1. PharmacoVigilance: Development of PhV systems and processes VICH Workshop, Dar Es Salaam, Tanzania, 24 June 2015

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 Different levels of PhV systems > 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

4. 4 Developing the PhV system > Draft legislation framework for PhV (avoid details) > Plan PhV-system in competent authority: responsibility, level of ambition, cooperation in region, practical work, etc > Define responsibilities and obligations of companies > Align with international definitions > Consult draft plans with stakeholders – companies and vets > 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

5. 5 Implementing the PhV system > Training? > Communication and awareness plan 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 > Data input management > Start analysing across substances, products, species > Consider using a risk-based approach, where the surveillance intensity is proportional to the expected risk level

6. 6 1. PhV requirements in legislation > 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.

7. 7 2. Plan PhV-system in authority > 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, product group analysis and request corrective actions

8. 8 The responsibility of the authority > To establish a PhV system: collect information evaluate scientifically collate with data on use monitor compliance of companies do inspections 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 Spread the PhV-understanding > 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

10. 10 Filing system for AE-reports > 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

11. 11 EU experience > Pharmacovigilance system based on Spontaneous reports PHV Database and product database 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 2015: The EU legislation is currently under revision, also concerning pharmacovigilance requirements)

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 Practical approach in national agency: spontaneous AE-reports Immediately after AE-report is received: > Apply 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)

14. 14 Practical approach in national agency: PSURs > 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 regional products (i.e. EU region) Agreement on fixed data lock-points per substance Letter to company: OK, or occasionally changes in the product information/leaflet, or further investigation requested.

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 Other PhV information exchange between authorities > 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

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

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