FDA e-CTD Overview from a Programmer`s Perspective

Document technical information

Format pdf
Size 1.2 MB
First found Aug 19, 2016

Document content analysis

Language
English
Type
not defined
Concepts
no text concepts found

Persons

Ben F. Wilson
Ben F. Wilson

wikipedia, lookup

Organizations

Places

Transcript

FDA e-CTD Overview from a
Programmer’s Perspective
Cindy Song
July 2016
OUTLINE
● eCTD Overview
● Guidance
● Module 5
● Study Data Standardization Plan and Submission
Planning
● Some Points of Considerations
● Final Remarks
|
2
eCTD Overview
- Guidance
●  What is eCTD
●  The Electronic Common Technical Document (eCTD) is CDER/CBER’s
standard format for electronic regulatory submissions.
●  Final Guidance for Industry: Providing Regulatory Submissions in
Electronic Format – eCTD Specifications (May 2015)
●  eCTD TECHNICAL CONFORMANCE GUIDE (Oct 2015)
●  Providing Regulatory Submissions In Electronic Format —
Standardized Study Data (Dec 2014)
●  STUDY DATA TECHNICAL CONFORMANCE GUIDE (Mar 2016)
●  See the eCTD website www.fda.gov/ectd for further information
|
3
|
4
eCTD Overview
- Guidance
May
2015
|
5
Organization of the eCTD – 5 Modules
M1. ICH Region Specific
https://en.wikipedia.org/wiki/Electronic_common_technical_document
|
6
eCTD Modules
Headings and hierarchy folder structure
Module 1 - Administrative Information
Module 2 - Summaries
2.7 Clinical summary
2.7.1 Summary of Biopharmaceutic Studies and Associated Analytical
Methods
2.7.2 Summary of Clinical Pharmacology studies
2.7.3 Summary of Clinical Efficacy [indication]
2.7.4 Summary of Clinical Safety
2.7.5 References
2.7.6 Synopses of individual studies
Module 3 – Quality
Module 4 - Nonclinical Study Reports
Module 5 - Clinical Study Reports
|
7
eCTD Module 5
Headings and hierarchy folder structure
Module 5 Clinical Study Reports
5.2 Tabular listing of all clinical studies
5.3 Clinical study reports and related information
5.3.1 Reports of biopharmaceutic studies
5.3.2 Reports of studies pertinent to pharmacokinetics using human
biomaterials
5.3.3 Reports of human pharmacokinetic (PK) studies
5.3.4 Reports of human pharmacodynamic (PD) studies
5.3.5 Reports of efficacy and safety studies [Indication]
|
8
eCTD Module 5
An Example
5.3.5 Reports of efficacy and safety studies [Indication]
5.3.5.1 Study reports and related information of controlled clinical studies
pertinent to the claimed indication
Study 1
Protocol
Randomization scheme
Documentation of Statistical Methods and Interim Analysis Plans
Protocol deviation list
Case report forms
……
Annotated CRF
SDTM datasets, define.xml, SDRG
Analysis datasets, define.pdf, ADRG
Programs
Study 2
5.3.5.2 Study reports and related information of uncontrolled clinical studies
|
9
STUDY DATA SUBMISSION GUIDE
● 
Final Guidance for Industry: Providing Regulatory Submissions in
Electronic Format – eCTD Specifications (May 2015)
● 
eCTD TECHNICAL CONFORMANCE GUIDE (Oct 2015)
●  Providing Regulatory Submissions In Electronic Format —
Standardized Study Data (Dec 2014)
●  STUDY DATA TECHNICAL CONFORMANCE GUIDE (Mar 2016)
●  FDA Data Standards Catalog v4.4 (Aug 2015)
●  Study Data Standardization Plan (May 2015)
|
10
STUDY DATA SUBMISSION GUIDE
● 
Required December 17, 2016 for NDA, ANDA, and certain BLA
submissions, or December 17, 2017 for certain IND submissions
Implementation
Guide Version
SDTM 3.1.2
CDER,
CBER
CDER,
CBER
CDER,
CBER
CDER,
CBER
ADaM 1.0
CDER,
CBER
SDTM v3.2
SDTM v3.1.3
Version 3.1.2
Amendment 1
[1]
[2]
FDA
Center(s)
Date Support
Date
Begins (MM/DD/ Requirement
YYYY)
Begins (MM/DD/
YYYY)
10/30/2009
03/15/2018 [1]
03/15/2019 [2]
12/17/2016 [1]
12/17/2017 [2]
12/17/2016 [1]
12/17/2017 [2]
12/17/2016 [1]
12/17/2017 [2]
Ongoing
12/17/2016 [1]
12/17/2017 [2]
8/17/2015
12/01/2012
08/07/2013
For NDAs, ANDAs, and certain BLAs. See section II.A of the Providing Regulatory Submissions In
Electronic Format — Standardized Study Data guidance document
For certain INDs. See section II.A of the Providing Regulatory Submissions In Electronic Format —
Standardized Study Data guidance document
|
11
STUDY DATA SUBMISSION PACKAGE
SDTM
datasets xpt
ADaM
datasets xpt
Annotated
CRF
eCTD study data submission package
SDTM
Define/
SDRG
ADaM
Define/
ADRG
BIMO
Listings/
dataset
Programs
for datasets
and TLGs
|
12
Study Data Standardization Plan
●  Sponsor to initiate discussions at the pre-NDA stage
●  The Standardization Plan should include, but is not
limited to the following:
1.  List of the planned studies
2.  Type of studies (e.g., phase I, II or III)
3.  Study designs (e.g., parallel, cross-over, open-label
extension)
4.  Planned data standards, formats, and terminologies
and their versions or a justification of studies that
may not conform to the currently supported
standards
|
13
STUDY DATA SUBMISSION PANNING
Study ABC123
Complete
by
Stat
Prog Review Review
1st round
Review
complete
Review final
doc ready
Task
Creation
SDTM specs
SDTM datasets
SDTM transport
SDTM define xml & pdf
SDTM annotated CRF
SDRG
ADS specs
ADS datasets
ADS transport
ADS define
ADRG
Efficacy programs/
descriptions
Safety Programs/
descriptions
BIMO site listing
BIMO (clinsite dataset)
A. Smith
A. Smith
A. Smith
A. Smith
B. Miller
B. Miller
C. Johnson
C. Johnson
C. Johnson
C. Johnson
C. Johnson
1/1/2015F. Wilson
2/1/2015F. Wilson
2/1/2015F. Wilson
3/1/2015F. Wilson
3/1/2015F. Wilson
4/1/2015F. Wilson
2/1/2015F. Wilson
3/1/2015F. Wilson
3/1/2015F. Wilson
4/1/2015F. Wilson
4/1/2015F. Wilson
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
H. Sun
2/1/2015
2/15/2015
2/15/2015
3/15/2015
3/15/2015
4/15/2015
2/15/2015
3/15/2015
3/15/2015
4/15/2015
4/15/2015
4/30/2015
4/30/2015
4/30/2015
5/31/2015
5/31/2015
5/31/2015
5/31/2015
5/31/2015
5/31/2015
5/31/2015
5/31/2015
D. Williams
4/1/2015G. Li
J. Taylor
4/15/2015
5/31/2015
D. Williams
E. Zhao
E. Zhao
4/1/2015G. Li
3/1/2015G. Li
4/1/2015G. Li
J. Taylor
J. Taylor
J. Taylor
4/16/2015
4/1/2015
4/18/2015
5/31/2015
4/30/2015
5/31/2015
|
14
Points of Considerations
SAS DATA SETS
● 
● 
● 
● 
● 
● 
● 
Perform data set checks
●  Proc Content to check the datasets: eg. dataset label, variable, label,
format/informat etc.
Make sure that SAS data sets have the following properties:
● 
● 
● 
● 
Variable length >=3 bytes
Variable names <= 8 characters
Variable labels <= 40 characters
No user defined format / informat in datasets
Resize data (should save as a permanent SAS dataset, because we
need to read the variable attributes, eg. variable length)
Split data sets if need
Pinnacle 21 validation
Address the validation findings
●  May need to update the dataset / specifications
Create XPT files
|
15
Points of Considerations
SAS Transport Files
●  SAS XPORT Transport Format selected by FDA
●  Processed by the XPORT engine in Version 6 of SAS software
● 
● 
and later, and by PROC XCOPY in Version 5
An open, published file format developed by SAS Institute
●  By US law, the FDA must remain "vendor neutral." The
FDA cannot endorse or require use of any specific
vendor's product
●  Specifications for the XPORT transport format are in the
public domain. Data can be translated to and from the
XPORT transport format to other commonly used formats
without the use of programs from SAS Institute or any
specific vendor
Compare to CPORT transport file format
|
16
Points of Considerations
Define.xml and Define.pdf
●  Both define.xml and define.pdf are required for SDTM
●  Define.pdf required for ADaM/ADS (define.xml may be
required very soon)
●  Dataset in XML format (xx.xml) may be required soon
●  XML improves navigation for regulatory review
●  To create define file ●  Final datasets metadata
•  Ensure all information is complete and updated
•  If additional programming notes are prepared, ensure the
programming notes comply to CDISC standards
●  Final datasets XPT files
|
17
Points of Considerations
Submission Ready Programs
● 
● 
● 
● 
● 
● 
A trend from regulatory agency
●  More and more submissions are requested with programs
Black-box company-tools not recommended
Straight code is very much encouraged
Less macros, Macro names should be consistent with their contents
Clean up programs and documents
Follow Good Programming Practices
● 
● 
● 
● 
● 
● 
Header with clear documentation
Adequate commenting
Proper indentation
No hardcoding
Check for clean logs
•  no error, warning, uninitialized, merge with multiple values, invalid, out of
range etc.
QC according to company SOPs
|
18
Points of Considerations
SDRG and ADRG
● 
● 
SDRG – Study Data Reviewer’s Guide
● 
Why do we prepare SDRG and ADRG?
ADRG – Analysis Data Reviewer’s Guide
FDA Study Data Technical Conformance Guide
● 
PhUSE CSS (Computational Science Symposium) templates and
guidance available
SDRG guide
SDRG template
ADRG guide
ADRG template
|
19
Study Data Folders
(Study Data Technical Conformance Guide v3.0, March 2016)
ADaM data sets in transport fmt
Define.pdf (& Define.xml)
ADRG.pdf
ADaM creation programs
TL&F creation programs
ADS data sets in transport format
Define.pdf (& Define.xml)
ADRG.pdf
aCRF
SDTM data sets in transport format
Define.xml & Define.pdf
SDRG.pdf
|
20
Final Remarks
●  eCTD Module 5 for Clinical Studies
●  Study Data Plan and Preparation
●  Considerations for SAS Datasets and Programs
●  Programming Package can include
●  SAS Xport Transport Files and splits
●  Define.xml and Define.PDF
●  SDTM Annotated CRF
●  Programs
●  SDRG & ADRG
●  Follow Study Data Folder for Easy Automation of
Review Package
|
21
Contact Information
Cindy Song
Director, Programming Group Head
Currently in Beijing
Phone: (10) 65634953
email: [email protected]
|
22
Backup Slides
|
23
DMF
● 
Drug Master File or DMF is a document prepared by
a pharmaceutical manufacturer and submitted solely at its discretion to the
appropriate regulatory authority in the intended drug market. There is no
regulatory requirement to file a DMF. However, the document provides the
regulatory authority with confidential, detailed information about facilities,
processes, or articles used in the manufacturing, processing, packaging,
and storing of one or more human drugs. Typically, a drug master file is
filed when two or more firms work in partnership on developing or
manufacturing a drug product. The DMF filing allows a firm to protect
its intellectual property from its partner while complying with regulatory
requirements for disclosure of processing details.
● 
SEND - Standard for Exchange of Nonclinical Data
|
24
|
25
|
26

Similar documents

×

Report this document