Upload
sgs
View
161
Download
0
Embed Size (px)
Citation preview
FDA/EMA INSPECTION READINESS ANTICIPATE AND BE READY FOR GROWING
REGULATORY EXPECTATIONS IN EARLY PHASE
CLINICAL TRIALS
ANNICK VAN RIEL
2 SGS BIOPHARMA DAY – OCTOBER 25, 2016
FDA – EMA GCP INSPECTIONS CHALLENGES
GCP inspection
Clinical inspection of registration trials submitted in support
of marketing application of new drug products, to ensure
data integrity
subject’s safety
Challenges
Globalisation of clinical trials - same trials used to support
• Marketing Authorization Application (MAA) to EMA
• New Drug Application (NDA) and Biologics License Application
(BLA) to FDA
3 SGS BIOPHARMA DAY – OCTOBER 25, 2016
FDA – EMA GCP INSPECTIONS SIMILARITIES AND DIFFERENCES 1/2
Topic FDA EMA
General BIMO program - since 1977
Routine (80%) ~ NDA
For cause (20%) ~ IND
GCP inspections since 1997
Routine
Triggered
GCP FDA CDER Title 21 CFR parts
11/50/54/58/312/314
Less details vs ICH GCP
ICH Topic E6
Directive 2005/28/EC
Clinical Trial Directive 2001/20/EC
Local requirements
Announcement Announced / unannounced Formal announcement letter
Preparation Inspection plan
documents from application dossier
Central / local inspection plan
Site to provide documents
Conduct Data reliability/subject protection
Systems / processes to obtain data
/ ensure subject protection
4 SGS BIOPHARMA DAY – OCTOBER 25, 2016
FDA – EMA GCP INSPECTIONS SIMILARITIES AND DIFFERENCES 2/2
Topic FDA EMA
Reporting Closing meeting
Observations in 483
General classification
(NAI – VAI – OAI)
Negative inspection
- rejection of data
- Disqualification of investigator
Closing meeting
no written summary
Grading per finding (critical, major,
minor)
Negative inspection
-Negative opinion
-Rejection of data
-Restrictions on SPC
-Refusal MAA
NAI (No action indicated) – VAI (Voluntary action indicated) – OIA (Official action indicated)
5 SGS BIOPHARMA DAY – OCTOBER 25, 2016
FDA – EMA GCP INSPECTIONS JOINT INSPECTIONS BECOMING ‘STANDARD’
More ‘joint’ inspections FDA + EMA
Identify gaps in processes
Expand outside US / EU
Focus sponsors and CRO as well as sites
Focus on triggered inspections
More ‘parallel’ inspections with exchange of inspection
reports
* Report on the Pilot EMA-FDA GCP initiative, September 2009 – March 2011 (EXT/INS/GCP/56289/2011)
6 SGS BIOPHARMA DAY – OCTOBER 25, 2016
ICH E6 (R2) - HOT TOPICS REFLECTING RECENT GCP INSPECTION FINDINGS 1/2
Sponsor Risk Management at the core of Quality
To implement for QMS and Monitoring
To incorporate risk science, ALCOA communication, record
keeping
Risk based monitoring
Closing the loop of significant non-compliance
Identification / Root cause analysis / correction and
prevention
Human Factor Analysis
Oversight by investigators
Delegation oversight
Quality and control at all times of data and documents
provided to sponsor
7 SGS BIOPHARMA DAY – OCTOBER 25, 2016
ICH E6 (R2) – HOT TOPICS REFLECTING RECENT GCP INSPECTION FINDINGS 2/2
Technology
Paper access control, data perenniality and ALCOA at the
basis
Validity, longevity, fidelity of data
Standard processes to avoid that real-time data influence trial
outcomes early in the process
Control by site of the generated data
Vendor oversight by sponsor
Sponsor oversight of tasks delegated to CROs
CRO to ensure transparency of data and tasks
Final guideline by November 2016
8 SGS BIOPHARMA DAY – OCTOBER 25, 2016
EU CLINICAL TRIAL REGULATION 563/2014 CLINICAL RESEARCH WITH HIGH PATIENT SAFETY
What’s New?
No more national interpretation of Directive
Single trial application covering all EU countries involved
SUSAR reporting coordinated across EU
Predictable application timelines
Transparent clinical trial reporting
Flexibility in TMF content and monitoring
Trial registration in database
• prior to start (<-> FDA : 21 days after FPFV)
• Phase I registration (<-> FDA : exempted)
• US trials to adhere
Applicable in 2017/2018
9 SGS BIOPHARMA DAY – OCTOBER 25, 2016
HOW CAN WE BE PREPARED ?
10 SGS BIOPHARMA DAY – OCTOBER 25, 2016
INSPECTION READINESS A CULTURE OF COMPLIANCE
Inspection readiness as “STATE OF BEING”
not as preparation activity
Management as active participant in a commitment to a
“Culture of Compliance”
Quality Management / Control
Digital solutions for data, document and quality
management
eSource, CTMS, eTMF, QMS…
Routine internal audits
11 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL - PURPOSE
Continuous Quality Improvement
Quality Data Collection performed according to
Protocol
ICH-GCP, GDP and local regulations
SOP / WI
Risk assessment
Management enforcement
12 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL - APPROACH
Plan
Objectives / processes
Do
Implementation
Check
Monitor / evaluate
testing the results against
objectives
Act
Apply actions necessary for
improvement if the results
require changes
Shewart Cycle (WE Deming)
13 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL - PROCESS
A NEW DIRECTION
100% QC defining Critical QC Check Points
“Spot check” activity
Based on Risk Analysis
Against GCP / GDP / protocol
Electronic + manual
Cross – functional
Daily/weekly/Monthly
Protocol Related Guidelines
Ice ECG rechecks Drug screen Centrifuge setting …
GCP
Documentation
Version control signatures corrections empty fields black pen …
GDP
14 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL – SPOT CHECKS
IQC SPOT CHECK
TACTILE approach
OFFICE
Set-up IF
Signature process All docs present
FLOOR
Screening, pre-dose – Dosing FU – Samples – Lab –
Pharmacy
Drug screen ECG – ICF
Prescription Log Centrifuge settings…
PROCESS approach
DAY -1 to Day 2 24h post-dose
Predose – Dosing FU – Samples – Lab
Pharmacy
Drug screen ECG – ICF
Prescription Log Centrifuge settings…
Predefined # studies – randomly identified
15 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL – ELECTRONIC QC
100% sampling and review
What Why Function Frequency
OOR values GCP PI Weekly
Time between ECG GCP CTN Monthly
Eligibility GCP PI Daily
Events pre-dose GCP PI Weekly
Heights GDP CTN / CLT / TOA Monthly
Lab centrifuge setting GCP CLT Monthly
Lab storage in time GCP CLT Monthly
Rescreening of a volunteer GDP RSO Monthly
Time on paper source same as in eSource GDP CTN / CLT / TOA Monthly
16 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL – TRENDING
17 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CASE STUDY CPU QUALITY CONTROL - REPORTING
Reporting tool
Monthly QC meetings / minutes / actions
Actions ~ Root Cause Analysis / CAPA
Management commitment
Who Responsibility
Team lead GCP related actions / evidence
Management Team GDP related actions / evidence
IQC Collection of EVIDENCE
Senior Management GCP and GDP TRENDING
Outcome: Spot checks linked to risk modus
18 SGS BIOPHARMA DAY – OCTOBER 25, 2016
CONCLUSION QUALITY COMPLIANCE LEADS TO INSPECTION READINESS
Spot check
Manual QC
Electronic QC
Management
accountability
Trending
CULTURE OF COMPLIANCE
19 SGS BIOPHARMA DAY – OCTOBER 25, 2016
Life Sciences van Riel Annick
Director CPU Antwerpen
SGS Phone:: + 32 (0) 3 217 25 60
Clinical pharmacology Unit Antwerpen Fax: + 32 (0) 3 217 25 81
Lange Beeldekensstraat 267 E-mail : [email protected]
B 2060 Antwerpen
BELGIUM Web : www.sgs.com/lifescience
THANK YOU FOR YOUR ATTENTION
+ 41 22 739 9548
+ 1 866 SGS 5003
+ 65 637 90 111
+ 33 1 53 78 18 79
+ 1 877 677 2667
+ 33 1 41 24 87 87
20 SGS BIOPHARMA DAY – OCTOBER 25, 2016
QUESTIONS ?
21 SGS BIOPHARMA DAY – OCTOBER 25, 2016