1. Regulated Product Submission Eileen M. Girten, MS i3 Statprobe 1DIA Education SIAC

2. Electronic Submission US History Prescription Drug Fee and User Act (PDUFA) for more efficient FDA review process PDUFA III and electronic common technical document (eCTD) PDUFA IV goal – paperless submission system by 2012 DIA Education SIAC2

3. All-electronic Submission Process FDA Part 15 hearing in December 2006 Incompatible software/electronic systems Unintended transformation Lifecycle management Costs Training resources DIA Education SIAC3

4. Need for standards Standards reflect actual business practices/scenarios Collaboration among standards development organizations (SDO), regulatory authorities (RAs), and industry Call for global standards from CDISC, SDOs, ICH, and PhRMA DIA Education SIAC4

5. Establishing standards How can different entities define the same concept? Consensus-based definitions Terminology standards Data exchange standards DIA Education SIAC5

6. The Pros and Cons of eCTD Structured one-way message Alternative to paper-based submission XML standard Structure and document structure linked Lifecycle management Mandated by EMA, but not FDA DIA Education SIAC6

7. Alternative to eCTD: RPS Submissions - similar types of information Can be used for various regulatory submissions Defines structure, not content DIA Education SIAC7

8. Alternative to eCTD: RPS 2-way communication between applicant and RA Standard exchange message using XML Collaborative effort among industry, RA, Health Level Seven (HL-7), and IT DIA Education SIAC8

9. Structure of RPS RPS consists of  Header  Message information  Submission message Application consists of  Submission  Submission units  Submission unit message DIA Education SIAC9

10. RPS and Submission Types Resubmissions Presubmissions Supplements NDAs BLAs INDs Master Files DIA Education SIAC10

11. Using RPS for Regulatory Submission Recycle content – lifecycle management Structure separate from standard Accommodates updates DIA Education SIAC11

12. RPS Timeline RPS R1 - normative standard 2007 RPS R2 - better definitions RPS3 – international requirements and test messages Testing for RPS R3 began late 2010 and expected to end late 2011 Goal – normative standard approval in 2012 DIA Education SIAC12

13. RPS – Pilot Testing Several pharmaceutical companies participated – some joint testing Tested several application types (eg, NDAs, INDs, 510Ks) Identified issues that led to changes DIA Education SIAC13

14. RPS Timeline ICH Guidance Regional implementation guides DIA Education SIAC14

15. Preparing for RPS Collaborate with vendor Regularly visit RPS Wiki Web site (http://wiki.hl7.org/index.php?title=Regula ted_Product_Submissions) for updateshttp://wiki.hl7.org/index.php?title=Regula ted_Product_Submissions Look for upcoming guidances and workshops (including DIA) DIA Education SIAC15

16. References US Food and Drug Administration. FDA’s Critical Path Initiative. http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative. Accessed February 14, 2010. PDUFA IV Information Technology Plan, May 2008. US Food and Drug Administration. Jenkins J. Structured content in the life sciences: Benefits beyond regulatory compliance, CML Publishers Journal, Issue 3, http://www.xmlpublishersjournal.com/2010/Issue3_September2010.html. Last updated September, 2010. US Department of Health and Human Services, CDER, CBER, Guidance for Industry. Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions Using eCTD Specifications. June 2008, Revision 2. US Department of Health and Human Services. Guidance for Industry. Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing. Food and Drug Administration. May 2009. Food and Drug Administration, Public Hearing, Electronic Submission of Regulatory Information and Creating an Electronic Platform for Enhanced Information Management, December 18, 2006. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Press Release. Chicago, IL, October 21-26, 2006. Leveraging ICH Efforts to Increase Globalization. Health Level Seven (HL 7) Web site. http://www.hl7.org/index.cfm. Accessed August, 2009. DIA Education SIAC16

17. References (cont’d) European Medicines Agency, EMEA Implementation of Electronic-Only Submissions and Mandatory eCTD Submissions in the Centralised Procedure: Statement of Intent. London, December 2008. Willoughby C, Fridsma D, Chatterjee L, Speakman J, Evans J, Kush R. A standard computable clinical trial protocol: the role of the BRIDG model. Drug Inf J. 2007;41:383-392. Fridsma DB, Evans J, Hastak S, Mead CN. The BRIDG project: A technical report. J Am Med Inform Assoc. 2008;15(2):130-137. FDA Data Exchange Standards Initiatives, Regulated Product Submission (RPS) Standard Status. Powerpoint presentation. http://www.fda.gov/downloads/ForIndustry/DataStandards/RegulatedProductSu bmission/UCM174101.pdf Williams G. Regulated Product Submission Release 3 Project Plan, Version 0.2, Last updated February 8, 2010. http://wiki.hl7.org/index.php?title=Regulated_Product_Submissions http://wiki.hl7.org/index.php?title=Regulated_Product_Submissions GFORGE DSTRU1 Feedback 03-Apr-2007, https://gforge.nci.nih.gov/plugins/wiki/index.php?DSTUR, last accessed 09-Oct- 2010 https://gforge.nci.nih.gov/plugins/wiki/index.php?DSTUR Testing Team Roster, 01-Mar-2007 DIA Education SIAC17