eln and drug development one common platform for all€¦ · eln and drug development – one...

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


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


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


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


Agenda





Public6


• 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


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


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


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


Agenda





Public11


• 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


• Sections in alignment with chapters of final Report

• RD LIMS providing full traceability of samples

Collaboration by Structured

Documentation

Public13


• Legally relevant document stored

within eLN@TRD

• Report for distribution as PDF

with digital signature

Creating an Official Report

Public14


Agenda





Public15


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


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


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


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


• 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


• 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


Inserting Data

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• Transfer during write up of Protocol


Inserting Data

Public23


• Select Value to be transferred


Inserting Data

Public24






• «Drag&Drop» value to selected field

Inserting Data

Public25




• «Drag&Drop» value to selected field

Inserting Data

Public26


• Documentation in structured way

• Time saving compared to «old» process ~90 %

• One source of data, reducing errors

Inserting Data

Public27


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


The Future

• Extension of Spotfire to include analytical data

• Interfacing with instruments

• Data created by CROs

• Migration

Public29


• 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

eln and drug development one common platform for all€¦ · eln and drug development – one...

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