20140311 - Catel 01_ Effective lean deployment to FDA approval
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Transcript of 20140311 - Catel 01_ Effective lean deployment to FDA approval
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 1
Effective lean deployment to reduce time to FDA approval
March 11, 2014
Cyrille Catel, ASQ CSSBBAssociate Director, Continuous Improvement & PMO Lead
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 2
Focus at stake…
Department vs. value stream approach
The Performance Management loop
- Ensuring proactive project and risk management
- Complying with the Quality Management System and Good Clinical Practice
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 3
Lead-time & punctuality baseline –from Last Subject Out (LSO) to Top Line Data (TLD)
Kick-off Final APO Final protocol FSI LSO DBL TLD ICTR
Clinical trial lead time: from few months to few years depending on the Phase (I/II/III)
Who is on the critical
path?
How to improve
planning maturity?
SOURCE: baseline Biometrics wave Sep-Dec 2013
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 4
Impact at stake –time to market is one facet of the Operational Excellence
OperationalExcellence
Time to FDA
Lead time
Tactical Implementation Plan
(12 months / 12 weeks)
Maturity
Lead Time?
Internal resource?
Delays and backlog recovery?
External cost?
Additional deliverables?
Sustainability
Efficiency
First Time Quality
On-time delivery
QSM1 & GCP2 compliance
Productivity
Problem solving
1 Quality Management System 2 Good Clinical Practice
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 5
Grünenthal approach
Improve synchronization along the R&D matrix
Improve the way of working at team level3
Instill proactive project and risk management2
1
1 Quality Management System 2 Good Clinical Practice
Foster standards as a lever to close the improvement loop and ensure compliance with QSM1 and GCP2
4
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 6F
un
ctio
n
Fu
nctio
n
Project
Fu
nctio
n
Fu
nctio
n
Project
Project
Improve the synchronization along the R&D matrix1
Role
Alignment of priorities
Synchronization of functions
Risk management
…
Role
Resource management and allocation
Process optimization and best practices sharing
…
“Strong coordination
between function and
project axis required”
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Instill proactive project and risk management –by implementing the Performance Management loop
Project
plan
Planning of
Deliverables and
Resources
AExecution
follow-up and
performance
dialogue
B
Problem logging,
Solving and
escalation
C
KPIs /
Performance
Tracking / Impact
tracking
D
Standards
E
2
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Proactive project and risk management –through problem solving
Functio
ndriven2
Project
driven1
1 Core study team 2 Extended study team 3 Complete study team
2
Backward looking
- Study KPIs review
- Assess recovery or re-planning needs for
non-delivered commitments
- Review open problems and decide on
escalation needs
Forward looking
- Review next week planning
- Identify potential risks
- Alignment and prioritization
Weekly alignment meeting3A B C
D
E
Progress and delivery review
Identification of issues
Capacity management
Problem solving
Weekly team KPIs review
Daily Whiteboard meeting2A B C
D
E
Progress and delivery review
Identification of issues
Risk mitigation and
prioritization review
Problem solving
Daily Whiteboard meeting1A B C
D
E
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Improve the way of working at team level –Daily whiteboard meeting along the primary axis13
1 Function or Project axis
A B C
D
E
Create transparency:
Progress toward plan
Risks and dependencies
Blocking and irritating issues
Example at Functional team
Ensure:
Adjustment and mitigation
Rapid escalation(top-down and bottom-up)
Instill:
Team spirit
Requirement:
Daily 10-15 minutes max
Mandatory presence
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 10
Visual management to support problem solving –Implementation example at core study team level
Project
plan
(MSP)
Project
plan
Weekly commitments
Team resource
overview
CW49
Team Commitment Status Commitment Status Commitment Status Commitment Status Commitment Status Commitment Commitment Commitment Commitment
15 random subjects
/week Newsletter
CA submission of AM2 in
remaining countries
EC submission of AM2 in
ES and AT
Respond to incoming
deficiency letters (validation
of submission package)
Respond to incoming
deficiency letters
Respond to incoming
deficiency letters
Investigator Meet in HU
Adapt CRF to AM2
Update Lab specs
Final presentations for
CRA meeting
Motivate CRAs to
enhance recruitment
(Meeting in FFM)
Final CAPA plan Dr.
Veenendaal
Review Safety Plan
Update
CAPA Plan Dr.
Veenendaal
Motivate CRAs to
enhance recruitment
(Meeting in FFM) MVR review MVR Review MVR Review
Status Report
Update of Paper process
for IMP return PD DEVA2 update
Follow-up on TMF QC check
Follow-up on recruitment
enancement activites
Follow-up on TMF QC
check
Create and provide to
Operations the Missing
Pages and Open Queries -
Reports
Findings from PK-, PG,
IVRS-Reconciliation
providing to Operations
Feedback to Update of
SDTM stucture
Max Flow - Invoice
tracking for Accovion
GB Migration to new eCRf
acc. to amendment 1
Completion Guidline for
review to Operations
Clarification of the
finding: MRL- ECG unable
to evaluate
instruction for
unscheduled ECG
reporting
by country and dropout
analysis Accovion clarifications
SAP finalization -PPS
definition
MRL #9
PD DEV A1 updated draft
PD DEV A1 discussion with
team
newsletter review and
substantial rewrite
central TMF update
Accovion clarifications for
answered queries
DEVA1 update alignment
within project SAP comments alignment
DEVA1 update final for
next steps at Accovion
Review update specifica6tions
central lab after AM1 MRL #9
instruction for
unscheduled ECG
reporting
Review eCRF update after
AM1
PPS definition
Review eCRF completion
guideline update after AM1
CW50 CW51 CW1
Study
deliveries
CO
RE
STU
DY
TEA
M
CW2
Mon Tue Wed Thu Fri
CW50 CW51 CW52
Mon Tue Wed Thu Fri Mon Tue Wed Thu Fri Mon Tue Wed Thu Fri
Team Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence Presence
A A A A A P P P P A P A A A A
P P P HO P P P P A A A A A A A
P P P P A P P P P A A A A A A
P P P P P P P A P P A A A A A
A A P P P P P P P P A A A A A
P P P P P P P P P P A A A A A
A P P A P P P P P P P A A A A
CO
RE
STU
DY
TEA
M
A
No. Item Category Root cause/consequences/impact 1. Action I
2. Action II …
Owner Start date End date Priority Status CO-team
1 Site audit findings allocated to GOSL, why not to CSM?
(GGP)
Process JKu JKu 23-May-2013 medium open GOSL
2 Review + approval local ICF (NGa) Process not done by CSM or no CSM
appointed
meeting JKu - how to progress? GGP 13-May-2013 open GOSL
4 Questionnaires (NMH) Process versioning not harmonized
trial identifier missing
finding JTyrell: email AEsser
10Jun
1. follow-up by STM, MZ, QS (Elke
Ufer) - done
2. request questionnaire issues
from all CO's (done)
3. PSS (done 30Sep2013)
GGP 29-May-2013 high 75% GOSL
5 Protocol deviation reporting Process Protocol deviation plan, fraud &
misconduct
1. PSS 5 Sep - done
3. PSS 11 Nov - done
3. FU PSS scheduled for 28 Nov
(and furhter bi-weekly until
resolution)
VK 23-May-2013 high 25% GOSL
6 GxP relevant issues (GGP)
confidential information which needs to be
exchanged within the study team but not with all
(budget, TMP documents, status reports, QC
monitoring reports)
Process where to file? 1. fu with GOPLs wrt status
reports -done, waiting for answer
2. meeting with H. Netz, GOSL,
STM
new eroom will be established
for complete GCD
3. where to file STM minutes?
(question CBe)
GGP 14-May-2013 75% GOSL
7 GCP online training (CL, NGa) Training Infonetica: test too difficult,
questions too complex,
ambiguous questions
short-term solution for affected
trial found, analysis ongoing
IS 16-Apr-2013 16-May-2013 high interim-
solution
GOSL
7 GCP online training Training approval of access to Infonetica
done via 2 persons in CO but
insufficient; not all countries
covered by Infonetica nor by local
language trainings
alignment with GGP, PSS with IS BS 5-Jun-2013 14-Jun-2013 high solved GOSM
3 CTA: RA preparation (BSt) Process no preparation by RA meeting with T. Hujbers (JKu) TH high 75% GOSL7-May-2013
Problem board (short term)
Long term issue
Date
raisedChallenge description
(clear description to nail the particular challenge down)Proposed countermeasure Status Owner
Target
Date
before
escalation
GOPL ICL OVM GECD GLCD CO GBM GRA Others
11-Nov-13
Protocol deviation meeting needed to discuss PD category 3 -
difficult to find timeslot with Core STM PPS slot used SO 20-Nov-13
13-Nov-13
Gisela on sick leave (duration unknown) - Potentially blocking SAP
finalization/TLD definitions none Cla 18-Nov-13
25-Nov-13
Potentially blocking: definition of PDs and DEVA1 discussion
blocking the PD process
Several PSS took place to define the PD
definitions Ach, SO 11-Dec-13
25-Nov-13
CI signatures on amendment 1 delay CA/EC submission of
amendment 1 (DK) none Cla 29-Nov-13
27-Nov-13
Science colleagues have limited capacities due to high amount of
unplanned alerts; this endangers the medical review and protocol
deviation review
Develop recovery plan, e.g. consider to
have one person concentrating on the day-
to day issues?
Cla to escalate to DR and Ahä Cla 03-Dec-13 13-Dec-13
11-Nov-13 High amount of regular meetings reduces overall working time
Undergo pilot phase; escalate if this issue
remains Ach 13-Dec-13
13-Nov-13 Gisela on sick leave (duration unknown) -affects AM review
Forward amendment to Giacomo
(combined review planned) MW 13-Nov-13
21-Nov-13
MRL #8 time line 20Nov not met due to workload, therefore queries
could not be sent to Accovion
new timeline of 26 Nov 2013 was chosen
to be acceptable without bloking other
deliverables SO, Ach 26-Nov-13
25-Nov-13 FI003 randomizing subjects that do not meet IN/EX Visit of Lead CRA at site FI003 Cla, Ach 29-Nov-13
28-Nov-13 Availability of team and vendors over X-mas period
Cla addressed issue in meeting on 28 Nov;
ME and DR will act as coverage; others to
be determined Cla 13-Dec-13
Line escalationProject escalation
Blo
ckin
g is
sues
Irri
tati
ng
issu
es
C
3A B C
D
E
KPI1
D
1 Key Performance Indicators
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 11
Example of solved problems and structural improvement
Project
axis
Function
axis
Opportunistic problem resolution Structural improvement
Early detection of CA/EC1 submission of
Amendment delay caused by pending
signatures
Safety plan overdue
Pending PD2 definition blocking the PD review
process. This situation create a backlog of PD
review
Team member got sick. Study Team was able
to mitigate to avoid delaying SAP3 finalization
and TLD4 definition
1 Competent Authority / Ethical Committee 2 Protocol Deviation 3 Statistical Analysis Plan 4 Top Line data
Capacity management and team member
re-allocation to cover sick team member and
ensure on-time delivery of committed
contribution
Best practices gathering and sharing
Risk identification and mitigation
Overlap internal Clinical Operation and CRO
Standard Operating Procedure ownership
re-defined
Roles & Responsibilities clarified
3
C
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 12
Standards as a lever to close the improvement loop and ensure compliance with QSM1 and GCP2
Standards
Plan
DoCheck
Act
Plan
DoCheck
Act Standards
Time
Continuous
Improvement
Standards1
E
4
1 Quality Management System + Best Practice Documents 2 Good Clinical Practices
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 13
Standards embed a whole set of documents –with different purpose, focus, and dynamic
4
Content
Scope
Maintenance frequency
Lay-out
Best Practice documents
Quality Management System (SOPs1,
etc.)
Dominant axis is “how” to perform tasks
Primarily within one function
No fixed cycles, continuously improved per experts
One-pager
Dominant axis is “what” to perform
Primarily cross-function
Fixed review cycles(hardly updated in between)
Multi-pagers
Purpose
Strategic “know-how”
Simplification & Standardization
Skills development to ensure autonomy of all members
Reduction of skill variability
Helps to focus on everyone strengths
Mandatory knowledge
Adherence to regulations and GCP2
Training On the job coaching by experts
Individual fluency regularly assessed and documented in skill matrix
Self reading and online testing
Class training
A B C
D
E
1 Standard Operating Procedures 2 Good Clinical Practice
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 14
GRA productivity (indexed FTE1) – 1 year post wave
Levers identified and
implemented
Gatekeeping to filter demand and
define priorities
Monthly alignment and performance
review with interfaces
Several initiatives for simplification
and process optimization
successfully completed resulting in:
• 700+ hours of backlog eliminated
• 62% reduction of number of
dossier for one mature
compound
• Reinvestment in Regulatory
Intelligence(direct request from customers)
• Workload absorption
Impact example –Global Regulatory Affairs Transformation wave Sep-Dec 2012
1 Full-Time Equivalent
30
41
Re-investment
Volume absorption
Re-allocated FTE
Vacancies cancelled
Baseline Oct 2012
-27%
Actual Dec 2013
4.5 1
1.5
4
100.0
11.0 2.4 3.7
9.8
73.2
Index 100 = Baseline Oct 2012
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Implementation of clear data
handling timelines and
responsibilities
Several initiatives for simplification
and process optimization to:
• Foster standards
• Simplify documentation
requirements
• Reduce over-processing and
rework
Decrease of skill variability within
teams
Levers identified and to be
implemented
1 Last Subject Out 2 Data Base Lock 3 Top Line Data 4 Full Time Equivalent
Impact example –Biometrics Transformation wave Sep-Dec 2013
Lead Time Phase II/III – projection 1 year post wave
Productivity (indexed FTE1) – projection 1 year post wave
Index 100 = Baseline Oct 2013
33.539.5
-15%
Efficiency gain Projection
Dec 2014
Baseline Oct 2013
6
100.0
15.2
84.8
GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL Page 16
As a recap…
Department vs. value stream approach
– In R&D context, both function and project axis are important and strong coordination between the two is required
Implementing a mechanism such as the Performance Management loop have helped Grünenthal R&D to
Problem logging, Solving and escalation
Standards
Execution follow-up and performance
dialogue
KPIs / Performance Tracking / Impact
tracking
Planning of Deliverables and Resources
Project
plan
A B C
D
E
1 Quality Management System 2 Good Clinical Practice
– Instill proactive project and risk management
– Foster compliance with the QMS1 and GCP2