The Role of the QP in MA Compliance

Transcription

1 The Role of the QP in MA Compliance Breda Gleeson, Market Compliance Inspector IMB GMP & Market Compliance Information Day Dublin, October 14 th, 2010 Slide 1

2 Objectives Outline the responsibilities of the QP in MA Compliance Convey the importance for the QP to have assurance in MAH systems and processes Provide guidance on how best the QP can gain such assurance Slide 2

3 Legal Requirements Medicinal Products (Control of Manufacture) Regulations, S.I. No.539 of 2007 Article 13(3)(a) - The function of the qualified person is to ensure that every batch of medicinal product is manufactured and checked in compliance with the provisions of the marketing authorisation Slide 3

4 Certification of MA Compliance Basic arrangements for batch release defined by the MA MAH responsible for maintaining MA in line with technical and scientific progress MAH office or global regulatory office with local representation May or may not be part of the same corporation as the manufacturer Often based in location separate to the site of manufacture Slide 4

5 Certification of MA Compliance QP required to rely in part on the MAH Third party reliance should be well founded Reliance based upon Controls in place at the MAH for assuring regulatory compliance Quality management system supporting those controls and activities Slide 5

6 How can the QP gain assurance? Technical Agreement Compliance Checks Product Quality Review Knowledge of MAH Systems and Procedures QP Assurance Audit of MAH Office Slide 6

7 Knowledge of MAH Systems and Procedures MAH should have a well defined quality management system All activities pertaining to the maintenance of MAs controlled by the QMS Evidence of effectiveness Appropriate oversight of the quality system Self-inspection programme Competent Authority inspections Slide 7

8 Considerations. How is registered product information managed and controlled by the MAH? How are regulatory commitments and regulatory changes managed, tracked and implemented? How are commitments and changes communicated to the manufacturing site? Slide 8

9 Considerations. At what point in the process are commitments and changes communicated to the manufacturing site? What documentation is provided to the QP to support batch certification / release activities, and how is this generated and controlled? Slide 9

10 Compliance Checks Verification of compliance status and identification of system / process gaps at MAH Office Sample size and frequency of checks dependent upon Number of MAs held by MAH Major changes in MAH systems or processes Compliance history Checks should be documented Slide 10

11 Technical Agreement Important to have well defined and documented division of responsibilities Consideration given to the inclusion of the following responsibilities: Communication of regulatory commitments and changes to the manufacturing site Tracking regulatory changes and commitments and ensuring their implementation within the agreed timeframe Slide 11

12 Technical Agreement Generation and updating regulatory information file in use at manufacturing facility Co-ordinating quality defect / adverse reaction investigations and recall actions Reporting quality defects to Competent Authorities Generation and review of PQRs Management of stability programme Provision for audits Requirement for MAH to notify QP of serious systematic failures Slide 12

13 PQRs Verify compliance and identify MA noncompliance trends via the review of MA variations submitted, granted and refused Changes carried out to the processes or analytical methods Quality related returns, complaints and recalls Post-marketing commitments TAs Slide 13

14 Audit of MAH Office Invaluable means of assessing the effectiveness of systems and procedures Not a formal requirement, but strongly advisable if significant MA non-compliances identified Provision for audits included in TA Slide 14

15 IMBs Monitoring of MA Compliance MAH Inspections GMP Inspections Sampling & Analysis Quality Defects & Recall Programme Slide 15

16 MA Non-compliance Case Study Q1 2010: IMB review performed on the compliance of package leaflets (PL) in a number of Irish marketed anti-depressant products Main finding - none of the required suicide warnings included on the PL of two products Quality defect investigation triggered Non-compliant batches recalled to pharmacy level MA non-compliance issue more extensive Company committed to a PL review of its entire product portfolio Slide 16

17 MA Non-compliance Case Study Q2 2010: PvG inspection at MAH office No formal QMS in place Procedure for processing regulatory changes breached on several occasions Severe difficulty in establishing current approved documentation for some products IMB requested the voluntary suspension of QP certification / release of a number of products Slide 17

18 MA Non-compliance Case Study Q2 2010: Joint IMB / CA inspection of MAH office Systems in place insufficient to ensure MA compliance Lack of confidence in compliance of products on the marketplace Review being performed by company was insufficiently robust Lack of detailed protocol Checks not adequately documented Lack of appropriate QA and QC Critical deficiency issued Slide 18

19 MA Non-compliance Case Study Company requested to Suspend compliance review until detailed procedure in place Submit detailed investigation protocol for IMB / CA approval Extend review to include all artwork components and CMC-type changes Compliance review investigation report to be submitted to IMB / CA Slide 19

20 MA Non-compliance Case Study Competent Authorities notified Other Supervisory Authorities Class II Rapid Alert issued Outcome of non-compliances Number of products recalled across a number of markets Cessation of QP certification / release Slide 20

21 MA Non-compliance Case Study Current status of compliance review Investigation protocol for artwork review approved and company's review is ongoing Investigation protocol for CMC review under approval IMB / CA re-inspection of MAH office scheduled for Q Slide 21

22 Conclusion QP has a role in assuring MA compliance Should have in place a plan for obtaining and maintaining assurance in the MAH systems and procedures Should be able to verify that assurance is well founded Slide 22

23 Thank You Slide 23