1. Operating with Scientific Content DIA Dialogue on Structured Content Management Dec 2, 2010 Melanie Clare, GSK Ruedi Blattmann, LSCP Michael Brennan, J&J Gary Gensinger, FDA Mo Gould, Morphiris Brooke Hinkson, Genzyme

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3. Key Elements of the Vision to Reality LSCP, Ruedi F. Blattmann, Managing Partner View: Extensive re-use of content for multiple purposes across the product lifecycle thereby enhancing information value and reducing costs Globally harmonized structured content authoring processes focused on required outcomes and taking advantage of integrated content repositories Clear definition of stewardship and governance for content objects (topics) Optimized search and retrieval capabilities (in context!) Optimized organizational agility to meet new market challenges, including patent expirations, timely and efficient Rx to OTC switches, enterprise collaboration in virtual teams, etc. Drug Information Associationwww.diahome.org3

4. Where to Start with Product Information Drug Information Associationwww.diahome.org4 Toxicology Report Discovery Non-Clinical Development Clinical Development Regulatory Approval Product Launch Commercial Development Pharmaceutical Development Manufacturing Medical and Scientific Affairs Analytical Method Stability Protocol Regulatory Affairs IND/eIND IMPD/eIMPD IND/eIND IMPD/eIMPD Clinical Study Report Drug Safety, Surveillance and Epidemiology NDA/MAA eCTD NDA/MAA eCTD SNDA PSUR SOP Batch Record Lifecycle Stages & Stakeholders Example Documents (Content Components managed at a level of granularity that facilitates re- use) Formulary Submission Dossier Medical Information Letter Product Master Sales Aids Advertising Copy Marketing Campaigns Labeling SPL/PIM Labeling SPL/PIM ICSR Annual Report PI to start here

5. EXAMPLE: Content Re-use within Nonclinical, but many other Opportunities … within PI Lifecycle M4 4.2.1 Pharmacology study 4.2.2 Pharmacokinetics 4.2.3 Toxicology study 4.3 Literature References To M2 2.4 & 2.6.1 – 2.6.7 introduction, tabulation & summaries Author Reviewer Publisher Approver Study Protocol X MONTH(s) ORAL TOXICITY STUDY OF XYZ Study Report X MONTH (s) ORAL TOXICITY STUDY OF XYZ IN RAT 5.6. Observations and Measurements 5.6.2.4. Immunopheno typing 5.6.4.3. Tissue Collection and Evaluation 8. Conclusions Author Reviewer Publisher Approver EXAMPLE – Start define Granularity (Target Audience in Lifecycle) & launch re-use in the eCTD Dossier strucuture, creation process Creation / Use of Template - Population to automation Content Components (e.g. topics) enhancing value on path forward Author Reviewer Publisher Approver Toxicology Report Discovery Non-Clinical Development Clinical Development Regulatory Approval Product Launch Commercial Development Analytical Method Stability Protocol IND/eIND IMPD/eIMPD IND/eIND IMPD/eIMPD NDA/MAA eCTD NDA/MAA eCTD SNDA Labeling SPL/PIM Labeling SPL/PIM Annual Report PI Label Creation PI Label Creation Example Evolution of Information Value Chain Drug Information Associationwww.diahome.org5

6. Example of Requirements for Granularity Increase Drug Information Associationwww.diahome.org6 New PIM Version = Higher Granularity / More Semantics PIM Version 2.7.2 PIM Version 2.7.5

7. Example SCA & Formats: EMA’s View (Source: PIM Concept V2, 1209) Many challenges in managing labeling activities. System used before PIM involves exchanging MS Word and PDF files. Main challenges in Word-based system are: Maintaining consistency in repeated information: Whenever a change is made to certain information in one document, the same change has to be made in all places where that information appears In the Word-based system, maintaining the required consistency is time consuming and potentially error prone Ensuring everyone is working on the same version: The number of versions of Word or paper documents increases as an application progresses, making it difficult to ensure that the applicant, the EMA, and the NCAs are all working on the same version Consolidating many comments from multiple sources: In the Centralized Procedure, comments come from reviewers in all NCAs but must be consolidated into a single coherent version for sending to the applicant Getting the formatting and other technicalities right: A lot of effort is spent by all parties on checking that the formatting complies with the QRD templates and generating PDF files to check that the information looks right SCA: Structured Content Authoring … Drug Information Associationwww.diahome.org7

8. Re-use Illustrative Slides Dr. Michael Brennan

9. The “Real” Problem We manage information at the document level –Review –Approval –Versioning However, the information (“topics”) that we typically need to access or reference is represented at a more granular level –Section (e.g., contraindication section of a product label) –Paragraph –Sentence The information topic most likely is not changing with each version of a document, yet the topic often “inherits” the meta-data from document context within which it appears –Central driver for adoption of SPL and PIM We need an effective means to access and reference information that is not entirely dependent on navigation via a table of contents We need the capability to query information and know the context within which it is represented to determine whether that is indeed the information we need to access Drug Information Associationwww.diahome.org9

10. Consider a Clinical or Non-Clinical Report Drug Information Associationwww.diahome.org10 DraftReviewApproveSubmitRe-Use? Where do we see the opportunities for re-use for a document that has a “simple” life cycle?

11. Consider Possible Opportunities to Query & Referenced “Tagged” Content as Part of Authoring + Approval Process Drug Information Associationwww.diahome.org11 DraftReviewApproveSubmitRe-Use? Reference or link to “authoritative sources” for key topics/information Is the report supported/aligned with Approved “authoritative sources”? What is the status of the referenced information? Can I point to source of key information?

12. Business Use Case Opportunities ( re-use/references from guidance) Drug Information Associationwww.diahome.org12

13. 13 Business Use Case Opportunities (re-use/references from guidance) Drug Information Associationwww.diahome.org

14. XML Technical Opportunities eCTD xml ToC M1 regional xml M2 2.2 2.3 2.4 2.5 2.6 2.7 M3 3.2.S 3.2.P 3.2.A 3.3 M4 4.2 4.3 M5 5.2 5.3 5.4 QOS Introduction Substance S.1 General S.2 Manufacture S.3 Characterisation S.4 Control of Drug Substance S.5 Reference Standards/Materials S.6 Container Closure S.7 Stability 2.3.P Product P.1 Description & Composition P.2 Pharmaceutical Development P.3 Manufacture P.4 Control of Excipients P.5 Control of Drug Product P.6 Reference Standards/Materials P.7 Container Closure System P.8 Stability 2.3.A Appendices … 2.3.R Regional … Identify structure 1.Enforce structure 2.Navigate to structure points 3.Create composite ToC 4.Support granular life- cycle actions 5.More? M3.x … M3.x … M3.x … Identify relationships between structures 1.Support reference 2.Support re-use eCTD Component Meta Data Type, Id, Version, … Identify meta data Type, Id, Version… Identify subcomponents 1.Support granular navigation 2.Support granular reference/re-use 3.Support ref/re-use granular pedigree Stability Data IDMP Data TablesFiguresGraphs Structures 3.Support reference/ re-use pedigree Drug Information Associationwww.diahome.org14

15. Dialogue Conclusions

16. Try –Visualie the ‘horizontal’ future, try it! Learn –Learn from trying, and from others in the SCM network Implement –Small or big steps: but away from documents and towards information management Going Forward Drug Information Associationwww.diahome.org16