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Boris Braylyan

Global Lead,

Information Management – Pfizer Inc.

eCTD v4.0Perspectives on Implementation

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Disclaimers:

This presentation outlines a general technology

direction. Pfizer Inc. has no obligation to pursue any

approaches outlined in this presentation or to develop

or use any functionality mentioned in this

presentation. The technology strategy and possible

future developments are subject to change and may be

changed at any time for any reason without notice.

The views and opinions expressed in this presentation

and any related discussion(s) are solely those of the

individual presenter(s) and may not express the views

of and opinions of Pfizer Inc.

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eCTD v4: Perspectives on Implementation

Benefits

Preparations

Concerns

Challenges and Opportunities

Single Regulatory Standard Across Regions

• Eliminates separate regional

XML, DTD and schemas

• No more updating tools with

new DTDs/schemas for

individual regions

• Majority of updates to

Controlled term lists only

• Plug-and-Play is easier

• Results in Quicker turnaround

from vendors providing updates

• Replaces the need for

regional implementation of

Study Tagging Files (STF)

and Node Extensions

Benefits

<?xml version="1.0" encoding="UTF-8"?>

<!DOCTYPE ectd:ectd SYSTEM "util/dtd/ich-ectd-3-

2.dtd">

<?xml-stylesheet type="text/xsl" href="util/style/ectd-2-

0.xsl"?>

<ectd:ectd xmlns:ectd="http://www.ich.org/ectd"

xmlns:xlink="http://www.w3c.org/1999/xlink" dtd-

version="3.2">

<m1-administrative-information-and-prescribing-

information>

<leaf operation="new" xlink:href="m1/us/us-

regional.xml" xlink:type="simple" checksum-type="md5"

checksum="b5ebb584f36ce752a9de2ac710abacba"

ID="us94060">

<title>us-regional</title>

</leaf>

</m1-administrative-information-and-prescribing-

information>

<m2-common-technical-document-summaries>

<m2-2-introduction>

<leaf operation="new" xlink:href="m2/22-

intro/introduction.pdf" xlink:type="simple" checksum-

type="md5" ID="94060-1697253" application-

version="PDF 1.4"

checksum="f8c246f02d6fe20a810b2b3288e68a80">

<title>CTD Introduction</title>

</leaf>

</m2-2-introduction>

<m2-3-quality-overall-summary>

<m2-3-introduction>

<leaf operation="new" xlink:href="

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Structure and Re-use

• Structure is independent of application format

• There is no Table of Contents stored within Regulated

Product Submission (RPS) standard

• Changes to the ICH and regional structure no longer required

in schema – Just a change to the Controlled Vocabulary

Terms

• Enables Re-Use

• Unique identifier approach means documents can be

referenced/reused more effectively

– Across a Submission Unit (Sequence)

– Across an application

– Across different applications

Benefits

More Stable and Versatile

• Removes ‘Append’ operation that caused lifecycle

issues in the past

• v4.0 enables metadata corrections

• Section attribute information in eCTD v3.2.2 cannot be

updated

– Currently required to create new section, delete

documents and then add them back as new in the new

section

Benefits

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EU Grouping / Worksharing

In v3.2.2 individual

eCTD sequences

had to be created

for each product in

the grouping/

workshare

v4.0 will enable a

single eCTD to be

created and

reference

appropriate

documents

Benefits

Potential for Two-Way Communication

Receive questions and other communications

back from the Health Authority as eCTD v4.0

Ability to keep track of status of the application

through metadata provided back by the Health

Authority

Implementation across regions may be limited

• Further discussion required in the EU

Benefits

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Flattened, Flexible Folder Structure

Benefits

E

T

C

Benefits

Significantly

reduces issues

with long file

paths

Flexibility of

folder structure

Getting Ready for eCTD v4Always be prepared

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Some Assembly Required

Machine friendly - Human unfriendly• Designed and structured for systems to read

• Tools required to create/manage and view eCTD v4.0

• Difficult to make manual corrections/fixes

• With eCTD v3.2.2 it was easy to manually create a pilot submission

• eCTD v4.0 submissions much more complex to create without tools

Prepare

Tool Implementation

eCTD v4.0 requirement for tools raises questions about vendor models:

• Maintenance release?

• Lower impact to business, but vendors not covering their costs

• New module?

• Vendors will charge

• New tool?

• Vendors will charge

• Additional impact to applicants for training users and adapting processes to new solution

separate from eCTD v3.2.2 publishing solution

• When will vendors be ready?

• Need build, view and review solutions in place at applicants and health authorities respectively

before eCTD v4.0 can be truly implemented

• Do costs to applicants and health authorities outweigh the benefits?

Prepare

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Transitioning from v3.2.2

• Not a ‘baseline’, but a way to continue the lifecycle

• Current eCTD view will be transitioned, but not anything pre-

eCTD

• How to transition?

– Tools will be needed

– Conversion/Transition won’t be reviewed by Health

Authorities

– Structure ONLY: Applicant can’t fix or modify content

Prepare

eCTD v4 – Challenges and Concerns

Anything worth doing is worth doing right…

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4.3

2.5

3.5

4.5

2.4

4.4

1.8

2.8

2 2

3

5

0

1

2

3

4

5

6

Category 1Category 2Category 3Category 4

Series 1 Series 2 Series 3

Continuous Improvement

The specification/implementation must continue to

improve to achieve the full benefits promised when

we started on the RPS journey

– 2-way communication

– Maximize component reuse model

Concerns

• Regions are still not completely aligned: eCTDv4.0 being implemented differently per region

Single standard, but slight differences in the way it will

be implemented

Have not achieved a “single global submission”;

Applicants will still have to create regional versions

Change Control

Any regional updates requiring model/schema changes will need to go through International Conference on Harmonisation (ICH) and HL7• Cannot just implement regionally (unless it does not

impact the model/schema)

• More cumbersome and will take longer to make and implement changes (but we do have a single standard and these changes should be much less frequent)

Concerns

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Reliance on Tools

Will vendors be ready?

• Are drivers and profits significant enough to fuel rapid

R&D?

Manual fixes very difficult in v4

• Previously possible work-arounds won’t be so easy

with v4.0

Concerns

Timing is Everything

When to make the move to v4.0?

Concerns

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Case for Consideration: Phased Implementation

1. A product may be moved to eCTD v4.0 in one region

2. Still need to produce v3.2.2 for other regions not accepting v4.0 yet

3. Continued need for non-eCTD electronic submissions/paper for international marketsa) Will we be able to clone/reuse v4.0 components for

v3.2.2 & Non-eCTD electronic Submissions (NeeS)?

b) A non harmonised implementation phase will mean excessive costs for Applicants; Need to drive for alignment as quickly as possible

Concerns

Case for Consideration: Health Authority Unknowns

1. When will other eCTD markets move to eCTD

v4.0?

a) e.g. Australia, Canada, South Africa, Saudi Arabia,

Oman, Thailand…

2. Will other markets directly implement eCTD

v4.0 or introduce v3.2.2 as a stepping stone?

3. Aligned adoption and implementation of v4.0

would significantly lower costs through

maximisation of reuse

Concerns

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The Missing Links

Global companies must ensure the flatter folder structure:

Is the same across eCTD regions

Adheres to all regions to avoid reworking of inter-document hypertext links• Tools may assist: If the links are created/stored in the

build solution

• New standard, different structure: eCTD v4.0 will require reworking links to meet v3.2.2 standards for other regions

Concerns

Getting Up to Speed

User training and acclimatisation

likely to be complex

• More metadata than v3.2.2

• Expect training issues initially – will take

time to develop internal organisational

courses and resources

• Confusion likely from lack of understanding of

differences between eCTD v3.2.2 and v4.0

(particularly if using both standards concurrently)

• High-level business processes should not be affected,

but expect significant operational changes

Concerns

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Challenges and Opportunities

Expect additional problems to arise as we gain

experience working with v4.0

Expect teething problems with any big change

to a standard

Ask