Presented by Antoinette Azevedo, e-SubmissionsSolutions.com at Documentation and Training Life Sciences, June 23-26, 2008 in Indianapolis.
Life sciences regulatory authorities in North America, Europe and Japan have been developing standards for drug and biologic registration submissions in electronic format for over ten years. The current version of the format—electronic Common Technical Document (eCTD)—has been the recommended format since 2005 and is on the way to becoming mandatory. This presentation will provide an overview of best practices to enable a sponsor to prepare a compliant eCTD for regulatory authority review.
A California biotech submitted an eCTD to the US FDA in summer 2005. This company used commercial-off-the-shelf publishing software, experienced consultants, and in-house staff to compile this eCTD. This drug was the biotechs first candidate for commercialization. The biotech was partnered with big Pharma to assist with sales and marketing after the FDA authorized the drug for marketing. The biotech hired a sales force of nearly 200 in anticipation of FDA approval.
The FDA issued a refuse-to-file on this eCTD in fall 2005, due to problems with the PDF files and navigability of the content of the submission. The company’s market capitalization dropped 50% overnight. The company had to recompile the submission, by reworking the source files and rebuilding the XML backbone. The new version of the eCTD was resubmitted in early 2006. The FDA accepted the resubmission for review.
However, in May 2006 the FDA issued an approvable letter, that meant the drug could be approved in the future if certain conditions were met (meaning yet another delay in being able to market the product, plus additional expense to conduct further clinical studies). In June, 2006, the big pharma company terminated the partnership with the biotech. In July 2006, the biotech laid off their sales force. In August, 2006, the biotech laid off 100 more employees. In September 2006, the biotech had a meeting with FDA to discuss what additional studies and analysis was needed. Finally, in January 2007, the biotech announced plans to resubmit its NDA by end of second quarter 2007.
This presentation will describe:
* Regulatory and business drivers behind the eCTD format
* Technical components of an eCTD
* Practical implications of collecting documents and data over the discovery, development, application review, and post-marketing lifecycle phases of a drug or biological product
* Global picture for adoption of the eCTD format
* Future direction for the eCTD format
* Role of electronic document management in the eCTD lifecycle
* Top 12 Issues FDA Has with eCTD and how to avoid them
* Preparing submission-ready source documents and data for submission in eCTD
* Whether to purchase an eCTD publishing system or to outsource.
* How to prepare for the technical challenges of eCTD
1. Preparing Compliant
eCTD Submissions
Antoinette Azevedo, President
e-SubmissionsSolutions.com
DocTrain Life Sciences, Indianapolis, IN
24 June 2008
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2. Agenda
RTF Case Study
What Can Go Wrong?
How to Assure Compliance of Source
Files?
eCTD Workflow
Questions & Discussion
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3. Four Keys to eCTD Success
Content Process
Standards Technology
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5. The Guidance on RTF . . .
July 2006, US FDA, “Providing Regulatory Submissions in Electronic Format – Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD
Specifications,” Revision 1, 7087rev.pdf.
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6. A Picture through Stock Price
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7. Summer 2005
Small California Biotech-- Submits NDA in eCTD
format to FDA CDER
eCTD publishing system
PDF toolkit
Electronic document management systems
Documentum
OpenText LiveLink
Consultants
PDF preparation
eCTD publishing & QC
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8. The Business Overview
NDA is company’s first candidate for
commercialization
Company is partnered with big pharma
who will assist with international sales
and marketing post-approval
Company hires 200 person sales force in
anticipation of approval
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9. Fall 2005
FDA issues Refuse to File (RTF) under
PDUFA timeline
Inadequacy of individual PDF files
Navigability of content of submission
Market capitalization drops 50%
overnight
Analyst conference call
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10. Early 2006
Small biotech prepares resubmission
Rework source files
Rework CTD folder/file structure
Rebuild XML backbone
FDA accepts resubmission for review
under PDUFA timeline
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11. May 2006
FDA issues “approvable” letter under
PDUFA:
Drug could be approved in future if certain
conditions could be met
“Conditions” to be determined in future
meeting with FDA
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12. June 2006
Big pharma company withdraws from
partnership
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13. July 2006
Small biotech lays off sales force
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14. August 2006
Small biotech lays off more than 100
additional employees
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15. September 2006
Small biotech has meeting with FDA
concerning “approvable” conditions
Additional studies required
Additional analysis required
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16. January 2007
Biotech announces plans to resubmit
NDA by 2Q2007
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17. August 2007
FDA accepts NDA for review
FDA sets PDUFA action date of
12 December 2007
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18. December 2007
Company Announces Sale and Leaseback
of Real Estate Assets
Deal valued at $109M
Net $61M after fees, expenses, etc.
Leases back corporate headquarters
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19. December 2007
FDA issues “approvable” letter under PDUFA
deadline:
Objective/subjective trial in elderly
Comparator safety study
Preclinical evaluation during 3rd trimester of pregnancy
Company cuts half its workforce
Company prepares meeting request to FDA
Ceases all clinical development and pre-
commercialization activities for candidate drug
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20. January 2008
Founder-President-CEO resigns after 14
years of service
Granted a formal meeting with FDA
during 1Q08 to discuss 2007 Approvable
Letter
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21. February 2008
Hope springs eternal . . .
$20.0 million upfront license fee paid for drug
candidate rights for Japan
Balance sheet assets of $276.7 million
10 indications
Three programs in Phase 1-2 for 7 indications
Three research programs
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22. What Can Go Wrong
with an eCTD?
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23. FDA’s Top 12 Issues for
eCTD Success*
12. SPL must be in “SPL” folder
11. Use elements and leaf titles correctly
10. Always reference all files in the XML backbone(s)
9. Include Module 1 in All eCTD Submissions
8. Make sure all application numbers are 6 digits
7. Make sure all sequence numbers are 4 digits
6. Do not use node extensions
5. Verify that all MD5 checksums are correct
4. All documents should conform to eCTD granularity
3. All XML must use standard components
*Source: Virginia Ventura, FDA CDERPDF hyperlinks & bookmarks
2. Be sure all Office of Business Process Support are correct
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1. Include TOCs in all PDF documents
24. Technical Issues with eCTD*
12. SPL must be in “SPL” folder
11. Use elements and leaf titles correctly
10. Always reference all files in the XML backbone(s)
9. Include Module 1 in All eCTD Submissions
8. Make sure all application numbers are 6 digits
7. Make sure all sequence numbers are 4 digits
6. Do not use node extensions
5. Verify that all MD5 checksums are correct
3. All XML must use standard components
*Source: Virginia Ventura, FDA CDER Office of Business Process Support
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25. Technical Issues with Source
Files*
4. All documents should conform to eCTD granularity
2. Be sure all PDF hyperlinks & bookmarks are correct
1. Include TOCs in all PDF documents
*Source: Virginia Ventura, FDA CDER Office of Business Process Support
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26. What is
CTD/eCTD? Module 1
Not part of CTD
Module 1
Regional Info
2.1 Table of Contents
2.2 Introduction
Module 2
2.3 2.4 Nonclinical 2.5 Clinical Summary
Overview Overview
Quality
Overall
2.6 Nonclinical 2.7 Clinical
Summary
Summary Summary
Module 3 Module 4 Module 5
Quality Safety Efficacy
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27. What is CTD/eCTD?
Submission
“nda121212”
Sequence “0000” with
5 modules
Sequence “0002” with
4 modules
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28. Where is XML Required?
“XML backbone”
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29. As the FDA Sees an eCTD
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30. Where is XML Required?
Module 1 Regional
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31. Where is XML required?
Structured Product Labeling
(SPL)
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32. Where is XML required?
Module 4 Study Tagging File
(STF)
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33. STF for Module 4
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34. Where is XML required?
Module 5 Study Tagging File
(STF)
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35. STF for Module 5
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36. Potential Problems with XML
Sponsor’s hand coding of XML
eCTD publishing vendor misinterpretation of
XML document type definition (DTD)
Sponsor’s usage of eCTD publishing system
eCTD publishing vendor not providing enough
guidance and control of user actions
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37. What is XML?
Document/data interchange standard
Originated from SGML/HTML
Replaces traditional submission table of
contents
Rules for individual instances contained
in Document Type Definitions (DTD) or
Schemas
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39. Challenges of eCTD:
The Numbers
According to FDA CDER:
NDAs will have multiple submissions over their life-
cycle
Of 10 most active eNDAs:
6 had 111 to 139 submissions
1 had 185 submissions
1 had 202 submissions
Of eSubmissions:
One initial submission had 5478 files
One eCTD supplement had over 15,000 files
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40. Challenges of eCTD
Document Authoring -- Creation of PDFs
highly dependent on use of word
processor
Templates
Styles
Cross references – how & to what
Within document
Outside document
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41. Challenges of eCTD
Granularity of content organization
Module 2: Quality, Nonclinical, Clinical summaries
Module 3: Quality
Module 4: Nonclinical study reports
Module 5: Clinical study reports
Regional differences
US
Integrated Analysis of Safety (IAS—formerly ISS)
Integrated Analysis of Efficacy (IAE—formerly ISE)
EU
Expert reports
CRFs – in or out
CRTs – in or out
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42. Challenges of eCTD
Collecting documents/data from study sites
Case Report Forms
Cost/time to convert to compliant electronic format
Consistency of organization
Changes of study protocol
Different CROs involved in different study phases
Electronic Data Capture (EDC)
Location of queries & data correction forms (DCFs)
Does my drug’s indication imply need to review CRFs?
Which CRFs will I need to submit?
Deaths/Drops/Serious AEs
All
Other
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43. Challenges of eCTD
Documents/data from study sites
Data
Can all the data be delivered in electronically-reviewable
format?
Can I convert from proprietary formats into SAS XPT
compliant formats?
Excel
Access
Other
Will the agency review my electronic datasets?
Stability
Nonclinical
Clinical
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44. Challenges of eCTD
Electronic Document Management Systems (EDMS) vs.
Shared File System
How do I know I have the final, approved document?
What if the final, approved document changes?
What is the effective version for a submission sequence?
Do I have the time/budget/resources to implement EDMS?
Will the EDMS meet the needs of my entire enterprise?
Will the EDMS integrate with my e-Submission publishing
process and tools?
How do I assure the EDMS is 21 CRF 11 compliant?
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45. eCTD Challenge: The Granularity
FDA CDER Study Tagging Files
Scope – nonclinical & clinical study reports
Lifecycle – from initial IND to product end-of-
life
Small unit of document granularity
Hyperlinking between files
Hyperlinking between submission serial numbers
A cultural change for most CROs and authors
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49. US, EU, Japan Experience To
Date
Problems with PDF Files
Lacking navigation aids:
Bookmarks
Hyperlinks
Document tables of contents
Absolute paths on hyperlinks
Security
File format
Incorrect granularity
Referencing proprietary style sheets
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50. Conclusion from Experience to
Date
System is needed to produce XML backbone
Source documents and data need to be
submission-ready & compliant with
requirements
Sponsors need intimate knowledge of the XML
output of their commercial-off-the-shelf (COTS)
systems
Sponsors must understand how agencies use
the components of an eCTD for review
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51. Four Keys to eCTD Success
Content Process
Standards Technology
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52. How to Assure Compliance
of Source Files?
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53. Credits & Disclaimers
MS Word templates courtesy Sage Submissions LLC
http://www.sagesubmissions.com/
MS Office version 2000 Professional
Adobe Acrobat 2007 Professional
http://www.adobe.com/products/acrobat/index.html
MS Windows XP Professional 5.1 (SP2)
ISIToolbox Pharma Edition 5.5.1
http://www.imagesolutions.com/Default.aspx?alias=www.
imagesolutions.com/isitoolbox
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54. Credits & Disclaimers
Enfocus PitStop Professional 7.01
http://www.enfocus.com/product.php?id=855
eCTD sample courtesy GlobalSubmit
http://www.globalsubmit.org/
Parsing/validating samples courtesy
GlobalSubmit & ING America
http://www.ingamerica.com/
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55. FDA Portable Document
Format Specifications
http://www.fda.gov/cder/regulatory/ersr/
PDF_specification_v11.pdf
Examples follow . . .
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56. PDF Version 1.4
Options:
“Reduce file size”
Output by EDMS
or eCTD
publishing system
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57. Embed Fonts
Not needed
for standard
font sets
Options
Converting
from MS
Word
Setting in
Acrobat
Distiller
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58. Embed Fonts
Options
Embed from within
Acrobat Standard or
Professional
Done on a text blocks
Not recommended
unless no other option
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59. Embed Fonts
Options
Enfocus PitStop
Professional
Done a line at a time
Not recommended
unless no other option
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62. Source of Electronic Document
Avoid scanning unless no other choice
Create PDFs from intelligent source
MS Office—Word, Excel, PowerPoint
Other word processors, spreadsheets, etc.
ASCII text
PDFs should be:
Searchable
Copy & paste to edit in other documents
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63. If You Must Scan
Document Type Resolution
Handwritten notes 300 dpi (black ink)
Plotter output graphics 300 dpi
Photographs—b&w 600 dpi (8 bit gray scale)
Photographs—color 600 dpi (24 bit RGB)
Gels and karotypes 600 dpi (8 bit grayscale depth)
High pressure liquid chromatography 300 dpi
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64. Lossless Image Compression
for Scanned Documents
Black & White Image Color & Grayscale
CCITT Group 4 Fax Zip/Flate
Reduce file size
No loss of data
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68. Hypertext Linking
Navigation improved for PDF documents
Hypertext links for:
Annotations
Related sections
References
Appendices
Tables or figures
For anything not located on same page
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69. Table of Contents & Hyperlinks
Hyperlinks designated by blue text or rectangles
with thin lines
Blue text for PDFs from intelligent source
Thin rectangles only option for scanned documents
Tables of Contents
Hyperlinked
Invisible rectangles and blue text preferred
eCTD publishing system can automate some
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71. Use Relative Paths for
Hyperlinks
eCTD publishing system should generate automatically
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72. Use Relative Path for Hyperlinks
However!
Acrobat still
shows relative path
Link report courtesy Image Solutions, Inc.
ISIToolbox Pharma Edition
Bookmark & Link Auditor,
Export Bookmarks and Links
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73. Bookmarks Hierarchy
= TOC Up to 4 Levels
eCTD publishing system should generate automatically
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74. Bookmarks & Hyperlinks
Magnification
= Inherit Zoom
eCTD publishing system
should generate
automatically
Link/Bookmark report courtesy
Image Solutions, Inc.
ISIToolbox Pharma Edition
Export Bookmarks and Links
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76. Initial View = Bookmarks & Page
eCTD publishing system should generate automatically
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77. File Naming & Folder/File Path
Use lower cases letters
Avoid special characters
except hyphens
File/folder path:
230 characters for full
folder/file path
64 characters for folder
names
eCTD publishing system
should generate/truncate
automatically
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78. Verbally Communicated
Requirements
Open to TOC
Optimize for Fast Web View
Font size
12 point font for text
10 point for tables (9.5 pt)
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79. Open to TOC Page
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81. Optimize for Fast Web View
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82. Institute Standards for Data
Inside and outside suppliers
Datasets – must have complete
documentation
Datasets table of contents
Variable definition file—complete
Datasets in SAS transport
Annotated CRF (for human studies)
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87. eCTD Single “Document” Workflow
Compile to
Collect Source Verify Single Files or Release for
Documents Completeness Study Tagging Files Publishing
& Data (STF)
If incomplete,
Incorrect, or
PDF Deliverables – Individual Files Content revised
Bookmarks & hyperlinks
Tables of contents
Pagination 1 through n
Optimized for fast web viewing
File Format 1.4
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88. eCTD Submission Workflow
Prepare Repository Insert Content in Insert Cross- Output
for Handoff eCTD Outline Document Hyperlinks for QC
Set Submission Adjust Submission
& Document & Document Issues?
Attributes Attributes
• Invalid XML
• Source document changed
• Dead or missing bookmarks or hyperlinks
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89. Components of an EDMS
Authoring
Client
Scanner
EDMS Server
Rendition Server RDBMS
for PDF Renditions & File Store
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90. Components of Submission
Publishing System e-Submission
Publishing
Client
File
Server
FDA
ESG
EDMS Server, Publishing Server,
RDBMS & RDBMS p-Submission
& File Store
Web
Server
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91. TimeLine for Implementation
Implementation Steps 1Q 2Q 3Q 4Q 5Q 6Q
Gather EDMS & eCTD system requirements;
determine validation requirements
Identify potential vendors; select short list
Prepare & issue RFP, reduce vendor list, start
negotiations
Order & install hardware; install EDMS software,
perform IQ/OQ validation
Train users, help desk, administrators; perform
EDMS UAT & PQ validation
Install & validate eCTD software. Produce small
submissions – INDs, Annual Reports, Amendments,
Supplements, Safety Updates
Produce marketing application & submit
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92. Consistency of
eCTD across ICH
Vendors’ ability to offer Sponsors’ systems
inexpensive solutions ability to manage
for multiple eCTD lifecycle metadata
markets’ requirements over drug’s lifetime
eCTD Critical Success Factors
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93. eCTD: Challenges to Sponsors
Return on Investment (ROI)
Cost of systems, training, process redesign
Cost of noncompliance
Speed, efficiency
Submission compilation
Agency review process
Lead time to application submission
On-going compliance
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94. eCTD: Benefits to Sponsors:
Electronic content for sponsor’s internal access
(Potentially) faster agency review
Higher quality agency review
Demonstrated lower cost of production
compared with paper
Faster time from database lock to submission
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95. Status of eCTD Requirements
FDA CDER
eCTD mandated January 1, 2008+ for electronic
submissions
CBER
Accepting both eCTD and eBLA
Sometimes e-submission mandatory (fast-track, rolling
submissions)
FDA CDRH
Guidances required
Informal pilots underway
Turbo 510K http://www.fda.gov/cdrh/cesub/index.html
Global Harmonization Task Force (GHTF) and STED
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96. Status of FDA ESG
e-Sub May 2006 May 2007 Feb 2008 Total
AERS 9,109 12,917 247,925
CDER 20 1,009 15,931
CBER 6 101 2,146
CDRH 153 75 3,364
CVM 414
Totals 9,228 14,201 269,780
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97. Business Case for ESG
1500 submissions (non-AERS)
Manual submission of electronic media &
supporting paper = $111,183
ESG startup (training, security certificates,
hardware) = $30,999 . . . $20.00+
Time/resource efficiency for Sponsor &
Agency
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98. Business Case Against Paper
10 copies, 100 volume submission
$163,290 Total
$147,000 = printing
$5,790.00 = binder materials
$10,500.00 = shipping
Does not include labor to assemble, page
stamp, manual TOCs, binding, QC, labeling,
packing
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99. Four Keys to eCTD Success
Content Process
Standards Technology
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100. Status of eCTD Requirements
EU/Japan/Canada
PDF reviewers’ aids accepted along with paper
volumes
eCTD dependent on each country’s information
technology infrastructure
Needs early & frequent communication to determine
ability to accept & review
Rest of World
Highly dependent on information technology
infrastructure to review e-submissions
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101. EMEA eCTD Statement of
Intent
1 July 2008 – accept eCTD or non-eCTD
electronic-only
1 January 2009 – strongly recommend eCTD or
non-eCTD; paper an exception
1 July 2009 – strongly recommend eCTD; paper
and other formats an exception
All applications (new and existing)
All submission types for Centralised Procedure
Rapporteurs & CHMP members receive no paper or
other electronic formats beyond this date
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102. Japan eCTD Experience
MHLW statistics as of December 2007:
Original Applications = 6 (13 sequences)
Reference Applications = 52 (70 sequences)
Total = 58 (83 sequences)
Free eCTD Validator
Integrating eClinical Trial and eSubmission
throughout drug development lifecycle
CDISC standars for clinical trial data
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103. Health Canada eCTD Transition
Phase 1 – Co-submission
Original Submission: eCTD Format on CD and DVD along with full
paper-based submission in CTD format
Subsequent Submissions: Continue use of both formats
Phase 2 - Hybrid submission
Original Submission: eCTD format on CD and DVD along with
Module 1 and 2 only in paper-based CTD format
Subsequent submissions: Submit Modules 1 & 2 in both formats
Original & Subsequent Submissions: Modules 3 to 5 may be subject
to print-on-demand requests
Electronic-only
Original Submission: eCTD format with no accompanying paper
Subsequent submissions: Do not revert to paper-based CTD
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104. Health Canada: Criteria for Participation in
the Hybrid Filing Format Pilot
Guidance January 25, 2006 December 31, 2007
Comparison (for pilot beginning on June 30, (effective immediately)
2006)
Candidate Submission has priority review status New Drug Submissions (NDSs),
submission Submission qualifies under the Abbreviated New Drug Submission
types Notice of Compliance with conditions (ANDS), Supplement to a New Drug
(NOC/c) policy Submission (SNDS), Supplement to a
Health Canada does not have Abbreviated New Drug Submission
capacity or ability to perform (SANDS)
electronic review NDS labeling only if the original
Submission to be assigned to a submission was filed in the co-submission
reviewer on contract or a teleworker or hybrid filing formats
Notifiable Change submissions and annual
updates of Notices of Change related to a
previously filed eCTD submission that was
filed in the hybrid filing format
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105. Health Canada: Criteria for Participation in
the Hybrid Filing Format Pilot
Guidance January 25, 2006 December 31, 2007
Comparison (for pilot beginning on June 30, (effective immediately)
2006)
Conditions Submission has Priority Review Health Canada does not have the
where status capacity and ability to perform an
candidate will Submission qualifies under the Notice electronic review
not be of Compliance with conditions Submission to be assigned to a
considered (NOC/c) policy reviewer on contract
Health Canada does not have the
capacity and ability to perform an
electronic review
Submission to be assigned to a
reviewer on contract or a teleworker
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106. Health Canada:
Implementation Considerations
Issue Co-Submission Hybrid Submission Electronic-only Submission
(Guidance Section 6.1) (Guidance Section 6.2) (Guidance Section 6.3)
Paper content Complete paper-based Modules 1 & 2 in paper No paper
CTD format
Legal record Paper-based submission eCTD submission eCTD submission
Signature Wet ink signature Digitized or scanned copy Electronic signature
required of signed document
Letter of Stating that material in Stating Modules 1 & 2 in Not applicable
Attestation eCTD format exactly eCTD format exactly
matches material in CTD matches material in CTD
Technical pre- Recommended Required To be determined
submission
consultation
Print on Not applicable <500 pages – done by To be determined
demand Health Canada
>500 pages – done by
sponsor on request
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107. FDA Status--Part 15 Hearing
Request for public input to influence development of new
policy/regulation
What do you think about an all-electronic submission
environment?
What do you think about implementing an electronic
platform to promote electronic sharing and exchange of
research and regulatory information?
Public rule being written to mandate electronic
submissions across all Centers of FDA—”years” to reach
final rule
RFI issued for public-private partnership to implement all-
electronic submission environment
http://www.fbo.gov/spg/HHS/FDA/DCASC/e-Platform-RFI/listing.html
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108. FDA Datasets Status -- Study
Data Tabulation Model (SDTM)
FDA Public Meeting February 1, 2005
http://www.fda.gov/oc/datacouncil/presentations.html
Steps being taken by FDA to require submission in electronic format:
Stability datasets – HL7
Animal datasets – tabulation & analysis-ready
Human datasets – tabulation & analysis-ready
Profound change from business as usual
Agency
Sponsors
CROs
Vendors
Additional resources:
http://www.cdisc.org/
http://www.hl7.org/
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109. FDA Status—Electronic
Submission Gateway (ESG)
May 2006 – implemented Electronic Submission Gateway
to enable fully-electronic bidirectional communication
http://www.fda.gov/esg/
If sponsor has electronic signature policy & technology in
place, no paper is required with submissions
Forms (1571, 356h) and documents which require
original wet signature on hardcopy
Acceptable formats
Scanned signatures
Digital signatures
Flattened digital signatures
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110. FDA Status--RPS
Regulated Product Submission (RPS) under
development
Create one model for submission of regulated product
information
Framework for sponsors to send regulatory information
Reviewers able to consistently locate requisite content
Animal and human products—human therapeutics,
medical devices, food additives, veterinary
Worldwide use
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111. FDA Status--RPS
Development under HL7
Randy Levin of FDA CDER one of three Co-Chairs
HL7 being recognized as standards body by ICH
Status
June 2005 RPS Project initiated
Sept. 2006 first test submission to FDA
2010+ implemented as extension to eCTD
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112. RPS--More Information
RCRIM’s TC:
https://www.hl7.org/Special/committees/rcrim/index.cfm
RPS Information Page
https://gforge.nci.nih.gov/plugins/wiki/index.php?Regulated%20
Product%20Submission&id=234&type=g
HL7 tools
https://www.hl7.org/Library/data-
model/V3Tooling/toolsIndex.htm
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113. FDA—SPL Resources
Providing Regulatory Submissions in Electronic
Format – Content of Labeling
http://www.fda.gov/cder/guidance/6719fnl.pdf
SPL Standard for Content of Labeling
Q&As
http://www.fda.gov/cder/guidance/7074fnl.pdf
FDA proposes to perform Indexing of SPL:
http://www.fda.gov/cder/guidance/7662dft.pdf
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114. FDA Data Standards Council
http://www.fda.gov/oc/datacouncil/
Structured Product Labeling
Drug Registration
Drug Listing
Regulated Product Submission
CDISC Data Standards
Stability Data Standards
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115. FDA Resources for CTD
Regulatory Submissions in Electronic Format –
General Considerations
http://www.fda.gov/cder/guidance/4156dft.pdf
eCTD Backbone Files Specification for Module 1
http://www.fda.gov/cder/regulatory/ersr/Module1Spec.pdf
eCTD Backbone Files Specification for Modules 2
through 5
http://www.fda.gov/cder/regulatory/ersr/module2-5spec.pdf
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116. FDA Resources for CTD
eCTD Backbone Files Specification for
Study Tagging Files (STF)--Module 4 &
Module 5
http://www.fda.gov/cder/regulatory/ersr/FDA%20implementatio
n%20of%20STFv2-6.pdf
Comprehensive Table of Contents
Headings and Hierarchy
http://www.fda.gov/cder/regulatory/ersr/5640C
TOC-v1.2.pdf
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117. FDA Resources for CTD
Study Data Specifications--Datasets
http://www.fda.gov/cder/regulatory/ersr/Studyd
ata-v1.3.pdf
Portable Document Format
Specifications
http://www.fda.gov/cder/regulatory/ersr/PDF_specification_v11.pdf
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118. Summary
EU & Japan & Canada – eCTD preferred format for
electronic; CTD required format for paper
US – CTD preferred format for paper
Rest of World-- ability to accept & review varies widely
eCTD preferred format for e-Submissions
eCTD remains optional except FDA CDER
Paper submissions required by most countries
Agency cannot legally accept electronic-only
Agency IT infrastructure inadequate to perform electronic
review
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119. eCTD Success! Critical Success Factors:
Faster time to market
Happier stockholders
Greater employee & management
satisfaction
Lower cost of production
Simultaneous global submissions
Healthier patients
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