1 Building an eSubmissions System Ed Tripp Program Director Abbott Laboratories.

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Building an eSubmissions System

Ed TrippProgram Director Abbott Laboratories

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Pharmaceutical Drug Applications

Typical drug product is 10 years in development Must apply for approval by Regulatory Authority (such as FDA) before marketing Must show both safety and efficacy Typical approvals approximately 1 year

after submission

Exclusivity determined by patent life

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Size of a Submission

10 years of data and document Typical 1,000 volumes In paper that stack is 16 stories tall

7 to 20 gigabytes of documents and data Reviewer expects to be 3 mouse clicks from any data Heavily bookmarked and hyperlinked

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Cost Model

IntroductoryStage

GrowthStage

MaturityStage

Decline Stage

TotalMarketSales

Time

End of Patent Life, Generic Competition Enters Market

Regulatory Approval

• Average Drug ends exclusivity at about $400MM/year• Delay in submission approval compresses curve• Cost of delay $1MM per day ($12.68/second)

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Key Documentum Functions

Workflow and Electronic Signature Speed and Accuracy

Organization (Indexing/Folders) Key to putting together successful NDA for

the FDASecurity regarding Documents Patient Records – Insider Information

Multiple document types Word, Excel, SAS, Image, + others all need

to be combined in a easy to read format

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Current State?

How do you store documents and data and how do you process Submissions?

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Source Documents

Check all that apply

CMC Clinical Non clinical

Regulatory

DMS

File share

Local discs

Paper system

Are your Document Management Practices–Well documented?

–Disciplined?

–Ad hoc?

How are they managed today?

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Source Documents

Check all that apply

CMC Clinical Non clinical

Regulatory

US

EU

Japan

Canada

Caribbean

India

China

Where are they located?

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What Will You Keep in the Submission System?

A. Only documents to be submitted?B. Documents that may be submitted?C. Submission and Trial Master file

documents?D. Documents and data sets?E. XML Labeling?F. All of the above

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Submissions: What Regions Will Be Supported?

USEUJapanCanadaAustraliaOthers?

For Submissions?For Document Management?

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Submissions: What Process Do You Currently Use?

Submissions in Paper Printed from electronic files Xerox and Paginate

Submissions Electronic eCTD eNDA eBLA eIND Other electronic formats

What do you want to support with your new system?

Submission types Products: Only Drugs? Include Vet Meds? Device?

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Migration

Will you be migrating documents into the new system From retiring docbase? From File Share? From Local Files? From system you acquired?

Migration can be 10%-20%of your total project cost!

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Security Model

Who has access in the new system?

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Document Based

By Document Most management

overhead Who Decides?

By Doctype

State

Clinical Ops

Clinical CMC RA Non Clin

Draft Version

Read Browse Browse Browse

Approved Read Read Read Read Read

Superseded Read Read Read Read Read

Obsolete Browse

None None None None

Example: ClinSupply Doctype

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Function Based Security

All in function have same rights Example: Everyone in clinical function

can view and edit draft documents

Moderate number of groups to manage Provided you think of functions

broadly Harmonize processes where possible

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Role Based

All in a given role have same rightsExample:

State

Author Reviewer Approver

Draft Version

Relate Read

Approved Read Read Read

Superseded Read Read Read

Obsolete Browse

Browse Browse

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System Ownership

Most documents by created by R&DSubmissions responsibility of RADocument Ownership

2%

8%

15%

75%

ClinicalNon clinicalQualityRegulatory

Typical percentages

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Deployment

How do you deploy the system? Thick Client? Thin Client? Application Delivery Software?

Do you deploy the same way everywhere?What is your enterprise bandwidth for each site?

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Document Repository Structure

How to best configure a for users?

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Document/Folder Structure

By Product? How development thinks and works

By Submission? How regulatory thinks and works

Who creates structure? IT request? User tool to create from a template? Created from metadata?

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How Many States?

DraftFormattedReviewedRoutingApprovedFDA ApprovedSupercededObsolete

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How Many Different Lifecycles?

LabelingCorrespondenceSubmission documentsData setsTemplatesCompiled publicationsVirtual Documents

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How Will You Handle Draft Versions?

Deletion on approval or retain?Start with v0.1 or v1.0?Does a change in properties trigger a new version?

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Will You Use Electronic Signatures?

Is an eSigned document identified vs non signed but approved document?Will you use SAFE?Will you use UID and Password?

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Do All Documents Process Through Workflows?

Can you delegate a workflow?Can priorities be assigned?Can you add workflow participants?What will trigger user notification? When they have a task? When documents become approved? When documents change state? When one person rejects a document?

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Workflow Considerations

Can you include multiple documents? Will multiple documents have

individual outcomes?

Can documents be promoted without workflows? Who can promote documents?

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Workflow Example

SupersededvX.0

DraftApproved*

vX.0DraftvX.Y

ForReview

Workflow

PendingvX.Y

For Approval Workflow

*Becomes superseded if a newer version is approved starting at 2.0.

ObsoletevX.0

Rejected

w/Comments

New Draft Version

Manual transition performed by user

Automatic transition performed by system

For eSignature Workflow

User Promote

User edits

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What Will You Audit Trail?

All actions taken?Approval functions only?Are audit trails available to the user?

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How Will You Handle Amendments and Errata?

Do you need to change your current practice to version the whole document?How do you relate an errata page to the document?Do all both Clinical and Non Clinical have the same process?

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Can You Annotate Documents in Review?

Can all reviewers see all annotations?Can you annotate off line?Do annotations get purged? When?

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Content Creation

Scan Content OCR or not?

Create with Templates Will you manage templates in the system Will you make them available outside the system Who owns the templates

Create from blankCreate from copy of existing DocumentVirtual DocumentsImport ContentAre there document relationships

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Content Creation Continued

When is a rendition triggered? Upon check in? Only if content is changed? Only when moving beyond draft state? What file formats?

Who can create content?Who can edit content? Centralized Medical Writers?

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What File Types and Applications Do You Support?

Documents MS Word (what version) Adobe Acrobat (FDA requires v1.4 PDF) XML Text files

Graphics JPG

Data SAS Transport XML

Others?Need to specify application version and service packs

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Bookmarks and Hyperlinks

Will your system create bookmarks from Word document styles? Training implications

Who creates bookmarks for scanned documents?How do you create and manage hyperlinks? Internal to documents Cross document hyperlinks

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Where Will You Store a Submission?

You need to publish to a fileshare Consider eCTD, other electronic submissions, files to generate a paper submission Docbase?

Do you want active links? How do you move all folders and files?

File Share? Need a security process

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Metadata Management

Its not just about the content

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Metadata

Will you create a doc unique ID? You WILL migrate in the future, so think

about a unique ID that does not change from Docbase to Docbase.

Will you utilize value assist?Are there non required fields? Why?Can changes be made to metadata without versioning a document? Submission number may not be known at

time of submission

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Will You Utilize Dictionary Files?

Who manages the files?What is the update process?Are there relationships? Example: a Clinical Study has one Number and

many investigators

Document the authoritative source of terms ICH specification NCI EVS Thesaurus Snomed or Medra Other

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How Will You Use Metadata?

Do you pass metadata to submission software? DocID for filename eCTD leaf title Species Indication Other STF metadata

What metadata do you expose for searching Is the out of the box search tool sufficient Full text indexing? Is it worth performance issues?

Do you need a reporting tool?

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External Interface Needs

Do you work with Partners? Provide access to part of your

system? Work through FTP? Internet Portal?

Who manages access and content?

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Internal Interfaces

Bulk import solutionScanning solutionSubmission tracking systemCommitment tracking systemEmail systemOther docbasesRendering servicesReporting toolsPublishing software

Will published submission reside in the docbase

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Training Considerations

How savvy is your organization?

Secretary has to do my e-mail

IT comes to me for help

How do they learn best? ILT CBT Webcasts

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Training Continued

How familiar is the organization with electronic submissions? eCTD?Docbase related topics

More complex Security Version Management Meta Data Search functions

Authoring related topics Submission Ready Documents Template use Software restrictions

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Sample Architecture

Inside Firewall

File Share

Documentum

Development Environment

Documentum

Training Environment

Documentum

QA/Val Environment

Documentum

Production Environment

Paper Publishing

eCTD Publishing

Development Environment

Paper Publishing

eCTD Publishing

QA/Val Environment

Paper Publishing

eCTD Publishing

Production Environment

Docs and DataSubmission

Sub

missio

n

Electronic Submission Gateway

Web Portal for Partners

Rendering Software

User Tools

MS Office

Templates

Adobe

Annotation

SPL Labeling

Scanning Software

Bulk Import Tool

Future Integration:Submission TrackingCRF TrackingInternal collaborative space

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Build vs. Buy

Not all configurations are created equal Configurations you can do internally Configurations that must be delivered

What is your internal IT expertise?Do you keep up with releases or keep systems as is for several years?

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The Environment Is Not Stable

eCTD r3.3.3RPS r2XML ProtocolsXML datasetsSPL r4Electronic clinical data capture

Make sure you can react to

changes for the next 5-8

years

Make sure you can react to

changes for the next 5-8

years