Pharmacovigilance inspections: what HPRA expects Michael McDonald, PhD HPRA Veterinary Medicines Information Day 13 June 2018, Hilton Hotel Dublin Airport, Dublin.

Purpose of inspections Monitor compliance of MAHs with their PhV obligations Verify MAHs have a PhV system in place to assume responsibility for VMPs on the market so that appropriate action may be taken by the MAH when necessary Verify MAHs have a QPPV at their disposal, who is responsible for the establishment and maintenance of the PhV system Verify MAHs have a deputy QPPV available to them and that back-up procedures apply in case of absence of QPPV Ensure corrective and preventative action is taken for any non compliances identified 16/05/2019

The HPRA inspection programme Conducting inspections of veterinary MAHs since 2009 Eleven veterinary PhV inspections conducted to date National inspection programme reviewed and developed annually Coordination with European network for centrally authorised products Inspections may be routine or targeted Routine inspections Targeted inspections Part of ongoing monitoring programme Specific issues are identified that indicate that a PhV system may be non-compliant or there is potential for increased risk of non-compliance 16/05/2019

MAHs may be prioritised based on factors such as: Routine inspections MAHs may be prioritised based on factors such as: Number of MAs held Type(s) of products authorised Subcontracted PhV responsibilities Significant organisational changes PhV compliance profile 16/05/2019

Conduct of inspections Typically, two to three days in duration Inspection team consists of inspector(s) and one assessor Key components examined: Organisation inc. defined roles and responsibililities for PhV The QPPV and deputy The Detailed Description of the Pharmacovigilance System The quality management system Adverse event case processing and reporting Periodic Safety Update Report preparation and submission Signal management inc. safety variations Contracts and agreements with third parties Examined through combination of document review and interviews 16/05/2019

Conduct of inspections Deficiencies categorised according to EU agreed definitions, as: Critical Major Minor Findings discussed with MAH throughout inspection, in so far as possible Confidential inspection report prepared and issued to MAH MAH response may request correction of any factual errors and should include proposed corrective and preventative actions 16/05/2019

Vet PhV inspection findings 2009-2018 Examples Incomplete or late training Written procedures for key PhV activities missing or not well defined Late submission of PSURs or SAEs Failure to submit follow-up information on AEs or incorrect classification of AEs Top three areas 16/05/2019

Other common findings and how they can be avoided Contractual agreements unclear with respect to PhV roles and responsibililties 24 hour access to QPPV PhV audits – internal and external Failure to define processes to ensure collection of AEs from all potential sources Access to a veterinarian, if required 16/05/2019

Key areas examined during inspection QPPV Backup arrangements are clearly detailed Adequate documentation is maintained regarding QPPV responsibilities and oversight DDPS DDPS regularly reviewed and maintained Variations submitted to competent authorities as necessary 16/05/2019

Key areas examined during inspection PSURs and AEs SOPs are in place, adequately cover all activities, and are reviewed and updated as necessary Accurate and complete records from time of case creation to close-out! Timely reporting to HPRA Contracts and agreements Signed and dated contracts/agreements in place with all relevant third parties Roles and responsibilities regarding PhV clearly defined 16/05/2019

Key areas examined during inspection Signal detection and literature searches Written procedures in place, with responsibilities and timelines clearly defined Appropriate methodology, use of data sources and periodicity Safety variations managed in a timely manner Product quality complaints Interface between Quality Assurance and PhV Product quality complaint and AE logs review and reconciliation 16/05/2019

Key areas examined during inspection Written procedures Written procedures, defining processes for all relevant PhV activities Periodic review, with subsequent updates where necessary Training Ensure all relevant personnel have received at least basic PhV training and that the collection of AEs is assured Training records complete and up-to-date 16/05/2019

Queries? For queries relating to the HPRA’s veterinary PhV inspection programme contact compliance@hpra.ie For queries regarding specific PhV obligations for veterinary MAHs and the underpinning standards contact vetsafety@hpra.ie 16/05/2019

Thank you