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eLN and Drug Development –
One Common Platform for All
Dietmar Flubacher, Senior Fellow
Basel
November 04, 2016
Novartis Pharma AG
Chemical & Analytical
Development
Novartis Pharma AG, Chemical & Analytical Development
Agenda
1. eLN@TRD – A Global Application
2. Different Workflows for Different Departments
3. Reports as “Official Document”
4. Structured Documentation for Further Analysis
Public2
Novartis Pharma AG, Chemical & Analytical Development
eLN@TRD – a Global Application
Public3
• eLN@TRD is used for non-GxP
documentation
• Users: > 600 users
– >500 Full access, ~100 Read Only
– Departments:
– Chemical Development (CHAD)
and Process Analytic (PA)
– Particle Engineering (PEN)
– Chemical Physical Properties (CPP)
– Pharmaceutical Development (PHAD)
– Local Supply Center (LSC, ReadOnly)
– ChemOps
– Sandoz
BaselMengeš
Hyderabad
Cambridge
Emeryville
San CarlosChangzhou
Shanghai
Novartis Pharma AG, Chemical & Analytical Development
eLN@TRD – The Setup
• Servers located in Switzerland
– Servers hosting and maintenance outsourced
– Additional Development- (as VM) and Test-System
• Main Team and PE-contacts located in Basel
– 1st level support by local SuperUsers
– 2nd level support by externals (D-ploy GmbH)
– 3rd level support by PE (located in India)
• Further Development
– 1-2 SuperUsers per functional group with Admin-Training
– Global adjustment is done by SuperUsers
Public4
Novartis Pharma AG, Chemical & Analytical Development
eLN@TRD – Growing within TRD
Public5
01.01.2010 31.10.2016
01.01.2011 01.01.2012 01.01.2013 01.01.2014 01.01.2015 01.01.2016
02.04.2012Migration to v12.1
30.06.2011 - 09.04.2012
Preparation of Migration
24.07.2012
Onboarding Formulation (PHAD)
09.03.2014
Onboarding Safety Lab
02.01.2016
Onboarding SANDOZ (Menges)
01.01.2010Full Roll-out
v11.3 eLN@TRD
17.04.2015
Roll-out eLN@TRD/Spotfire
Interface
12.08.2016
Onboarding Manufacturing
(ChemOps/MST)
28.01.2013
Onboarding Process Analytics
25.07.2014
Implementaion Equipment Management
31.01.2011
Reorganization of Users
Novartis Pharma AG, Chemical & Analytical Development
Agenda
1. eLN@TRD – A Global Application
2. Different Workflows for Different Departments
3. Reports as “Official Document”
4. Structured Documentation for Further Analysis
Public6
Novartis Pharma AG, Chemical & Analytical Development
• Separating «Content» and «Users»
• Privileges are granted on «User Group»-
level
• Users can manage their privileges
IT-support not required for managing
access
«Content» and «Users»
Public7
Novartis Pharma AG, Chemical & Analytical Development
Chemical Process Development, PEN, CPP and MST
• User based notebooks created by form tool supporting this process
• Notebooks contain only CPD-specific experiments
• Specific Notebooks for specific requirements
Pharmaceutical Development
• Notebooks based on application route and created during project setup
• Write access provided by «Project Responsible» by drag/drop to «Project members»
Process Analytics
• Notebooks are created for each year
• Word wide write-access for all PA-members
Safety Lab
• One notebook for global access, all safety related information in one source
• Notebooks contain only SafetyLab-specific experiments
The Project as Focal Point
Public8
Novartis Pharma AG, Chemical & Analytical Development
Add Inn: R&D LIMS
• Synthetic Experiments ↔ Process Analytics
– 15 Methods defined (HPLC purity, GC purity, HPL Assay, GC/MS, ...)
– 2371 requests in 2015
– Problem: Sample vs. Sequence
• Synthetic Experiments ↔ Safety Lab
– 6 Methods defined (DSC, SEDEX, RADEX, ...)
– 1153 requests in 2015
Benefits:
– Planning Tool
– Traceability
– Important information is provided by request
Public9
Novartis Pharma AG, Chemical & Analytical Development
Add Inn: Equipment Management
• Tracking of calibration status for all equipment used in
different departments
• Referencing and tracking of used equipment for QRA
(Quality Risk Analysis) and COI (Carry over of
Impurities)
Public10
Novartis Pharma AG, Chemical & Analytical Development
Agenda
1. eLN@TRD – A Global Application
2. Different Workflows for Different Departments
3. Reports as “Official Document”
4. Structured Documentation for Further Analysis
Public11
Novartis Pharma AG, Chemical & Analytical Development
• Creating a Calo-report involves the
contributions of several persons
• In a classical approach, the
experiments are performed and the
report is created as separate
document
Why not using eLN@TRD as
collaboration platform and the
report is the «printout» of the
experiment
First Comment: «This will not work!»
Collaboration Within a Team
Public12
Novartis Pharma AG, Chemical & Analytical Development
• Sections in alignment with chapters of final Report
• RD LIMS providing full traceability of samples
Collaboration by Structured
Documentation
Public13
Novartis Pharma AG, Chemical & Analytical Development
• Legally relevant document stored
within eLN@TRD
• Report for distribution as PDF
with digital signature
Creating an Official Report
Public14
Novartis Pharma AG, Chemical & Analytical Development
Agenda
1. eLN@TRD – A Global Application
2. Different Workflows for Different Departments
3. Reports as “Official Document”
4. Structured Documentation for Further Analysis
Public15
Novartis Pharma AG, Chemical & Analytical Development
During chemical process
development a lot of data
are generated around a
single chemical reaction.
In the past these data have
been copied/pasted from
eLN@TRD into
Excel/Word. This process is
time consuming and prone
to human error
Visualization and Analysis of Data
Public16
Novartis Pharma AG, Chemical & Analytical Development
Project Scope
Public17
Scope of 1st Generation
Ease
of
Imp
lem
en
tati
on
Low
Moderate: requires alternative
DATA INPUT into eLN@TRD
Difficult: requires fundamental
changes to DATA INPUT into
eLN@TRD
Easy: data already in
structured form in eLN@TRD
MediumHigh
Yield Purity
TimesTemp.
Stoichiometry
Detailed
analytical
data
Addition
rate
Heat/cool
rate
Rest
Solvent
Novartis Pharma AG, Chemical & Analytical Development
Baseline – Time Required to
Extract Data
How much time is needed to extract data into an Excel sheet?
ca. 3 minutes per experiment, ~ 10% of the data points extracted were incorrect
• Time spent on extracting data per year:
– >15’000 standard experiments per year assume 50 % used for data extraction
– >7’500 experiments used for extraction 3 min per experiment
– ~400 h/year or ~50 working days spent on extraction of data
Public18
Novartis Pharma AG, Chemical & Analytical Development
Challenge: Standardization of
Input but Maintain Flexibility
• All processes are different
• The knowledge and understanding of the process is
increasing during development. Therefor different
parameters are of interest over time.
– Hard coded templates is not a solution
– Extensive drop-down menu will always not include all needs
• Version-control to reduce filters (typos, ...)
Defining master-template and use of references
Public19
Novartis Pharma AG, Chemical & Analytical Development
• Ranking by 8 people eachwith 3 votes
• Allocation of stickers topreferred solution(s)
• 2 strongly preferredsolutions:
Drag&Drop 9 votes
eLN Template 15 votes
• A combination of bothsolutions-transferring datadirectly from theexperimental protocol to theeLN template is veryattractive
Workshop on Input of Data
Public20
Novartis Pharma AG, Chemical & Analytical Development
• Defining Master-Template by users for each reaction
• Adding only References to «Template»-folder ensures only one common template for all
• Data pair «Value»/«Description» provides solution to Flexibility vs. Standardization
Defining and Use of Master
Templates
Public21
Novartis Pharma AG, Chemical & Analytical Development
Inserting Data
Public22
• Transfer during write up of Protocol
Novartis Pharma AG, Chemical & Analytical Development
Inserting Data
Public23
• Transfer during write up of Protocol
• Select Value to be transferred
Novartis Pharma AG, Chemical & Analytical Development
Inserting Data
Public24
• Transfer during write up of Protocol
• Select Value to be transferred
Novartis Pharma AG, Chemical & Analytical Development
• Transfer during write up of Protocol
• Select Value to be transferred
• «Drag&Drop» value to selected field
Inserting Data
Public25
Novartis Pharma AG, Chemical & Analytical Development
• Transfer during write up of Protocol
• Select Value to be transferred
• «Drag&Drop» value to selected field
Inserting Data
Public26
Novartis Pharma AG, Chemical & Analytical Development
• Documentation in structured way
• Time saving compared to «old» process ~90 %
• One source of data, reducing errors
Inserting Data
Public27
Novartis Pharma AG, Chemical & Analytical Development
Yield and Purity of all
Experiments
Which reagents have
been used how often and
in which experiment
Correlations between
yield/purity and any
process parameter
Visualization in Spotfire
Predefined Graphical Representations for Different Needs
Public28
Novartis Pharma AG, Chemical & Analytical Development
The Future
• Extension of Spotfire to include analytical data
• Interfacing with instruments
• Data created by CROs
• Migration
Public29
Novartis Pharma AG, Chemical & Analytical Development
• CHAD Synthesis/Analytics
• Bosshard, Andreas
• Cao, Yudong
• Eijgel, Andreas
• Flubacher, Dietmar
• Gerber, Gilles
• Hook, Christine
• Mathes, Christian
• Müller, Sibylle
• Naehrig, Daniel
• Richter, Yvonne
• Stierlin, Stephane
• Venturoni, Francesco
• Wicky, Regine
• Yang, Yao
• Spotfire
• Rajamani, Ramesh (NBS)
• Zünd, Gemma
• CPP
• Chang, Shelley
• Towler, Chris
• Widmer, Toni
• Zhang, Lijun
• PEN
• Hautle, Cathrine
• Meister, Tanja
• Muminovic, Jasmin
• Mut, Larissa
• Wiedmer, Alain
• Safety Lab
• Hoehn, Pascal
• Lanz, Marian
• ChemOps
– Glutz, Markus
– Koehler, Nils
– Rautenkranz, Cedric
The Team
Public30
• PHAD
• Besseyrias, Philippe
• Cherkupally, Laxman
• De Waard, Hans
• Fernandes, Patricia
• Gilardoni, Elodie
• Graner, Oliver
• Kollipara, Sivacharan
• Rogue, Christelle
• Taillemite, Julien
• Volpatti, Sophie
• Sandoz
• Crnugelj, Martin
• Plantan, Ivan
• Selic, Lovro
• 2nd Level support
• Milis, Aleksandar
• Schweikert, Martin
Thank you