confused by fda guidance on standardized study data for electronic submissions?
TRANSCRIPT
Confused by FDA Guidance on Standardized Study Data for Electronic Submissions?
Ben Vaughn
• Principal Statistical Scientist
Rob Woolson
• Chief Strategist-Biostatistics & Standards for Regulatory Submissions
Context
FDA has been accepting electronic submissions (as we currently think of them) since the 1999 eNDA Guidance was issued
In 2003 the eCTD Guidance was issued, formalizing the structure of electronic submissions and made a requirement for electronic submissions in 2008
CDER began accepting SDTM in 2004, however FDA had not previously made this a formal requirement
ContextElectronic Standardized Study Data Timeline
(Source: Fitzmartin, PhUSE 2014)
FDASIA 745A(a) Guidance
Binding Guidance Requiring Submissions in Electronic Format
•“Beginning no earlier than 24 months after the issuance of a final guidance issued after public notice and opportunity for comment, submissions under subsection (b), (i), or (j) of section 505 of this Act or subsection (a) or (k) of section 351 of the Public Health Service Act shall be submitted in such electronic format as specified by the Secretary in such guidance.”
Which submissions must be
submitted electronically?
Certain INDs
NDAs
ANDAs
Certain BLAs
Also includes subsequent
submissions, including amendments.
FDA Implementation of New
Requirements
Draft guidances
will be posted for
review
Comment period
Finalization period
Final guidance
announced and posted
No earlier than 24 months
after a final guidance is
issued
Summary of FDASIA 745A(a)
GuidanceUmbrella document to describe the process
This is a BINDING GUIDANCE
Since this is a BINDING GUIDANCE, failure to follow the technical conformance rules can result in a REFUSAL TO FILE.
Assume that this Guidance, and subsequent technical guidances, will apply to all submissions to CDER and CBER.
eStudy Data Guidance
Binding Guidance Requiring a Standardized Data Format
• “This guidance implements the electronic submission requirements of section 745A(a) of the FD&C Act for study data contained in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and investigational new drug applications (INDs) to the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER) by specifying the format for the electronic submission of such submissions. Submissions that are not submitted electronically and electronic submissions that are not in a format that FDA can process, review, and archive will not be filed or received …”
Which submissions must follow a
standardized data format?
Certain INDs
NDAs
ANDAs
Certain BLAs
Also includes subsequent submissions, including
amendments.
Some exemptions: devices, some INDs.
What standardized formats
MUST be used?
Some examples
•Exchange format: .pdf, .xpt, .xml
•Clinical data: SDTM
•Analysis data: ADaM
•Terminology: CDISC controlled terminology, MedDRA
The standards, formats, and terminologies
specified in the Data Standards Catalog
posted to the FDA’s web page.
And what if standardized
formats are not used?
“The FDA will not provide waivers to submit data that do not conform to any FDA-supported study data standard. However, sponsors or applicants may apply for a waiver from the requirement to use specific versions of standards, formats, or terminologies.”
Timing of Specific Requirements
• Studies starting 24 months after the ‘Transition Date’ – the March 15th after the Federal Register notice
Guidance (e.g., a new
standard)
• Studies starting 12 months after the ‘Transition Date’ – the March 15th after the Federal Register notice
Standards Version Update
Working with the FDA
Meetings with FDA
• Use established FDA-sponsor meetings (e.g., pre-IND, EOP2, etc.) to discuss the study data standardization plan
• Technical questions related to data standards can be submitted at any time to the technical support team identified by each Center; a Type C meeting can be requested for substantive issues
Implementation Support
Summary of eStudy Data
GuidanceFirst Guidance document under the 745A(a) umbrella.
This is a BINDING GUIDANCE
Since this is a BINDING GUIDANCE, failure to follow the technical conformance rules can result in a REFUSAL TO FILE.
Assume that this Guidance, and subsequent technical guidances, will apply to all submissions to CDER and CBER.
Study Data Technical
Conformance GuideTechnical Specifications Document
• Guidance supplements eStudy Data Guidance
• Provides technical specifications briefly described in the eStudy Data Guidance
• Is a single document containing earlier recommendations contained in the Common Data Issues Document and the Study Data Specifications Document.
Study Data Tech Guide -
Contents
Study Data Tech Guide
Background
•Provides technical recommendations; non-binding
•FDA acknowledges that there may be variability in implementation
•Though, deviate at your own risk
•This is intended to be a living document where the FDA updates technical recommendations, preferences, and errors to avoid
Study Data Tech Guide
Study Data Standardization Plan (include in the IND). Should include the following:
• List of planned studies
• Types of studies
• Study designs
• Planned data standards
• List of justifications for studies that do not conform
Study Data Tech Guide
Study Data Reviewer Guide. Should include the following:
• Study protocol, title, number, version
• Study design
• Standards, formats, terminologies
• Description of study datasets
• Data standards conformance validation rules, versions, and issues
Study Data Tech
Study Data Submission Format:
• CDISC: FDA’s strongest endorsement of SDTM/ADaM
In Conclusion …
Read the Guidances
Start conversations with FDA at pre-IND stage regarding data standards
Educate, educate, educate