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

xavier.tey1@allergan.com

+65-64115447/ 88098510