20140311 - catel 01_ effective lean deployment to fda approval

GRÜNENTHAL Name der Präsentation DatumGRÜNENTHAL

Effective lean deployment to reduce time to FDA approval

March 11, 2014

Cyrille Catel, ASQ CSSBBAssociate Director, Continuous Improvement & PMO Lead


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


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


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 approach

Improve synchronization along the R&D matrix

Improve the way of working at team level3

Instill proactive project and risk management2

1


Foster standards as a lever to close the improvement loop and ensure compliance with QSM1 and GCP2

4

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Project

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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”


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


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


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


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


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


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


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


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


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


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


– Instill proactive project and risk management

– Foster compliance with the QMS1 and GCP2