[Federal Register: March 13, 2007 (Volume 72, Number 48)]
[Notices]               
[Page 11370-11371]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr13mr07-65]                         

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0064]

 
Electronic Case Report Form Submission; Notice of Pilot Project

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Notice.

-----------------------------------------------------------------------

SUMMARY:  The Center for Drug Evaluation and Research (CDER) and the 
Center for Biologics Evaluation and Research (CBER) in the Food and 
Drug Administration (FDA) are seeking sponsors interested in 
participating in a pilot project to test the submission of case report 
form (CRF) data provided electronically in extensible markup language 
(XML) based on the Operational Data Model (ODM) developed by the 
Clinical Data Interchange Standards Consortium (CDISC). This pilot will 
test the ability of a new data format to support all

[[Page 11371]]

review activity, which our current submission format is incapable of 
doing. Data supplied in ODM format by sponsors during the pilot project 
will not replace any regulatory requirements for submitting CRFs. We 
anticipate that a successful pilot will allow CDER and CBER to 
routinely accept CRFs from studies employing electronic data capture 
(EDC) in ODM format in marketing applications provided in electronic 
format.

DATES:  Submit written or electronic requests to participate in the 
pilot project by September 10, 2007. General comments on the pilot 
project are welcome at any time.

ADDRESSES:  Submit written requests to participate and comments 
regarding this pilot project 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments
.


FOR FURTHER INFORMATION CONTACT:  Armando Oliva, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 6310, Silver 
Spring, MD 20993-0002, 301-796-0514.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the opportunity to participate in a pilot project 
being conducted by CDER and CBER involving the testing of the ODM 
standard developed by the CDISC, with the goal of replacing the 
existing portable document format (PDF)-based CRFs derived from 
clinical trials that use EDC and, therefore, lack paper CRFs. 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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cdisc.org
).

    Under existing Federal regulations (21 CFR 314.50), applicants must 
provide CRFs with a marketing application. Since November 1997, under 
21 CFR part 11, we have accepted CRFs in electronic format instead of 
paper. FDA has issued several guidances that provide recommendations 
concerning electronic submissions. In the Federal Register of October 
19, 2005 (70 FR 60842), FDA announced the availability of a guidance 
entitled ``Providing Regulatory Submissions in Electronic Format--Human 
Pharmaceutical Product Applications and Related Submissions Using the 
eCTD Specifications'' (http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or 

http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/gdlns/esubapp.htm). In section III.E.3. of that 

guidance, FDA recommends that applicants submit an individual subject's 
complete CRF as a single, PDF file. The guidance recommends that if a 
paper CRF was used in the clinical trial, the submitted CRF should be a 
scanned image of the paper CRF, including all original entries with 
modifications, addenda, corrections, comments, annotations, and any 
extemporaneous additions (i.e., audit trail). The guidance further 
recommends that if EDC was used in the clinical trial, the applicant 
should submit a PDF-generated form or other PDF representation of the 
information (e.g., subject profile).
    Based on our experience, PDF-based CRFs from clinical trials that 
employ EDC are not ideal to support all review activity. Although the 
PDF-based CRFs for trials that use EDC can provide a record of the 
observations collected during the trial (i.e., the data) and additional 
information about what was collected (metadata), they typically do not 
provide an audit trail. CDER and CBER are interested in adopting a new, 
standard format that can replace the PDF-based CRF and that can 
reliably provide all three components of the CRF in an electronic 
format: Data, metadata, and audit trail.
    The ODM is an XML-based standard that facilitates the electronic 
exchange of clinical trial data, metadata, and audit trail. We are 
working with CDISC to develop the capabilities within CDER and CBER to 
review CRFs using ODM. CDISC employed the current production version 
(Version 1.2) of the ODM on the CDISC Web site, and we performed some 
initial testing of limited CRF data in ODM. To help in this 
development, we are launching this pilot project and seeking sponsors 
willing to provide CRFs in ODM format to test our capabilities to 
review these files. However, data supplied during the pilot project 
will not replace any regulatory requirements for submitting CRFs.
    The purpose of this pilot project is to obtain additional 
experience with ODM-based CRFs. We anticipate that a successful pilot 
will allow CDER and CBER to routinely accept CRFs from studies that 
employ EDC in ODM format in marketing applications submitted in 
electronic format.

II. Pilot Project Description

    This pilot project is part of an effort to improve the quality of 
CRFs provided to CDER and CBER in electronic format and to improve the 
centers' capability to review these files. Eventually, CDER and CBER 
expect to recommend new technical specifications for the submission of 
CRFs that are derived from clinical trials that employ EDC and, 
therefore, lack paper CRFs.

A. Initial Approach

    Because only a limited number of sponsors are needed (i.e., 
approximately five), CDER and CBER will use their discretion in 
choosing participants, based on participants' previous experience 
submitting CRFs in accordance with existing guidance. Participants 
should be willing to provide the same CRFs in two formats: PDF, in 
accordance with existing guidance, and ODM. If PDF-based CRFs have 
already been submitted as part of an existing new drug application or 
biologics license application on file with the agency, then 
participants need only provide the ODM-based CRFs with the same 
information. Having the same information available in both PDF and ODM 
provides the best opportunity to compare the two formats.

B. How to Participate

    Written 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.

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: March 5, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-4451 Filed 3-12-07; 8:45 am]

BILLING CODE 4160-01-S