Presentation on the good clinical practice inspections consultation, feedback received and next steps

1. Good Clinical Practice Inspections
Consultation to introduce a pilot program of voluntary GCP
inspections
Dr Katherine Clark
Director of Licensing and Certification
Manufacturing Quality Branch
Medical Devices & Product Quality Division, TGA
ARCS 2019

2. Consultation on a pilot program for Good Clinical Practice (GCP)
Inspections
• Background
• Feedback on Consultation
• Next steps
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3. Background
• In an increasingly complex and global clinical trials environment, and unlike all comparable regulatory
approaches, the current regulatory schemes provide the TGA with limited opportunity to identify and manage
risk.
• An internationally aligned regulatory framework will strengthen and support Australia’s position in a
competitive global clinical research market.
• A domestic GCP inspections program will address a gap in the current regulatory oversight of the conduct of
Australian clinical trials.
• A domestic GCP inspections program will play an important role in assuring protection of participants in
clinical trials, and data quality, reliability, and acceptability upon which international regulatory approval
decisions are made.
• Clearer powers to manage findings of non-compliance will remove ambiguity to the benefit of all involved in
clinical trials in Australia.
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4. GCP inspection pilot program
Good Clinical Practice is an international ethical and scientific quality standard for designing, conducting,
recording and reporting of clinical trials. (Integrated Addendum to ICH E6(R1): Guideline for Good Clinical
Practice E6(R2) 2016)
Clinical trials in Australia are required to comply with the Guideline for Good Clinical Practice (Regulation 12AD).
The Guideline is primarily intended to ensure that:
1) The rights, safety and well-being of trial participants are protected; and
2) The clinical trial data are credible
Unlike other similar regulators TGA has not had a routine GCP inspection program.
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5. GCP inspection pilot program
TGA is planning to perform a 12 month GCP inspection pilot program. The pilot program will be:
• Voluntary
Volunteers have been sought through the consultation
• At investigator sites for clinical trials of medicines
Investigator sites for clinical trials of medicines will be selected
• At no charge
There will be no fees charged for the pilot program
• Internationally harmonised
The GCP inspection procedures will be harmonised to European Union published procedures
• Inform a routine inspection program
The feedback from the pilot program will inform the needs and approach for a routine inspection program
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6. GCP inspection pilot program
GCP audit procedures modelled on the European Medicines Agency
GCP audit procedures adopted from Chapter IV, Volume 10, Clinical Trials, of the Rules Governing Medicinal Products
in the European Union published by the European Medicines Agency.
(see http://ec.europa.eu/health/documents/eudralex/vol-10/index_en.htm )
• EMA procedures and guidance
– EMA/839541/2015 Guidance for the conduct of good clinical practice inspections
– EMA/431265/2017 Annex I to guidance for the conduct of good clinical practice inspections – investigator site
– EMEA/INS/GCP/197223/2005 Procedure for conducting GCP inspections requested by EMEA
– EMEA/INS/GCP/197219/2005 Annex I to procedure for conducting GCP inspections requested by the EMEA:
investigator site 5

7. Consultation on a pilot program for Good Clinical Practice (GCP)
Inspections
• Background
• Feedback on Consultation
• Next steps
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8. Consultation
• The TGA sought comments from interested stakeholders this January (from 11 January 2019 to 22 February 2019)
• The consultation asked four main questions:
– What are your thoughts on a pilot GCP inspections program and proposed establishment of a routine program
following the pilot?
– Would you consider to be a clinical trial site inspected under the pilot program?
– Would the release of inspection findings to the approving HREC and/or authorising institution be an appropriate
mechanism for managing issues relating to the conduct of the trial or data integrity?
– What impact, if any, would a domestic GCP inspections program have on Australia’s competitiveness as a place
to conduct clinical trials?
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9. Feedback on Consultation Paper
Consultations closed 22
February 2019
43 submissions were
received
• Medical technology, biotechnology or pharmaceuticals sector10
• Local District Health Services/Networks/Public Health Organisations6
• Federal or state government stakeholders6
• Medical research institutes/not for profit entities4
• Universities4
• Industry associations or peak bodies4
• Dedicated early phase units3
• Contract research organisations3
• Individuals2
• Private healthcare group1 8

10. Consultation on a pilot program for Good Clinical Practice (GCP)
Inspections
• Background
• Feedback on Consultation
• Next steps
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11. Next Steps
• Report to Minister on the Consultation
• Liaise with potential volunteer sites to arrange
investigator site inspections under the pilot
program
• Conduct pilot GCP inspections
– Voluntary
– Investigator sites
– Pharmaceutical medicines
– 3 days duration
– No charge/fee
– Modelled on EMA procedures and guidance
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12. Pilot Program of GCP Inspections
• Notification, planning and preparation
• Agenda, logistics and initial document requests
Pre-inspection
• Opening meeting
• Interview sessions and document reviews
• Closing meeting
Inspection
• Issuance of inspection report
• CAPA response
• Close-out
Post-inspection
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13. Pilot Program of GCP Inspections
• Examination of aspects related to the implementation, progress and
termination of the clinical trial, including evidence of communication with the
HREC and regulatory authorities
Legal and Administrative
• Examination of the implementation of the trial at the site, including
qualifications and experience of site personnel, delegation of authority,
standard operating procedures, facilities and equipment, source of IMP,
monitoring and auditing records*
Organisational
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14. Pilot Program of GCP Inspections
• Determination of whether participant consent was obtained in accordance with the
GCP guidelines (and HREC and Institutional requirements)
Informed Consent
• Review of whether the trial was conducted according to the study protocol by
source data verification, particularly, inclusion/exclusion criteria, endpoints and
safety data
Clinical Trial Data
Management of the IMP used in the trial
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15. Pilot Program of GCP Inspections
• At the end of the inspection, the inspector will hold a closing meeting with the inspectee. The main
purpose of this meeting is to present inspection findings and comments to the inspectee.
(EMA/839541/2015)
• These items will be described in the Inspection Report and the deviations classified as minor (or
other), major and critical. (EMA/359169/2016)
• Gradings of inspection findings will be based on EMA/359169/2016 Appendix 1
Management of observations from the pilot program inspections
• The inspectee will be asked to provide responses to the findings and provide a CAPA plan to
address any major deviations.
• The TGA will communicate with the inspectee to resolve any observed issues.
• Where issues are not resolved or any critical deviations are observed this will be further discussed
with the inspectees and potentially advised to the HREC / Authorising institution for awareness and
oversight.
• Individual GCP inspection outcomes are not planned for publication.
Managing non-compliance observed from the pilot program inspections
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16. Next steps
• Refine inspection processes and (further) develop guidance documents
• Report to Minister (and stakeholders) on the pilot GCP inspections program, confirm funding
arrangements for ongoing program
• Commence ongoing domestic inspection program if approved
• Continue to contribute to global harmonisation as part of international working group(s)
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