1. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. Joel Finkle Senior Strategist Regulatory Informatics CSC Regulatory Solutions Group March 2011 RPS Status Update

2. I.RPS Project History3 II.RPS Model Overview13 III.Ballot and Implementation Plan35 RPS Status Update

3. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. Origins of RPS Two major goals Provide for the Next Major Version to the ICH eCTD standard ICH eCTD 4.0 will be based on RPS Support changes in granularity Support changes to metadata Better support for Master Files Better support for bundled supplements Support for two-way communication Provide a standard that the US FDA can implement across all centers Centers other than Drugs and Biologics need different document types ICH eCTD has hard element names that map to TOC sections Two-way communication Lower support and training costs by having only one review system RPS History

4. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS Release 1 Created for FDA Requirements Known that it would not meet all needs Did not include all ICH requirements Rapid schedule to permit FDA implementation Approved as an HL7 ANSI Standard March 2008 Has not been implemented

5. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS Release 2 Additional Requirements Incorporated Two-way communication requirements for FDA were included Contact Parties: Senders and Receivers Related Context of Use for revisions, related documents Additional information for Devices (CPM CMET) EU Requirements begin to be incorporated Approval information (especially useful for EMA with multiple regulators) Documents can be tagged for particular review agencies (e.g. labeling) Approved as Draft Standard for Trial Use in 2010 DSTU had large participation Significant testing done Vendor prototype tools were available As it went to ballot, additional requirements from EU and Japan appeared Will not be balloted as a Normative Standard

6. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS Release 2 Version 2 Formerly called Release 3 R2 did not go to normative ballot PROJECT NAME: RPSr3 BALLOT NAME: RPSr2 D2 (DSTU 2) EXPECTED STANDARD NAME: RPSr2 Additional ICH, regional EU and Japan requirements Major changes to structure Document concept Support for multiple files as a single document All Study Tagging Files features and then some Submission Groups Thorough examination of content life cycle

7. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. Content Warning The following slide presents frightening, complex structures The ones after that provide overviews of the 6 major acts in the standard Submission Unit Submission Application Document Context of Use Review RPS Model Overview

8. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS Overview

9. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Submission Unit Root of the message A package of information: equivalent to ICH Sequence Provides further categorization of submission sequences Identifies sender and receiver Identifies which Submissions the sequence pertains to (see next page) and assigns a Sequence Number within the Submission Carries all the Contexts of Use (described later)

10. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Submission A series of submission units in support of a regulatory activity Initial Application Supplement or Variation Annual Report May be subsetted by Reviewable Units US FDA CDRH Requirement May be used by other authorities Each belongs to one Application (see next page) May have multiple Review activities Supports EU need for one regulatory activity to be approved by many agencies (described later) Has Mode (submission type for EU) May be grouped into SubmissionGroup May have contact information`

11. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Application Provides organization for the regulated product class Defines the dossier type e.g. NDA, 510K, MAA, etc. Has Procedure (EU only) Centralised, National, Mutual Recognition or Decentralised. Identifies countries References other applications Used in Master Files Owns the Keywords Metadata STF-like identifiers Owns the Documents (next page)

12. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Document Either a physical file, or set of IDs of other documents Permits hierarchically structured documents Previously handled by STFs, but this can also roll up granularity Documents have codes and keywords like Context of Use (see next page) Used like STF tags and metadata Does not specify place in submission – thats for the Context of Use

13. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Context of Use Similar to eCTD Leaf Has codes to identify location in dossier Flexible for any submission type Presentation order determined by submission structure, Priority in connection to Submission Unit Points to Document Points to Keywords May be limited to particular Submissions (workshare) …or Agencies (e.g. labeling for different EU countries) May be linked or related to other ContextOfUse items

14. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. RPS: Review Review information is used primarily by EU, where the review status may differ for each authority and it is important to keep track of what doses, etc. are approved in each region Still needed: a status code other than the HL7 status

15. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. When will we get there? Ballot for Draft Standard in September 2011 Vendors, agencies and sponsors being solicited for testing Likely earliest approval is September 2012 Likely earliest FDA adoption is late 2013 EU/Japan will not implement until approved as an ISO standard Not determined yet whether this will be a JIC RPS Ballot and Implementation Plan

16. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. Preparation for Ballot Model One possible item to add (submission status using regulator terms) Definitions to be copied from Glossary Model Walkthrough In review, in good shape Glossary In draft, trying to reconcile between plain english and HL7-ese Storyboards Completed Schema Waiting for finalization of Model Tutorial Information Above and beyond ballot requirements Significant effort toward Implementation Guide

17. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. Challenges Adoption EMA and Japan will not accept until it is an ISO standard FDA will not implement before late 2012 at the earliest Because there is an existing standard for Drugs and Biologics (eCTD), requirement to use RPS will be phased in Controlled Vocabularies Many controlled lists are needed Context of Use is the biggest one – need both eCTD and other submission types Many of the Keywords will need vocabularies (some already exist) Submission Types, Application Types, Document Types Regulatory Statuses Relationships between controlled lists and review systems has not been worked out, for example: For Safety reports, a keyword such as Species is of lower precedence than the Context of Use For Quality, a keyword such as Drug Substance is of higher precedence than many levels of Context of Use

18. © 2011 Health Level Seven ® International. All Rights Reserved. HL7 and Health Level Seven are registered trademarks of Health Level Seven International. Reg. U.S. TM Office. THANK YOU RPS Status Update