1. ISO/HL7 27953 Specification: Individual Case Safety Report (ICSR) Release 2 Lise Stevens Data Standards Project Manager FDA CBER/ADRM Bioinformatics Support Staff April 10, 2012

2. 2 Discussion Topics  Overview of the ISO/HL7 27953 Specification  ICH Conformance Profile  FDA Adoption, Testing and Implementation

3. 3 ISO/HL7 27953 Multi-part international standard for AE reporting: 27953-1 (Part 1) is an over-archiving reporting specification for adverse event (AE), product problem and consumer complaint reporting 27953-2 (Part 2) is a conformance profile for human pharmaceuticals reporting between regulated industry and regulators

4. 4 ISO/HL7 27953-1 Over-archiving specification that supports: AE, product problem and consumer complaint reporting for all FDA regulated products Harmonized 2008 requirements from international standards setting groups: ICH E2B, VICH, GHTF Additional requirements harmonized with HL7 Patient Safety Workgroup

5. 5 ISO/HL7 27953-2 ISO implementation conformance profile based upon: Updated ICH E2B(M) reporting guideline ICH regional requirements: EU, Japan and US

6. 6 ISO/HL7 27953 Accepted by HL7 as Normative Standard September 2010 Finalized as an ISO International Standard as of December 2011 Accepted by the American National Standards Institute January 2012

7. 7 ICH Conformance Profile ISO/HL7 27953-2 is a conformance profile that will replace ICH E2B(M) New specification supports: Adoption and implementation consistency ICH “core” reporting requirements specified in ICH E2B(R3) guideline (XML schema, data elements and vocabulary) Regional reporting requirements ICH regulators will issue additional reporting guidance as regional appendices

8. 8 FDA Adoption CDRH adopted the HL7 ICSR Release 1 specification for its electronic medical devices reporting program (eMDR) in 2006 CVM pre-adopted ICSR Release 2 in 2010 to support electronic animal drug AE reporting from industry based upon VICH Guideline (GL 42) CBER began implementation planning in 2011 to support electronic vaccine AE reporting from industry in support of new regulation for mandatory electronic submission of postmarket AEs

9. 9 CBER Testing and Implementation Goal is to remain consistent with ICH guidance, but extend or make use of additional XML schema tags to accommodate vaccine requirements

10. 10 VAERS and ICH E2B XML Example ` Component section for VAERS Box 18 Component section for VAERS Box 19 and ICH E2B B.1.7.1

11. 11 CBER Testing and Implementation Phase I covers electronic vaccine reporting from industry based upon the ICH conformance profile 27953-2 and VAERS-1 form Goal is to support a phased development and implementation to support all CBER-regulated products: Phase I: Vaccines FY 2012 Phase II: CBER ANDA, BLA, NDAs: e.g., Blood components, including Fatalities, Blood Bags, Plasma Expanders FY 2013 Phase III: CBER-regulated devices FY 2014

12. 12 CBER Pilot Testing Working with contractors to enhance FDA tools: Pragmatic Data XFORM: Expands 2010 pilot BAH eSubmitter:  Leverages CDRH eMDR development  Expands CDER version to support VAERS-1 and updated E2B specification Anticipate UAT testing: Summer 2012

13. 13 CBER Implementation Goal is to be ready to receive production submissions to support new regulation: Currently working on CBER infrastructure enhancements Already identified changes to industry guidance Companies have 1 year to comply with rule Do not anticipate approval of waivers Expect to have draft guidance ready for FDA General Counsel review when ICH Step 4 Guideline is signed November 2012

14. 14 Acronyms ANDA = Abbreviated New Drug Application BAH = Booz, Allen and Hamilton BLA = Biologics License Application CBER = Center for Biologics Evaluation and Research CDER = Center for Drug Evaluation and Research CDRH = Center for Devices and Radiological Health CVM = Center for Veterinary Medicine EU = Europe FDA = Food and Drug Administration GHFT = Global Harmonization Task Force (Devices) HL7 = Health Level Seven ICH = International Conference on Harmonisation ISO = International Standards Organization NDA = New Drug Application UAT = User Acceptance Testing US = United States VICH = Veterinary International Conference on Harmonisation XML = Extensible Markup Language