[Federal Register Volume 73, Number 161 (Tuesday, August 19, 2008)]
[Notices]
[Pages 48383-48385]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-19197]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0428]


Electronic Study Data Submission for Phase 3 Janus Operational 
Pilot; Notice of Pilot Project

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Center for Drug Evaluation and Research (CDER) is seeking 
sponsors interested in participating in a pilot project to test the 
submission and processing of clinical study data provided 
electronically in a standardized format. This pilot will test the data 
extract, validation, and load procedures developed to populate 
``Janus,'' the study data repository component of a common, standards-
based infrastructure that is being developed jointly by the Food and 
Drug Administration (FDA) and the National Cancer Institute (NCI) to 
support the exchange of clinical research data. The pilot also will 
test a new XML (extensible markup language)-based submission format for 
standardized clinical study data. We anticipate that a successful pilot 
will enable CDER to routinely receive, process, and store all 
standardized clinical study data in a

[[Page 48384]]

data warehouse environment that will enhance the center's capability to 
manage and review standardized study data.

DATES: Submit written or electronic requests to participate in the 
pilot project by November 17, 2008. General comments on the Janus 
operational pilot project are welcome at any time.

ADDRESSES: Submit written requests to participate and comments 
regarding this pilot project to the Division of Drug Information, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-
0002. Submit written comments to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Bobbie Witczak, Food and Drug 
Administration, 5600 Fishers Lane (HFD-070), Rockville, MD 20857, 301-
796-4126.
    For specific questions regarding Voluntary Genomic Data 
Submissions, please contact: Federico Goodsaid, Food and Drug 
Administration, 10903 New Hampshire Ave, Bldg. 51, rm. 2148 Silver 
Spring, MD 20903, 301-796-1535

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing an opportunity to participate in a pilot project 
that involves the ongoing development and testing of a repository for 
standardized clinical study data (the Janus study data warehouse). This 
pilot will test the electronic receipt, processing, and storage of 
standardized clinical study data, including the successful validation 
and loading of data into the Janus study repository and subsequent 
access of that data by reviewers using a combination of analytical and 
visualization tools. The Janus study data repository is the data 
warehouse component of a common, standards-based infrastructure that is 
being developed jointly by FDA and the NCI to support the exchange of 
clinical research data. Janus is designed to enhance the agency's 
capability to manage and review standardized study data.
    CDER has been accepting voluntary electronic submissions of 
standardized clinical study data since July 2004.\1\ Applicants wishing 
to provide clinical study data in standardized format are advised to 
follow the Study Data Tabulation Model (SDTM) defined by the Clinical 
Data Interchange Standards Consortium (CDISC). CDISC is an open, 
multidisciplinary, nonprofit organization that has established 
worldwide industry standards to support the electronic acquisition, 
exchange, submission, and archiving of clinical trial data and metadata 
for medical and biopharmaceutical product development (http://www.cdisc.org).
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    \1\ See http://www.fda.gov/bbs/topics/news/2004/NEW01095.html.
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    Under current regulations, applicants are required to provide case 
report tabulations (i.e., study data) for certain studies included in a 
marketing application (see 21 CFR 314.50). In guidance for industry 
titled ``Providing Regulatory Submissions in Electronic Format--Human 
Pharmaceutical Product Application and Related Submissions Using the 
eCTD Specifications,'' FDA makes recommendations about how to submit 
documents in electronic format for investigational new drug (IND) 
applications, biologic license applications (BLAs), and new drug 
applications (NDAs) using the electronic common technical document 
(eCTD) specifications. In Section III.E.4 of that guidance, FDA refers 
to the CDISC SDTM as the Study Data Specification for voluntary 
electronic submission of clinical study data.
    In addition, FDA is planning to amend the regulations governing the 
format in which clinical study data and bioequivalence data are 
required to be submitted for NDAs, BLAs, and abbreviated new drug 
applications (ANDAs).\2\ This proposal would revise FDA's regulations 
to require that clinical data submitted for NDAs, BLAs, and ANDAs, and 
their supplements and amendments: (1) Be provided in electronic format 
and (2) use a standardized data structure, terminology, and code sets 
as referenced in FDA guidance to enable efficient and comprehensive 
data review.
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    \2\ See http://www.reginfo.gov/public/do/eAgendaViewRule?ruleID=279292. (FDA has verified the Web site 
address, but FDA is not responsible for any subsequent changes to 
the Web site after this document publishes in the Federal Register.)
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    The Janus study data repository is being developed by FDA and NCI 
through the Interagency Oncology Task Force (IOTF), which was 
established in 2003 to enable the two organizations to share knowledge 
and resources to facilitate the development of new cancer drugs and 
speed the development and their delivery to patients. As part of the 
IOTF agreement, FDA is working with NCI to build tools and an 
environment that facilitates and streamlines electronic interaction and 
collaboration among FDA and its stakeholders in the regulatory review 
process. The Janus initiative is part of a larger effort to implement a 
common, standards-based electronic infrastructure that supports the 
submission, validation, data warehousing, access, and analysis of 
structured scientific data to support regulatory review.
    Phase 1 of the Janus implementation effort was a proof of concept 
pilot that successfully demonstrated the ability to load SDTM data into 
Janus, extract data from Janus using commercial-off-the-shelf (COTS) 
query tools, and produce data from Janus in SDTM format. Phase 2 of 
this initiative involved development of an operational pilot that 
includes a data import and validation facility, the integration of 
reviewer tools with the Janus repository, and provision of reviewer 
access to the data via selected analytical and visualization tools. 
Validation criteria for processing SDTM submissions were developed for 
use in that pilot based on the SDTM implementation guide and FDA 
business requirements. The SDTM validation specification for Janus 
established the business rules for error-checking functions that 
determine whether SDTM submission data can be loaded successfully into 
the Janus repository.\3\
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    \3\ See SDTM Validation Specification 1.0, Nov. 2007 at http://www.fda.gov/oc/datacouncil/janus_operational_pilot.html.
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    CDER has received a limited number of SDTM submissions since it 
began accepting these standardized datasets. Our experience with these 
submissions during the phase 2 pilot has shown that additional 
collaboration with sponsors will be needed on the preparation, 
submission, and analysis of SDTM datasets to facilitate a common 
understanding of the data quality requirements that are necessary to 
realize long-term benefits of an integrated clinical trials data 
repository.
    As a result, FDA is now announcing the start of phase 3 of the 
Janus operational pilot, which will enable a wider stakeholder 
community to participate in the Janus development initiative. The goals 
of the phase 3 pilot are as follows:
    <bullet> Transition the phase 2 pilot to operational production;
    <bullet> Test the electronic processing of standardized clinical 
study data, including the successful validation and loading of data 
into the Janus study repository and subsequent access to that data by 
reviewers using a combination of analytical and visualization tools;
    <bullet> Test a new XML-based submission format for CDISC content 
(CDISC-HL7

[[Page 48385]]

messages, see below) currently under development;
    <bullet> Extend the Janus logical data model and service-oriented 
architecture to support submission of CDISC-HL7 messages;
    <bullet> Integrate with NCI's Enterprise Vocabulary Service (EVS);
    <bullet> Test the integration and analysis of clinical study data 
stored in Janus with pharmacogenomic data currently being received 
through the Voluntary Genomic Data Submissions (VGDS) program.\4\
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    \4\ See http://www.fda.gov/cder/genomics/VGDS.htm.
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    A desired outcome of the phase 3 pilot is a production environment 
that supports the routine processing and management of all structured 
clinical study data provided in regulatory submissions.
    The phase 3 operational pilot will also test a new submission 
format. Currently, SDTM datasets are provided in SAS transport format. 
FDA recognizes the limitations of the outdated SAS transport format and 
intends to transition towards a new, more robust XML-based submission 
format. FDA is currently sponsoring a project within HL7\5\ to develop 
a standard XML exchange format (called ``messages'') for standardized 
clinical study data content as defined by CDISC. This ``CDISC Content 
to HL7 Message Project'' will enable the exchange of clinical study 
data in a standardized HL7-XML-based format. We believe this will 
facilitate loading study data into Janus and provide additional 
benefits. A successful phase 3 pilot will also enable FDA to routinely 
accept HL7-XML-based clinical study data submissions.
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    \5\ Health Level Seven in an American Standards Institute 
(ANSI)-accredited standards development organization operating in 
the health care arena. See http://www.hl7.org. (FDA has verified the 
Web site address, but FDA is not responsible for any subsequent 
changes to the Web site after this document publishes in the Federal 
Register.)
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    Concurrent with the phase 3 pilot, CDER also will be exploring ways 
to integrate related data standards initiatives with the Janus effort. 
These related initiatives include the enhancement of the current Janus 
logical model to incorporate preclinical and pharmacogenomics data and 
product safety data. Future efforts will continue to focus on business 
information requirements for managing product life-cycle data across 
all FDA regulated products.

II. Pilot Project Description

    This pilot project is part of an ongoing effort to improve the 
efficiency of the review of study data within CDER. As we gain 
additional experience from this pilot, CDER expects to update its study 
data submission technical specifications as part of a continuing 
process to improve the quality of clinical study data provided 
electronically.

A. Approach

    CDER is seeking applicants who have submitted or are planning to 
submit in the near future (i.e., within 6 months of publication of this 
notice) SDTM files in a regulatory submission in accordance with 
existing guidance and technical specifications. Our experience during 
phase 2 has shown that SDTM files routinely fail the Janus validation 
procedures and cannot be loaded into Janus automatically. Pilot 
participants should agree to work closely with Janus technical staff to 
review the validation errors, correct them, and resubmit the files. The 
ability to successfully load data into the Janus repository is an 
important pilot milestone. Experience gained as a result of working 
with participating sponsors during this pilot will help us improve the 
validation criteria, which subsequently will help improve the quality 
of future study data submissions. Pilot participants will also gain 
valuable experience in creating and submitting quality standardized 
data submissions. Of particular interest are pilot participants who are 
also able to provide pharmacogenomic data (i.e., VGDS) with the CDISC 
data. This will enable us to test the integration of clinical data 
stored in Janus with pharmacogenomic data. Although a VGDS is not 
required to participate in this pilot, it is a desirable component of 
the pilot and is encouraged whenever possible.
    From this pool of pilot participants, we are also seeking five to 
eight companies willing to supply study data in the new HL7 XML format 
(in addition to SDTM datasets) for testing, processing, and loading 
into Janus. FDA will provide some technical support with the new HL7 
XML format, such as help in understanding and interpreting the new 
specifications. Those who participate in this part of the pilot also 
will be provided secure access to their data in Janus so they can test 
the integrity of their data within the Janus environment. Although the 
SDTM files are part of a regulatory submission, all of the activities 
involved in this pilot will be conducted outside of a regulatory 
setting. That is, the SDTM datasets will be reviewed according to 
current review practices for any electronic dataset submission, and 
pilot activities will not impact the regulatory review clock, will not 
affect or delay reviewability assessments, filability decisions, or any 
regulatory actions.

B. How to Participate

    Requests to participate in the pilot project should be submitted to 
the Division of Dockets Management (see ADDRESSES). Requests are to be 
identified with the docket number found in brackets in the heading of 
this document. The pilot enrollment period will last 6 months following 
publication of this notice. The pilot is expected to last approximately 
1 year, but this duration will be subject to change as the pilot 
progresses. Updates to the pilot will be publicly posted on the FDA 
Janus Operational Pilot Web page.\6\
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    \6\ See http://www.fda.gov/oc/datacouncil/janus_operational_pilot.html.
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III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this pilot 
project. Submit a single copy of electronic comments or two paper 
copies of any mailed comments, except that individuals may submit one 
paper copy. Comments are to be identified with the docket number found 
in brackets in the heading of this document. Received comments may be 
seen in the Division of Dockets Management between 9 a.m. and 4 p.m., 
Monday through Friday.

    Dated: August 8, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-19197 Filed 8-18-08; 8:45 am]
BILLING CODE 4160-01-S