Pharmacovigilance Inspections Time to panic? Marie-Odile Hendrickx, DVM, MRCVS Pfizer Animal Health 13 December 2010

Transcription

1 Pharmacovigilance Inspections Time to panic? Marie-Odile Hendrickx, DVM, MRCVS Pfizer Animal Health 13 December 2010

2 Content Legal basis What do agencies want? What happens Before During After How do you prepare for it? Industry wishes Conclusions 2

3 Did you say Inspections? Legal basis: Directive 2001/82/EC Art 80 Role of the MAH: to have an appropriate system of Pharmacovigilance (PhV) Role of the Agency & Competent Authorities: to verify, on behalf of the community that the MAH satisfies the requirements as laid down in this Directive and its amendments (Directive 2004/28/EC) MONITORING of COMPLIANCE 3

4 Inspections for what? - 1 Routine inspections Targeted inspections when triggers are reached No specific concerns Specifics concerns Inspections of contractors, licensing partners The agencies want reassurance that the MAH are fulfilling their obligations regarding the PhV requirements laid down by the legislation 4

5 Inspections for what? - 2 To improve post marketing surveillance To help and advise MAHs as necessary If severe breaches are observed repeatedly penalties can be imposed 5

6 What happens? Before the inspection Notice usually given by agency, a few weeks to a few months Information may be requested prior to the inspection SOPs and other procedures Information from DDPS Listing of expedited cases for a given period Calendars of PSURs for compliance with 60 days Third party agreements Product related issues Agreement on logistics, participants, inspection plan 6

7 What happens? During the inspection -1 Opening meeting Introductions Attendees: Inspector(s), PhV staff, QA staff, Management Objectives and the remit of the inspection are agreed Inspection itself, can be a few hours to a few days, ensure that you have a room allocated for the inspectors and staff who know what their role is 7

8 What happens? During the inspection -2 May include Review of PhV cases, documentation and processes: reconstruction of a case, from original data collection, through follow up to reporting PSURs elaboration and risk benefit assessments Review of procedures and their application Interviews with staff involved in all PhV activities, from receptionists to sale reps Review of staff training records, CV, job descriptions 8

9 What happens? During the inspection -3 And Demonstration of the database, looking at maintenance, archiving, security and disaster recovery processes Third party contracts Quality Management system in place Review of archives Process for literature reviews 9

10 What happens? During the inspection -4 Exit Meeting Attendees include the Inspector(s), QA Management, PhV staff and Management To ensure an understanding of findings, not to debate Can provide updates or correct misinformation 10

11 What happens? During the inspection -5 Opportunity to respond to findings as appropriate (some issues may need to be discussed internally prior to making a commitment for follow-up) No written list of findings at this stage but all findings will be described by the inspector Agreement on next steps: the issue of the inspection report 11

12 What happens? After the inspection Inspections draft report issued for comments Final report usually within 4 weeks of inspection Can be a listing of deficiencies classified in critical, major and minor, comments and recommendations, Can be a statement of compliance or non compliance and the issues to be addressed Response from MAH expected usually within 30 days with response plan to address issues If critical findings, may warrant a follow up inspection 12

13 How to prepare for an inspection? -1 Not a last minute activity, should be addressed as part of the Quality Management of PhV Use the guidance provided by legislation, Guidelines, QA teams Quality management system in place SOPs and procedures Training of all concerned staff Regular internal audits of PhV activities and systems should ensure that gaps, issues are identified and addressed Would recommend every 2-3 years Anytime when there is a major change in the PhV system Internal audit prior to a planned inspection Ensure suitable management involvement 13

14 How to prepare for an inspection? - 2 As soon as you are notified Inform your QA group and management and request their presence on the day(s) of inspection Book meeting rooms and assign tasks Ensure the availability of key people (EUQP for example) on the day and adequate resources for dealing with the paperwork Contact inspectors and engage communication 14

15 How to prepare for an inspection? - 3 Other activities May run a refresher to your staff Recommend an internal audit if last one was a while ago Address any easy fix findings Don t make major changes to procedures just prior to the inspection but show that you have identified some issues and your plans to address them Training of concerned staff prior to inspection on do s and don ts on the inspection day On the day: Don t panic! 15

16 Main points of discussions so far -1 Third party contracts Signal detection Congruence of data in house and communicated to/by authorities Training and knowledge of staff involved in PhV activities Periodicity of literature searches Product defect questions Others? 16

17 Main points of discussions so far - 2 Job descriptions Procedures - presence, content, process Validation, conformity of IT systems to EU requirements for electronic submissions Electronic reporting/importing Third country reporting Availability of local and EU QPs for PhV and their back-up Feasibility of urgent 24 hours safety restriction Training: tests for checking training efficacy 17

18 Variety is the spice of life! Areas for clarification: Purpose of inspections Sometimes part of GMP, or GCP inspections or pure PhV inspection Should all inspections be the same? Or tailored to the activity of the site? Diversity of interpretations of requirements between inspectors Fee? No fee? Per site? Per activities? 18

19 Variety is the spice of life! (continued) Inspectors affiliations Human sector vs Veterinary personnel EMA/CVMP mandated inspections vs National inspections GMP personnel Scope of inspection Focus on SOPs Short and sweet inspections (1 to 2 hours) Full PhV inspections (3 days) Based on the activity of the site? h2 19

20 Folie 19 h2 You could also address EMA inspections vs. country based inspections - how are they different? who would be involved? how they are reported? etc harlow_hl;

21 Conclusions Important event for MAH and others inspected Need careful preparation and follow up If well prepared can be quite rewarding as high visibility event at the MAH Don t become complacent afterwards Always an opportunity to learn and improve! Opportunity to gather more support from management Still fairly new area so likely to evolve to a more structured process? 20