Experience of : eSubmission for FDA & eCase Files for US Courts

Experience of :Experience of :ee--Submission for FDA &Submission for FDA &

ee--Case Files for US Courts Case Files for US Courts

Jinsoo Kim Image Solutions, Inc.Product Evangelist President/CEO

2002 PDF Conference West 2

AgendaAgenda

New Drug DevelopmentFDA Electronic Submission HistoryWhy FDA Choose PDF Format?Electronic Submission FormatPharmaceutical Company Issues & ApproachReview ToolsBenefits/Influence of e-SubmissionsFuture Direction

FDA Electronic SubmissionFDA Electronic Submission


New Drug DevelopmentNew Drug Development

PHASE I

PHASE II

Post-Marketing

Surveillance

PHASE IV

Adverse Reaction Reporting

Surveys/ Sampling Testing

Inspections

PHASE III

Pre-clinical R&D Clinical R&D NDA Review

InitialSynthesis

AnimalTesting

Range: 2 MOS. - 7 YRS.AVG: 24 MOS.

Range: 1-3 YRS.AVG: 18 Month FDA Time AVG: 5 YRS.

30 Day Safety Review

Range: 2-10 YRS.

NDA ApprovedNDA Submitted

Industry TimeFDA Time Sponsor/FDA Meeting Encouraged

Average 100 Months = 8 YRS & 4 Months


FDA Electronic SubmissionFDA Electronic Submission

12Km (7.5 Miles) of Paper per Year for New Drug SubmissionAverage 7 Years R&D and 2 Years FDA ApprovalReducing Approval Time is a Critical CANDA (Computer Assisted New Drug Application) ApproachFDA Show the interest on PDF based Electronic Submission in 1996



History of eSubmission in FDAHistory of eSubmission in FDA

... September 1997 CANDA (Computer Assisted New Drug Application)

September 1997 Guidance for Industry Archiving Submissions in Electronic Format —NDAs

January 1999 Guidance in Providing Regulatory Submissions in Electronic Format — General Considerations (CDER & CBER)

January 1999 Guidance for Industry Providing Regulatory Submissions in Electronic Format —NDAs (CDER)

November 1999 Guidance in Providing Regulatory Submissions to the CBER in Electronic Format — BLA, PLA, ELA and NDA

November 1999 Guidance in Providing Regulatory Submissions to the CBER in Electronic Format — BLA, PLA, ELA and NDA

January 2001 Guidance for Industry Providing Regulatory Submissions in Electronic Format —ANDAs (CDER) : Draft


Why FDA Choose PDF Format?Why FDA Choose PDF Format?

Strong Document ComponentsLong-term Archival Format• Software Lifetime is Short than Drug Lifetime• Compatibility & Support Issue

Easy to Use and Easy to NavigateEasy to Create (Production Cost)Industry Standard Format


ApproachApproach

Benefit to Both FDA and Pharmaceutical Companies by Eliminating Paper RequirementStep by Step Approach• Year 1997 – CRF & CRF Section First • Year 2002 – Whole Sections

Pilot with Industry for New TechnologyGuidance Manual• Not Ruling but Guiding • Room for Negotiation


The Guidance of eThe Guidance of e--SubmissionSubmission

Data Format• Electronic Document – PDF File• Electronic Dataset – SAS System XPORT Format

Media

No limitDigital Tape - Digital Equipment Corp. DLT 20/40 and 10/20 GB

Greater than 3.25GB

1 to 5 CDsCD-ROM ISO 9660Less than 3.25GB

1 to 103.5 inch DOS Formatted Floppy Disks

Less than 10MB

UnitsMedia and formatSize of Submission


PDF File FormatPDF File Format

Readable by Acrobat Reader 3.0Font• Font Embedding• Blue Font Color for the Hypertext Link (CBER)• “New Times Roman”, 12 Point

Page Orientation• Landscape Page to Landscape Orientation

Scanning Image• 300 DPI Resolution, CCITT G4 Fax Compression


Page NavigationPage NavigationHypertext Linking & Bookmarks• Improve Navigation• Invisible Box in TOC Page – CDER• Blue Text Hypertext Link – CBER• Bookmark no more than 4 level• Relative Link• If text body refer different page, put hypertext link• Inherit Zoom

What to Hypertext Link & Bookmark?• Table of Contents• Tables, Figures• Publications• Other References• Appendices


Other ConsiderationsOther ConsiderationsPage Numbering• No Need to provide pagination for the entire submission• TRY PDF page number to be same with document page

number

Other Attributes• Document Information Field• Open Dialog Box• Naming PDF File – 32 character• Indexing PDF Document• Security – Do not impose• Plug Ins – OK for the Creation, not require for the

review


Electronic NDA StructureElectronic NDA StructureNDA Number

Labeling

356H.PDF

NDATOC.PDF

Summary

CMC

…

Amendtoc.pdf

suppltoc.pdf

Study #

Site #

Patient #.PDF

Patient #.PDF

COVER.PDF

CRFTOC.PDFCRF

Other


ee--Submission DemonstrationSubmission Demonstration


FDA Submission ExperienceFDA Submission Experience

Over 200 Submission is DONE by ISI


Pharmaceutical Company IssuesPharmaceutical Company Issues

Cost and TimePaper and / or Electronic Copy Facilitating the Review Process (Approval Time)


3 Step Approach3 Step Approach

Step 1 - Out Source All Sections of the Submission

Step 2 - Out Source and In-house• In-house - Study and Summary Report• Out Source - CRF, CRT

Step 3 - All In-house• Document Management System• CRF Management System• Publishing System• Tools


Review ToolsReview Tools

Text CopyTable CopyGraphic Copy Annotation Markup ToolsOpen / Close Bookmark in a Single ClickPDF e-mail


Benefits/Influence of eBenefits/Influence of e--SubmissionsSubmissions

Fast Review• Quick Navigation

– Bookmarks, CTOC– Hyper Text Links, References

• Copy & Paste – Text, Table and Picture• Word & Full-text Search

Short PreparationLower CostStorage Space and Paper Management


Reduction of PaperReduction of Paper

0%

25%

50%

75%

100%

1997 1998 1999 2000


Future DirectionFuture Direction

XML – Backbone for TOC and Structure DocumentPDF – Content and Legacy Document

US Court US Court -- CM/ECFCM/ECF(Case Management / Electronic Case Files)(Case Management / Electronic Case Files)


What is CM/ECF?What is CM/ECF?

Joint project of the Administrative Office of the U.S. Courts and the federal courtsTo replace existing paper based case management systemsWith a new system based on current technology, new software, and increased functionalityThis new system will give federal courts the ability to maintain electronic case files and offer electronic filing of court documents over the Internet


Benefits for Attorneys & PublicBenefits for Attorneys & Public

Case information is available for viewing and downloading to attorneys and the public• at any time from locations other than the courthouse• via the Internet through the PACER system at a cost of seven

cents per page and free for their own cases

Parties, the judge, court staff and the public can review the case file simultaneouslyRegistered attorneys can file case documents 24h/7d over the Internet from their offices or homes right up to the filing deadlineImmediate Filing Notice by e-mailCost of participation for attorneys is very low


MilestoneMilestone

Bankruptcy courts is being implemented nationally over a two-to-three year period starting March 2001The district court began to roll out nationally in May 2002The CM/ECF system for appellate courts is expected to be ready for use mid-2003 CM/ECF is currently in use in forty-five courtsMillions of cases are on CM/ECF systems, and thousands of attorneys across the country are filing documents electronically


PDF Format as an Only FormatPDF Format as an Only Format

It allows a document to retain its pagination, formatting and fonts no matter what type of computer is used to view or print the documentIt is an open standard formatEasy to Create


Procedural RulesProcedural Rules

Local Rules mended in 1996 to authorize electronic filing• Rule 5(e) of the Federal Rules of Civil Procedure• Rule 5005(a) of the Federal Rules of Bankruptcy Procedure• Rule 25(a) of the Federal Rules of Appellate Procedure• Rule 49(d) of the Federal Rules of Criminal Procedure

Federal Rules of Bankruptcy Procedure, which went into effect December 1, 2001• Rules 5(b), 6(e) and 77 of the Federal Rules of Civil Procedure• Rules 7005, 9006 and 9022 of the, authorize service of

documents by electronic means if parties consent.

Most courts that offer electronic filing have issued an authorizing local rule


Process DiagramProcess Diagram

ScanInsert Document Separation Sheet

Document Separation

Title:

Author:

Subject:

Title:

Author:

Subject:

Title:

Author:

Subject:Title:

Author:

Subject:

Jinsoo Kim

NDA Sub…

Manual

Title:

Author:

Subject:

Jinsoo Kim

NDA Sub…

Manual

Title:

Author:

Subject:

Jinsoo Kim

NDA Sub…

Manual Index

TIFF

TIFF

PDF Conversion TIFF

DocComposer

• Case #• Judge• Document Type• Case Admin. Name

Main PDF Output

Judge 01

Judge 02

Judge 03

…

001 – Case 1234 : Document Type 1 Admin 01

Admin 02

…

002 – Case 1234 : Document Type 2



…

Export

Upload CM/ECF System


PDF OutputPDF Output

Main PDF Output

Judge 01

Judge 02

Judge 03

…

001 – Case 1234 : Document Type 1 Admin 01

Admin 02

…




…


IssuesIssues

Large Volume• NJ Bankruptcy Court – 20,000 pages per day

Many Small Page DocumentTo Many Manual Steps


Realities of Processing TimeRealities of Processing Time

Upload45%

Job Switching30%

Scan15%

PDF Conversion

10%


Performance FactorsPerformance Factors

User InterfaceProcessScanningIndexingPDF ConversionUploading


User InterfaceUser Interface

5%Tiled ImageImage Window is too small

30%Hot or Function Key Mapping on Frequently used Function

Moving Mouse

Performance Increase

EnhancementIssue


ProcessProcess

20%Batch ProcessingJob Switching Time

10%Job SeparationJob Over Qualification

20%Automated Job/Work FlowComplicated Steps


EnhancementIssue


ScanningScanning

10%Use Scanning StyleMixed Paper Size Scanning

10%Automatic CleaningImage Cleaning

10%Automatic DetectionPage Orientation Setting

30%Scan AheadSerial Steps on Scanning and other works (DB Insert…)


EnhancementIssue


IndexingIndexing

15%Highlight Possible Data Location

Finding Data Location

10%Keep Previous Data for next Entry

Retyping Same Data

10%SmartMatch (Automatic Selection by OCR)

List Box Selection

30%OCR Selected Area by drawing box

Manual Data Entry


EnhancementIssue


PDF ConversionPDF Conversion

10%One Step TechnologyToo Many Steps

20%Fast Hidden Text Creation

Hidden Text Creation

25%Fast TIF to PDF Conversion (20 PPS)

Conversion Speed is Slow


EnhancementIssue


UploadingUploading

15%Use Indexed Data for the Attribute Setting

Setting Attributes

20%Use Indexed Data for the Object Naming

Manual Object (File) Naming

30%Use Indexed Data for the Folder Selection

Browse / Select Output Folder


EnhancementIssue


Overall Productivity IncreaseOverall Productivity Increase

79.4%Uploading

65%PDF Conversion

80.9%Indexing

73%Scanning

58.4%Process

36.5%User Interface

Productivity Increase

Category

Parallel Impact

Serial Impact

~8 Times Productivity Improvement


SolutionsSolutions

DocComposer™• Scanning• Document Separation• Indexing• PDF Conversion• Export into Uploading Work Area

Acrobat Plugins• Copy Path – Copy PDF Full Path Name into Clipboard• Custom Field Stamper

– Date & Time into PDF Field– Set Hidden File

• Expiration Detection – After 30 days, move or delete files


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Experience of : eSubmission for FDA & eCase Files for US Courts