Discussion of RQA Inspection Feedback Andy Fisher, Lead Senior GCP Inspector
Dossier submission to Inspection There are no processes that define that the inspection must take place within a certain timescale post receipt of dossier. Scheduling of inspections is based on risk, unplanned triggers etc. We will look at ensuring that feedback to the organisation regarding the status of their inspection scheduling after a certain time has passed would be appropriate. 2
GCP Inspection Reports (2015-2018) 2017-2018 is incomplete/not QC checked Reporting Time of GCP Inspection Reports 2015 ‐ 2016 Reporting Time of GCP Inspection Reports 2016 ‐ 2017 Reporting Time of GCP Inspection Reports 2017 ‐ 2018 (Individual Reports and Median) (Individual Reports and Median) (Individual Reports and Median) 120 120 120 100 100 100 92 Days Since Last Inspetion Date/Last Document Provided Days Since Last Inspetion Date/Last Document Provided Days Since Last Inspetion Date/Last Document Provided 80 80 80 60 60 60 52.5 49 46.5 42 40 40 40 37.5 35.5 34.5 33 29 20 20 20 20 8 0 0 0 Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units 3
Median Inspection Reporting Times (Years 2004 ‐ 2005, 2005 ‐ 2006, 2006 ‐ 2007 and 20017 ‐ 2018 have not been QC checked and are incomplete. Some closing dates were not available at the times of the metrics report issue for the other years) 140 120 Days Between Last Inspection Date/Date Last Document Provided and Report Issue Date 100 80 60 40 20 0 2004 ‐ 2005 2005 ‐ 2006 2006 ‐ 2007 2007 ‐ 2008 2008 ‐ 2009 2009 ‐ 2010 2010 ‐ 2011 2011 ‐ 2012 2012 ‐ 2013 2013 ‐ 2014 2014 ‐ 2015 2015 ‐ 2016 2016 ‐ 2017 2017 ‐ 2018 Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units Current SOP MEDIAN 4
• Timescale for report is after last site inspection • Full data for 2015-2017. 2017-2018 is on limited reports issued/data entered • Increase in 2017/2018 – may be lowered once all data collected • Median time is slightly beyond current target (35 calendar days) and slight trend to longer timescales • Some late reports, but organisation is informed as is GCP Management 5
GCP Inspection Closure Times (2015-2018) 2017-2018 is incomplete/not QC checked Closing time of GCP Inspection Reports 2015 ‐ 2016 Closing time of GCP Inspection Reports 2016 ‐ 2017 Closing time of GCP Inspection Reports 2017 ‐ 2018 (Individual Inspections and Median) (Individual Inspections and Median) (Individual Inspections and Median) 350 700 250 300 600 200 194 250 500 Days Between Report Issue and Closing Statement Issue Days Between Report Issue and Closing Statement Issue Days Between Report Issue and Closing Statement Issue 150 200 400 150 300 100 132 131 226 108.5 76.5 76 100 200 200.5 186 59 50 55 111 50 100 0 0 0 Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units 6
Median Inspection Closing Times (Years 2004 ‐ 2005, 2005 ‐ 2006, 2006 ‐ 2007 and 20017 ‐ 2018 have not been QC checked and are incomplete. Some closing dates were not available at the times of the metrics report issue for the other years) 350 300 Days Between Date of Report Issue and Date of Issue of Closing Statement 250 200 150 100 50 0 2004 ‐ 2005 2005 ‐ 2006 2006 ‐ 2007 2007 ‐ 2008 2008 ‐ 2009 2009 ‐ 2010 2010 ‐ 2011 2011 ‐ 2012 2012 ‐ 2013 2013 ‐ 2014 2014 ‐ 2015 2015 ‐ 2016 2016 ‐ 2017 2017 ‐ 2018 Commercial Sponsor Commercial CRO Non Commercial Commercial Phase 1 Units MEDIAN 7
• Full data for 2015-2017. 2017-2018 is on limited reports issued/data entered • Timescale is from final report to closing statement, response review times are not currently captured in our trackers • Shows an increasing trend in time to close inspections – potential reasons: • Patience waiting for additional responses • Impact Assessments/Investigations • Multiple Responses received • Quarterly Reporting • Delay in issue of closing statement • We will start to track MHRA GCP Inspectors response review times. 8
Does the time taken reflect that lengths/complexity of reports and subsequent responses review etc. increases with non-compliance? • Metrics report 2016-2018 issued 11 th May 2018. 9
2016/2017 Investigator Site 2015/2016 2014/2015 Percentage of inspections with at least 1 critical finding 2013/2014 Phase 1 2012/2013 Year (April - March) (*=no QC or incomplete) 2011/2012 CRO 2010/2011 2009/2010 Non Commercial 2008/2009 2007/2008 2006/2007* Commercial 2005/2006* 2004/2005* 100 90 80 70 60 50 40 30 20 10 0 Percentage 10
2016/2017 Percentage of inspections with at least 1 critical and/or major finding 2015/2016 Investigator Site 2014/2015 2013/2014 Phase 1 Year (April - March) (*=no QC or incomplete) 2012/2013 2011/2012 CRO 2010/2011 2009/2010 Non Commercial 2008/2009 2007/2008 2006/2007* Commercial 2005/2006* 2004/2005* 100 90 80 70 60 50 40 30 20 10 0 Percentage 11
Reasons for increasing non-compliance? DISCUSSION? 12
Internal Audit Reports MHRA GCP Inspectors continue only to request these where considered necessary to investigate serious non-compliance. Evidence of auditing is requested, but this does not need audit reports. 13
Remote Access to eCRF, eTMF • Organisations will regularly offer remote access for eCRF. • Set up of access to systems prior to inspection is required. • Remote access and inspection of eTMF is NOT undertaken. • Remote access to eCRF may be undertaken by inspectors as part of inspection planning. • Access to eSystems is required during inspections. • Sometimes access is sometimes requested to be left open to systems that can be remotely accessed post inspection as they may be useful to re visit as part of report writing (e.g. SOPs) • No plans to do remote inspections. 14
Inspection Focus eTMF • Unless a previous critical in this area so there is CAPA to assess, the eTMF system itself ad surrounding processes are not a focus of the inspection, it only becomes so once it is has been seen to impede review • Check audit trail to see if TMF up to date (compliance check) • Organisation should be able to demonstrate compliance (that relates to subject safety and data integrity) – eTMF systems vary in how easy this is to assess and this is substantial when compared to paper. If an organisation wishes to maintain a poor system that does not facilitate review, inspection time on site will ultimately require to increase and critical findings issued. • Numerous examples of engagement with stakeholders on eTMF, including entire day workshop in 2017. Completed Trial for discontinued Development Programme • Selection of trials to demonstrate processes too (e.g. Reporting, particular eSystem etc.) it is not just the nature of the trial. • Any trial can be selected for compliance evaluation. MHRA duplicated a finding (regarding RSI) from a PV inspection 15
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