CDISC FDA Electronic Submission

www.cytel.com
CDISC Electronic Submission
Kevin Lee
JSM
August 6th, 2013
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www.cytel.com ©2013 Cytel Statistical Software & Services Pvt. Ltd.
Disclaimer
2
Any views or opinions presented in this
presentation are solely those of the author and
do not necessarily represent those of the
company.

Why?
3

Golden Rule by Simon Sinek
4
What
How
Why

Agenda
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• Why do we care CDISC electronic submission?
– Recent Regulatory changes
– FDASIA and PDUFA V
• How can we prepare CDISC electronic submission?
– eCTD version 3.2.2 and Data Standard Strategy
• What do we prepare CDISC electronic submission?
– CDISC components
– CDISC electronic submission
• Conclusion
• Questions & Answers

Current Status of eSubmission in FDA
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Current Status in CDISC Submission
7
CDISC submission
• In 2010, CDER received an average of over 650
datasets/week, with 23% of active NDAs containing
CDISC/SDTM data
• In 2011 this number has increased to an average 39%
in SDTM and 32% in ADaM

Significant Regulatory Changes
8
FDA Safety and Innovation Act
(FDASIA)
• signed into law on July 9, 2012.
• expands the FDA’s authorities and
strengthens the agency's ability to
safeguard and advance public
health.
• Main impacts for us - reauthorizes
the fifth instance of Prescription
Drug User Fee Act (PDUFA V)

PDUFA V commitment by FDASIA
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• Provides FDA with the necessary resources to
maintain a predictable and efficient review process
for human drug and biologic products.
• FDA will continue to receive a source of stable and
consistent funding during fiscal years 2013-2017
that will allow the agency to fulfill its mission to
protect and promote public health by helping to
bring to market critical new medicines for patients

PDUFA V commitment in section 7
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A. To enhance the quality and efficiency of FDA’s review of
NDAs, BLAs, and INDs, FDA shall consult with
stakeholders, including pharmaceutical manufacturers
and other research sponsors, to issue draft guidance on
the standards and format of electronic submission of
applications by December 31, 2012.
B. FDA will issue final guidance no later than 12 months
from the close of the public comment period on the draft
guidance. Such final guidance and any subsequent
revisions to the final guidance shall be binding on
sponsors, applicants, and manufacturers no earlier
than twenty-four months after issuance of the final
guidance.

PDUFA V commitment in section 7 (2)
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C. Requirements for electronic submission shall be
phased in according to the following schedule:
1. Twenty-four (24) months after publication of the
final guidance: All new original NDA and BLA
submissions, all new NDA and BLA efficacy
supplements and amendments, all new NDA and
BLA labeling supplements and amendments, all
new manufacturing supplements and
amendments, and all other new NDA
submissions.
2. Thirty-six (36) months after publication of the
final guidance: All original commercial INDs and
amendments

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D. ….., initial FDA guidance shall specify the format of
electronic submission of applications using eCTD version
3.2.2 unless, after notice and an opportunity for
stakeholder comment, FDA determines that another
version will provide for more efficient and effective
applicant submission or FDA review.

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E. Clinical Terminology Standards: …., FDA shall develop
standardized clinical data terminology through open
standards development organizations (i.e., the Clinical
Data Interchange Standards Consortium (CDISC)) with
the goal of completing clinical data terminology and
detailed implementation guides by FY 2017.
1. FDA shall develop a project plan for distinct therapeutic
indications, prioritizing clinical terminology standards
development within and across review divisions.

More Updates from FDA on DIA 2013
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• FDA is currently developing eCTD v 4.0.
• Implementation Target – Mandatory eCTD submission
– NDA and BLA : March 2016
– Commercial INDs : March 2017
• Based on the current implementation schedule, FDA
begins receiving eCTD v 4.0 submission in 2016

How do we prepare CDISC eSubmission?
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• eCTD(Electronic Common Technical Document) v
3.2.2 for electronic submission
• Data Standard Strategy for CDISC

Electronic Common Technical Document
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• Introduction of eCTD – an interface for industry to
agency transfer of regulatory information
• Most recent version – v3.2.2
• Define
– Module and its contents
• Module 1 – Administrative information
• Module 2 – eCTD summary document
• Module 3 – Quality
• Module 4 – Non-clinical Study Reports
• Module 5 – Clinical Study Reports
– File formats (i.e., pdf, txt, xml, xpt and etc)

Electronic Common Technical Document
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Data Standard Strategy
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• Purpose – to reinforce CDER’s on-going commitment
to the development, implementation and maintenance
of data standard program on regulatory submissions.
• Objectives
– Development of TA standards
– Replacement of SAS XPORT files
– Requirement of eSubmission
• Data Standard
– CDER initiated 55 key TA domains
– CDISC will be implemented and enhanced to support TA
standard development

TA Data Standard Prioritization
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Data Standard Strategy
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What do we prepare
for CDISC eSubmission?
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• CDISC components
according to CDISC
compliances
• Its electronic formats
according to eCTD

CDISC Clinical Trial Process
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PRN
(Protocol)
eCRF
ODM.xml, L
AB
SDTM TFLADaM
SAP
CDASH
CSR

CDISC components in eSubmission
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• Protocol
• SAP
• eCRF
• SDTM
• ADaM
• SEND
• CSR
• Define.xml

Additional components in eSubmission
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• ADaM SAS programs
• Efficacy SAS programs (sometimes)

Formats of files according to eCTD
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• Protocol – pdf (i.e., study001-protocol.pdf)
• SAP – pdf (i.e., sutdy001-sap.pdf)
• eCRF – pdf (i.e., sutdy001-blankecrf.pdf)
• SDTM – xpt (i.e., dm.xpt, ae.xpt, ds.xpt, and etc)
• ADaM – xpt (i.e., adsl.xpt, adae.xpt, adtteos.xpt, and etc)
• SEND – xpt (i.e., dm.xpt, se.xpt, bw.xpt, and etc)
• CSR – pdf (i.e., sutdy001-csr.pdf)
• Define.xml – xml or pdf (i.e., define.xml/define.pdf)
• ADaM SAS programs – txt (i.e., c-adsl-sas.txt)
• Efficacy SAS programs – txt (i.e., t-14-01-001-ds-sas.txt )

Naming convention of files
according to eCTD
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• Lower case of letter from “a” to “z”
• Number from “0” to “9”
• “-” hypen
• No special character ( #, %, $ and etc)
• File name should be less than or equal to 64
characters including the appropriate file extension
• The length of entire path of the file should not exceed
230 characters. (m5/datasets/study001/sdtm/ae.xpt)

pdf file guideline according to eCTD
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• Version – 1.4 thru 1.7 are acceptable
• Fonts
– Standard : Arial, Courier New, Times Roman
– Sizes : range from 9 to 12 point ( Times New Roman 12-point
font is recommended for narrative text )
• Page
– Print area : 8.5 inches by 11 inches
– Margin : at least ¾ inch

SAS xpt file guideline according to eCTD
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• Length
– Variable length is less than or equal to 8
– Variable label is less than or equal to 40
– Dataset length is less than or equal to 8
– Dataset label is less than or equal to 40
• Dataset Size – less than 1 GB (LB1, LB2, and so on)
• The length of character variables should be minimized
(i.e., if the maximum length of USUBJID is 20 character
long, keep the length as 20, not 200)

Module 5 CSR Reports
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CSR, SAP, Protocol

CDISC Datasets eSubmission
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ADaM datasets, Define.xml
ADaM SAS programs
SDTM
datasets, Define.xml, SDTM
annotated blank eCRF

CDISC compliance
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• SEND : config-send-3.0.xml
• SDTM : config-sdtm-3.1.3.xml
• ADaM : config-adam-1.0.xml
• Define : config-define-2.0.xml
• CDISC compliance by OpenCDISC

Conclusion
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• Before : “should” in FDA documents means
that something is suggested or
recommended, but not required.
• After : “should” could mean required.
• CDISC electronic submission will be
mandatory sometime in 2016 or 2017.

Contacts
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• Email address : Kevin.lee@cytel.com
• Linkedin :
– Profile : www.linkedin.com/in/kevinlee1995/
– Group : CDISC ADaM
• Tweet : @kevinlee_pharma or @cdisc_adam

Questions?
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CDISC FDA Electronic Submission

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