Development and eCTD submission

Process & Contents

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 Rajeev Kashyap TIPT

Time Methods Materials

Environment Communication
Personnel

Initiating
Process Planning Executing
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Cost cutting &Processing Time

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 The XML eCTD DTD describes the

hierarchical structure according to the CTD
as defined by the ICH M4 Expert Working
Group.
 The XML eCTD instance covers the entire
submission including all hierarchical levels
and includes references to each individual
file.
 The submission should include a Style sheet
that supports presentation of the XML
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 Directory Structure: A structure of directory

and files
 XML eCTD: Intention to have links from leaf
element.
eCTD empty template included in ICH Web site be
available for 50 years in PDF –XML(Extensible mark-up
language) and the graphics in JPEG, PNG,SVG, GIF format.
eCTD should have checksums for each file.
 Contents file.
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 The number of eSubmissions to the FDA now over 60,000 .

 Regulatory agencies in the U.S., EU, Japan, and Canada in
the areas of eSubmission strategy, document and records
management,
 Compliance software integration.
• Efficiency
• Problems with paper
• Industry and modern trends
• Competitive edge
• FDA “encouragement”
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• New Drug Applications (NDAs)

• Supplemental NDAs (sNDAs)
• Investigational New Drug
Exemptions (INDs)
• Clinical Trial Authorization
(CTAs) filed in EU
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 Electronic versions of Agency-Required Regulatory

Submissions

• IND, NDA, BLA, Correspondences, Safety

Reports
• CTA - other marketing apps…
• eCTD vs. hybrid esub
• Format: PDF, XML, SAS, MSWord, JPG
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 ICH - guidelines
The eCTD has five modules
 1 Administrative Information and
Prescribing Information
 2 Common Technical Document
Summaries
 3 Quality
 4 Nonclinical Study Reports
 5 Clinical Study Reports

There are two categories of

modules:
 Regional module: 1 (different for
each region; i.e., country)
 Common modules: 2-5
(common to all the regions)
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Not part of the eCTD

Regional Administrative information
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 Regional guidance will provide the
specific instructions on how to
provide the administrative forms
and detailed prescribing
information.
 There will be local requirements for
both the content and electronic
component of module 1.
 The eCTD backbone was developed
to enable the transfer of the
regional information included in a
regulatory dossier
 A description of the submission
including appropriate regulatory
information.
 A listing of the sections of the
submission filed as paper,
electronic, or both paper and
electronic.
 A description of the electronic
submission including type and
number of electronic media,
 Approximate size of the
submission, and if appropriate,
characteristics concerning the
media (e.g.,format used for
DLT tapes) .
 A statement that the
submission is virus free with a
description of the software
used.
 The regulatory and information
technology points of contact
for the submission
 Administrative Information &
Prescribing Information.
Cover Letter
Form 356h
labelling information (Draft)
Cartoon and Containers Labels
Clinical Trials label.
Pack inserts
Investigator Boucher
Financial Disclosure
Exclusivity Certificate
Patent certificate
Risk management plan
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Rajeev Kashyap TIPT
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 A document can be equated to a file for an

electronic submission .
 A document is defined for a paper
submission as a set of pages, numbered
sequentially and divided from other
documents by a tab
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 The granularity of the paper and electronic submissions should

be equivalent, although if a paper submission is updated to be an
electronic submission, some changes in granularity could be
introduced to facilitate on-going lifecycle management.
 Optionality of granularity for the Quality Overall Summary is
provided in order to accommodate different levels of complexity of
products. The applicant can choose the level at which the QOS is
managed.
 One document should be submitted for each drug substance
 For a drug product supplied with reconstitution diluent(s), the
information on the diluent(s) should be provided in a separate part
“P” document
 One document for each indication should be submitted, although
closely related indications can be within a single document
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 <m3-2-s-2-manufacture>
 <m3-2-s-2-1-manufacturer>
 <leaf ID="xxx" operation = "new" xlink:type = "simple“
checksum-type="md5" checksum= "xxx"
 xlink:href = "m3/32-body-data/32s-drug-sub/xxx/32s2-
manuf/xxx" application-version = "xxx">
 <title>xxx</title>
 </leaf>
 </m3-2-s-2-1-manufacturer>
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 Building blocks:
 PDF files for text*
 MD5 transport files for checksum data*
 Connected through XML backbone
 Looks like a web page
 Viewing
 Links and bookmarks
 Search keywords, metadata
 Managing lifecycle (Append, Replace, Delete)
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• Document Storage and • In addition to esub

Transfer tools:
• EDMS v/s file system
• Balance version control,
• eCTD Compiler Tool
security and flexibility • Major IT project!
• Validation/upgrade
• Acrobat
• Migration
• Conversion from MSWord
• Implementation
• PDF version compatibility • External Links
• Plug-in Tools
• Publishing PDF docs
• Bookmarks, links, …
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• Regulatory submission • SPL - Structured

strategy and technology Product Labeling
• Electronic and paper
submissions to Regulatory
• Gateway
Agencies for drug implementation
registration • Fill able forms + Digital
• Template for authoring Sigs: 356h, 1571…
regulatory docs
• Submission lifecycle
• eCTD, hybrid electronic
submissions
tracking + archiving
• Liaise with FDA on Esub
requirements
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• Drive electronic • Keep Upper

submission acceptance Management informed
and adoption within
of:
company
• Lead software • new regulatory
implementation projects submission
• Cross functional training requirements
and awareness of Esub • how to adopt new
initiatives technology and
• Esub guidance and processes to
specification sustain competitive
interpretation
advantage
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PAPER V/S ESUB COMPARISON

• E-publishing software • E-publishing software
• Authoring templates - • Still based on e-
MSWord templates
• Volumization • Document info,
• Volume TOC creation descriptive metadata*
• Overlays: page • PDF Table of contents
stamps, master creation*
headers/footer info • Navigation: Bookmarks,
• Print: multiple copies links (automation key)
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• Clinical QC √-list
• Medical Writing √-list
• QA reports
• Publishing work practices
• CLINICAL SUMMARY REPORTS Publishing
work practice
• CSR Appendix √-list
• Electronic PDF √-list
• Guide for eSub ready Docs
• Scanned Document √-list
• eQC √-list
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Process Agreements
• eCTD Taskforce: Reg • eCTD Task force
Ops, Reg Affairs,
Medical Writing, and • Med Writing – Reg. Ops
other functional group – Data Mgt – other
representation functional group reps
• Company-wide • File Transfer
“awareness”
• EDMS
• Presentations at • File share
Project Team
meetings • eRooms
• eArchival
• Templates and Training
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STRENGTHS WEAKNESS

OPPORTUNITIES THREATS
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• Electronic Submissions Gateway

• created as required by [The
Prescription Drug User Fee Act ] PDUFA
IV legislation as the single point of
entry for the receipt and processing of
electronic submissions to the FDA
 PDUFA enable FDA to accelerate its drug
evaluation process without compromising
review quality.
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 New Drug Applications (NDAs)

CDER Central Document Room:
FDA/Center for Drug Evaluation and Research
(CDER)
Central Document Room (CDR)
5901-B Ammendale Road
Beltsville, MD 20705-1266
 Abbreviated New Drug Applications (ANDAs)
Office of Generic Drugs
7500 Standish Place
Rockville, MD 20855
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 Rajeev Kashyap TIPT

 ICH Website: http://www.ich.org/cache/compo/276-254-1.html

 SPL Resources: http://www.fda.gov/oc/datacouncil/spl.html

 CPage: http://www.fda.gov/cder/regulatory/ersr/ectd.htm
Submit electronically via the Gateway: http://www.fda.gov/esg/
CDER's eCTD Validation Criteria:
http://www.fda.gov/cder/regulatory/ersr/validation_specs.htm
 Daily Med Approved Labels:
 http://dailymed.nlm.nih.gov/dailymed/drugList.cfm?startswith=T
 CDISC Standards:
http://www.cdisc.org/models/def/v1.0/index.html
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