Innovation at ACD/Labs

Andrew Anderson

Outline• ACD/Labs General Introduction – across Research and Development• Industrial Trends

– Automation– Externalization– Quality by Design

• “Assembled” Applications:– Impurity Profiling: Externalization and QBD– Metabolite Identification: Automation and Externalization

• Founded in 1994• 150+ employees worldwide• Headquarters in Toronto, Canada

• Sales offices located in USA, Canada, UK, Germany, France & India• Global network of authorized distributors• In-house software development• A privately owned company

About ACD/Labs

Our Customers Include

300+ Pharmaceutical and Biotech companies

650+ Academic, Government, and Research Organizations

250+ Chemical and CPG companies

Analytical & Chemical Intelligence and

Knowledge Management

Enterprise Solutions & Informatics Services

Molecular Characterization & Decision Support

ACD/Labs Operates in the Following Business Segments Across Industries

target

HIT

lead

candidate

confirmedNDE

in development

in manufacturing

Percepta Batch

Name Batch

Combi-, HT- screening, logD, Sol, ADMET filters, registration

fragment-based, natural product: screening and characterizationSpectrus Workbooks, NMR Experts,

ASV, Structure Elucidator

Synthetic support: separation, chiral method selection; structure verification and confirmation

Spectrus Processor for Bench Chemists, Experimental Design

Percepta Structure Design, Impurity Pack

Spectrus/Percepta Impurity Solution, Structure Elucidator

Lead optimization on ADMET

Name

Spectrus, MetaSense, Luminata Solutions

AutoChrom

Spectrus Portfolio, Integration, Sample Management

Impurity identification, elucidation, characterization

Patenting, registration

Method development; pre-formulation

Degradation study; stability; leachables

Metabolism study, knowledge management

Impurity troubleshooting, LIMS support

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ACD/Labs in Pharmaceutical R&D

Value Hierarchy

Redefining Fundraising – Data : The Intelligent Fundraiser Blog [Internet]. [cited 2015 Aug 27]. Available from: http://www.pursuant.com/blog/redefining-fundraising-data/

AUTOMATION

Analytical Knowledge Management

Archiving data

Automated Molecular Characterization, Analytical Data Handling & Knowledge Management

Processed DataRaw

Data

Subset of Domain Specific Data

Client App, Vendor Software, Spectrus App

Data ArchiveACD/Labs

AutomatedSolutions

ACD/LabsAutomation

Domain Specific Knowledge Generation• Structure elucidation

• NMR • Purity Check

• Small molecule QC at cmpd registration• QC for Compound Management

• Chromatography method prediction – chiral and achiral

• Meta-analyses for instrument management• Metabolite ID

ACD/Spectrus Clients Thick Thin

Instrument Integration

Instrument Integration

Instrument Integration

EXTERNALIZATION

Externalization

Externalization

“Andrew will also share some of PepsiCo’s experiences in how to work effectively with intermediaries, and he will touch upon the promise of enabling connected innovation with modern informatics frameworks.”

Document-Driven Decision Making Molecular Characterization in an Externalized R&D Lifecycle

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17

Forced Degradation

60 Pages

Certificate of Analysis

1 Page

ELN

LIMS

Servers

InstrumentComputers

Archive

Key Cross-Industry Externalization Challenge: Abstraction

Reduction of Complex Quality Data in Modern R&D and Collaboration Environments

• Rich, Connected Data are abstracted to Numbers, Text and Pictures.

• Any Specialized Searching of abstracted data requires vendor software, segmented by technique or instrument brand – Efforts underway at Pistoia, Allotrope, Etc.

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AbstractionReduction of Complex Quality Data in Modern R&D Environments:

Disparate, Internal/External Environments

Enriched, Specialized Informatics Tools

• Molecular Structure• Image Processing• Biological Assay• Bioinformatics (sequence encoding, etc.)

• What do our modern systems have for Analytical Data?

Chromatography

Our Core: digital Molecular Characterizationfrom Assembled Data

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MS MS MS

All All All

Analytical data is at the foundation of everything an R&D organization does…

QUALITY BY DESIGN

Quality by DesignImpact on Process Development

QBD and Impurity Profiles

Why are these three Chemical Components critical to control?Input Materials + Unit Operations

Final Product CQAUnit

Operation 3Input Material 3Unit

Operation 2

• Let’s consider a relatively simple Chemical Reaction:

Input Material 2Unit Operation 1Input Material 1

QbD and Critical Quality Attributes

OH OH

CH3

O

CH3

CH3

O

O CH3

O

OHO

CH3COCl

THF

KMnO4

THF

CH3Cl, AlCl3

For Final Product, what are the Parameters for all subsequent Unit Operations, and Material Attributes for all subsequent Input Materials which define its Critical Quality Attributes?

Chemical Component Categories• Intended Conversion• Carryover • Unintended Conversion

CQA:• Measure Intended

Conversion• Assess Carryover Risk• Assess Risk of Presence of

Unintended Conversion

Impurity Maps to Establish CQAs

Impurity Profile Information

Search?

Analyze?

Interpret?

IMPURITY PROFILING

Batch Comparisons

METABOLITE IDENTIFICATION

Externalized MetID Study

• For Externalized Studies – the “results” will be submitted via PDF or maybe digital structures

• Can we as scientists verify the results?• Can we easily review the supporting analytical

results?

Data Input Metabolite Detection and Identification Knowledge Management

Biotransmap

Summary table

BPC and XIC Kinetic/Stability

Plot

Project navigator

MetaSense™ Summary View

39

Biotransmap

Summary table

Mirrored Plot

Project navigator

Metabolite structure and Fragment structure

XIC/BPC

MetaSense™ Metabolite View

40

BPC/XIC

Summary Table

Extracted MS2 and MS3 spectra

MetaSense™ Spectrum-centric

41

Global BT Map

Local BT Map

MetaSense™ Overall BT

42

MetaSense™ on the Web

• Web-based metabolite ID decision support

• Java script based “plugin”• Nimble light client for

dissemination of results• Web browser independent