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Case Study Update on Structured Content Approaches at Genzyme

Monica Mehta

Director, Regulatory Operations

The views and opinions expressed in the following PowerPoint slides arethose of the individual presenter and should not be attributed to Drug

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Agenda

Background Background Plans for 2009 SCM Business Case Development Plans and next steps

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Agenda

Background Background Plans for 2009 SCM Business Case Development Plans and next steps

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Background

Recognized the value of SCM Recognized the value of SCM approaches in submission development and compilation for global submissions

Conducted a Proof of Concept in 2008

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Co duc ed a oo o Co cep 008

Content will be:

SCM Perceived Benefits

Authored once in a manner that is independent of formatting, publishing or viewing considerations and then reused and repurposed for use in a variety of submission documents;

Tagged for inclusion/exclusion in submission documents

Stored in a content library from where it can be linked

Dynamically assembled into global submission documents

Delivered to a variety of channels or media

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Easily searched for reuse and maintenance

Reviewed at a granular content level or at a composite document level based on reviewer or organizational preferences

Rendered or presented based on the regional agency requirements including different formats and languages (translations)

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Objective

SCM Proof of Concept Objective

Analyze the potential for utilizing structured content concepts and techniques to the content authoring processes in providing efficiencies in the compilation of global submissions.

Focused on the quality related content for submissions in CTD (Proprietary), Redacted (Non Proprietary) and ASEAN

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Redacted (Non-Proprietary) and ASEAN presentations.

The Proof of Concept utilized Virtifys Structured Content Management (SCM) solution as the technology platform.

Successfully demonstrated

SCM POC Resultsy

the following for a document Editing Structure and Content Map Linking Content Redacting Proprietary Content Tagging/Replacing Content Viewing/Rendering the same document in

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g gdifferent formats ICH or ASEAN CTD

Export to Word, PDF or HTML

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Agenda

Background Background Plans for 2009 SCM Business Case Development Plans and next steps

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Develop a roadmap Identify Submissions, Geography or Therapeutic

Transition to SCMIdentify Submissions, Geography or Therapeutic area for a pilot

Collect metrics Demonstrate the Benefits Identify Best Practices and Lessons Learned

Organizational Change Management Process Roles and Responsibilities Supporting Tools and technologies

Ed ti i ti

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Education, awareness, communication and training

Technology choices are critical Solutions should support global, long-term needs Must be open, scalable and extensible

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Build on the success of the POC

Plans for 2009

Identify business processes which could benefit from SCM approaches

Develop strong business case Qualitative and Quantitative

Align with Structured Protocol initiative

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Develop RFI for vendors

Develop Transition Plan

Agenda

BackgroundBackground Plans for 2009 SCM Business Case Development

Communications Process Scope SIPOC Analyses Examples Alignment with Structured Protocol Initiative

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Alignment with Structured Protocol Initiative Quantitative Business Case Model Lessons Learned and Best Practices

Plans and next steps

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Now I can find all of the documents ever created!

Communication: Why SCM

SCMSCM

documents ever created!

But what I need is to know which documents

have the correct information for my

purpose!

-- and where are the supporting documents

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Research Preclinical Quality Clinical Regulatory MarketingManufacturing

Search Search SearchSearch Search SearchSearch

pp gand data!

Companiesspendtoomuchtimecreatingnewdocuments,rewritingexistingdocuments,repairingformatandapplyingmetadatatodocumentsthatprovidethesameproductinformationfor

TooMuchRework

SCMSCM

Communication: Why SCM

differentaudiences.

Intodaysbusinessmodels,contentiscreatedinmultiplelocations,sometimesbymultipleauthorsandfrequentlymovedfromonerepositorytoanothermakingitdifficulttofindandtrack.

Assignmentofsufficientandmeaningfulmetadatatoenableworkflow automation, security, findability and interoperability of

LackofDiscoverability

Ineffective Automation,

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workflowautomation,security,findabilityandinteroperabilityofdocumentsacrosssystemsislaborintensiveandtimeconsuming.

Authoringandcontentsearchsystemsareisolatedinfunctionalareasiloswhichmakesitdifficultforauthorstoavoidrewritingandcontentconsumerstodiscovercrossfunctionalinformation.

IneffectiveAutomation,SecurityandFindability

StovePipeSystems

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Createdocumentsfromreusablecontent(i.e.,buildingblocks)oftextanddata,thesystemautomatically

Reuse&RepurposeContent

SCMSCM

Communication: SCM User Benefits

appliesformattingandmetadataratherthanauthors.

Statusistrackedatboththetopicanddocumentlevelmakingiteasiertounderstandwhatpartsofadocument,(i.e.,topics),arereadyforreview,andwhichremain.

Metadataisatboththetopicanddocumentlevel

EnhanceTransparency

ImproveWorkflow,

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penablingthesystemtoautomaticallyandselectivelynotifyusersoftheirwritingand/orreviewtasks.Withtopics,userssearchandnavigatetofindcontenteitherbysubjectmatter(i.e.,thetopic)ordocument.

p ,SecurityandFindability

WriteitOnceinamannerthatisindependentofformatting,publishing or viewing considerations and then reuse and repurpose for

SCMSCM

Communication: SCM User Benefits

publishingorviewingconsiderationsandthenreuseandrepurposeforuseinmultiplesubmissiondocuments

Applyeffectivemetadatatoimprovesearchanddynamicallyassembleglobalsubmissiondocuments

Storeallcontentinasinglesourcelibraryfromwhereitcanbediscovered,linkedandreusedformultiplepurposes

bl h d f l ll l b

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Publishdocumentsforinternaluseaswellasregulatorysubmissions

Reducerereviewbyreusingcontentatagranularleveloratacompositedocumentlevelbasedonreviewerororganizationalpreferences

Republish,dontrewritecontentbasedonregionalagencyrequirementsincludingdifferentformatsandlanguages(translations)

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On the surface, structured content takes unnecessary re-work out of the business process i e copy & paste

Communication: SCM and Business Process Maturation

SCMSCM

the business process, i.e., copy & paste

Structured content also opens the door to enable maturation of business processes

Content is created in more standardized business processes Carried out with predictable results by internal or external resources Based on accepted standards for data, terminology and readability

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Automatically evolving over time and aligned to business purpose With measurable work effort and tracking of improvements

Bottom line, more time is dedicated to quality of the result and achievement of business objectives

Content ReusedUse of a text fragment, without modification, in multiple documents

SCMSCM

SCM: Real World Example

For example: Reuse in:Clinical Protocol: ICH E6(R1) Clinical Study Report: ICH E36.2 Background and Rationale 7. IntroductionProtocol Synopsis-Objectives 8. Study Objectives6.3 Study Objectives and Purpose 8. Study Objectives

Content Re-purposedProvision of text to users in multiple roles to provide context and supporting

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Provision of text to users in multiple roles to provide context and supporting information for multiple business uses

For example: Re-purpose information for:Clinical Protocol: ICH E6(R1) Clinical Study Report: ICH E36.9 Statistical Methods-Efficacy Analysis 9.5.1 Efficacy Evaluation6.9 Statistical Methods-Safety Analysis 9.5.2 Safety Evaluation6.13 Data Management and Monitoring 9.6 Data Quality Assurance

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Clinical: Process: Phase III Clinical Trial

SCMSCM

SCM: Genzyme Process Scope

Process steps to design, conduct, collect data, analyze and report

Nonclinical: Process steps to design, conduct, collect data, analyze and report

CMC Analytical Testing: Process steps to prepare, execute, collect data, analyze and report

Labeling: Develop Target Product Profile

Process: Repeat Dose Toxicology Study

Process: Stability Testing

Process: Label Development

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Develop Core Data Sheet Develop Package Inserts SPL; PIM etc

Administrative: Process steps for submissions to comply with local regulations for drug development

and marketing Process steps for submissions and regulatory communications to implement a products

global regulatory strategy

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Process: Comply With Local Regulations Implement Global Regulatory Strategy

Designing the Protocol

Protocol Reusable text is

Writing the Protocol Using the Protocol

So rce Output

SCMSCM

Design, Develop and Use a Clinical Protocol

Medical Writer selects clinical protocol template based on study design,

experience and standardsMedical Writers & Clinical Scientists

write study specific text using MS Word

document is published and

delivered to clinical sites

Reusable text is mapped to future

clinical documents

Clinical Trial Management

Study Hypothesis

XML

Study configuration information is

delivered to clinical systems

Source

Process

p

Consumer

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Text is collaboratively reviewed and

updated

Management Systems

Clinical Data Management

SystemsXML

Templates apply previously created

reusable text to reduce re-writing

e-Data Collection Systems

XML

Input

Process

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Target Product Profile

CCDS documentReusable text is

Core Data Sheet Labeling

So rce Output

SCMSCM

Design, Develop and Use a CCDS

Research, Development and Marketing provides input to define the target

product

Labeling creates and maintains the CCDS

CCDS document is published and made available from LiveLink

mapped to future pre-clinical and

clinical documents

Local markets refer to the CCDS for

labeling submissions

Source

Process

p

Consumer

Medical Affairs

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Text is collaboratively reviewed and

updated, continuously

Templates apply previously created

reusable text to reduce re-writing

Input

Process

Medical Affairs refers to the CCDS in responding to

customer questions

Internal decision making bodies refer

to the CCDS as a product profile

Consumer

Drug R&D Timeline

Years -3 -2 -1 C 1 2 3 4 5 6 7 8 9 10

A Document is an information snap-shot but product information continuously evolves

SCMSCM

MarketedPre-market

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Drug R&D Timeline

Years -3 -2 -1 C 1 2 3 4 5 6 7 8

Target Product Profile

Global Development Plan: A Series of Snapshots over time

Indications and Usage Target

Dosage and Administration

Dosage Forms and Strengths

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Use in Specific Populations

Drug Abuse and Dependence

Overdosage

Launch

www.diahome.orgLinked to Supporting Content and Data

Overdosage

Description

Clinical Pharmacology

Nonclinical Toxicology

Clinical Studies

Patient Counseling Information

Research Preclinical Quality Clinical Regulatory MarketingManufacturing

Posting Trial Results Determination to post results of a trial

Process: Phase III Clinical Trial

SCMSCM

Process Scope of Trial Registration & Results Posting

Where the trial results should be posted When (e.g., post-study, interim, )

After product approval (posting is in context of all studies as submitted) After completion of study (one study at a time) Delay in posting for incomplete study or new indication (file request to delay, requires IND Information)

Gather existing trial information Tables, lists and figures (TLFs) CSR (interim, final, errata) Clinical Trial Management information IND/IB/IMPD Registration posting List of publications (peer reviewed if results are presented)

Create posting content

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p g Author additional topics

Character length summaries of:- Patient Disposition (Patient Flow)- Outcome Measures (e.g., PK)

- Efficacy or Safety or Both (tabular, no narrative)- Adverse Event Information (SAE, Non-serious AE)

Posting trial results to Regulatory Authority Data elements required by Regulatory Authority

Maintaining trial results posting Interim to Final Links to new publications with results

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BackgroundAuthorization to conduct a Phase 3 clinical study usually requires the study be registered and approved in advance for countries where clinical sites are located. Posting of results may also be required

Goal

SCM Business Case: Clinical Trial Registration and Result Posting

SCMSCM

Description

The data elements and content components required for trial registration are standardized as elements of the protocol and other documents or data elements required in design of the study

Metadata is standardized and templates are defined to enable automatic assembly of trial registration elements by country

The data elements and content components required for results posting are standardized as elements of the study report and otherdocuments or data elements provided with the study report

Metadata is standardized and templates are defined to enable automatic assembly of trial results elements for posting by country

Integrate data and content for Phase 3 clinical study trial registration documents to minimize the time required for authoring, review and approval of new content

Benefits

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Elimination of manual transcription errors and time to transfer data and content elements to registration/results package

Reduce time and resource required for initial and updated registration or results posting

Improve consistency and quality of data and content elements for registration or results posting

Opportunity Cost

Inability to reduce time for transfer of data or content to registration or results postings

Inability to reduce time to review and ensure data and content qualityProcess Maturity Perform Manage Define Quantify Optimize

Objective

Current State

Gather Summarize andDraft Review

ProjectSubmit

Start Process End Process

Update

Clinical Trial Registration and Result Posting Current State SIPOC Business Process Model

SCMSCM

GatherInformation

SummarizeandIntegrate

RegistrationPackage

RegistrationPackage

ProjectManagement

RegistrationPackage

Supplier/Source Input Process Output Consumer

[i] Clinical Trial Management System

Clinical trial sites Access CTMS to determine location of trial sites

List of countries for trial registration

[r] BMRAC Program Dev. & Ops.

[r] BMRAC Program Dev. & Ops.

List of data elements required for registration

Work with Regulatory Affairs

Clinical Trial Registration Package for each country

[i] Regulatory Authority

[r] Biomedical Data Sciences

Tables lists and figures from Access tables, lists and figures to

[r] Clinical Research Protocol Synopsis Access Protocol Synopsis

[r] Regulatory Affairs Access IRiS information

UpdateRegistration

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[r] Regulatory Affairs Access IRiS information

[r] Regulatory Affairs Access IND information

Legend [r] Role involved in conduct of a business process

[i] Information source or application

Relies upon labor intensive manual processes to copy and paste information from source to trial registration documents

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GatherInformation

SummarizeandIntegrate

DraftRegistrationPackage

ReviewRegistrationP k

ProjectManagement

SubmitRegistrationP k

Start Process End Process

SIPOC Business Process Model

UpdateRegistration

Clinical Trial Registration and Result Posting Future State

SCMSCM

g gPackage

gPackage

Supplier/Source Input Process Output Consumer

[r] Regulatory Affairs List of countries and data elements required for registration

Work with Regulatory Affairs Clinical Trial Registration Package

[i] Regulatory Authority

[r] Biomedical Data Sciences

Tables lists and figures from Access tables, lists and figures

[r] Clinical Research Protocol Synopsis Access Protocol Synopsis

[i] Clinical Trial Management System

List of clinical sites and countries Access Clinical Trial Management information

g

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[r] Regulatory Affairs Access IRiS

[r] Regulatory Affairs Access IND

Legend [r] Role involved in conduct of a business process

[i] Information source or application

Labor intensive content transfer steps are removed, reducing level of effort and potential for error

Structured Protocol Template Development

Structured Protocol in the scope of the Clinical Data Standards program at Genzyme

SCMSCM

Standards program at Genzyme

Process for structuring the global protocol template: Identify content in the protocol which could potentially be structured Identify content as data vs text vs free (ie, unique)

Define rules and exceptions for structuring

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Structured protocol templates will be based on industry standards and variability will be based on Genzyme-defined implementation of these standards (ie, preferences)

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Quantitative Business Case: Structured Protocol

Develop a quantitative business case model for Structured Protocol Timebox the effort

F 2 3 l t d t b t t th &

SCMSCM

Focus on 2 3 programs selected to best represent the pros & cons Gather only the data needed on cycle times and resources from the selected

programs, find the balance of enough data to be credible while not overburdening resources

Create a model (based on the data) to project the future state with SCM for each program

Candidate Programs A recent program representing Genzymes evolving business strategy, A legacy program representative of the norm in how Genzyme conducts clinical

t di

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studies A Phase I focus, one program where we look at a small set of representative

Phase I studies A Phase III focus, one program where we look at a pivotal Phase III study Etc.

Lessons Learned and Best Practices

Focus on the business process and information content involved

SCMSCM

involved Do not discuss final document output or format Do not discuss tools and technologies

Talk in business terms

Clearly articulate business case for the organization

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Clearly articulate business case for the organization

Develop models and simulations to articulate the best practices

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Agenda

Background Background Plans for 2009 SCM Business Case Development Plans and next steps

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Identified business processes

Summary 2009 Accomplishments

p

Business case development in progress

Identified ways of having SCM conversations

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y gwith stakeholders

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Plans and Next Steps

Complete Business Case DevelopmentComplete Business Case Development

Decide on Prioritized SCM Initiatives

Gather detailed Business Requirements

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Issue RFI to Vendors RFI Development Vendor Assessment

SCM Candidate Future Development Projects

SCMSCM

Structured Content Management

Clinical Protocol Template(s)

Statistical Analysis Plan (SAP)

Clinical Study Report (CSR)

Informed Consent (IFC)

Non Clinical Study Report

Stability Testing Results

Batch Analyses

Drug Product Specifications

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Core Data Sheet Investigators Brochure (IB)

Integrations with Systems: IVRS, EDC, CTMS, CDMS, Registries

Package Insert

Clinical Trial Registration and Results Disclosure

Data Management Plan (DMP)

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Q&A

SCMSCM

Monica MehtaMonica MehtaDirector, Regulatory Operations

Genzyme Corporationmonica.mehta@genzyme.com

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