhV, surveillance, timelines ~ (VICH GLs) Obligation for companies to receive AE-reports from vets/users/owners analyse the AE-reports and survey their products in general inform authorities. Possibility for authorities to inspect or control that companies comply analyse data from PhV or other sources take necessary actions based on PhV. Possibility/obligation for vets/users/owners to report directly to authorities. 1. PhV requirements in legislation

7. 7 Define PhV-responsibility (who does what) Realistic ambitions Aim for regional cooperation if possible, because large-scale PhV-data are more useful and work-sharing between authorities is beneficial The company should be responsible for the PhV surveillance and PhV reporting of their products The authority should perform controls and request corrective actions 2. Plan PhV-system in authority

8. 8 8 The responsibility of the authority  To establish a PhV system: o collect information o evaluate scientifically o collate with data on use o monitor compliance of companies o do inspections o take action  Initiate assessment of safety concerns  Define risk management measures or implement conditions and restrictions on products  Encourage reporting of adverse events by vets/users/owners  Communicate safety concerns and mitigation measures

9. 9 Encourage reporting: Receipt letter to vets/users/owners, (and companies) who have reported AEs Personal response to a few reporters if additional information is needed Annual PhV-report in Vet magazine PhV-presentation for all graduating vets Education: module on PhV in vet university Ad-hoc presentations at vet conferences and Industry association meetings AE-reporting form easily available Spread the PhV-understanding

10. 10  From paper  small electronic system  database  Simple (vet-specific) database with international compatibility is preferable  Tools for analysing data in the database are VERY important!  There are hurdles for a large regional/international database, for example: IT-compatibility for existing national databases Product database (same product with different names must be ”linked”) Who is responsible for analysing data ”Access to data”-agreements Filing system for AE-reports

11. 11 Pharmacovigilance system based on Spontaneous reports PSURs – Periodic Safety Update Reports (defined reporting dates) Signal detection in database Follow-up and changes to product information when necessary PhV inspections Information to vets, users and owners about safe use of products, which is what PhV is really about! (footnote 2014: The EU legislation is currently under revision, also concerning pharmacovigilance requirements) EU experience

12. 12 EU-Pharmacovigilance scope  Animal safety serious and non-serious adverse reactions  Lack of expected efficacy  Off-label use / misuse  Humans reacting after exposure  Violations of residue levels  Potential environmental problems

13. 13 Immediately after AE-report is received:  case-number and letter of receipt  causality assessment by Agency-vet  decision on action/no-action, or request more information, etc  PhV-report forwarded to Company NB: Protection of personal data of reporter/owner may be required  Filing in national and/or in EU database (at EMA) Practical approach in national agency: spontaneous AE-reports

14. 14  Periodic safety update reports (PSURs) are received from the companies in a periodic schedule, or on request includes all AE-reports and other PhV-information since last PSUR and a benefit-risk evaluation for the product Received and assessed for national products Work share for EU-products (i.e. regional) Agreement on fixed data lock-points per substance Letter to company: OK, or occasionally changes in the product information/leaflet, or further investigation requested. Practical approach in national agency: PSURs

15. 15 Minimal requirements of an AE report Identifiable reporter Animal (species) Suspected product Adverse event  However, many more details are desired and possible to fill in to the database/reporting form

16. 16  Rapid Alert (EUDRANET = Secure intranet system between all EU authorities): sent to all member states, if urgent actions are needed  Non-Urgent Information System: to share and discuss specific trends or cases between member states Other PhV information exchange between authorities

17. 17 Reference documents (EU) Regulation (EC) No 726/2004 (Title III Chapter 3) and Directive 2001/82/EC (Title VII) Volume 9 (b) – Guidelines on Pharmacovigilance for Medicinal Products for Veterinary Use. http://ec.europa.eu/health/files/eudralex/vol-9/vol_9b_2011- 10.pdf http://ec.europa.eu/health/files/eudralex/vol-9/vol_9b_2011- 10.pdf (footnote 2014: The EU legislation is currently under revision, also concerning pharmacovigilance requirements)