IRISS Lifecycle Group Joe Cipollina – Pfizer Ted Hanebach – canreg Shy Kumar – Datafarm Inc. Alastair Nixon – GlaxoSmithKline Kevin Wing - eCTDConsultancy Kick Off Meeting, August 5 th 2009

Problem Statement “The concept of lifecycle of eCTD submissions is an area of concern, particularly because eCTD creation and viewing tools can apply different interpretations of logic to the same lifecycle scenario resulting in differences in display of the same information”

How will the Lifecycle Group Work? Identify specific issues and write up concept paper Gather public opinion Discuss & debate the issue, come to consensus Formulate a position, which can be described in either: –A White Paper which will be circulated for consideration through the usual channels –A question for the relevant authorities (ICH or regional). Questions will be sent directly to the relevant authority by a nominated individual on behalf of the group.

Example eCTD Concept - Viewing Principles –Industry and regulators see the same dossier –Different views can be applied but use of the message standard ensures consistency

Common eCTD Lifecycle Views Sequence –Delta view showing a single sequence only with no relationships to other sequences in the application Current (from p6-3, 6-4 of ICH eCTD Specification v3.2) –Follows ICH definition, everything that has not yet been replaced or deleted Cumulative –Everything that has ever been submitted Regulatory Activity –All sequences that fall into a ‘Regulatory Activity’ – defined regionally, eg in EU, all sequences with a related sequence = 000n, plus sequence 000n itself Country view (EU only) –All EU m1 documents with attribute = my country or = common

Examples of issues... 1.Do deletes get displayed in current view? –Is current view everything not yet deleted or replaced, or the most recent event under each element? 2.Is it possible to do lifecycle across sections? –(Doc 1 was in location A, replace it with Doc 2 in location B) 3.Append – what happens if the document I append to gets replaced? 4.Broken links – if I delete content, is it a big issue if links from other documents take me to that content?

Examples of issues... 5.Provision of extra copies of data – leaf plus document, leaf pointing to existing document in previously submitted sequence, or link only (no new leaf)? 6.Does display of sections per ICH attribute (such as manufacturer) create a misleading view of the CTD and restrict lifecycle management? 7.How should eCTD leaves that point to the same document (within or across lifecycle sequence) be displayed to assist reviewer comprehension? 8.What order should elements be displayed in –in sequence view? –in the current dossier, multiple sequences?

Specific Example: 8. Ordering of elements in current view – see IRISS-LCM Concept Paper, Impact of eCTD Display on Lifecycle Management Same set of sequences in 4 different viewing tools

GSK Submission Additional data used for missing sections from EU DTD Node extensions added for the sections Early days, lack of experience We replaced across sections

RMP first RTQ (180) last Tool 1

RTQ first Additional Data last Tool 2

Additional Data first RTQ last Tool 3

RTQ last RTQ (180) first Tool 4

Tool 1Tool 2Tool 3Tool 4 RMP (0005)RTQ (0005)Additional (0000)RTQ 180 (0004) RTQ (0005)RMP (0005)NE1.3.6Additional (0000) RTQ (0003)RTQ 180 (0004)NE1.8RTQ-Clin (0001) Additional (0000)RTQ (0003)NE1.8>RMP (0005)Exec Summ (0001) Label just (0001)NE1.9Label just (0001) RTQ-Q (0001)RTQ-Clin (0001)Exec Summ (0001)RTQ-NC (0001) RTQ-Q (0001) RTQ-Clin (0001)RTQ-Q (0001)RTQ-NC (0001)RTQ (0003) Label just (0001)Exec Summ (0001)RTQ-Clin (0001)RTQ (0005) RTQ 180 (0004)Additional (0000)Label just (0001)NE RTQ (0003)NE 1.8 RTQ 180 (0004)NE 1.8> RMP (0005) NE 1.9 RTQ (0005)NE 1.9

Tool 1Tool 2Tool 3Tool 4 RMP (0005)RTQ (0005)Additional (0000)RTQ 180 (0004) RTQ (0005)RMP (0005)NE1.3.6Additional (0000) RTQ (0003)RTQ 180 (0004)NE1.8RTQ-Clin (0001) Additional (0000)RTQ (0003)NE1.8>RMP (0005)Exec Summ (0001) Label just (0001)NE1.9Label just (0001) RTQ-Q (0001)RTQ-Clin (0001)Exec Summ (0001)RTQ-NC (0001) RTQ-Q (0001) RTQ-Clin (0001)RTQ-Q (0001)RTQ-NC (0001)RTQ (0003) Label just (0001)Exec Summ (0001)RTQ-Clin (0001)RTQ (0005) RTQ 180 (0004)Additional (0000)Label just (0001)NE RTQ (0003)NE 1.8 RTQ 180 (0004)NE 1.8> RMP (0005) NE 1.9 RTQ (0005)NE 1.9 Highest sequence first, within sequence = alphabetic al, nodes last Lowest sequence first, within sequence = retain order of elements, Nodes? NB RMP (0005) displayed under NE Highest sequence first, within sequence = retain order of elements, nodes last NB Additional 0000 & RTQ 180 do not follow this ? NB RMP (0005) displayed under NE

Lifecycle a challenge.. In 0000, 0001, 0004 RMP was in node extension called “m1-8-pharcovig” In 0005 RMP was in EMEA specific element under m1.8, (not node extension), but replacing RMP in original node extension Tool 1 and 2 –display in specific element as provided in seq 0005 Tool 3 and 4 –display under 1.8 NE –inheriting location from modified file, ignoring element location in 0005

First Lifecycle Group Topic Can we generate recommendations for lifecycle views? Are there any rules we could consider suggesting as CRs?

Questions?