Medical Device Labeling; Submission of IVD Symbols Glossary

Guidance for Industry and FDA
Staff
Use of Symbols on Labels and in
Labeling of In Vitro Diagnostic
Devices Intended for Professional
Use
Document issued on: November 30, 2004
The draft of this document was issued on October 28, 2003.
The information collection provisions in this guidance have been approved under OMB
control number 0910-0553. This approval expires 10/31/2007. An agency may not
conduct or sponsor, and a person is not required to respond to, a collection of information
unless it displays a currently valid OMB number.
For questions regarding this document contact Paula Silberberg, Office of Communication,
Education and Radiation Programs, Center for Devices and Radiological Health, 240-2763234; Terri Garvin, Office of In Vitro Diagnostic Devices Evaluation and Safety, Center
for Devices and Radiological Health, 240-276-1326; or Sheryl Kochman, Office of
Blood Research and Review, Center for Biologics Evaluation and Research, 301-827-6123.
U.S. Department of Health and Human Services
Food and Drug Administration

Center for Devices and Radiological Health
Center for Biologics Evaluation and Research

Contains Nonbinding Recommendations

Preface
Public Comment
Written comments and suggestions may be submitted at any time for Agency consideration
to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers
Lane, Room 1061, (HFA-305), Rockville, MD, 20852.
Alternatively, electronic comments may be submitted to
http://www.fda.gov/dockets/ecomments. When submitting comments, please refer to
Docket No. 2003D-0383. Comments may not be acted upon by the Agency until the
document is next revised or updated.

Additional Copies
Additional copies are available from the Internet at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/UCM085404.htm
or
or http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/UCM085679.pdf
You may also send an e-mail request to dsmica@fda.hhs.gov to receive an electronic
copy of the guidance or send a fax request to 301-847-8149 to receive a hard copy.
Please use the document number (4444) to identify the guidance you are requesting.
Or, you may contact:
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
Phone: 800-835-4709 or 301-827-1800

Contains Nonbinding Recommendations

Table of Contents
Introduction......................................................................................................................... 1
Background ......................................................................................................................... 2
Legal Considerations .......................................................................................................... 3
FDA Recognizes Selected ISO 15223 and EN 980 Medical Device Symbols................... 5
For In Vitro Diagnostic Devices ......................................................................................... 7
For Professional Labels and Labeling................................................................................. 7
Glossary of Terms............................................................................................................... 7
Educational Outreach.......................................................................................................... 8
Application of Guidance to Other Symbols........................................................................ 8
Implementation ................................................................................................................... 9

Contains Nonbinding Recommendations

Guidance for Industry and FDA Staff
Use of Symbols on Labels and in Labeling
of In Vitro Diagnostic Devices Intended
for Professional Use
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.

I.

Introduction

This document provides guidance on the use of selected symbols in place of text to
convey some of the information required for in vitro diagnostic devices (IVDs)
intended for professional use by 21 CFR 809.10, FDA’s labeling requirements for in
vitro diagnostic devices, and 21 CFR parts 610 and 660, FDA’s labeling requirements
for biologics (including IVDs) that are licensed under the Public Health Service
(PHS) Act. These recommendations apply to the use of symbols on the labels and in
labeling only of IVDs intended for professional use, and not for over-the-counter or
prescription home-use IVDs. This guidance does not address the use of “unique and
generally recognized” symbols to identify the manufacturer of a device, as described
in Section 502(u) of the Food, Drug and Cosmetic Act.
Note: The term “symbols” used throughout this guidance refers to the use of
graphical symbols without equivalent accompanying text.
This guidance is intended for both industry and FDA.
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.
1

Contains Nonbinding Recommendations

The Least Burdensome Approach
The issues identified in this guidance document represent those that we believe should be
addressed before your device can be marketed. In developing the guidance, we carefully
considered the relevant statutory criteria for Agency decision-making. We also considered
the burden that may be incurred in your attempt to follow the guidance and address the
issues we have identified. We believe that we have considered the least burdensome
approach to resolving the issues presented in the guidance document. If, however, you
believe that there is a less burdensome way to address the issues, you should follow the
procedures outlined in the “A Suggested Approach to Resolving Least Burdensome
Issues” document. It is available on our Center web page at
http://www.fda.gov/cdrh/modact/leastburdensome.html.

II.

Background

The market for in vitro diagnostic devices is international. European Union (EU)
member countries have attempted to harmonize their national legislation governing IVDs
through the European Union’s Directive on In Vitro Diagnostic Medical Devices,
(Directive 98/79/EC) (“IVD Directive”). The EU’s IVD Directive went into full effect
on December 8, 2003. As of that date, IVD products marketed in the EU must comply
with the IVD Directive and bear the CE mark (mark showing that the product is certified
for sale in the European community) to indicate compliance.
The EU’s IVD Directive and FDA regulations in 21 CFR 809.10, 21 CFR part 610, and
21 CFR part 660 all require substantial information to appear on the IVD itself and/or in
its labeling. The IVD Directive specifically allows each EU member state to require that
such information appear in its national language, so that a single IVD could be required
to bear labeling in multiple languages in order to be sold in the EU. As an alternative, the
IVD Directive encourages that, in place of text, IVDs use symbols from harmonized
standards to convey the required information. Given that the use of national languages
may be required by individual member states and that most IVDs and their packaging are
quite small, the IVD Directive’s symbols provision represents an avenue through which
manufacturers can achieve compliance in an international marketplace.
Similarly, the use of symbols helps IVD manufacturers to create uniform labels and
labeling for the United States and European Union (and any other countries that may
permit use of symbols from these international standards), instead of needing designated
labels for each marketplace. Because symbols take up less space than the text for which
they may substitute, the use of symbols promotes less crowded and more legible IVD
labels. An additional advantage is that there are likely to be fewer labeling errors when
using a single label, rather than having one set of labels for use in the United States and
another set for use in the European Union. Of course, it is essential that the symbol
convey the substance of the deleted text and be widely understood.

2

Contains Nonbinding Recommendations

III.

Legal Considerations

FDA regulations in 21 CFR 809.10 and 21 CFR parts 610 and 660 define information
required to appear on the label and in labeling for IVDs marketed in the United States.
These regulations specify the content of labels and labeling and the order in which this
information should be presented. With a few exceptions, these regulations do not specify
wording that manufacturers must use to meet these requirements.
Under Section 502(c) of the Food, Drug, and Cosmetic Act (the Act), a drug or device is
misbranded “If any word, statement, or other information required by or under authority
of this Act to appear on the label or labeling is not prominently placed thereon with such
conspicuousness (as compared with other words, statements, designs, or devices, in the
labeling) and in such terms as to render it likely to be read and understood by the
ordinary individual under customary conditions of purchase and use." The information
required by 21 CFR 809.10 and 21 CFR parts 610 and 660 thus must also meet the
requirements of Section 502(c) of the Act.
For a symbol to be used to convey information required by the regulations, it must be a
“term” that is “. . . likely to be read and understood by the ordinary individual under
customary conditions of purchase and use.” This guidance addresses specific symbols
from two harmonized international standards that FDA believes can satisfy this
requirement. Thus, in accordance with section 514(c) of the Act, FDA recognizes these
specific symbols for use on the label and in the labeling of certain IVDs. (See Federal
Register of April 28, 2003 (68 FR 22391); corrected with respect to the extent of
recognition by October 28, 2003 (68 FR 61448). In this context, we narrowly define the
“ordinary user” as the professional user of IVDs. The “customary conditions of purchase
and use” are within the laboratory environment. Through the process for recognizing
international consensus standards, under section 514(c) of the Act, FDA received
acceptable evidence in the form of a user comprehension study conducted in the United
States that indicates that this target audience can understand labels and labeling that use
the 25 symbols identified here in place of equivalent text.
Use of these symbols can also help to satisfy the “conspicuousness” requirement of
section 502(c). As explained above, most IVD devices are small and have limited label
space. By using symbols in place of some textual statements, manufacturers may
enhance the legibility of labeling and thus improve the “conspicuousness” of required
information. In the study submitted to FDA in support of recognition of these standard
symbols, participants overwhelmingly favored the use of the tested symbols in place of
the text equivalents.
This guidance document recognizes that the symbols for which comprehension data have
been presented to, and accepted by, the FDA through the consensus standards recognition
process may be used as terms to communicate to professional users of IVDs information

3

Contains Nonbinding Recommendations
required under 21 CFR 809.10 and 21 CFR parts 610 and 660.1 Manufacturers remain
responsible for adhering to the substantive requirements of these provisions, and to all
other labeling requirements under the Act and regulations.
As stated above, some provisions of 21 CFR 809.10 and 21 CFR part 660 do specify
particular labeling language. As a matter of enforcement discretion, FDA does not intend
to object to the use of:
•

the symbol consisting of the letters “IVD” in a box in place of the statement “For
In Vitro Diagnostic Use” required by 21 CFR 809.10(a)(4), 809.10(b)(5)(ii),
660.28(b)(13), and 660.55(b)(10)

•

the symbol that represents “For IVD Performance Evaluation only” in place of the
statement, “For Investigational Use Only. The performance characteristics of this
product have not been established.” Because FDA equates this symbol with this
statement, required by 21 CFR 809.10(c)(2)(ii), use of this symbol should be
limited to those IVDs that are subject to that requirement. IVDs that may be
subject to other labeling requirements regarding their investigational or research
status, such as the requirements of 21 CFR 812.5(a), 809.10(c)(2)(i), or 312.6(a),
must continue to bear the textual statements required by those provisions and
should not bear this symbol.

The symbol that represents “Authorized representative in the European Community” is
not needed to fulfill the labeling requirements of 21 CFR 809.10 or 21 CFR parts 610 or
660, as U.S. regulations do not require this information to be provided. IVD
manufacturers who wish to use this symbol on the label or labeling to be used in both the
U.S. and European Union in order to fulfill European labeling requirements may do so as
long as the use of this symbol does not violate other U.S. labeling requirements. For
example, if the “Authorized representative in the European Community” symbol is used
in a manner that interferes with the communication of information required by U.S. law,
the device could be misbranded under section 502(c) of the Act.
21 CFR 801.15(c) says that a device is misbranded under section 502(c) of the Act
unless:
“All words, statements, and other information required by or under authority of the act to
appear on the label or labeling shall appear thereon in the English language: Provided,
however, That in the case of articles distributed solely in the Commonwealth of Puerto
Rico or in a Territory where the predominant language is one other than English, the
predominant language may be substituted for English.” Because, as explained above,
FDA concludes that the symbols from international consensus standards recognized in
this guidance document can be understood by relevant users in the United States and thus
satisfy the underlying requirements of section 502(c), the Agency does not intend to
interpret their use to violate 21 CFR 801.15(c). This interpretation is consistent with
international harmonization.
1

4

Contains Nonbinding Recommendations

IV. FDA Recognizes Selected ISO 15223 and EN 980
Medical Device Symbols
In accordance with the consensus standards recognition process, established by section
514(c) of the Act, in the Federal Register of April 28, 2003 (68 FR 22391), FDA
published a notice recognizing certain standards for use in premarket reviews including
the two standards listed below concerning the use of symbols in labeling. In the Federal
Register of October 28, 2003 (68 FR 61448), FDA published a notice correcting the
April 28th notice with respect to the extent of the recognition of the two standards. FDA
recognizes 25 symbols for IVD devices for professional use from the following two
international consensus standards:
•
•

ISO 15223, Medical Devices – Symbols to be used with medical device labels,
labeling and information to be supplied
EN 980, Graphical symbols for use in the labeling of medical devices

The following chart displays the symbols with their definitions.

5

Contains Nonbinding Recommendations

6

Contains Nonbinding Recommendations
Validation data introduced in FDA’s consensus standards recognition process satisfies
FDA that professional users of IVDs, the intended audience for this labeling, will
understand the 25 symbols identified above. Specifically, industry-sponsored studies
conducted in the United States with professional laboratory test users from a variety of
educational backgrounds demonstrated end-user comprehension of the symbols in
context, with an accompanying glossary and other educational outreach. Sections V and
VI of this guidance explain the limitations of this recognition, which flow from the
validation data.

V.

For In Vitro Diagnostic Devices

FDA recognizes use of these symbols only for the labels and labeling of in vitro
diagnostic devices. Recognition supports FDA’s efforts to harmonize its regulatory work
with international standards-making bodies. Recognition is supported by the scope and
results of the studies performed and submitted to FDA. FDA has not received reports of
studies supporting use of any additional symbols on IVDs, nor supporting recognition of
any symbols for use on other devices, for which ordinary users and conditions of
purchase and use would differ from IVDs.

VI.

For Professional Labels and Labeling

FDA recognizes these symbols only for use on the professional label and in the
professional labeling of in vitro diagnostic devices. FDA does not recognize the symbols
for use in the labels and labeling of over-the-counter or prescription home-use IVDs.
Validation data introduced through FDA’s consensus standards recognition process
supported the use of symbols for IVD professional labels and labeling, not for consumer
labeling.

VII.

Glossary of Terms

FDA recommends that a glossary of terms accompany each IVD to define all of the
symbols used on that device’s labels and/or labeling. This glossary may also contain
other symbols identified by FDA in its recognition of ISO 15223 and EN 980, whether or
not used in labeling for the particular device. The glossary allows users to become
familiar with the meaning of the symbols and also acts as a reference for users to look up
any definitions they may not recall. In these respects, the glossary helps to satisfy the
requirements of Section 502(c) of the Act by ensuring that IVD users, under customary
conditions of use, have access to necessary reference materials, making it more likely that
they can understand the symbols. Since users can keep the package insert readily
accessible, FDA encourages the inclusion of the glossary in the package insert. The

7

Contains Nonbinding Recommendations
glossary accompanying the IVD may be a separate labeling piece in the form of a
separate sheet of paper or card while IVD labeling is being updated and revised, but FDA
recommends that to ensure ease of access, the glossary of symbols ultimately appear as
part of the package insert accompanying the IVD.

VIII.

Educational Outreach

FDA recommends that manufacturers conduct an educational outreach effort for the
intended audience to enhance the understanding of newly introduced symbols. The
educational outreach should target the various professional users of IVDs (e.g., laboratory
technologists, nurses, laboratory assistants, medical assistants). FDA recommends the
following possible methods for education:
•
•
•
•
•

print materials such as glossaries, wall charts, articles in the laboratory
press
information on industry web sites
dear health care provider letters
advertisements in professional journals
training sessions

The educational outreach should extend to all of those involved in the IVD distribution
chain, such as wholesalers and distributors, who need to be aware of symbols relating to
expiration date and storage requirements.
Such educational programs also help satisfy the requirements of Section 502(c) of the Act
by creating an environment in which IVD users are likely to understand the symbols
used.
FDA recommends that the manufacturers evaluate the educational outreach activities to
determine if these activities are effective in educating IVD users to comprehend the
meaning of the symbols.

IX.

Application of Guidance to Other Symbols

CDRH will consider recognizing other symbols for use on the labels and in the labeling
of IVDs through FDA’s consensus standards recognition process. For additional
information about this process, refer to the web page for FDA’s Standards Program:
http://www.fda.gov/cdrh/stdsprog.html.

8

Contains Nonbinding Recommendations

X.

Implementation

For IVDs intended for professional use for which FDA has approved an application for
Premarket Approval (PMA), manufacturers may change the labeling to include FDA
recognized symbols in place of equivalent text without approval of PMA supplements.
Other changes to labeling may require new PMA submissions, in accordance with 21
CFR 814.39(b). PMA holders that implement this type of change should notify the
Agency of the change in the next annual report to the PMA, in accordance with 21 CFR
814.84. Similarly, biologics license holders that implement this type of change should
notify the Agency of the change, which the Agency will consider an editorial or similar
minor change, in the next annual report to the Manufacturers Biologics License
Application (BLA), in accordance with 21 CFR 601.12(f)(3)(A). Manufacturers may
substitute recognized symbols in place of equivalent text on existing labels and labeling
for IVDs intended for professional use that received Premarket Notification [510(k)]
clearance without submitting a new 510(k). (For information on other labeling changes
that may require submission of a new 510(k), please see 21 CFR 807.81(a)(3), and
FDA’s guidance document, “Deciding When to Submit a 510(k) for a Change to an
Existing Device,” available at http://www.fda.gov/cdrh/ode/510kmod.pdf.)
Manufacturers and importers should report to FDA any adverse events that arise from the
use of symbols in labeling of IVDs intended for professional use, as required by 21 CFR
part 803. Reporting forms and instructions are available at
http://www.fda.gov/medwatch/safety.htm.

9