[Federal Register Volume 72, Number 191 (Wednesday, October 3, 2007)]
[Notices]
[Pages 56363-56364]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-19468]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0343]


Electronic Nonclinical Study Data Submission; 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, in a 
regulatory setting, the electronic submission of nonclinical study data 
using the Standard for Exchange of Nonclinical Data (SEND). The purpose 
of this pilot is to test the ability of a new electronic data format to 
support nonclinical review activity. The pilot also will involve a 
collaboration of FDA, available pilot participants, and the SEND 
Consortium to update and create a new draft SEND implementation guide. 
FDA anticipates that a successful pilot will enable CDER to routinely 
accept nonclinical study data electronically in SEND format, instead of 
paper or portable document format (PDF), in investigational new drug 
applications (INDs), new drug applications (NDAs), and biologics 
licensing applications (BLAs).

DATES: Submit written or electronic requests to participate in the 
pilot project by January 2, 2008. 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://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Bobbie Witczak, Food and Drug 
Administration, 5600 Fishers Lane HFD-070, Rockville, MD 20857, 301-
827-3938.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing an opportunity to participate in a 3-year pilot 
project in a regulatory setting being conducted by CDER involving the 
ongoing testing of SEND, a nonclinical data model developed by the 
Clinical Data Interchange Standards Consortium (CDISC) . The ultimate 
goal of the pilot is to replace the existing paper/PDF-based listings 
of nonclinical study data.
    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). CDISC is currently facilitating the extension 
of the same standard for nonclinical data, termed SEND, through the 
efforts of the SEND Consortium. Where possible, the standards developed 
for clinical datasets and metadata, as described in the overall Study 
Data Tabulation Model (SDTM), are being used to develop a standardized 
dataset format for nonclinical studies.
    Under current regulations, applicants must provide tabulated 
nonclinical data from animal toxicity studies as part of NDA (21 CFR 
314.50) and IND (21 CFR 312.23) applications. In a 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 to INDs, BLAs, and 
NDAs using the electronic common technical document (eCTD) 
specifications. CDER currently receives nonclinical study data either 
on paper or as electronic PDF files. These formats do not support the 
agency's ability to easily receive, validate, display, or evaluate the 
data using modern, computer-based review and analysis tools. As part of 
FDA's effort to modernize its information technology systems and 
improve efficiency, the agency is planning to transition from the 
traditional paper/PDF formats to a true electronic data format for 
submission of nonclinical data for regulatory review.
    Recently, CDER has adopted a standard for clinical study data based 
on the CDISC SDTM standard. In addition, CDER entered into a CRADA 
(cooperative research and development agreement) with PharmQuest 
Corporation, Inc., for the development of data validation, viewing, and 
analysis tools to evaluate standardized nonclinical datasets based on 
SEND. The FDA believes the use of standardized SEND datasets, together 
with new and better analysis tools, will increase the efficiency of 
agency review and evaluation of nonclinical data.
    CDER recently completed a related pilot project (phase 1) that 
asked for volunteers from industry to submit sample nonclinical 
datasets in the SEND format outside of a regulatory setting (68 FR 
3885; January 27, 2003). The phase 1 pilot also evaluated data 
validation and analysis tools specifically designed to validate 
datasets according to the current SEND standard and to enable a 
reviewer to efficiently display and evaluate data from animal toxicity 
studies submitted in the SEND format. The phase 1 pilot resulted in 
development of a SEND Implementation Guide (Version 2.3; November 
2005), which is available on the CDISC Web site (http://www.cdisc.org/models/send/v2.3/SENDV2.3ImplementationGuide.pdf). The SEND 
Implementation Guide describes the process for formatting nonclinical 
data from single- and repeat-dose animal toxicity and carcinogenicity 
studies for submission purposes. The pilot also resulted in the 
development of specialized software tools for validating, displaying, 
and analyzing SEND-formatted nonclinical data.
    As a continuation of this testing process, this new pilot (phase 2) 
will enable FDA to evaluate animal toxicity data submitted in SEND 
format in a regulatory setting by comparing SEND-formatted data 
provided electronically as SAS transport file (XPT version 5) datasets 
with data provided in PDF.
    In addition, in the intervening time period between the publication 
of the SEND implementation guide version 2.3 (November 2005) and now, 
some changes have been made to the SDTM for clinical data, making it 
desirable to update the SEND implementation guide to ensure harmonized 
implementation of the CDISC study data standard across both clinical 
and nonclinical data. There is also a plan to expand the SEND 
implementation guide to include a pharmacokinetics domain, more 
detailed implementation examples, and, eventually, other nonclinical 
study types. As a result, FDA will not conduct the pilot using the 
existing SEND implementation guide version 2.3. Instead, phase 2 will 
include an initial collaboration among FDA, available pilot 
participants, and the SEND Consortium to update and create a new draft 
SEND implementation guide before FDA receives any datasets for 
regulatory review. The current status of

[[Page 56364]]

both the pilot project and the draft SEND implementation guide can be 
found on the FDA SEND Web page at http://www.fda.gov/oc/datacouncil/send.html. Before creating and submitting nonclinical datasets, pilot 
participants should ensure that they use the most recent draft version 
of the SEND implementation guide.

II. Pilot Project Description

    This pilot project is part of an ongoing effort to improve the 
efficiency of the review of nonclinical data within CDER. Eventually, 
as experience from the ongoing pilot is gained with various types of 
nonclinical studies, CDER expects to recommend new technical 
specifications as part of a continuing process for the submission of 
nonclinical study data provided electronically and eliminate the need 
to provide paper/PDF-based data listing.

A. Approach

    CDER is seeking a limited number of sponsors (i.e., approximately 
five to eight) to participate in the phase 2 pilot. The duration of the 
pilot is expected to be approximately 3 years, but it may be extended 
as needed. Participants should be familiar with SEND (e.g., from 
involvement in the phase 1 pilot) and be willing to provide the same 
nonclinical study data in both PDF and SEND formats to an existing IND. 
The PDF must comply with all applicable regulations, including those in 
part 11 (21 CFR part 11)\1\. To achieve the goals of the pilot, FDA 
intends to exercise additional enforcement discretion with regard to 
part 11 requirements as applied to data submitted in SEND format under 
this pilot. That is, we do not intend to take enforcement action 
against data submitted in SEND format, under this pilot, to enforce 
compliance with those portions of part 11 that remain in effect. The 
SAS transport files (version 5) should be based on the SEND format. 
Having the same data available in both PDF and SEND formats provides 
the best opportunity to compare the two and evaluate the accuracy and 
reliability of the SEND format. Although the PDF version will continue 
to be the version used for archival purposes during the pilot, both 
data formats (i.e., PDF and SEND) will be used by FDA for regulatory 
review purposes. Before receiving any SEND data, FDA and pilot 
participants will work with the SEND Consortium to update the SEND 
implementation guide, which will then be used during the pilot.
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    \1\ See, ``Guidance for Industry; Part 11, Electronic Records; 
Electronic Signatures--Scope and Application,'' August, 2003; http://www.fda.gov/Cder/guidance/5667fnl.htm
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    For the purposes of this phase 2 pilot, full study reports of the 
following types of animal toxicity studies will be requested for 
submission to an existing IND in the appropriate CDER review division: 
(1) Repeat-dose toxicity studies of 14 days duration to 12 months 
duration in any species, (2) life-time carcinogenicity studies in rats 
or mice, or (3) 6-month carcinogenicity studies in transgenic mice. 
Studies should include toxicokinetic data, if available. For submission 
of carcinogenicity studies, the appropriate CDER and International 
Conference on Harmonization (ICH) guidances should be consulted. The 
submission should contain both the ``Tumor Dataset for Statistical 
Analysis'' (i.e., tumor.xpt, as described in Appendix 1 of the Study 
Data Specifications document; version 1.3; dated 2006-11-27) as well as 
the SEND-formatted datasets for the entire study. Depending on the 
ongoing efforts of the SEND Consortium to expand the SEND 
implementation guide, additional nonclinical study types may be piloted 
in the future. If so, FDA will post on the FDA SEND Web page an updated 
list of study types the agency will accept in this and any future 
pilots. We anticipate that a successful phase 2 pilot, which includes 
implementation of any needed changes to the SEND implementation guide 
and/or the data validation, viewing, and analysis tools, will allow 
CDER to routinely accept specific types of nonclinical study data 
provided electronically as SAS transport file (XPT version 5) datasets 
based on the SEND format. In the case of carcinogenicity studies, a 
successful phase 2 pilot will enable submission of the entire 
carcinogenicity study data in the electronic SEND format, thus 
eliminating the need for a separate submission of the electronic tumor 
dataset (i.e., tumor.xpt).

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. As mentioned above, it is recommended that interested 
participants be familiar with SEND and/or have been involved in the 
previous phase 1 pilot.

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: September 26, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-19468 Filed 10-2-07; 8:45 am]
BILLING CODE 4160-01-S