Guidance for Industry
Providing Regulatory Submissions
in Electronic Format — Content of
Labeling
(PDF
version of this document)
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
April 2005
Electronic Submissions
Additional copies are available
from:
Office of Training and Communications
Division of Drug Information, HFD-240
Center for Drug Evaluation and Research
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
(Tel) 301-827-4573
http://www.fda.gov/cder/guidance/index.htm
or
Office of Communication, Training
and
Manufacturers Assistance, HFM-40
Center for Biologics Evaluation and Research
Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448
http://www.fda.gov/cber/guidelines.htm
Phone: the Voice Information
System at
800-835-4709 or 301-827-1800
U.S. Department of
Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
April 2005
Electronic Submissions
Guidance for Industry
Providing Regulatory Submissions in Electronic Format —
Content of Labeling
This
guidance represents the Food and Drug Administration's (FDA's)
current thinking on this topic. It does not create or confer any
rights for or on any person and does not operate to bind FDA or
the public. You can use an alternative approach if the approach
satisfies the requirements of the applicable statutes and
regulations. If you want to discuss an alternative approach,
contact the FDA staff responsible for implementing this guidance.
If you cannot identify the appropriate FDA staff, call the
appropriate number listed on the title page of this guidance.
This is one in a series of guidance documents
intended to assist applicants making regulatory submissions to FDA
in electronic format. Agency guidance documents on electronic
submissions will be updated regularly to reflect the evolving nature
of the technology and the experience of those using this
technology.
The Agency is adopting new technology for
processing and managing labeling and labeling changes, including the
content of labeling submitted electronically. This guidance
describes how to submit the content of labeling using the Structured
Product Labeling (SPL) standard, which is based on extensible markup
language (XML).
This guidance discusses issues related to the
submission of the content of labeling in electronic format for
marketing applications for human drug and biologic products,
including new drug applications (NDAs), abbreviated new drug
applications (ANDAs), and biological license applications (BLAs) for
biological products that meet the definition of drug in the Federal
Food, Drug, and Cosmetic Act. The content of labeling is the
labeling required under 21 CFR 201.100(d)(3) including all text,
tables, and figures (commonly referred to as the package insert or
professional labeling). This guidance applies to the content of
labeling provided with original submissions, supplements, and annual
reports. Copies
of the formatted label and labeling and specimens of enclosures
required elsewhere in the regulations (e.g., 21 CFR
314.50(e)(2)(ii)), including carton and container labels, must still
be submitted either electronically in Portable Document Format (PDF)
or on paper.
For a list of guidances that are under
development on electronic submissions, see the guidance
Regulatory Submissions in Electronic Format — General Considerations.
The general considerations guidance also addresses issues (e.g.,
appropriate file formats, media, and submission procedures) that are
common to all submission types.
FDA's guidance documents, including this
guidance, do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency's current thinking on a topic
and should be viewed only as recommendations, unless specific
regulatory or statutory requirements are cited. The use of the word
should in Agency guidances means that something is suggested
or recommended, but not required.
On December 11, 2003, FDA published final
regulations (the electronic labeling rule) requiring the submission
of the content of labeling in electronic format for marketing
applications (68 FR 69009). The requirements of the electronic
labeling rule can be found in § 314.50(l) for NDAs, § 314.94(d) for
ANDAs, § 601.14(b) for BLAs, and § 314.81(b) for annual reports to
marketing applications. The effective date of the rule was June 8,
2004. The regulations specify that the content of labeling must be
submitted electronically in a form that FDA can process, review, and
archive. The regulations also state that FDA will periodically
issue guidance on how to provide the electronic submission. This
guidance provides information on how to submit the content of
labeling in electronic format.
The regulations require that the content of
labeling be submitted in a form that we (FDA) can process, review,
and archive. Since 1999, FDA has been receiving the electronic
content of labeling in Portable Document Format (PDF), and this
format has allowed us to process, review and archive the content of
labeling. Recently, however, recommendations from the Institute of
Medicine and the National Committee on Vital and Health Statistics
and mandates in the Medicare Prescription Drug, Improvement, and
Modernization Act of 2003 (Public Law 108-173) have created a new
role for electronic labeling information. Electronically formatted
content of labeling will be used to support health information
management technologies such as electronic prescribing; the
electronic health record (EHR), which will provide health care
providers, patients, and other authorized users access to patient
information in electronic format; and the
DailyMed, a new way to distribute up-to-date and comprehensive
medication information in a computerized format for use in health
care information systems.
We have determined that our current procedures
using PDF are not adequate to support these electronic initiatives.
To support the new programs, the Agency is changing the way it
processes, reviews, and archives the content of labeling. The
Agency is adopting a new technology for exchanging information
between computer systems based on Clinical Document Architecture (CDA).
CDA was developed by Health Level Seven (HL7), a standards
development organization accredited by the American National
Standards Institute (ANSI). CDA allows information to be exchanged
in extensible markup language (XML) and is the standard being
investigated for the EHR.
FDA, working with other parties in HL7 (experts
from HL7, industry, and technology solution providers), has adapted
CDA for labeling in an HL7 standard called Structured Product
Labeling (SPL). When compared with PDF, SPL exhibits the following
advantages.
·
SPL allows the exchange of information between
computer systems in a way that cannot be accomplished with PDF. For
example, the information in SPL can be used to support health
information technology initiatives for improving patient care.
·
The exchange of labeling changes with SPL can be
easier and more efficient for both FDA and manufacturers when
compared with PDF. For example, with SPL, only those sections or
data elements of the labeling that are changed would need to be
checked rather than the entire labeling.
·
SPL allows automation of comparison of text by section
and comparison of specific drug information data elements.
·
SPL can also be used to exchange information needed
for other submissions, such as drug listing, thus eliminating
redundant data collection and improving efficiency.
The Agency is developing an automated system
using SPL for processing and managing labeling and labeling changes.
The Center for Drug Evaluation and Research has identified SPL in
public docket number 92S-0251 as a format that FDA can use to
process, review, and archive the content of labeling. During our
transition to the automated system, the Agency is able to accept the
content of labeling in either PDF or SPL file format. After the
automated system is implemented, PDF will no longer be a format that
we can use to process, review, and archive the content of labeling.
The change to SPL will apply only to those submissions with content
of labeling files that are provided after the implementation of the
automated system. At this time, it is our goal to complete the
transition to SPL format for content of labeling submissions for
approved prescription drugs by fall 2005.
This guidance applies to the content of
labeling for any marketing application (ANDAs, BLAs, NDAs)
submission required to be submitted in electronic format under §§
314.50(l) 314.81(b)(2), 314.94(d), and 601.14(b).
Prior to
the implementation of the automated system, we will be able to
receive content of labeling in PDF or SPL file format. After
implementation of the automated system, we will only be able to
receive content of labeling in SPL format.
This guidance describes how to submit the
content of labeling using XML based on the HL7 SPL specifications.
For information on how to submit the content of
labeling using PDF based on the Adobe Systems Incorporated
specifications, see the current Agency guidance on providing
regulatory submissions in electronic format.
Please refer to the HL7 published
specifications for Structured Product Labeling (SPL) for details on
how to create the content of labeling file for submission to FDA.
The SPL specifications can be obtained from HL7 (www.hl7.org).
Additional details on creating SPL for submission to FDA can be
found in the HL7 document SPL Implementation Guide for FDA
Content of Labeling Submissions. The implementation guide may be
found on the HL7 web site at http://www.hl7.org. Links to SPL-related
documents located on the HL7 Web site and additional SPL-related
resources (including the most recent updates, stylesheet files for
viewing SPL files, and example labels) can be found at the FDA Web
site at
www.fda.gov/oc/datacouncil/spl.html.
Bookmarks commonly included in the PDF content
of labeling files to sections within the labeling are not needed
because the tags in the SPL file provide this functionality. SPL
does not replace various methods used for negotiating labeling
changes (e.g., FAX, Word files). Prior to the implementation of the
automated system, FDA can accept content of labeling submitted in
SPL file format only in a complete SPL file. Submission of multiple
versions of the labeling (e.g., “proposed” or “current”) and
submission of the history.pdf file can be eliminated only
after the implementation of the automated system.
Content of labeling must be provided in
electronic format (§§ 314.50(l), 314.94(d), 601.14(b), and
314.81(b)), even when it is part of a paper submission.
Before implementation of the automated system, you should
follow the procedures in either this guidance or Agency guidance on
submitting electronic NDAs or BLAs
for information on how to submit the content of labeling
electronically. After implementation of the automated system, you
should follow the procedures in this guidance for submission of the
content of labeling electronically.
Note: In order for FDA to process, review, and
archive electronic content of labeling, all submissions, including
annual reports, must be made in accordance with certain provisions
of 21 CFR part 11 specified in the electronic labeling rule (§§
314.50(l), 314.94(d)(1), 601.14(b), and 314.81(b)) and sent to the
appropriate central document room facilities specified in public
docket number 92S-0251. Electronic documents that are sent directly
to division document rooms or to reviewers bypass the controls
established for the receipt and archiving of documents and,
therefore, are not considered official documents for review.
If you
have any questions on technical issues related to providing the
content of labeling in submissions according to the recommendations
in this guidance, please contact the appropriate electronic
submission coordinator at
esub@cder.fda.gov or
esubprep@cber.fda.gov.
Specific questions pertaining to content should be directed to the
appropriate review division or office.
The
content of labeling
SPL files should be placed in a single folder titled spl.
The spl folder is used for all submissions in SPL whether they are
part of an electronic submission or a paper submission.
If the
content of labeling in
SPL is provided with an electronic submission, you should
place the spl folder in the appropriate folders for
labeling. For additional information on organizing the submission
folder in an electronic submission, see current Agency guidance on
providing regulatory submissions in electronic format.
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Date created: April 20, 2005 |