Powering Impurity Lifecycle ManagementArvin Moser, M.Sc.

ENC user meeting 2017

Background on Impurities

• The impurities in pharmaceuticals are unwanted chemicals that remain with the active pharmaceutical ingredients (APIs) or develop during formulation or upon aging of both API and formulation.

• Impurities can be hazardous such as mutagenic (affect genetic material), teratogenic (affect environment/fetus), carcinogenic (cause cancer)

• Affects quality, safety, and efficacy of the product• Great interest in controlling and monitoring impurities to

meet regulatory requirements

Analytical Knowledge Management

Search?

Analyze?

Interpret?

Food & Flavors Workflow

C. Scheidig , M. Czerny , P. Schieberle J. Agric. Food Chem., 2007, 55, pp 5768–5775

LaunchPhase 1Toxicological testingFirst into man

Phase 2Early clinical trials

Phase 3 / Technology TransferFull clinical trialsPrepare for launch

Discovery

Why is impurity management important?

Limited knowledge Known impurity

• Name• Structure• Amount

• Formation• Removal

• Specification

The challenge?• A large amount of complex data is generated• Information stored in multiple computer systems• Many people work on our projects in different groups and

locations

Why?• To ensure our medicines are safe by

controlling our process• To meet regulatory requirements

• From Steve Coombes at AstraZeneca

Typical Questions

What is the current route? Route (Commercial)Route (Development)

How are they formed and controlled?

Fate of impurity BFate of impurity A

What impurities do we seeand how much?

Impurities i PhenolImpurities in MethylImpurities i AcetateImpurities in Aspirin

0.12

Batch 123

<0.050.080.20

Have we seen this impurity before and where does it elute?

What is this other peak?

Where has it come from and is it a concern?

What is this new peak?

What does the spectrum look like?Pharmaceutical Technology & Development

• From Steve Coombes at AstraZeneca

• Multi-technique, multi-vendor supported processing, reporting, spectral database searching, & database creation.

What capabilities do you have access to?

Live Data in Spectrus Processor

Analytical Knowledge ManagementSynthesis or formulation

steps

Gold Standard Spectrum

Batch Specific Spectra/

Chromatograms

Table of all components and their classification

All components with Area % take directly from analytical data so

you can see values per component at a specific stage

SM 1

Imp 1Dimer

Imp 2Cyclised derivative

THF

Imp 3N-methyl

Imp 4SM1 Dimer

SM 2

Alanine

Imp 9Difluoro

Imp 11Uradine

IM 1

Imp 13IM1 Isomer

Imp 15Dichloro

SM 2

IM 2

Imp 31IM2 Isomer

Imp 32Dimethyl

Imp 22IM 1 Dimer

IM 1

SM 3

Imp 8Dichloro

Imp 16Trichloro

ACD1253

IM 2

Imp 48Hydroxy

Imp 8Monochloro

SM 3

ACD1253

IM 2

Imp 48Hydroxy

Imp 8Monchloro

Stage 0Starting Materials

Stage 3Starting Materials

Stage 1 Stage 2 Stage 3 Stage 4

To be released at Pittcon

Analytical Knowledge Management

Table can be modified to show at anytime in a project a component

has appeared

SM 1

Imp 1Dimer

Imp 2Cyclised derivative

THF

Imp 3N-methyl

Imp 4SM1 Dimer

SM 2

Alanine

Imp 9Difluoro

Imp 11Uradine

IM 1

Imp 13IM1 Isomer

Imp 15Dichloro

SM 2

IM 2

Imp 31IM2 Isomer

Imp 32Dimethyl

Imp 22IM 1 Dimer

IM 1

SM 3

Imp 8Dichloro

Imp 16Trichloro

ACD1253

IM 2

Imp 48Hydroxy

Imp 8Monochloro

SM 3

ACD1253

IM 2

Imp 48Hydroxy

Imp 8Monchloro

Stage 0Starting Materials

Stage 3Starting Materials

Stage 1 Stage 2 Stage 3 Stage 4

To be released at Pittcon

Analytical Knowledge Management

…or any point that the component has appeared in a batch or project

IRM Table of Entities

• This table contains all information associated from the reaction scheme

Luminata Compounds

Searching the Table of Entities

• Right click on the table and select Search Data

Searching by Molecule

• Within ChemSketch, you can search exact structure, similar structure, parent or reactant

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 Critical Quality Attributes

Live DataFrom Instrument Data to Control Summaries with one

system

Additional Details• Oracle & Postgres• Connecting to in-

house registration system (ELN, LIMS, Archives, etc.)

• Permissions control• Audit trials• Internet Portal• Support for

ChemDrawreactions

• Overlay and compare NMR, MS and

4/11/2017 Advanced Chemistry Development, Inc. (ACD/Labs) 22

ENC Hospitality Suite

Sunday-Wednesday7:00-11:00 PMSuite: Acacia

Visit our hospitality suite for great games, contests, and refreshments.

Plus we’ll have a new limited edition t-shirt to give away!

Scientific Posters

• Computer Assisted Structure Elucidation of Two Biflavonoidsfrom the Leaves of Ochna MauritianaG.A. Dziwornu,1 N.R. Toorabally,2 M.G Bhowon,2 S. Jhaumeer-Laulloo,2 S. Sunassee,1,3 A. Moser,4 D. Argyropoulos5

• Impurity Lifecycle Management: Visualising a Vast Array of NMR and Other Analytical DataSteve Coombes,1 John Nightingale,1 Azalea Micottis,1 Albert Van Wyk,2 Peter Russell,2 Dimitris Argyropoulos,2 Stephane Albrecht2

• Characterization of Heavily Contaminated Sites using NMR SpectroscopyDarcy Fallais,1 Brent G. Pautler,2 Arvin Moser,2 James G. Longstaffe1

4/11/2017 Advanced Chemistry Development, Inc. (ACD/Labs) 23

Some Humor…

• I make bad chemistry jokes because all the good ones Argon

• Q: Why do chemists enjoy working with ammonia?A: Because it's pretty basic stuff.

• Q: What did one ion say to the other?A: I've got my ion you.

• Q: What did the chemist say when he found 2 isotopes of helium?A: HeHe

4/11/2017 Advanced Chemistry Development, Inc. (ACD/Labs) 24