Pharmaco Vigilance Development of Ph V systems and

Pharmaco. Vigilance: Development of Ph. V systems and processes

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

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

Developing the Ph. V system Steps 1. Draft legislation framework for Ph. V (avoid details) 2. Plan Ph. V-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 4

Implementing the Ph. V system • 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 Ph. V-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 5

1. Ph. V requirements in legislation • Definitions of adverse events, scope of Ph. V, 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 Ph. V or other sources • take necessary actions based on Ph. V. • Possibility/obligation for vets/users/owners to report directly to authorities. 6

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

The responsibility of the authority � To establish a Ph. V 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 8 8 reporting of adverse events by vets/users/owners � Communicate safety concerns and mitigation measures

Spread the Ph. V-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 Ph. V-report in Vet magazine • Ph. V-presentation for all graduating vets • Education: module on Ph. V in vet university • Ad-hoc presentations at vet conferences and Industry association meetings • AE-reporting form easily available 9

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 10

EU experience 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 • Ph. V inspections • Information to vets, users and owners about safe use of products, which is what Ph. V is really about! (footnote 2014: The EU legislation is currently under revision, also concerning pharmacovigilance requirements) 11

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

Practical approach in national agency: spontaneous AE-reports Immediately after AE-report is received: 13 case-number and letter of receipt causality assessment by Agency-vet decision on action/no-action, or request more information, etc Ph. V-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: PSURs Periodic safety update reports (PSURs) are received from the companies in a periodic schedule, or on request • includes all AE-reports and other Ph. V-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. 14

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

Other Ph. V information exchange between authorities 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

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_9 b_201110. pdf 17 17 (footnote 2014: The EU legislation is currently under revision, also concerning pharmacovigilance requirements)