SINGAPORE RESEARCH ETHICS CONFERENCE (SREC) 2018 INVESTIGATOR SITE AUDIT AND INSPECTION FINDINGS – OVERVIEW AND LESSONS LEARNT Xavier Tey Senior Manager Global R&D Quality (GRDQ) Allergan
SINGAPORE RESEARCH ETHICS CONFERENCE (SREC) 2018
INVESTIGATOR SITE AUDIT AND INSPECTION FINDINGS – OVERVIEW AND LESSONS LEARNT
Xavier Tey
Senior Manager
Global R&D Quality (GRDQ)
Allergan
DISCLAIMER/DISCLOSURE
Presentations are intended for informational purposes only and do not replace independent professional judgment. Statements of fact and opinions expressed are those of the participants individually and, unless expressly stated to the contrary, are not the opinion or position of my company or its affiliates.
KEY TOPICS
Points of Considerations: Preparation for a Site Inspection/ Audit
Trends/ Common Issues of Clinical Investigator Site (CIS) Regulatory Inspections & Audits
CIS Perspective: Considerations/ Recommendations for Quality/ Compliance Enhancement
Q&A
PREPARATION FOR A CIS AUDIT/ INSPECTION Always do things RIGHT ** Irreversible issues/errors
Focus: Proper management/adequate oversight of trial activities
Confirmation of audit schedule: Availability of resources (study team/facility) and logistical arrangement
Protocol/procedural requirements
Study delegation, roles and conduct
Study board for key issues/trial decisions – Ready to speak to details
Collaborative, factual, professional, honest, confident
ANALYSIS OF CIS AUDITS – 2017
Q1 Q2 Q3 Q4
ISA 8 17 17 20
0
5
10
15
20
25
Num
ber
of
Audits
GCP Audits 2017-ISA
4
19
16
17
5
9
7
13
4
6 6
3
1
3 3
5
3
4
1
3
Q1 Q2 Q3 Q4
Most Common Observations (GCP Investigator Site Audits 2017)
Source/Supp Docs Prot Compliance IP Handling Inf Consent Monitoring
Q1 Q2 Q3 Q4
Source/ Supporting
Docs 4 19 16 17
Protocol Compliance 5 9 7 13
IP Handling 4 6 6 3
Informed Consent 1 3 3 5
Monitoring 3 4 1 3
CIS INSPECTION METRICS – HSA (2017) Relevant Link
Distribution of GCP Inspection Findings in 2017
CIS INSPECTION METRICS – US FDA (FY’2016)
Relevant Link
FY’16 International CI Inspections Classified All Centers* Most Common CIS Deficiencies
Failure to follow investigational plan and/or
regulations, or both
^Protocol deviations
Inadequate recordkeeping
^Inadequate subject protection – informed consent
issues, failure to report AEs
^Inadequate accountability for the IMP
Inadequate IRB communication
Note: ^Common issues for international inspections
CIS INSPECTION METRICS – EMA (2016) Relevant Link
Category: General
Essential Documents
Source Documentation
Qualification/ Training
SOPs
Contracts/ agreements
Category: Investigational Site
Reporting in CRF/diary
Protocol compliance (safety
reporting)
Protocol compliance (others)
Protocol compliance (selection
criteria)
Protocol compliance (assessment
of efficacy)
Category: Trial Management
Monitoring
Data Management
Clinical Study Report
Protocol/ CRF/ Diary/
Questionnaire Design
CIS INSPECTION METRICS – MHRA (2015/2016) Relevant Link
Top 5 Major Findings
1 IMP Management/ Pharmacy
2 CRF/ Source Data
3 Subject eligibility
4 Data integrity
5 Data Management
Critical Finding (1)
IMP Management
CIS INSPECTION METRICS – HEALTH CANADA (2015-2016) Relevant Link
CIS INSPECTION METRICS – CHINA FDA (2015-2017)
Substantial focus:
Data integrity/ traceability
Hospital Information System (HIS) vs Medical
charts
IP documentation (incl. CoA, CoC etc.)
Top 4 Areas of Findings
28.1% Study procedure records, traceability of
examination/ laboratory tests
12% Protocol deviations
11.8% IP management process/ records
10.1% Safety record/ reports
HOLISTIC VIEW: VARIOUS HA CIS INSPECTIONS/ AUDITS
Increased HA scrutiny and interactions between HAs – Importance of Inspection Readiness
Risk-based approach
Commonalities in key issues reported across inspections/ audits:
Source records/ data integrity
Protocol compliance/ adherence
IP management/ records
Informed consent process/ documentation
Safety reports
LESSONS LEARNT/ CONSIDERATIONS Topic-Specific Source Records/ Data Integrity
Adequacy/requirements
Data chain/flow (data/time/sequence)
Timeliness, accuracy & attributability
Protocol compliance/ adherence
Protocol discussion/practicality/ challenges
Clear understanding of protocol requirements
Study training, TA experience
Review/ QC (early phase/new staff)
*Handoffs *Guiding tool/reminder *Resources
IP management/ records
Temperature monitoring/device – Requirements &
Records (feasibility)
Temperature excursion – timeliness/follow up
Handoffs/temporary location of storage/temperature
Safety reports
Timeliness in assessment/ reporting/ follow up (*MD)
Regulatory/EC requirements
Events of special interest/ special reporting conditions
Source documentation – adequacy/ timeliness
Informed consent process/ documentation
Regulatory/ study requirement – TA/ population
Right version/ timeliness in re-consenting/ updates
Documentation – Adequacy/ sequence/ timeliness
Process/ time allocated
LESSONS LEARNT/ CONSIDERATIONS Proper training and oversight of activities
(new staff/less-experienced/ changes in protocol requirements)
Source Data Review (not just SDV)
Trending/viewing holistically interrelated data points via table/tabulation – Identify inconsistencies/errors/gaps
By subject, by procedure/sequence, by timepoint, by visit
Protocol design/Quality by Design (QbD)
Critical to Quality (CTQ) – CTTI
Protocol De-risking
General
Risk identification/management (Transcelerate QMS/ QRM) – processes/resources
Quality control/verification steps
Issue identification/management/CAPA (Transcelerate) and lessons learnt
Effective communication/ correspondence with Sponsor
Best use of resources (HA, EC, Sponsor, industry, network/intelligence)
Xavier Tey
Clinical Quality, Global R&D Quality, Allergan
+65-64115447/ 88098510