RiPAC Roche integrated Process Analytical & Chemical Data

Jean-Michel Adam1, Yaniv Cohen1 F. Hoffmann-La Roche AG 1Roche Pharma Research & Early Development - Roche Innovation Center Basel 2Roche Pharma Technical Operations IT, Basel

The Round Bottom Flask Has Evolved …

SM

Enolate

Enol triflate

Roche Lab 1965 Roche Historical Archives

Roche Lab 1930 Roche Historical Archives

Flow reactor

In-line FTIR

Automated reactors

We are Good at Generating Data …

Reaction Temperature/Heat Release Profile

NMR HPLC/GC LC/GC-MS

Process description (reagents, amounts, solvent, ….)

In-line analytics (PAT)

Yield / Quality / Impurity profile

Generate

Interpret

Design

Kinetic profiles

… At Storing/Searching within Single Data

Sources for (Single) Experiments … LIMS / ECM

Service and Open Access

NMR, HPLC, GC/LC-MS

X-Ray’s, ….

GMP compliant LIMS

(PTDA)

Lab GC/HPLC’s

Automated Lab Reactors

(T°, actions, sampling times, …)

PAT Tools (in-line FTIR, FBRM, ..)

Pdf’s

or LIMS ID

Outsourced analytics Pdf’s

… But not as Good at Combining Them over a Series of Reactions

pCMC Analytical Lab

DT Analytical Lab

(Optical rotations)

Key Objective: Knowledge Generation

Data

Information

Knowledge

(& Wisdom*)

Rapid generation of data

D2I & D2K

* See DIKW Pyramid

I/O & Tasks Landscape

What do you want to do/see/Correlate?

Route

Scouting

Screenings

Optimization

PAR

Robustness tests Regulatory

Data

Temp

Reagents

Dosing times Reaction times

Hold times Equiv.

Concentration

Yield

Purity Impurity control/tracing

PSD Polymorphs

Residual solvents

Stirring rate

SM/reagent quality

Lot tracing

Analy

tical m

eth

ods

Data

Acqu

isitio

n S

yste

ms

Heat release

Melting enthalpy

Navigate Correlate “Publish”

Scale-up

Produce

“Verify”

Inputs

Outputs

Equipment

Kinetics

“Current” Situation: Simple Example

Chromatographic data

Automated Reactor Reports

Manual

Copy/Paste

Excel Tables

manipulations

Integrated Process, Analytical & Chemical Data

Chemical Data Process Data From

Automated Reactors Analytical Data

Scripting Tool

+ +

SpotFire Front End

From Rapid Peak Tagging to Kinetics

Retrieve the official peak naming found in the HPLC data

or

Use of the Spotfire tagging functionality

…. and that’s it!

Kinetic profiles from different

reactions are aligned using a T0

feature (data comes from automated

lab reactor output).

Current Data Workflow: 2 Approaches

Web Panel

User’s Input

Chrom.

ALR

cELN

Launch Script Search

Extract Retrieve

Update

Tables …

User

Input Pipeline Pilot

MIS

JBOSS EDS

Virtualized DB

Chemically aware

SDMS

For data upload /

reprocessing

Information Link

Chemical Development Data Aggregation

pCMC Data Aggregation

Business Intelligence Tools (Custom applications)

Presentation

Layer

Business

Layer

Integration

Layer

Data

sources

Da

ta V

irtu

aliza

tio

n

Ente

rpri

se Info

rmation Inte

gra

tion P

latf

orm

LIMS (GMP) XML cELN SAP

Chemical Development

MIS Core - Layers Concept Yaniv Cohen

Next Steps

Deploy a chemically aware SDMS

Adapt the workflows and data aggregation/visualization tools

Provide additional/specific visualization interfaces

Connect to further data sources

Deploy beyond the early adopters

Acknowledgements

• My Great Support Team!

–Torsten Schindler: Pipeline Pilot Specialist

–Brian Jones: Spotfire & cELN Team

–Peter Hilty: Pipeline Pilot Administration & cELN Team

–Christian Blumenroehr: Spotfire Team

–André Thiele: Lab IT

• Discngine: Eric Leroux

• Mettler-Toledo Software: Beat Dietrich

• Chemical Development IT: Yaniv Cohen

• Chemical Development: Andreas Schuster(API), Robert Dilschneider

(Analytics), Stephan Lauper (Supply)