ShApING SuCCeSS IN phArMACeutICAL DeveLopMeNt

For everY MethoD. everY Step oF the WAY.

[ PHARMACEUTICAL DEVELOPMENT SOLUTIONS ]

[ PHARMACEUTICAL DEVELOPMENT SOLUTIONS ]

Developing innovative medicines is challenging enough without the added

pressure of having to do it faster than ever before – with the same or fewer

resources. No matter the size of your organization, the goal is the same:

move through development quickly without compromising data quality

or increasing costs. And help your organization’s products get to market

sooner, successfully.

how do you get there? Start by implementing solutions that enable you

to develop information-rich, reliable analytical methods – from day one –

containing the details necessary to make critical decisions at any step

in the development process. Make that knowledge globally accessible

so that progress never stops. By working with Waters, you can readily

advance your analytical technologies in a way that makes a difference

to your company’s bottom line.

UncovErinEFFiciEnciEs.

MaxiMizErEtUrnoninvEstMEnt.

PartnErWithWatErstogEtyoUthErE.

today.

[ PHARMACEUTICAL DEVELOPMENT SOLUTIONS ]

“WeatWatersunderstandthecriticalworkflowchallengesindrugdevelopmentlaboratorieswherestreamliningtheprocessofmethodscouting,optimization,

validation,andtransferisofutmostconcern.

“Everythingwedofocusesoncontinuedinnovationinlaboratoryinstrumentation,chemistries,andsoftwaretoaddresstheseissues.Keytooursuccessismaking

ourcustomerssuccessful.Byfosteringandsharingourapplicationsexpertise,

wemakesurethatscientistscanmaximizetheimpactofthesetechnologiesto

exceedtheirbusiness,research,ororganizationalgoals.

“Forward-lookingcompaniesarefastrealizingthatWaterssolutionsgeneratebenefitsandcostsavingsthatextendintoeveryareaofdrugdevelopment–

andturngreatscientificideasintosuccessfulproducts.”

Arthur G. CAputoExecutive Vice President, Waters Corporation, and President, Waters Business Operations

The range of selectivities available with Waters HPLC and ACQUITY UPLC® Columns allows you to quickly determine the best methodology for your sample.

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MS TIC

O

OO

OO

CH3 CH3 CH3

CH3

CH3 H

FW: 420.5821

C

Peak not identifiedby UV

Simvastatin

The easy-to-use ACQUITY UPLC System with the ACQUITY UPLC Photodiode Array Detector and SQ Mass Detector provides rapid and comprehensive peak detection.

FORCED DEGRADATION“…allofthemajordegradationproductsandimpuritieswereseparatedbytheUPLCapproachbutinhalfofthetimerequiredbytheHPLC...[with]aflatterbaseline,sharperpeaks,andverygoodretentiontimeprecision.…AnadditionalbenefitwiththeUPLCmethodisthatthemobilephaseconsumptionwasonlyabout20%ofthatoftheHPLCmethod.”

AstrAZenecA Journal of Chromatography a3

LEAD OPTIMIZATION

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BEH Phenyl

BEH C18

BEH Shield

BEH C8

upLC Method Scouting 2.1 x 50 mm, 1.7 µm

hpLC Method Scouting 4.6 x 150 mm, 5 µm

Acid acetonitrile screen* 2 hours 12 hours

Acid methanol screen* 2 hours 12 hours

Basic acetonitrile screen* 2 hours 12 hours

Basic methanol screen* 2 hours 12 hours

TOTAL 1 day 5 days *4 columns: 2 blanks, 2 replicates + re-equilibrate

METHOD SCOUTING“…theanalystcanachievefast,efficient,andreproduciblemethods.Theresultsarecompellingthat1.5to2µmsizedporousstationaryphaseparticlesusedwithhigh-performanceinstrumentationsuchastheACQUITYUPLCwillbecometheoptionofchoiceforthedevelopmentoffastLCmethodsinpharmaceuticaldevelopment…”

novArtis lCgC north ameriCa2

“If top 20 companies are to deliver sales growth… they will need to dramatically improve R&D productivity… those that cannot dramatically increase both the

number and quality of drugs will go the way of the dinosaurs.” 1

DO ONE wEEk’S wORTH OF METHOD SCOUTING IN jUST ONE DAy

DETECT pEAkS bEFORE THEy bECOME A pRObLEM

PRE-

CLIN

ICAL

“Developers, both large pharma and small/mid-tier pharma, are implementing new technologies to reduce late-stage

failures and contain rising development costs.” 4

IMpURITy pROFILEDON’T bE CAUGHT OFF-GUARD by pRE-ExISTING IMpURITIES LATE IN DEvELOpMENT.Acquire comprehensive impurity profiles with high resolution, sensitive ACQUITY UPLC methods.

STAbILITy“The[UPLC]methodwascompletelyvalidatedshowingsatisfactorydataforalltheparameterstested.Thismethodexhibitedanexcellentperformanceintermsofsensitivityandspeed.Itisastabilityindicatingmethodsuitableforrapidanalysisofprimaquinebulkdruganditsimpurities.”

University of MUMbAi, indiA Journal of pharmaCeutiCal and BiomediCal analysis 5

ROUTE OpTIMIZATIONNEvER LET ANALyTICAL SUppORT bE A bOTTLENECk IN pROCESS CHEMISTRy. With UPLC, enable faster decision-making for choosing the right synthetic conditions.

CANDIDATE SELECTION & CONFIRMATION

hpLC upLC

Total number of injections for sample set (Sample, standards, QC sample, blank)

58 58 Number of runs stays the same

Run time per injection at 1 mL/min (Equilibration time, run time, analysis time)

50 min 12 minAnalysis time reduces from 50 to 12 minutes per run

Total analytical time reduces from more than 6 business days to less than 2 by using UPLC for sample set

Total analysis time for injection set 48.33 hr 11.60 hr

Total volume of solvent per analysis 2945 mL 696 mLNet cost in solvent use decreases from over $34 to under $9 per analysis

Total cost for solvent use decreases by $1537 by using UPLC for sample set

Cost of solvent per liter $3.93 $3.93

Solvent cost per analysis $11.57 $2.73

Solvent disposal cost $23.13 $5.47

Total solvent usage cost $34.70 $8.20

IMpROvED OpERATIONAL EFFICIENCIES. IN pLAIN NUMbERS.

To support your overall business goals, the advantages of switching to UPLC® are clear. With a focus on the bottom line, ensure that your scientists exploit every advantage that UPLC brings to separations science. From instrumentation operation and maintenance to applications and information management solutions, Waters has educational courses to help your company maintain performance and compliance, while enhancing productivity.

“The fastest performing companies terminated projects earlier in development – 56% of all discontinued projects

were terminated in Phase I.” 4

Time1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00

%

0

Excipients

Acid

API

Acetate

Anhydro

Dimer

Simvastatin

UPLC produces separations that are both high resolution – and fast.

METHOD vALIDATION“Theindustryisverymuchinneedofaworkflow-based,configurablesystem…thatseamlesslyimplementsmethodvalidationrequirementsbutisinherentlyflexibleandmanagesthedata,[that]effectivelystandardizesanoftentediousandtime-consumingprocess.”

JAMes MorgAdo PfiZer globAl r&d

SUbMIT IND

CANDIDATE SELECTION & CONFIRMATION

Develop assays with SOP-driven compliant validation with Empower™ 2 Method Validation Manager. MVM collects and processes all validation data needed, eliminating manual data entry and reducing validation time by 50 to 80%.

INFORMATION-RICH CONTENT FOR CONFIDENCE THROUGH LATE-STAGE DEvELOpMENT

ELIMINATE ERRORS AND REDUCE vALIDATION TIME by 50 TO 80%

FORMULATION DEvELOpMENTwITH QUALITy by DESIGN TAkING HOLD IN DEvELOpMENT, THE NUMbER AND COMpLExITy OF pOTENTIAL FORMULATIONS HAS INCREASED DRAMATICALLy. Keep up with formulators’ analytical demands with ACQUITY UPLC separations, and batch processing and reporting with Empower 2 Software.

“Drugs developed by the fastest companies gained an average $1.1 billion each in incremental prescription revenue

compared to those of the slowest companies.” 4

Rely on real-time worldwide Waters support with Connections INSIGHT® remote monitoring and diagnostics.

A partnership with Waters provides you with the comprehensive laboratory technologies and expertise that enable you to get through development faster – and smarter.

Learn more at www.waters.com/methods

ACCELERATED STAbILITyARE yOUR METHODS RELIAbLE ENOUGH TO ACCURATELy DEFINE THE SHELF LIFE AND pACkAGING OF yOUR pRODUCT? Expedient method scouting with UPLC allows more time to be allocated to optimizing your method for robustness, resulting in long-term analytical method stability.

SCALE-UpwHEN MATERIAL IS REpRESENTATIvE OF THE COMMERCIAL END pRODUCT, yOU CAN’T AFFORD TO MISS ANy CRITICAL ANALyTICAL INFORMATION. The combination of ACQUITY UPLC System and Columns with Empower 2 Software’s peak detection capabilities gives you comprehensive sample analysis every time.

Streamline regulatory processes by automatically capturing, reporting, archiving, and transferring data for IND/NDA submissions with NuGenesis® SDMS.

Waters NuGenesis SDMS

LABORATORY STUDY DATA

Automates scientific data entry into Electronic Common Technical Document (eCTD) standard formats for regulatory submissions.

Chromatography dataMS dataUV dataGC dataLIMS dataBalance measurementsExcel, Word, Visio, PDF, or scanned content

21 CFR 11 compliant data management

ELECTRONIC SCIENTIFIC DATA MANAGEMENT SYSTEM

SCIENTIFIC DOCUMENT MANAGEMENT AND E-SUBMISSION

Captures, reports, and archives data from any and all lab instruments.

Centralizes e-information management of data storage, signatures, workflow, and approval.

TRANSFER TO QC“WithoutConnectionsINSIGHTSoftware,Iwouldhavelostanentireday’sworthofwork.ThevalueofConnectionsINSIGHTtechnologyisthatitprovidesearlywarningofsystemissuesthatcanbefixedquickly–andinmostcases,eliminatestheneedforanon-sitevisit...”

Qc cheMist contrAct MAnUfActUring lAb

Phase I / II / III

SUbMIT NDA

NO MATTER wHERE IN THE wORLD DATA ACQUISITION TAkES pLACE, ALL OF yOUR INFORMATION IS CENTRALLy LOCATED

kNOw THAT INSTRUMENT UpTIME IS MAxIMIZED

CLIN

ICA

L

LAUN

CH QC &MANUFACTURING

SaleS OfficeS:

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Waters Corporation 34 Maple StreetMilford, MA 01757 U.S.A.T: 508 478 2000F: 508 872 1990www.waters.com

t he BeSt SoLut IoNS For phArMAC eut ICAL Dev eLopMeNt

n ACQuItY ultraperformance® System and Columns

For reliable sensitivity, resolution, and analytical speed.

n empower 2 Software with Method validation Manager

Chromatography data management software for any size laboratory.

n NuGenesis Scientific Data Management System (SDMS)

Captures, reports, and archives data from all lab instruments.

n Waters Mass Spectrometry

From single or tandem quadrupole to time-of-flight,

for complete MS information.

n Waters Global Services

No matter where you are located, the service, support, and

training to keep your lab operating at its maximum.

references

1. Pharma 2005: An Industrial Revolution in R&D. PricewaterhouseCoopers. Nov 1998.

2. The Use of ACQUITY UPLC in Pharmaceutical Development. Jerkovich A, Lobrutto R, Vivilecchia R. Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, U.S.A. Supplement to LCGC North America. 2005; 15-21.

3. Use of Ultra-Performance Liquid Chromatography in Pharmaceutical Development. Wren SA, Tchelitcheff P. Analytical Development, PAR&D, AstraZeneca, Cheshire, UK. J Chromatogr A. 2006 Jun 30;1119 (1-2):140-6.

4. Tufts Center for the Study of Drug Development Impact Report. Sept/Oct 2006, Vol 8, No. 5.

5. Development and Validation of UPLC Method for Determination of Primaquine Phosphate and its Impurities. Dongre VG, Karmuse PP, Rao PP, Kumar A. Department of Chemistry, University of Mumbai, India. J Pharm Biomed Anal. 2007 Sep 16.

Waters, ACQUITY UPLC, ACQUITY UltraPerformance LC, Connections INSIGHT, NuGenesis, and UPLC are registered trademarks of Waters Corporation. Empower and The Science of What’s Possible are trademarks of Waters Corporation. All other trademarks are the property of their respective owners.

©2008 Waters Corporation. Printed in the U.S.A. February 2008 720002446EN LB-CP

www.waters.com/methods