Trends in Regulatory ComplianceTrends in Regulatory ComplianceNovember 8, 2000

Today’s agendaToday’s agenda

Overview of ESPS The state of electronic

submissions ESPS solutions: people, process,

and technology Question & Answer session

ESPS company overviewESPS company overview 191 employees worldwide. Corporate

Headquarters in Fort Washington, PA. Other locations include: La Jolla, CA Raleigh, NC Boston, MA London, UK

Public company since 6/17/99 (Nasdaq: ESPS)

Signed Xerox re-seller & technology agreement in March 2000

ESPS HighlightsESPS Highlights Leader in “Regulatory Publishing” Space (70%+)Leader in “Regulatory Publishing” Space (70%+)

Leader in the emerging multi-billion dollar Leader in the emerging multi-billion dollar knowledge knowledge publishingpublishing space. space.

First mover advantage with knowledge publishing suite of First mover advantage with knowledge publishing suite of products and services with products and services with ExpandedExpanded “Knowledge “Knowledge Publishing Suite”Publishing Suite”

Average revenue growth of 55% (last 3 years)Average revenue growth of 55% (last 3 years)

Strong Financial PositionStrong Financial Position

Cash positive, virtually debt free, Cash positive, virtually debt free,

Strong balance sheet, Strong Cash positionStrong balance sheet, Strong Cash position

Revenue GrowthRevenue Growth

$0.1$0.8 $1.1

$8.6

$17.9

$22.8

$0

$5

$10

$15

$20

$25

1995 1996 1997 1998 1999 2000

$ Millions$ Millions

Fiscal years ended March 31Fiscal years ended March 31

55% average three year growth55% average three year growth

ESPS mission statementESPS mission statement

ESPS, Inc., is the premier provider of knowledge publishing solutions that accelerate the assembly, management, and exchange of diverse, business-critical information for the eWorld.

Knowledge PublishingKnowledge Publishing

Wordicon.exe

Graph9.ico

Xlicons.exe

Pptico.exe

Accicons.exe

My:

Report

SOPs

Proposals

The process of consolidating multiple documents to communicate a concept effectively.

Convey information through publication organization, layout and cross-references.

Knowledge Publishing CycleKnowledge Publishing Cycle content is authored in one of 135 supported native applications

1 source files are collected, organized and rendered to a common PDF format

2

common document level elements are defined and applied across the compiled publication

3 publication is distributed to recipients or approvers via portal, e-mail, or in hard copy

4

TitlePage

footer

NewEmployeeGuide

Ver 3.5

ESPS Life Sciences customersESPS Life Sciences customers3M 3M (E)(E)

Abbott Abbott (E)(E)Agouron Agouron (E)(E)Alcon Laboratories Alcon Laboratories (MD)(MD)Allergan, Inc. Allergan, Inc. (MD)(MD)Alliance Pharm Alliance Pharm (E)(E)

Alza Alza (B)(B)American Home Products American Home Products

-Wyeth Ayerst (E)-Wyeth Ayerst (E)-Whitehall Robbins (OTC)-Whitehall Robbins (OTC)

Amgen Amgen (B)(B)AstraZeneca AstraZeneca (E)(E)AstraZeneca AstraZeneca (Ag)(Ag)Aventis Aventis (E)(E)

BASF BASF (Ag)(Ag) Baxter Healthcare Baxter Healthcare (MD)(MD)Bayer Bayer (Ag)(Ag)Biogen Biogen (B)(B)

NPS Pharm NPS Pharm (E)(E) Novartis Pharm Novartis Pharm (E)(E)Novartis Animal Health Novartis Animal Health (VM)(VM)NV Organon (NV Organon (E)E)Otsuka (Otsuka (E)E)PRA PRA (CRO)(CRO)Parke-Davis (Parke-Davis (E)E)Pfizer Pfizer (E)(E)Pharmacia (Pharmacia (E)E) PharmaNet PharmaNet (CRO)(CRO)Proctor and Gamble Proctor and Gamble (E)(E)Purdue Pharm Purdue Pharm (E)(E)Quintiles Quintiles (CRO)(CRO)Sankyo USA Sankyo USA (E)(E)Santen Pharm Santen Pharm (E)(E)Schering-Plough (Schering-Plough (E)E)Solvay Pharmaceuticals Solvay Pharmaceuticals (E)(E)TAP Holdings TAP Holdings (E)(E)

Centocor Centocor (E)(E)Chiron Chiron (B)(B)

Chugai Chugai (E)(E)Coulter Pharm Coulter Pharm (E)(E)Covance Covance (CRO)(CRO) DuPont Pharm. DuPont Pharm. (E)(E)DuPont DuPont (Ag)(Ag)Dura Pharm Dura Pharm (E)(E)Elan Elan (E)(E)Genentech Genentech (B)(B)Glaxo -SKB Glaxo -SKB (E)(E)Hoffmann LaRoche Hoffmann LaRoche (E)(E)Immunex Immunex (E)(E)Isis Pharm Isis Pharm (E)(E)

Johnson & JohnsonJohnson & Johnson(( E)E)Ligand Ligand (B)(B)

Molecular Biosystems Molecular Biosystems (B)(B)Mylan Pharmaceuticals Mylan Pharmaceuticals (G)(G)

Highly-Regulated Global IndustriesExternal Requirements

Highly-Regulated Global IndustriesExternal Requirements

Vertical Industries: Regulatory Agencies:

Pharmaceutical: FDA, EMEA, OSHA...Biotech: FDA, EMEA, SEC, HPB...CROs: FDA, EMEA, HPB...Chemical: EPA, OSHA, PMRA, EEA...Utilities: NRC, DOE, FERC, PUC, EPA...Telecom: FCC, PUC, SEC, EPA, OSHA...

Highly-Regulated Global IndustriesHighly-Regulated Global Industries

Plus internal compliance:

• SOPs

• GMPs

• Risk Management Plans

• Process Safety Management

• ISO 9000

• ISO 14000 standards

• And other critical information

The Burden of Compliance:Pharmaceutical

The Burden of Compliance:Pharmaceutical There are 4,000 global pharmaceutical/

medical products companies In the US, companies spent over 22.7

million hours Servicing 111 separate

reporting/record-keeping programs Resulting in 13.7 million annual

responses

The Burden of Compliance: ChemicalThe Burden of Compliance: Chemical Environmental Protection Agency has 324 separate information collection

programs Resulting in over 84.3 million annual

responses And over 119 million burden hours per

year

2525

Global “Paperwork” Compliance CostsGlobal “Paperwork” Compliance Costs

Source: Thomas D. Hopkins, “Regulatory Costs in Profile,” August 1996, 1997 OECD Data and IDC 1998

Compliance Costs

(millions)

45 46 46 47

U.S.Non-U.S.

125125

150150

175175

5050

7575

100100

90 92

9394

48 49

9698

$135billion

$138billion

$139billion

$141billion

$144billion

$147billion

5050

Worldwide Web Users

(millions)

250250

300300

350350

100100

150150

200200

7097

131

173

227

320

19971997 19981998 19991999 20002000 20012001 20022002

Traditional Regulatory Submissions: Publish 3 copies each 500,000+ pages

Final submission fills a tractor trailer truck

Two year development & publishing

timeframe

Project staff of 30 - 40 people Lengthy regulatory agency review cycle

impeded by millions of pages of paper Enter the CoreDossier solution...

The Truckload of Paper DilemmaThe Truckload of Paper Dilemma

InternetInternet

CoreDossierCoreDossier

Electronic Regulatory Submissions:Dramatically changes the internal review

cycle: Develop, review, approve and publish

concurrently Publish electronically to Internet,

corporate intranet, using HTML, XML, PDF, TIFF— and publish direct to paper.

Reduce cycle time and cuts required staff May shorten regulatory agency review cycle

The Truckload of Paper Solution

The State of Electronic Submissions

The State of Electronic Submissions

From FDA CDER…From FDA CDER…

Since November 1997:

45% of all applications had some electronic component

80% have electronic CRTs and/or CRFs

15% are complete submissions

Current regulatory trendsCurrent regulatory trends

One FDA reviewer states: “I electronic submissions”

Your competition is doing more in less time– Producing higher quality deliverables– Achieving simultaneous registration– Providing increased navigability

FDA views the program a great success

More guidances are coming

What is on the horizon?What is on the horizon?CTD and e-CTD November 2000

& May 2001CDER & CBER - joint guidance on advertising and promotional labeling

November 2000

CDER & CBER - joint guidance on eINDs

December 2000

CBER- electronic PMA/510K October 2001

CDER- DMFs and annual reports

September 2002

What is on the horizon?What is on the horizon?

EMEA Product information management EFPIA guidance on electronic submission

of MAAs

CDER Guidance on electronic submission of

investigator information

Why electronic submissions?Why electronic submissions?

Better quality than paper

Better organized information

Easier to process and to find documents

Same technology used for all reviews

Improved reviewer efficiency

Electronic submissions will be required

Starting with the end in mindStarting with the end in mind

“We are taking millions of dollars of information and turning it into a common document – it’s no easy task.”

- Chris Tanner GlaxoWellcome

Submission challengesSubmission challenges

Comply with latest electronic

guidances

Produce identical paper & electronic output

Meet submission deadlines Increase efficiency

““NDA”NDA”

Submission challenges:Submission challenges:

70 Customers…70 Methods…1 NDA70 Customers…70 Methods…1 NDA

Overall benefitsOverall benefits

Fewer resources needed

Quality improvements

Cost savings

Increased publishing capacity for simultaneous agency submissions

Compliant with FDA requirements for electronic submissions

Sample CoreDossier case studiesSample CoreDossier case studies Immunex

12/98 - Installed CoreDossier

3/99 - Shipped BLA to CBER; e-Sub shipped prior to paper

“[ESPS] has been great. Oh, and your software is pretty darn awesome!”

Sample CoreDossier case studiesSample CoreDossier case studies ISIS

3/98 - Used CoreDossier to electronically assemble 10-volume CMC section.

4/98 - Submitted the full 366-volume NDA to the FDA, then prepared an 80-volume MAA to EMEA.

“CoreDossier streamlined the internal review time by approximately four weeks. CoreDossier was one of the reasons that we were able to meet our partner deadlines, achieve our milestones, and receive progress payouts”

Case Study: PfizerCase Study: Pfizer

One recent NDA filing by Pfizer using CoreDossier yielded $600,000 in

specific cost reduction.

Task

Pfizer Legacy System

With ESPS’ CoreDossier

Assemble 3 Core Volumes of a NDA

1.5 Days 5 Minutes

Convert 45 Volume Submission to FDA Standards

10+ Days 1 Hour

ESPS Product Suite

kPublisher and CoreDossierkPublisher and CoreDossier CoreDossier

Typical User is Regulatory Operations/Regulatory Affairs Large, multi-volume, highly structured, often government

defined, relatively infrequent Supports regulatory and pre-market approval publishing

and complex functional requirements (CDER, CBER, DAMOS, CADDY, etc.)

kPublisher Occasional/casual publisher Smaller, single volume, more frequent Simple user interface, low training requirement Designed for larger user community within the enterprise

Provide enterprise-wide web based access to publications

Web-based review and approval of publications No client side technology ( no plug-ins or Acrobat ) Annotation and status based review model Full Text and meta data searching

Ability to organize and manage large collections of publications

Customizable interface by user and role