the role of the qp in ma compliance - hpra

The Role of the QP in MA Compliance

Breda Gleeson, Market Compliance Inspector

IMB GMP & Market Compliance Information DayDublin, October 14th, 2010

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

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

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

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

How can the QP gain assurance?

Slide 6

QP Assurance

Knowledge of MAH Systems and Procedures

Compliance Checks

Technical Agreement

Product Quality Review

Audit of MAH Office

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

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

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

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 documentedSlide 10

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

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

PQRs

• Verify compliance and identify MA non-compliance 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

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

IMBs Monitoring of MA Compliance

Slide 15

Quality Defects & Recall Programme

GMP Inspections

MAH Inspections

Sampling & Analysis

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


• 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


• 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 robustLack of detailed protocolChecks not adequately documented Lack of appropriate QA and QC

• Critical deficiency issued

Slide 18


• 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


• 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


• 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 Q4 2010

Slide 21

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

Thank You

the role of the qp in ma compliance - hpra

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