IRISS Lifecycle GroupJoe Cipollina – Pfizer

Ted Hanebach – canregShy Kumar – Datafarm Inc.

Alastair Nixon – GlaxoSmithKlineKevin Wing - eCTDConsultancy

Kick Off Meeting, August 5th 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 1 Tool 2 Tool 3 Tool 4

RMP (0005) RTQ (0005) Additional (0000) RTQ 180 (0004)

RTQ (0005) RMP (0005) NE1.3.6 Additional (0000)

RTQ (0003) RTQ 180 (0004) NE1.8 RTQ-Clin (0001)

Additional (0000) RTQ (0003) NE1.8> RMP (0005) Exec Summ (0001)

Exec Summ (0001) Label just (0001) NE1.9 Label just (0001)

RTQ-Q (0001) RTQ-Clin (0001) Exec Summ (0001) RTQ-NC (0001)

RTQ-NC (0001) RTQ-NC (0001) RTQ-Q (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 1.3.6

NE 1.3.6 NE 1.3.6 RTQ (0003) NE 1.8

NE 1.8 NE 1.8 RTQ 180 (0004) NE 1.8> RMP (0005)

NE 1.9 NE 1.9 RTQ (0005) NE 1.9

Tool 1 Tool 2 Tool 3 Tool 4

RMP (0005) RTQ (0005) Additional (0000) RTQ 180 (0004)

RTQ (0005) RMP (0005) NE1.3.6 Additional (0000)

RTQ (0003) RTQ 180 (0004) NE1.8 RTQ-Clin (0001)

Additional (0000) RTQ (0003) NE1.8> RMP (0005) Exec Summ (0001)

Exec Summ (0001) Label just (0001) NE1.9 Label just (0001)

RTQ-Q (0001) RTQ-Clin (0001) Exec Summ (0001) RTQ-NC (0001)

RTQ-NC (0001) RTQ-NC (0001) RTQ-Q (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 1.3.6

NE 1.3.6 NE 1.3.6 RTQ (0003) NE 1.8

NE 1.8 NE 1.8 RTQ 180 (0004) NE 1.8> RMP (0005)

NE 1.9 NE 1.9 RTQ (0005) NE 1.9

Highest sequence first, within sequence = alphabetical, 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?