[Federal Register Volume 81, Number 115 (Wednesday, June 15, 2016)]
[Rules and Regulations]
[Pages 38911-38931]
[FR Doc No: 2016-13989]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 660, 801, and 809

[Docket No. FDA-2013-N-0125]
RIN 0910-AG74

Use of Symbols in Labeling

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
issuing this final rule revising its medical device and certain
biological product labeling regulations to explicitly allow for the
optional inclusion of graphical representations of information, or
symbols, in labeling (including labels) without adjacent explanatory
text (referred to in this document as ``stand-alone symbols'') if
certain requirements are met. The final rule also specifies that the
use of symbols, accompanied by adjacent explanatory text continues to
be permitted. FDA is also revising its prescription device labeling
regulations to allow the use of the symbol statement ``Rx only'' or
``[rx] only'' in the labeling for prescription devices.

DATES: This rule is effective September 13, 2016.

FOR FURTHER INFORMATION CONTACT: For information concerning the final
rule as it relates to devices regulated by the Center for Devices and
Radiological Health (CDRH): Antoinette (Tosia) Hazlett, Center for
Devices and Radiological Health, Food and Drug Administration, Bldg.
66, Rm. 5424, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002,
301-796-6119, email<EMAIL_ADDRESS>    For information concerning the final rule as it relates to devices
regulated by the Center for Biologics Evaluation and Research: Stephen
Ripley, Center for Biologics Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver
Spring, MD 20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Executive Summary

Purpose of the Regulatory Action

    The final rule explicitly permits the use of symbols in medical
device labeling without adjacent explanatory text if certain
requirements are met. The medical device industry has requested the
ability to use stand-alone symbols on domestic device labeling,
consistent with their current use on devices manufactured for European
and other foreign markets. The final rule seeks to harmonize the U.S.
device labeling requirements for symbols with international regulatory
requirements, such as the Medical Device Directive 93/42/EEC of the
European Union (EU) (the European Medical Device Directive) and global
adoption of International Electrotechnical Commission (IEC) standard
IEC 60417 and International Organization for Standardization (ISO)
standard ISO 7000-DB that govern the use of device symbols in numerous
foreign markets.

Summary of the Major Provisions of the Regulatory Action in Question

    FDA has generally interpreted existing regulations not to allow the
use of symbols in medical device labeling, except with adjacent
English-language explanatory text and/or on in vitro diagnostic (IVD)
devices intended for professional use. Under the final rule, symbols
established in a standard developed by a standards development
organization (SDO) may be used in medical device labeling without
adjacent explanatory text as long as: (1) The standard is recognized by
FDA under its authority under section 514(c) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C. 360d(c)) and the symbol is used
according to the specifications for use of the symbol set

forth in FDA's section 514(c) recognition, or alternatively, (2) if the
symbol is not included in a standard recognized by FDA under section
514(c) or the symbol is in a standard recognized by FDA but is not used
according to the specifications for use of the symbol set out in the
FDA section 514(c) recognition, the device manufacturer otherwise
determines that the symbol is likely to be read and understood by the
ordinary individual under customary conditions of purchase and use in
compliance with section 502(c) of the FD&C Act (21 U.S.C. 352(c)) and
uses the symbol according to the specifications for use of the symbol
set forth in the SDO-developed standard. In addition, in either case,
the symbol must be explained in a paper or electronic symbols glossary
that is included in the labeling for the medical device. Furthermore,
the labeling on or within the package containing the device must bear a
prominent and conspicuous statement identifying the location of the
symbols glossary that is written in English or, in the case of articles
distributed solely in Puerto Rico or in a Territory where the
predominant language is one other than English, the predominant
language may be used. As with text used in device labeling, the use of
symbols must also comply with other applicable labeling requirements in
the FD&C Act, such as section 502(a) and section 502(f), and relevant
regulations such as 21 CFR part 801. In addition, the final rule allows
the use of the symbol statement ``Rx only'' or ``[rx] only'' for
labeling of prescription devices.

Costs and Benefits

    Benefits represent the reduction in costs associated with designing
and redesigning the labeling for medical devices that are currently
marketed in the United States and the EU. We estimate these annual cost
savings to roughly range between $7.9 million and $25.5 million at a 3
percent discount rate, and $7.7 million to $25 million at a 7 percent
discount rate. Costs represent the one-time administrative costs to
redesign labeling to incorporate a new or changed symbol, to the one-
time costs to create a symbols glossary that is included in the
labeling for the device, and the recurring costs to revise these
glossaries, as necessary. Annualized over a 20-year period, we estimate
these costs to range from $1.1 million to $3.2 million. Annualized over
a 20-year period, we estimate total annualized net to range from $6.8
million to $22.3 million at a 3 percent discount rate, and from $6.6
million to $21.7 million at a 7 percent discount rate.
    The use of stand-alone symbols in device labeling is optional under
the final rule. Those device manufacturers who now use labels without
symbols, or who use symbols with adjacent explanatory text, may
continue to do so. Therefore, medical device manufacturers would use
stand-alone symbols as allowed by the final rule only if they expect a
positive net benefit (estimated benefits minus estimated costs). Hence,
the final rule is expected to provide a net benefit to manufacturers
who opt to use the stand-alone symbols as allowed under this final
rule.

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                                   Total benefits annualized   Total costs annualized      Total net benefits
 Summary of costs and benefits of      over 20 years (in          over 20 years (in     annualized over 10 years
        the proposed rule                  millions)                  millions)               (in millions)
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    Total........................  $7.7 to $25.5............  $1.1 to $3.2............  $6.6 to $22.3.
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Table of Contents

I. Background
II. Comments on the Proposed Rule and FDA's Responses
    A. Options for Using Stand-Alone Symbols
    B. Matters Relating to the Extent to Which Symbols Can Be Used
    C. Labeling Information Not Required by or Under the Authority
of the FD&C Act
    D. Validation of Stand-Alone Symbols Contained in Standards Not
Recognized by FDA or Recognized for Only a Subset of Symbols,
Devices, or Users
    E. Symbols Glossary Requirement
    F. Implementation of the Final Rule
    G. Symbol Statement ``Rx Only'' or ``[rx] Only''
III. Compliance and Enforcement
IV. Legal Authority for the Final Rule
V. Economic Analysis of Impacts
VI. Paperwork Reduction Act of 1995
VII. Analysis of Environmental Impacts
VIII. Effective Date
IX. Federalism
X. References

I. Background

    FDA published a proposed rule to revise certain medical device and
biological product labeling regulations by explicitly allowing labeling
to contain certain stand-alone symbols. The proposed rule would allow
stand-alone use of symbols in device labeling if the symbol is
established as part of a standard developed by a nationally or
internationally recognized standards organization, is part of a
standard recognized by FDA for use in the labeling for medical devices,
and is explained in a symbols glossary that contemporaneously
accompanies the medical device (78 FR 23508, April 19, 2013). The
preamble to the proposed rule describes the background and the purpose
of the rule as well as discusses that FDA recognition of the standard
in which the symbol is contained would be under its authority in
section 514(c) of the FD&C Act (21 U.S.C. 360d(c)). We refer readers to
that preamble for information about the development of the proposed
rule. The Agency requested public comments on the proposed rule, and
the comment period closed on June 18, 2013.
    As discussed further in section II.A, in this final rule FDA is
making the following changes to the regulatory text of the final rule
as compared to the proposed rule: (1) Deleting the term ``standardized
symbol'' as that term was used in the proposed rule to refer only to
symbols in FDA recognized standards and the scope of this final rule
allows other alternatives; (2) providing that, in addition to symbols
in a standard recognized by FDA under section 514(c) of the FD&C Act,
the use of certain other SDO-established symbols is allowed; (3)
clarifying that the symbols glossary must ``be included in the labeling
for the device,'' in lieu of using the words ``contemporaneously
accompanies'' the device, providing that such glossary can be in paper
or electronic form, and that the labeling on or within the package
containing the device must bear a prominent and conspicuous statement
identifying the location of the symbols glossary; (4) adding a
definition of what we mean by the term ``standards development
organization (SDO)'' for purposes of this final rule; and (5) revising
the definition of ``symbols glossary'' to mean a compiled listing of:
(a) Each SDO-established symbol used in the labeling for the device;
(b) the title and the designation number of SDO-developed standard
containing the symbol; (c) the title of the symbol and its reference
number, if any, in the standard; and (d) the meaning or explanatory
text for the symbol as provided in the FDA recognition, or if FDA has
not recognized the standard or portion of the standard in which the
symbol is located or the symbol is not

used according to the specifications of the FDA section 514(c)
recognition, the explanatory text as provided in the standard. In
addition, in this final rule, we renumbered 21 CFR 660.2(c), 660.28,
660.35, 660.45, and 660.55 to improve the readability of these
sections. This final rule also contains conforming amendments to 21 CFR
660.20(a) and 660.50(a) that update references made in these sections
to certain of the renumbered provisions. As stated previously, in the
proposed rule, the Agency proposed to limit use of stand-alone symbols
in device labeling only to those symbols that an SDO established in a
standard that FDA recognized under its authority in section 514(c) of
the FD&C Act. The reason for FDA's reliance on its recognition process
in the proposed rule as a criterion for allowable stand-alone symbols
was that the process offered FDA the opportunity to determine that the
symbol was likely to be read and understood by the ordinary user under
customary conditions of use as required by section 502(c) of the FD&C
Act. In part, based on comments discussed in this document, which
raised issues regarding some aspects of the section 514(c) recognition
process, the Agency further considered the matter and concluded that
its recognition process under section 514(c) of the FD&C Act is not the
only way to ensure that the appropriate section 502(c) determination is
made. FDA determined that, as an alternative to its section 514(c)
recognition, manufacturers could themselves determine whether an SDO-
established symbol is likely to be read and understood by the ordinary
individual under customary conditions of purchase and use in compliance
with section 502(c) of the FD&C Act. This would be consistent with what
industry currently does when it uses text in labeling. We note,
however, that FDA has the authority to make the definitive
determination regarding compliance with the statute and can take
enforcement action against violations, as warranted.
    As provided in section 514(c)(1)(B) of the FD&C Act, a person can
use a standard recognized by FDA to meet a statutory requirement and
submit a declaration of conformity to FDA to certify that the device is
in conformity with the standard. Section 514(c)(1)(B) of the FD&C Act
further provides that a person may elect to use data, or information,
other than data required by a standard recognized by FDA to meet any
requirement regarding devices under the FD&C Act. Apart from such
compliance with the requirements of section 502(c) of the FD&C Act by
conforming to a standard recognized for that purpose under section
514(c), the manufacturer must determine itself that the labeling also
meets the other requirements of the FD&C Act, as it is the
responsibility of all persons labeling devices to assure statutory and
regulatory compliance. The final rule acknowledges the device
manufacturer's responsibility to comply with the requirements of
section 502(c) of the FD&C Act as well, by permitting the use of a
stand-alone symbol in labeling that the manufacturer has determined
meets such requirements. Accordingly, this final rule provides that a
stand-alone symbol is allowed to be used in device labeling if: (1) The
symbol is established in a standard developed by an SDO; and (2) the
standard is recognized by FDA under its authority under section 514(c)
of the FD&C Act and the symbol is used according to the specifications
for use of the symbol set forth in FDA's section 514(c) recognition, or
alternatively, if the symbol is not included in a standard recognized
by FDA under section 514(c) or the symbol is in a standard recognized
by FDA but is not used according to the specifications for use of the
symbol set out in the FDA section 514(c) recognition, the device
manufacturer otherwise determines that the symbol is likely to be read
and understood by the ordinary individual under customary conditions of
purchase and use in compliance with section 502(c) of the FD&C Act and
uses the symbol according to the specifications for use of the symbol
set forth in the SDO-developed standard. In addition, in either case,
the symbol must be explained in a paper or electronic symbols glossary
that is included in the labeling for the medical device. Furthermore,
the labeling on or within the package containing the device must bear a
prominent and conspicuous statement identifying the location of the
symbols glossary that is written in English or, in the case of articles
distributed solely in Puerto Rico or in a Territory where the
predominant language is one other than English, the predominant
language may be used. The additional option to use stand-alone symbols
established in SDO-developed standards that FDA has not recognized, as
permitted in the final rule, will result in more timely availability of
stand-alone symbols for use in device labeling, more convenience for
industry, and conserves limited Agency resources.
    See section III (Compliance and Enforcement) for our discussion to
help manufacturers determine, if the symbol is not included in a
standard or part of a standard that FDA has recognized under section
514(c) of the FD&C Act or if the symbol is used outside the
specifications of the FDA section 514(c) recognition, whether the
stand-alone use of the symbol in device labeling is likely to be read
and understood by the ordinary individual under customary conditions of
purchase and use in accordance with section 502(c) of the FD&C Act. In
section III, we also clarify that the other provisions of section 502
of the FD&C Act also apply to the use of stand-alone symbols, such as
section 502(a) of the FD&C Act if use of the symbol in its labeling
causes the labeling to be false or misleading and section 502(f) of the
FD&C Act if use of the symbol in device labeling results in inadequate
directions for use of the device. For clarity, in this final rule, we
have set out the definition of an ``SDO.'' For purposes of this rule,
we define an SDO as an organization that is nationally or
internationally recognized and that follows a process for standard
development that is transparent (i.e., open to public scrutiny), where
the participation is balanced, where an appeals process is included,
where the standard is not in conflict with any statute, regulation, or
policy under which FDA operates, and where the standard is national or
international in scope (see 76 FR 23508 at 23511). (See also FDA answer
to Question 18 (What organizations can develop consensus standards for
FDA recognition?) in the guidance document entitled ``Frequently Asked
Questions on Recognition of Consensus Standards; Guidance for Industry
and FDA Staff'' (September 2007), at. p. 7 (Ref. 1 and cited in the
proposed rule (76 FR at 23508 at 23509)).

II. Comments on the Proposed Rule and FDA's Responses

    We received submissions from 16 commenters, representing a cross-
section of individuals, professional and trade associations, and device
manufacturers. Almost all comments supported the objectives of the rule
in whole or in part. The great majority of comments either suggested
changes to specific elements of the proposed rule or requested
clarification of matters discussed in the proposed rule.

A. Options for Using Stand-Alone Symbols

    (Comment 1) Two comments raised the challenges and impracticality
of FDA authorization of symbols via section 514(c) recognition of the
standard in which the symbol is established. One of these comments
expressed concern that, under the

section 514(c) process, FDA recognition of certain symbols for certain
devices within the standards will present challenges to industry. For
instance, ``if FDA does not recognize the newest revisions of the
standards, discrepancies could require going back to define symbols in
text on labels.'' Another commenter claimed that by limiting the
recognition of symbols to certain devices, the Agency would be falling
considerably short of harmonizing with other regulatory bodies, which
is one major goal of this rulemaking. The comment went on to state that
the European Medical Device Directive does not limit the use of
recognized symbols to certain devices, i.e., does not limit which
symbols can be used nor does it limit the devices for which a symbol
can be used as long as the symbol is explained elsewhere in the device
labeling. The comment opined that requiring independent validation by
FDA of the stand-alone symbols established in standards would be an
unnecessary use of FDA resources.
    (Response 1) The changes in the final rule discussed previously
will address many, if not most, of these commenters' concerns. The
final rule gives the manufacturer the option of using a symbol
contained in an FDA recognized standard or determining for itself that
the SDO-established symbol is likely to be read and understood by the
customary purchasers and users of the device. Under the final rule, if
an FDA recognized standard is only for a subset of symbols or a subset
of devices, the manufacturer could submit its declaration of conformity
with that standard, and to address any symbols, devices, or users not
included in the FDA recognition, could determine for itself that use of
those symbols, on those devices, or for those users meets the
requirements of section 502(c) of the FD&C Act. This would be
consistent with what industry currently does when it uses text in
labeling. We note, however, that FDA has the authority to make the
definitive determination regarding compliance with the statute and can
take enforcement action against violations, as warranted. Furthermore,
manufacturers always have the option to request FDA recognition of
certain standards if the manufacturer does not want to determine for
itself the section 502(c) compliance of the use of the stand-alone
symbol in device labeling. See Guidance for Industry and FDA Staff
entitled ``Frequently Asked Questions on Recognition of Consensus
Standards'' (Ref. 1). Because manufacturers are not limited to use of
stand-alone symbols which are part of an FDA-recognized standard, the
final rule should not present the challenges raised by the commenters.
    When the symbol is not contained in an FDA-recognized standard,
this final rule requires that all stand-alone symbols used in device
labeling be established in a standard developed by an SDO, as is the
case for FDA recognition of standards under section 514(c) of the FD&C
Act. Our definition of an SDO is intended to include the attributes
that are required for voluntary consensus standards bodies, whose
standards Federal Agencies are allowed to use for regulatory activities
in lieu of a Government-developed standard. These attributes are
openness, balance of interest, due process, an appeals process, and
consensus (Refs. 2 and 3).
    The symbols established in standards developed by SDOs, as defined
in this final rule, will ordinarily have undergone the SDO's written
procedures for approval or issuance and validation, and the final rule
does not impose any additional requirements to revalidate that the
symbol meets the requirements of section 502(c) of the FD&C Act if it
is established in an FDA-recognized standard or has been appropriately
validated by the SDO. See section II.D (FDA response to comments 10 and
11). As explained in the preamble to the proposed rule, FDA considers
whether symbols have been validated through the standards development
organization process when determining whether to recognize the symbols
(see 76 FR 23508 at 23511). We also note that, contrary to the
commenters' assertion regarding independent FDA validation of stand-
alone symbols in a standard, FDA, as part of its section 514(c)
recognition process, does not independently validate the symbols. For
symbols in standards recognized by FDA under its authority in section
514(c) of the FD&C Act, FDA will have determined that the standard
containing the symbol was developed by an SDO and that the SDO used its
validation procedures in establishing the standard.
    Under the final rule, a stand-alone symbol that is allowed to be
used in device labeling is a symbol that: (1) Is established in a
standard developed by an SDO; and (2) is contained in a standard that
FDA recognizes under section 514(c) of the FD&C Act and is used
according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition, or alternatively, if the symbol is
not contained in a standard recognized by FDA under section 514(c) of
the FD&C Act or the symbol is contained in a standard recognized by FDA
but is not used according to the specifications for use of the symbol
set out in the FDA section 514(c) recognition, is determined by the
manufacturer to be likely to be read and understood by the ordinary
individual under customary conditions of purchase and use in compliance
with section 502(c) of the FD&C Act and is used according to the
specifications for use of such symbol as set forth in such standard. In
addition, in either case, the stand-alone symbol must be explained in a
paper or electronic symbols glossary that is included in the labeling
for the device. Furthermore, the labeling on or within the package
containing the device must bear a prominent and conspicuous statement
identifying the location of the symbols glossary that is written in
English or, in the case of articles distributed solely in Puerto Rico
or in a Territory where the predominant language is one other than
English, the predominant language may be used. In device labeling,
symbols that do not satisfy these criteria must be accompanied by
adjacent explanatory text.
    (Comment 2) Four comments requested that FDA authorize stand-alone
use of all the symbols contained in ISO 15223-1:2012. One of these
comments also encouraged the Agency to consider authorizing stand-alone
use of the symbols in international standards ISO 7000, ISO 7010, and
IEC 60417; another asked us to clarify that authorized stand-alone use
will include the symbols in ANSI/AAMI ES60601-1:2005 and supersede IEC
60601-1. A separate comment recommended authorizing stand-alone use of
the symbols in ``ISO standard BS EN 980.''
    (Response 2) As explained earlier in the Background section and
section II.A (FDA response to Comment 1), this final rule provides
additional flexibility by permitting the stand-alone use, in device
labeling, of symbols that are part of a standard recognized by FDA
under section 514(c) of the FD&C Act, as specified in the proposed
rule, or, alternatively, a manufacturer can use an SDO-established
symbol not included in a standard recognized by FDA or a symbol in a
standard recognized by FDA but not used in accordance with the
specifications for use of the symbol set forth in FDA's section 514(c)
recognition, if it otherwise determines that the symbol is likely to be
read and understood by the ordinary individual under customary
conditions of purchase and use in compliance with section 502(c) of the
FD&C Act. Because FDA recognition of the underlying standard is not the
only option for manufacturers, they are free to choose to select the

additional option provided by the final rule with regard to using
symbols established in the standards referenced in the comments. (See
also section III regarding compliance and enforcement).
    (Comment 3) Three comments stated that stand-alone symbols, once
recognized through the section 514(c) process, should be allowed for
all medical devices, rather than limited to use on any subset of
devices. All three commenters believed that the Agency's actions in
authorizing stand-alone symbols for IVD devices in the guidance
document entitled ``Use of Symbols on Labels and in Labeling of In
Vitro Diagnostic Devices Intended for Professional Use'' (November
2004) (the ``IVD Symbols Guidance'') at pp. 7-8 (Ref. 4), and in
proposing for this rule that standardized symbols should be limited to
a subset of devices, are confusing when limited use of stand-alone
symbols is authorized based on device category and user groups.
    (Response 3) FDA plans to continue to recognize symbols under its
authority in section 514(c) of the FD&C Act for subsets of devices and/
or subsets of users, as appropriate. Because the final rule does not
limit the use of symbols to those in FDA-recognized standards,
manufacturers have the option to use stand-alone symbols in the
labeling for any medical device, as long as the symbol is established
in a standard developed by an SDO and explained in a symbols glossary
as provided in the standard and the manufacturer determines that the
stand-alone symbol on its particular device otherwise satisfies section
502(c) of the FD&C Act. Because the Agency is providing additional
flexibility with regard to allowable stand-alone symbols, manufacturers
are not limited as a result of FDA's recognition of a standard for only
a subset of symbols, devices, or users. We note that use of stand-alone
symbols beyond the specifications for use set out in FDA's recognition
of the standard will require manufacturers to establish section 502(c)
compliance for those symbols, devices, or users not included in FDA's
recognition. If the manufacturer determines that the stand-alone symbol
on its particular device otherwise satisfies section 502(c) of the FD&C
Act, the manufacturer can use the stand-alone symbol in device labeling
established in the standard only within the specifications for use of
the symbol set out in the SDO-developed standard. Otherwise, a symbol
used outside of the specifications for use set forth in the SDO-
developed standard must be accompanied by adjacent explanatory text.
See Sec.  801.15(c)(1)(i)(C), as revised, in this final rule.
    CDRH encourages stakeholders to recommend appropriate standards for
FDA recognition under section 514(c) of the FD&C Act by following the
instructions located at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/ucm123739.htm.

B. Matters Relating to the Extent to Which Symbols Can Be Used

1. Proprietary Symbols
    (Comment 4) One of the comments stated that medical device
manufacturers should be permitted to use proprietary symbols as long as
the meaning of the proprietary symbol is described in documentation
supplied with the device. The comment points out that the European
Medical Device Directive allows the use of a symbol not developed as
part of a standard as long as the symbol is defined in the labeling for
the product.
    (Response 4) We believe the commenter is referring to the provision
in the EU's 1993 Medical Device Directive which states: ``Any symbol or
identification colours used must conform to the harmonized standards.
In areas for which no standards exist, the symbols and colours must be
described in the documentation supplied with the device.'' That is, the
comment refers to a proprietary symbol that is not contained in a
standard. Under the proposed rule and this final rule, for the use of a
stand-alone symbol in device labeling to be allowed, the symbol must be
established as part of a standard. In the preamble to the proposed
rule, the Agency stated that it does not intend to recognize
proprietary symbols (78 FR 23508 at 23511). This referred to
proprietary symbols contained in a standard.
    The Agency believes that proprietary symbols, whose use is subject
to the symbol owner's exclusive rights and not freely available to the
public, should be outside the SDO standards development process called
for in the proposed rule and finalized in this rule. See the earlier
discussion of SDO factors found in the National Technology Transfer and
Advancement Act of 1995 (Ref. 2) and Circular A-119 (Ref. 3) to be
considered when a Federal Agency uses standards developed outside the
Government (Section I. (Background)).
    Circular A-119 also provides that the Government use for regulatory
purposes of a standard developed by non-Government body must include
provisions requiring that owners of relevant intellectual property have
agreed to make that intellectual property available on a non-
discriminatory, royalty-free, or reasonable royalty basis to all
interested parties (63 FR 8553 at 8554). The term ``proprietary
symbol,'' and the comment, begs the question of whether such symbol
would be freely available to the public and whether the symbol's owner
has retained its exclusive rights. Because this final rule is limited
to symbols established in standards, it does not allow proprietary
symbols for use as stand-alone symbols. We note, however, that the rule
allows use of a proprietary symbol accompanied by explanatory text
adjacent to the symbol.
2. Pictograms
    (Comment 5) Two comments asked us to clarify that product graphics
or pictograms included in labeling, for example graphics showing the
steps for using a device, are outside the scope of the proposed rule.
One of the comments went further to assert that pictograms do not
require accompanying English text to explain their meaning.
    (Response 5) We agree that product graphics or pictograms included
in labeling, for example graphics showing the steps for using a device,
are outside this rulemaking. Symbols are not allowed for stand-alone
use in this final rule unless they are established in a standard
developed by an SDO and such graphics normally are not so established.
Product graphics are typically unique to the individual product. They
are not broadly applicable or used across a wide range of devices, and
are unlikely to be established in an SDO-developed standard. Because
the final rule is limited to symbols established in a standard, such
product graphics are outside the scope of this final rule.
    The Agency has interpreted its regulations generally to allow
graphics, pictures, or symbols to meet the labeling requirements of
this regulation except where it specifies particular labeling language
(78 FR 23508 at 23509). Having said that, if a stand-alone graphical
representation communicates required labeling information, such as
directions for use required by Sec.  801.5, the product graphic alone
is unlikely to satisfy regulatory requirements, even when used under
this final rule with accompanying adjacent English text, and further
labeling may be needed in addition to what this final rule requires to
explain the meaning of the symbol (see amended Sec. Sec.  660.2(c),
660.28, 660.35, 660.45, 660.55, 801.15(c)(1) and 809.10.

3. Symbols Used on Non-Device Medical Products
    (Comment 6) One comment argued that if a symbol is authorized for
stand-alone use in device labeling, then that symbol should be
authorized for all medical products, including for drugs or combination
products. According to the comment, ``a standard FDA recognizes'' means
a standard adopted ``for all Centers'' and for all FDA-regulated
products, not just devices. While acknowledging the ``procedural
issues'' associated with extending the scope of the final rule to non-
device medical products, the commenter recommended flexibility
``through enforcement discretion'' until the regulations for drugs and
non-device biological products can be updated to conform to the use of
stand-alone symbols on medical devices.
    (Response 6) The proposed rule would have authorized the stand-
alone use of symbols explained in a symbols glossary included in the
device labeling and contained in a standard recognized under section
514(c) of the FD&C Act, a provision applicable to medical devices only.
The final rule also provides for the use in device labeling of stand-
alone symbols if they are established in standards developed by an SDO,
the manufacturer determines that the symbols are likely to be read and
understood by the ordinary individual under customary conditions of use
and purchase and the symbols are explained in a paper or electronic
symbols glossary that is included in the labeling for the device.
Because this rulemaking revises only the device and certain biological
product labeling regulations, labeling for other FDA-regulated products
is outside the scope of this rulemaking. Manufacturers considering the
use of stand-alone symbols in labeling for other-FDA regulated products
should contact the appropriate Center for the product regarding the
permissibility of such use.
4. Combination Products
    (Comment 7) One comment asked us to clarify how the rule applies to
combination products, i.e., to medical products containing not only a
device constituent but also a drug or biological product, for example,
a drug/device combination.
    (Response 7) Stand-alone symbols may be used in accordance with the
final rule in the labeling applicable to a combination product as a
whole if the primary mode of action (PMOA) for the product (see 21 CFR
3.2(k) and (m)) is that of a device. Stand-alone symbols may also be
used in any separate labeling for the device constituent part of a
combination product, regardless of the PMOA for the combination product
(e.g., any separate labeling for the device constituent part of a
convenience kit or other copackaged combination product, see Sec.
3.2(e)(2)).
    The appropriate use of stand-alone symbols in any other labeling
associated with combination products is beyond the scope of this
rulemaking. Manufacturers considering the use of stand-alone symbols in
such other labeling for combination products should contact the lead
Center for the product regarding the permissibility of the proposed
use.

C. Labeling Information Not Required by or Under the Authority of the
FD&C Act

    (Comment 8) When adequate directions for use are known to the
ordinary individual, some devices may be exempt from adequate
directions for use (Sec.  801.116; see section 502(f)(1) of the FD&C
Act). Some prescription devices are likewise not required to bear
adequate directions for use if practitioners licensed by law to use the
device are commonly aware of the directions, hazards, warnings, and
other information necessary to use the device safely and for the
purpose for which it is intended (Sec.  801.109(c)).
    Three comments suggested that manufacturers marketing devices that
are exempt from adequate directions for use under Sec.  801.116 or
Sec.  801.109(c) would needlessly be burdened under this final rule to
create a symbols glossary to explain symbols that they are using
voluntarily to display information that is not required ``by or under''
the FD&C Act.
    (Response 8) The final rule requires a symbols glossary when a
stand-alone symbol is used to provide labeling information required by
or under the authority of the FD&C Act. (Sec.  801.15(c)(1)). The
commenters' understanding of FDA authority ``by or under'' the FD&C Act
is too narrowly focused on the regulations concerning adequate
directions for use under section 502(f)(1).
    A device that is exempt from section 502(f)(1) of the FD&C Act
under Sec.  801.116 or Sec.  801.109(c) may still be required to
include certain information in its labeling for other purposes in order
to provide a reasonable assurance of the safety and effectiveness of
the device. For example, a prescription device that is exempt from
section 502(f)(1) of the FD&C Act must still include, under Sec.
801.109(c), indications, effects, routes, methods, and frequency and
duration of administration, and any relevant hazards,
contraindications, side effects, and precautions in its labeling.
    Whether or not a medical device is exempt by regulation from
section 502(f)(1) of the FD&C Act, the device is still subject to the
other misbranding provisions of section 502. Consequently, we disagree
that directions-for-use symbols voluntarily used on devices exempt from
adequate directions for use under Sec.  801.116 or Sec.  801.109(c)
should be categorically exempt from the symbols glossary requirement
and the final rule.
    (Comment 9) In discussing the symbols glossary requirement, the
preamble to the proposed rule stated therefore, any stand-alone symbol
on the labeling for a device that conveys directions for use would be
subject to the symbols glossary requirements (78 FR 23508 at 23511).
One commenter interpreted this statement as limiting the symbols
glossary requirement to symbols for directions-for-use information
only. The commenter requested clarification that, under the final rule,
use of a symbol that does not convey directions for use, such as ``the
manufacturing site symbol, lot symbol, etc.,'' should therefore not
trigger the symbols glossary requirement.
    (Response 9) The preamble statement quoted in the comment refers to
directions-for-use symbols as an example, and not by way of limitation;
but we agree that clarification is appropriate.
    FDA device labeling regulations specifically require information
other than just directions for use, including the examples mentioned in
the comment. For example, under Sec.  801.1(a), the device label must
identify the name and address of the manufacturer, packer, or
distributor of the device. If an FDA-allowed stand-alone symbol is
used, for example, in place of the wording ``manufacturer:'' or
``manufacturing site:'' followed by a name and address, the final rule
requires that a symbols glossary must be included in the labeling for
the device to explain the meaning of the symbol to the device's user.
There are many FDA regulations that require device labeling
information; and the final rule, including the symbols glossary
requirement, applies to any device using a stand-alone symbol to
provide such information.

D. Validation of Stand-Alone Symbols Contained in Standards Not
Recognized by FDA or Recognized for Only a Subset of Symbols, Devices,
or Users

    (Comment 10) One comment asked the Agency to ensure that each
stand-alone symbol authorized under this rule

can be relied upon and be used by device manufacturers, without
separate validation by the manufacturer for its use on a specific
device. Another comment asked us to clarify that FDA would not
unnecessarily use its resources to revalidate symbols established in an
SDO-developed standard.
    (Response 10) The symbols established in standards developed by
SDOs will ordinarily have undergone the SDO's written procedures for
approval or issuance and validation (78 FR 23508 at 23511). In the
validation process, studies can demonstrate end-user comprehension of
the stand-alone symbol in the device labeling context; and validation
data specifically applicable to medical devices may be submitted to the
SDO for its review (78 FR 23508 at 23510, see for example AAMI/ANSI/ISO
15223-2:2010 (Part 2), Symbol Development, Selection and Validation).
    The final rule does not impose any additional requirements on
device manufacturers to revalidate that such symbols meet the
requirements of section 502(c) of the FD&C Act if the symbol is
established in an FDA-recognized standard or has been appropriately
validated by the SDO. FDA does not intend to invite requests for it to
validate or to revalidate a symbol allowed under the rule, i.e., a
stand-alone symbol established in an SDO-developed standard and
explained in the device labeling. However, we will consider information
as appropriate, including post-market surveillance data indicating that
a symbol used on a particular device is not understood by device users
(section 502(c) of the FD&C Act), or that it causes the labeling to be
false or misleading (section 502(a)), results in inadequate directions
for use of the device (section 502(f)), or otherwise causes the device
labeling to violate the misbranding provisions of section 502.
    (Comment 11) One comment questioned why, if the validation process
includes consumer testing, there was no analysis of this cost burden.
    (Response 11) The final rule does not impose any new requirements
for public participation in the standards development processes of SDOs
or for the establishment of symbols in SDO-developed standards. The
final rule does not affect the paperwork burden or cost associated with
the standards-development process establishing a symbol allowed by the
final rule, and therefore, no cost estimate or economic analysis of the
process is required.
    The final rule establishes certain procedures and conditions for
device manufacturers to use a symbol as a stand-alone symbol on medical
device labeling, including specifically, that the symbol must be
explained in a symbols glossary that is included in the labeling for
the device. The proposed and final rules do analyze the paperwork
burden and economic cost of these procedures and conditions, including
the required symbols glossary.
    The burden on persons seeking SDO development of standards
establishing symbols, including the validation of those symbols in the
standard, is a matter already considered under existing standards-
development norms and is otherwise in the control of the relevant SDO.
The final rule does not require the interested party to revalidate that
the stand-alone symbol meets the requirements of section 502(c) of the
FD&C Act if the symbol is established in an FDA-recognized standard or
has been appropriately validated by the SDO. Any validation needed in
order to comply with the requirements of section 502(c) of the FD&C Act
is under the requirements of that statute, and is not being imposed by
this final rule. Accordingly, there is no validation process required
by the final rule, and no cost estimate or economic analysis is called
for in the rule.

E. Symbols Glossary Requirement

    (Comment 12) Four comments state that, in the case of stand-alone
symbols established in an SDO-developed standard, a symbols glossary
``contemporaneously accompanying'' the device is unnecessary. Three of
these comments specifically refer to the symbols contained in ISO
15223-1 and contend that the symbols glossary requirement does not
harmonize with the European Medical Device Directive or with ISO 15233
because neither one requires an accompanying symbols glossary.
Alternatively, one comment suggested that the final rule should
establish a sunset limitation for the symbols glossary requirement, so
that, for example, the glossary rule would expire 2 years after the
publication of the final rule.
    (Response 12) FDA disagrees with the comments that its symbols
glossary requirement is not necessary and does not harmonize with the
European Medical Directive or with ISO 15233. The European Medical
Device Directive states that ``[i]n areas for which no standards exist,
the symbols and colours must be described in the documentation supplied
with the device.'' The Directive does not otherwise preclude requiring
documentation with such symbols. Many of the symbols contained in ISO
15223-1 explicitly restrict their use as follows: ``In Europe, this
symbol shall be explained in the information supplied by the
manufacturer.'' FDA is aware of many device manuals containing a
symbols glossary that would comply with this final rule, and has in the
past considered this a good practice. Furthermore, the IVD Symbols
Guidance (Ref. 4) recommends that a glossary of terms accompany each
IVD to define all the symbols used on that device's label and/or
labeling (at pp. 7-8). Following the effective date of this final rule,
FDA intends to withdraw the IVD Symbols Guidance.
    Concerning the comment recommending a sunset limitation on the
symbols glossary requirement, the Agency disagrees. The symbols
glossary is intended to allow 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 symbols
glossary helps to satisfy, although it does not satisfy on its own, the
requirements of section 502(c) of the FD&C Act by making it more likely
that users under customary conditions of purchase and use have access
to necessary reference materials to help them understand the symbols.
Accordingly, we do not believe that a sunset limitation on the symbols
glossary requirement is appropriate.
    (Comment 13) Four comments requested FDA to clarify the meaning of
the term ``contemporaneously accompanies the device'' in the symbols
glossary requirement of the rule, in particular whether the term
includes ``all varieties of written or electronic materials that are
connected to a manufacturer's marketing and sale of a product, even
when the materials are not physically with the medical device.'' Two of
these commenters believe that, in the case of prescription devices, the
rule should permit electronic display of the symbols glossary under
section 502(f) of the FD&C Act and that such electronic labeling should
be treated as accompanying the device for purposes of the rule. One
comment urged that a reference in the medical device labeling to an
online FDA glossary should satisfy the glossary requirement. Another
stated that electronic labeling is an accepted practice for IVDs in the
EU.
    (Response 13) In the proposed rule, one of the requirements for use
of stand-alone symbols was that such symbols be explained in a symbols
glossary that contemporaneously accompanies the device. FDA understands
that the term ``contemporaneously accompanies'' in the proposed rule
may have prompted

confusion, and we are revising the codified language of the final rule
to clarify that a stand-alone symbol must be explained in a paper or
electronic symbols glossary that is ``included in the labeling for the
device.'' We agree that flexibility is possible and appropriate to
satisfy the symbols glossary requirement. The new wording permits
flexibility in the form of the symbols glossary, as long as the
glossary is included in the labeling for the device.
    Furthermore, this final rule allows device manufacturers to provide
the symbols glossary by electronic means. We have changed the codified
to read ``the symbol . . . is explained in a paper or electronic
symbols glossary that is included in the labeling for the device.''
(See amended Sec. Sec.  660.2(c), 660.28, 660.35, 660.45, 660.55, and
801.15(c)(1), and new Sec.  809.10(g).) That is, the symbols glossary
can be provided by electronic means so long as the glossary is included
in the labeling for the device. This change also takes into account the
provisions of section 502(f) of the FD&C Act which provides that
required labeling for certain prescription devices and certain IVD
devices may be made available solely by electronic means. (See section
502(f) (``by electronic means'')).
    In the proposed rule, we inadvertently did not specify that the
labeling of the device must direct the purchaser and user as to the
location of the symbols glossary in the labeling for the device.
Without directions as to the location of the symbols glossary in the
labeling, the purpose of the symbols glossary would not be served.
Therefore, this final rule provides that the symbol is explained in a
paper or electronic symbols glossary that is included in the labeling
for the device and the labeling on or within the package containing the
device bears a prominent and conspicuous statement identifying the
location of the symbols glossary. For example, the statement could read
``The symbols glossary is provided [specify, e.g., in Section X of the
package insert, as a separate insert within the package, on the side
panel of the package, electronically at (insert URL address to symbols
glossary on manufacturer's Web site)].'' The statement must be in
English or, in the case of articles distributed solely in Puerto Rico
or in a Territory where the predominant language is one other than
English, the predominant language may be used.
    In the proposed rule, the term ``symbols glossary'' was defined in
the codified as ``a compiled listing of each symbol used in the
labeling of the device and of the meaning of or explanatory text for
the symbol.'' We are revising the codified language in the final rule
to define ``symbols glossary'' as ``compiled listing of: (1) Each SDO-
established symbol used in the labeling for the medical device; (2) the
title and designation number of the SDO-developed standard containing
the symbol; (3) the title of the symbol and its reference number, if
any, in the standard; and (4) the meaning or explanatory text for the
symbol as provided in the FDA recognition, or if FDA has not recognized
the standard or portion of the standard in which the symbol is located
or the symbol is not used according to the specifications for use of
the symbol set forth in FDA's section 514(c) recognition, the
explanatory text as provided in the standard (see amended Sec. Sec.
660.2(c), 660.28, 660.35, 660.45, 660.55, and 801.15(c) and new Sec.
809.10(g)). In finalizing the rule, we revised the ``symbols glossary''
definition to help accurately identify the SDO-developed standard
containing the symbol and the symbol in the standard.
    (Comment 14) One comment argued that a single copy of the glossary
should satisfy the rule when the same devices are shipped together in a
multipack. Another comment argued that replacement parts or disposable
components servicing the device with stand-alone symbols in their
labeling should be exempt from the glossary rule because the customer
would already have received the glossary information with the original
purchase of the device.
    (Response 14) In both of these situations, the premise is that
there is a stand-alone symbol that appears in the labeling for the
individual device unit or the replacing component.
    Typically, a replacement part for a medical device or disposable
component is used later in time than the replaced component. The
glossary delivered to the user with the original equipment might no
longer be available to explain the meaning of the stand-alone symbol on
the labeling for a replacement part. ``Any component, part, or
accessory'' of a device, if its intended use is to service the device,
is itself a device (section 201(h) of the FD&C Act (21 U.S.C. 321(h))).
Under the final rule, the symbols glossary requirement therefore
applies separately to replacement or disposable components when the
labeling for the replacing component bears a stand-alone symbol because
the symbols glossary must be included in the labeling for the device.
    Additionally, the individual units of a multipack shipment, like
replacement components, are likely to be used later such that the
glossary delivered to the user of a multipack shipment might no longer
be retained and available to explain the meaning of the stand-alone
symbol on the labeling for the remaining individual units after the
multipack is broken and the first unit or units are used. Under the
final rule, the symbols glossary requirement therefore applies to the
individual devices of a multipack shipment when the labeling for the
individual units bears a stand-alone symbol because the symbols
glossary must be included in the labeling for the device.
    To reduce the burden of the glossary requirement for individual
devices of a multipack shipment, manufacturers should consider the
final rule's provision for use of an electronic symbols glossary. Such
electronic glossary, however, must be included in the labeling for the
device. In such situations, FDA requires that the labeling for the
device must prominently and conspicuously include the URL address for a
Web site that displays the symbols glossary on the manufacturer's Web
site explaining the meaning of the stand-alone symbols used on that
device's labeling.

F. Implementation of the Final Rule

    (Comment 15) One comment asked FDA to clarify how much time
manufacturers will have to convert existing symbols in labeling to
stand-alone symbols.
    (Response 15) In the final rule, there is no required conversion to
stand-alone symbols. The final rule does not mandate the use of stand-
alone symbols. The use of stand-alone symbols is an alternative to
labeling without symbols and to the currently-allowed use of symbols
with adjacent explanatory text. Effective beginning on September 13,
2016 (see section VIII), the final rule expressly provides for the use
of symbols accompanied by adjacent explanatory text in the device
labeling (amended Sec. Sec.  660.2(c), 660.28, 660.35, 660.45, 660.55,
and 801.15(c)(1) and new Sec.  809.10(g)) and the use of stand-alone
symbols that meet the requirements of the rule.
    (Comment 16) One comment asked FDA to clarify whether manufacturers
need to file a new 510(k) notification under 21 CFR part 807, subpart E
or a Premarket Approval (PMA) supplement under 21 CFR part 814 when
they replace symbols currently used with adjacent English text with
stand-alone symbols and a symbols glossary in the device labeling.
    (Response 16) In most cases, manufacturers who wish to update their
device or product labeling only by

substituting text with one or more stand-alone symbols allowed under
the rule, or to remove explanatory text adjacent to such symbols
(without making any changes to the meaning of the labeling), do not
need to submit a new premarket submission prior to making that change.
In some cases FDA may require, through regulation or order, through a
special controls guideline, or on a case-by-case basis in reviewing
premarket submissions, specific language in device labeling, or may
require or prohibit use of symbols in a specific labeling context. For
example, devices subject to a boxed-warning labeling requirement must
strictly adhere to the exact language of the applicable regulation, and
any use of symbols in the warning should be reviewed and specifically
allowed by FDA in advance of such use.
    For medical devices with an approved PMA, manufacturers may
generally replace required information in existing labeling with
equivalent stand-alone symbols that are allowed under the rule without
the need to submit a PMA supplement. 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 Sec.  814.84. As with
510(k)-cleared devices, however, in some cases FDA may require, through
regulation or order, or on a case-by-case basis during premarket
review, specific language in device labeling, or may require or
prohibit use of symbols in a specific labeling context.
    Similarly, applicable biologics license holders that replace
required information with stand-alone symbols that are allowed under
the rule on the labeling for licensed products also regulated as
devices should notify the Agency of the change in the next annual
report to the manufacturer's Biologics License Application (BLA), in
accordance with 21 CFR 601.12(f)(3)(i)(A); and the Agency will consider
the change to be an editorial or similar minor change.
    Manufacturers may substitute stand-alone symbols that are allowed
under the rule for equivalent text on existing labels and labeling for
medical devices that received premarket notification (510(k)) clearance
without submitting a new 510(k) notification. For information on other
labeling changes that might require submission of a new 510(k)
notification, please see Sec.  807.81(a)(3).
    (Comment 17) Three comments urged FDA to maintain close cooperation
and communication with industry in order to implement timely updates of
the list of symbols permitted for stand-alone use through its
standards-recognition process and to keep up with the revision of
current international standards.
    (Response 17) Under this final rule, any stand-alone symbol
established in an SDO-developed standard and used in accordance with
the specifications of the standard is allowed, regardless of whether or
not FDA recognizes the standard or the part of the standard containing
the symbol, under section 514(c) of the FD&C Act. Under the final rule,
symbols established in a standard developed by an SDO may be used in
medical device labeling without adjacent explanatory text as long as:
(1) The standard is recognized by FDA under its authority under section
514(c) of the FD&C Act and the symbol is used according to the
specifications for use of the symbol set forth in FDA's section 514(c)
recognition, or alternatively, (2) if the symbol is not included in a
standard recognized by FDA under section 514(c) of the FD&C Act or the
symbol is in a standard recognized by FDA but is not used according to
the specifications for use of the symbol set out in the FDA section
514(c) recognition, the device manufacturer otherwise determines that
the symbol is likely to be read and understood by the ordinary
individual under customary conditions of purchase and use in compliance
with section 502(c) of the FD&C Act and uses the symbol according to
the specifications for use of the symbol set forth in the SDO-developed
standard. In addition, in either case, the symbol must be explained in
a paper or electronic symbols glossary that is included in the labeling
for the device. Furthermore, the labeling on or within the package
containing the device must bear a prominent and conspicuous statement
identifying the location of the symbols glossary that is written in
English or, in the case of articles distributed solely in Puerto Rico
or in a Territory where the predominant language is one other than
English, the predominant language may be used. Although FDA will
continue to participate with SDOs in the standards development process
and some of those standards may involve symbols in device labeling, the
final rule will not require the close industry coordination and
communication with FDA in order for firms to comply with the rule
because of its additional flexibility.
    (Comment 18) One comment recommended that when the Agency does not
recognize all the symbols established in a standard for stand-alone
use, it should clearly state why any rejected symbol is not included in
order for interested parties to get ``insights needed to validate the
symbols.''
    (Response 18) Under the final rule, the fact that FDA does not
recognize all the symbols established in a standard does not preclude a
manufacturer from determining that the stand-alone use of the symbol is
likely to be read and understood by the ordinary individual under
customary conditions of use and purchase. Therefore, the Agency will
not provide explanations of why it does not include certain symbols in
a standard in its recognition under section 514(c) of the FD&C Act as
requested by the commenter.

G. Symbol Statement ``Rx Only'' or ``[rx] Only''

    (Comment 19) Two comments related to the provision of the rule
authorizing use of the symbol statement ``Rx Only.'' One comment asked
whether validation will be required in order to use ``Rx Only'' on a
prescription device. The second comment asked whether FDA will be
issuing guidance to support use of the symbol statement ``Rx Only.''
    (Response 19) This final rule does not require validation by the
device manufacturer in order for it to use the symbol statement ``Rx
Only'' on its prescription device. The symbol statement ``Rx Only'' has
a separate statutory and regulatory history unrelated to the use of
standards as allowed in this final rule.
    As explained in the preamble to the proposed rule, section 126(a)
of the FDA Modernization Act of 1997 (FDAMA) (Pub. L. 105-115),
amending section 503(b)(4) of the FD&C Act (21 U.S.C. 353(b)(4)),
allows use of this symbol statement on the labels of drug products in
place of a full prescription use statement that indicates that the drug
must be dispensed with a clinician's prescription. FDAMA did not
explicitly make the permitted use of ``Rx Only'' applicable to medical
devices; however, the Agency published the guidance document entitled
``Alternative to Certain Prescription Device Labeling Requirements,''
January 2000 (the Rx Only Statement Guidance) (Ref. 5) stating that FDA
would exercise enforcement discretion for the use of ``Rx Only'' on
prescription device labels. FDA's reason for issuing that guidance
document was a desire to minimize the burden of creating device labels
and to make it flexible consistent with the statutorily permitted use
of the ``Rx Only'' symbol statement for prescription drug products. In
this rule, FDA is expressly allowing for use of ``Rx Only'' for the
labels of prescription devices to give device manufacturers the option
to use ``Rx Only'' in lieu of the longer statement currently in the
regulations. FDA has included this change in this rulemaking given the
changes involving symbols that the final

rule is making to other sections of FDA's labeling regulations.
    Because the statutory authority for using the symbol statement ``Rx
Only'' for drug products, and our purpose and intent in this final rule
extending it to prescription devices, are clear and satisfy the
misbranding requirements of section 502 of the FD&C Act pertaining to
the symbol statement ``Rx Only,'' the Agency does not intend to issue a
new guidance document regarding the use of ``Rx Only.'' We only restate
in this document what we said in the preamble to the proposed rule
about using the symbol statement ``Rx Only.'' It is important to note
that the word ``only'' must immediately follow the symbol ``Rx.''
However, the symbol statement ``Rx only'' does not necessarily need to
be bracketed in quotation marks, and the word ``only'' may appear in
upper or lower case letters, for example, Rx only, Rx Only, or Rx ONLY.
As in the case of labels for prescription drugs, the new label
statement for prescription medical devices may be printed as either
``Rx only'' or ``[rx] only.'' (See 67 FR 4904, February 1, 2002.) The
symbol statement ``Rx only'' in its entirety, or the [rx] symbol in the
symbol statement ``Rx only,'' may be printed in bold or in regular
type.

III. Compliance and Enforcement

    Under the final rule, manufacturers may use symbols in labeling in
the following scenarios. First, manufacturers may continue to use
symbols with adjacent explanatory text. See, e.g., Sec.
801.15(c)(1)(i)(C) in this final rule.
    Second, manufacturers may use a stand-alone symbol if the symbol is
contained in a standard that FDA recognizes under its authority in
section 514(c) of the FD&C Act for use on the labeling for medical
devices (or on a subset of medical devices), is used according to the
specifications for use of the symbol set forth in FDA's section 514(c)
recognition, and is explained in a paper or electronic symbols glossary
that is included in the labeling for the device and the labeling on or
within the package containing the device bears a prominent and
conspicuous statement identifying the location of the symbols glossary.
See, e.g., Sec.  801.15(c)(1)(i)(D) in this final rule. In this second
scenario, FDA has, through the section 514(c) recognition process, made
a determination that the symbol, is likely to be read and understood by
the ordinary individual under customary conditions of purchase and use
in compliance with section 502(c) of the FD&C Act. In this second
scenario where a manufacturer wishes to use a stand-alone symbol that
is in an SDO standard that has been recognized by FDA under section
514(c) to meet a requirement under the FD&C Act, such manufacturer
would submit a declaration of conformity to FDA that certifies that the
device is in conformity with the standard.
    In a third scenario, the stand-alone symbol is not included in a
standard that is recognized under FDA's section 514(c) authority or is
in a standard that is recognized under FDA's section 514(c) authority
but is not used according to the specifications for use of the symbol
set forth in FDA's 514(c) recognition, manufacturers may use such
symbol as a stand-alone symbol if the symbol has been established in a
standard developed by an SDO, the manufacturer has made a determination
that the symbol in the labeling for a particular device is likely to be
read and understood by the ordinary individual under customary
conditions of purchase and use in compliance with section 502(c) of the
FD&C Act, and such symbol is explained in a paper or electronic symbols
glossary that is included in the labeling for the medical device, and
the labeling on or within the package containing the device bears a
prominent and conspicuous statement identifying the location of the
symbols glossary. See, e.g., Sec.  801.15(c)(1)(i)(E) in this final
rule. In this third scenario where a manufacturer uses a symbol that
has not been recognized by FDA under section 514(c) of the FD&C Act or
uses a symbol from an FDA recognized standard but not in accordance
with the specifications for use of the symbol set forth in FDA's
section 514(c) recognition, the burden is on the manufacturer to
determine that the symbol is likely to be read and understood by the
ordinary individual under customary conditions of purchase and use such
that the use of the symbol in labeling is in compliance with section
502(c) of the FD&C Act. See, e.g., Sec.  801.15(c)(1)(i)(E)(3).
    To clarify the requirements of the final rule, we include the
following example:
    Standard Z is a standard developed by an SDO. The scope of Standard
Z is cardiac devices according to the specifications for use of the
standard set forth by the SDO. FDA recognizes the standard for use of
symbols in labeling for cardiac stents under its section 514(c)
authority. As such, FDA's recognition is for a subset of the devices
covered by Standard Z. Manufacturer A wishes to use stand-alone symbols
(symbols without adjacent explanatory text) from Standard Z on cardiac
stents. Manufacturer B wishes to use stand-alone symbols from Standard
Z on cardiac pacemakers. Manufacturer C wishes to use stand-alone
symbols from Standard Z on biliary stents, which are not cardiac
devices.
    Under the example, all the manufacturers could legally use the
symbols from Standard Z with adjacent explanatory text. See, e.g.,
Sec.  801.15(c)(1)(i)(C). Manufacturer A can legally use stand-alone
symbols from Standard Z in the labeling for cardiac stents, consistent
with FDA's recognition of Standard Z for cardiac stents. See, e.g.,
Sec.  801.15(c)(1)(i)(D). Manufacturer A must explain the stand-alone
symbols in a paper or electronic symbols glossary that is included in
the labeling for the device and the labeling on or within the package
containing Manufacturer A's device must bear a prominent and
conspicuous statement identifying the location of the symbols glossary.
See, e.g., Sec.  801.15(c)(1)(i)(D)(3). The symbol must be used
according to the specifications of FDA's section 514(c) recognition,
including the same meaning or explanatory text for the symbol in the
symbols glossary as provided in FDA's recognition of Standard Z. See,
e.g., Sec.  801.15(c)(1)(i)(D)(2). As discussed again later, if FDA
subsequently withdraws recognition of Standard Z because the stand-
alone symbol is not likely to be read and understood by the ordinary
individual under customary conditions of purchase and use, Manufacturer
A must stop using the stand-alone symbol. If FDA withdraws its
recognition of Standard Z for other reasons, the Manufacturer A may
continue to use the stand-alone symbols from Standard Z, that FDA no
longer recognizes, for cardiac stents (see, e.g., Sec.
801.15(c)(1)(i)(E)(2)); but the use must be consistent with the
specifications of Standard Z, including use of the explanatory text as
provided in Standard Z (see, e.g., Sec.  801.15(c)(1)(i)(E)(4)), and
the burden is on Manufacturer A to determine that the symbol's use is
likely to be read and understood by the ordinary individual under
customary conditions of purchase and use (see, e.g., Sec.
801.15(c)(1)(i)(E)(3)).
    With regard to Manufacturer B, this manufacturer wishes to use a
stand-alone symbol from Standard Z that would not be in accordance with
the specifications for use of the symbol set forth in FDA's section
514(c) recognition. When FDA recognized Standard Z, the scope of which
is cardiac devices, it limited the specifications for use of the
symbols to cardiac stents. Manufacturer B wishes to use the stand-alone
symbol from Standard Z on cardiac pacemakers.

Under the final rule, Manufacturer B may use stand-alone symbols
outside the scope of FDA recognition (see, e.g., Sec.
801.15(c)(1)(i)(E)(2)), but within the specifications for use of
Standard Z (see, e.g., Sec.  801.15(c)(1)(i)(E)(4)). In this scenario
where Manufacturer B uses a symbol from Standard Z that has not been
recognized under section 514(c) of the FD&C Act, the burden is on
Manufacturer B to determine that the symbol's use on cardiac
pacemakers, outside the scope of the FDA recognition, is likely to be
read and understood by the ordinary individual under customary
conditions of purchase and use. See, e.g., Sec.  801.15(c)(1)(i)(E)(3).
The same is true and same provisions apply if Manufacturer A uses a
stand-alone symbol on cardiac stents that is not in accordance with the
specifications for use of FDA's section 514(c) recognition. In these
cases, Manufacturer B (and Manufacturer A, if its use of the stand-
alone symbol is not in accordance with the specifications for use set
forth in FDA's section 514(c) recognition) must use the stand-alone
symbols of Standard Z consistent with the specifications for use of the
symbol set forth in Standard Z, including use of the explanatory text
as provided in Standard Z. See, e.g., Sec.  801.15(c)(1)(i)(E)(4).
    Finally, Manufacturer C wishes to use stand-alone symbols in
Standard Z for biliary stents. Under this final rule, this stand-alone
use is not allowed. As provided in this final rule, the use of stand-
alone symbols must be in accordance with the specifications for use of
the symbol set forth in the SDO-developed standard. Standard Z, as
developed by the SDO, specifies that it applies to cardiac devices. As
such, the use of stand-alone symbols from Standard Z in biliary stents
would not be in accordance with the specifications for use of the
symbols set forth in Standard Z. See, e.g., Sec.  801.15(c)(1)(i)(E)(4)
in this final rule that requires that a stand-alone symbol be used
according to the specifications for use of the symbol set forth in the
SDO-developed standard that FDA does not recognize. Accordingly,
Manufacturer C's use of the symbols from Standard Z on biliary stents
would require adjacent explanatory text. See, e.g., Sec.
801.15(c)(1)(i)(C) in this final rule.
    The final rule does not require the manufacturer to validate for a
particular device, the stand-alone use of a symbol established in an
SDO-developed standard, or part of a standard, that FDA has recognized
under section 514(c) of the FD&C Act. In addition, the final rule does
not require manufacturers to validate any stand-alone symbol. At the
same time, this final rule does not preclude device manufacturers from
undertaking any validation studies needed to assure that the use of the
stand-alone symbol is likely to be read and understood by customary
purchasers and users (section 502(c)) and complies with the other
misbranding requirements of section 502 of the FD&C Act.
    Manufacturers and importers should monitor complaints and adverse
events that might be related to inadequate understanding of labeling,
including misunderstanding about the meaning of stand-alone symbols
used in the device labeling. Manufacturers must report adverse events
as required by 21 CFR part 803. Reporting forms and instructions are
available at http://www.fda.gov/medwatch/safety.htm. If, for example,
postmarket surveillance data such as medical device reporting (MDR)
suggests that the users of the device do not understand the meaning of
a particular stand-alone symbol, and that such misunderstanding could
lead to a safety issue, the Agency may take enforcement action against
the device and device manufacturer.
    If FDA withdraws recognition of a standard (e.g., Standard Z in the
example) because the stand-alone symbol is not likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use, in that case, all manufacturers (both Manufacturers A
and B) must stop using the stand-alone symbol upon withdrawal of
recognition of the standard. FDA notes that it does not intend to take
enforcement action under section 502(c) of the FD&C Act on the basis
that the symbol is not likely to be read and understood by the ordinary
individual under customary conditions of purchase and use that
otherwise meets the requirements of this rule unless and until FDA
issues either a notice of SDO-standard withdrawal applicable to the use
or a symbol-specific Federal Register notice announcing FDA's
determination that the symbol is not likely to be read and understood
by the ordinary individual under customary conditions of purchase and
use as required by section 502(c), and, as such, the future date on
which FDA intends to take enforcement action against stand-alone use of
such symbol.
    In situations where FDA withdraws recognition of a standard, or
portion thereof, for reasons other than that the stand-alone symbol is
not likely to be read and understood as required by section 502(c) of
the FD&C Act, manufacturers may continue to use symbols within that
standard without adjacent text if the manufacturer determines that the
symbol is likely to be read and understood by the ordinary individual
under customary conditions of purchase and use in compliance with
section 502(c). Therefore, in the example, if FDA withdraws its
recognition of Standard Z for use of symbols in labeling for cardiac
stents for a reason other than that the ordinary individual is not
likely to read and understand the symbols under customary conditions of
purchase and use in compliance with section 502(c) of the FD&C Act,
Manufacturer A and Manufacturer B may continue to use their stand-alone
symbols under Sec.  801.15(c)(1)(i)(E) in this final rule. If FDA
provided a meaning or explanatory text in its recognition of Standard
Z, after the withdrawal Manufacturer A must use the symbols from
Standard Z according to the specifications of Standard Z, including the
same meaning or explanation in its symbols glossary as provided in
Standard Z for any remaining permitted use under the FDA withdrawal
notice. See, e.g., Sec.  801.15(c)(1)(i)(E)(4) and (iii)(B) in this
final rule.
    With regard to Manufacturer C, if it uses stand-alone symbols that
are outside the scope of the SDO-developed standard, FDA intends to
enforce compliance after the effective date of this final rule. See,
e.g., Sec.  801.15(c)(1)(ii) in this final rule.

IV. Legal Authority for the Final Rule

    A device is misbranded under section 502(c) of the FD&C Act if any
word, statement, or other information required by or under authority of
this act to appear on the label or labeling is not in such terms as to
render it likely to be read and understood by the ordinary individual
under customary conditions of purchase and use. Additionally, a device
is misbranded under section 502(a) of the FD&C Act if its labeling is
false or misleading in any particular. A device is also misbranded
under section 502(f) of the FD&C Act unless its labeling bears adequate
directions for use.
    Under section 201(m) of the FD&C Act, the term ``labeling'' means
all labels and other written, printed, or graphic matter: (1) Upon any
article or any of its containers or wrappers or (2) accompanying such
article. Under section 201(k) of the FD&C Act, the term ``label'' means
a display of written, printed, or graphic matter upon the immediate
container of any article; and a requirement made by or under authority
of the FD&C Act that any word, statement, or other information appear
on the label shall not be considered to be complied with unless

such word, statement, or other information also appears on the outside
container or wrapper, if any there be, of the retail package of such
article, or is easily legible through the outside container or wrapper.
    Section 514(c)(1)(A) of the FD&C Act authorizes FDA to recognize,
by publication in the Federal Register, all or part of an appropriate
standard established by a nationally or internationally recognized
standard development organization for which a person may submit a
declaration of conformity in order to meet a premarket submission
requirement or other requirement under the FD&C Act to which such
standard is applicable. Section 514(c)(1)(B) of the FD&C Act further
provides that a person may elect to use data, or information, other
than data required by a standard recognized by FDA to meet any
requirement regarding devices under the FD&C Act. Section 514(c)(2) of
the FD&C Act allows FDA to withdraw recognition of a standard through
publication of a notice in the Federal Register if FDA determines that
the standard is no longer appropriate for meeting a device requirement
under the FD&C Act.
    Section 701(a) of the FD&C Act (21 U.S.C. 371(a)) gives FDA the
authority to issue regulations for the efficient enforcement of the
FD&C Act.

V. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct us to assess all costs
and benefits of available regulatory alternatives and, when regulation
is necessary, to select regulatory approaches that maximize net
benefits (including potential economic, environmental, public health
and safety, and other advantages; distributive impacts; and equity). We
have developed a comprehensive Economic Analysis of Impacts that
assesses the impacts of the final rule. We believe that the final rule
is not a significant regulatory action as defined by Executive Order
12866.
    The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because this rule imposes no new burdens, we certify that the
final rule would not have a significant economic impact on a
substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before issuing ``any rule that includes
any Federal mandate that may result in the expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one
year.'' The current threshold after adjustment for inflation is $146
million, using the most current (2015) Implicit Price Deflator for the
Gross Domestic Product. This final rule would not result in an
expenditure in any year that meets or exceeds this amount.

Summary

    The final rule would provide medical device manufacturers with the
option to use symbols established in SDO-developed standards for stand-
alone use in labeling to communicate information to end users. Under
the final rule, manufacturers would be allowed to substitute labels
containing only written statements (text-only labels) or symbols with
adjacent explanatory text with a label containing stand-alone symbols,
provided that such symbols are established in a standard developed by a
SDO as long as: (1) The standard is recognized by FDA under its
authority under section 514(c) of the FD&C Act and the symbol is used
according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition, or alternatively, (2) if the symbol
is not included in a standard recognized by FDA under section 514(c) of
the FD&C Act or the symbol is in a standard recognized by FDA but is
not used according to the specifications for use of the symbol set out
in the FDA section 514(c) recognition, the device manufacturer
otherwise determines that the symbol is likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use and uses the symbol according to the specifications
for use of the symbol set forth in the SDO-developed standard. In
addition, in either case, the symbol must be explained in a written or
electronic symbols glossary that is included in the labeling for the
medical device. Furthermore, the labeling on or within the package
containing the device must bear a prominent and conspicuous statement
identifying the location of the glossary that is written in English or,
in the case of articles distributed solely in Puerto Rico or in a
Territory where the predominant language is one other than English, the
predominant language may be used. The use of such symbols must also
comply with other applicable labeling requirements of the FD&C Act,
such as section 502(a) and section 502(f). In addition, the final rule
allows the use of the symbol statement ``Rx Only'' or ``[rx] only'' for
labeling of prescription devices.
    Medical device manufacturers would only choose to use stand-alone
symbols, as allowed by the final rule, if they expect a positive net
benefit (estimated benefits minus estimated costs). Hence, the final
rule is expected to provide a non-negative net benefit to each
manufacturer that opts to use stand-alone symbols. Choosing to use
stand-alone symbols under the final rule would potentially reduce the
costs associated with designing and redesigning the labels on medical
devices that are currently marketed in the United States and the EU.
The estimated annual benefits range from $7.9 million to $25.5 million
at a 3 percent discount rate, and $7.7 million to $25.0 million at a 7
percent discount rate. Those that opt to use stand-alone symbols under
the rule would incur one-time administrative costs to redesign their
labeling and create a symbols glossary that is included in the labeling
for the device, and recurring costs to revise their glossaries, as
necessary. Annualized over 20 years, we estimate total costs to range
between $1.1 million to $3.2 million at a 3 percent discount rate, and
from $1.1 million to $3.3 million at a 7 percent discount rate.
Annualized over 20 years, net benefits range from $6.8 million to $22.3
million at a 3 percent discount rate, and from $6.6 million to $21.7
million at a 7 percent discount rate. The costs and benefits accrue to
the same entities, however, so any firm making the change to stand-
alone symbols would, on net, reduce costs.
    FDA also examined the economic implications of the final rule as
required by the Regulatory Flexibility Act. If a rule will have a
significant economic impact on a substantial number of small entities,
the Regulatory Flexibility Act requires Agencies to analyze regulatory
options that would lessen the economic effect of the rule on small
entities. We estimated the final rule's approximate impact on small
entities using the percent costs per device distinguishable by
Universal Product Code (UPC): The ratio between unit labeling costs and
revenues among small entities. Our estimates indicate that the average
percent costs per UPC ranges from 0.01 to 0.46 percent. Because
companies can choose whether or not to use stand-alone symbols under
the final rule, the Agency concludes that this final rule would not
have a significant adverse impact on any small entities. Furthermore,
our analysis suggests that

companies could reap moderate cost-savings by using stand-alone symbols
in device labeling. On average, companies that use stand-alone symbols
under this final rule could expect to receive an average annual cost
savings ranging from $1,500 to $4,500 per UPC. Because using stand-
alone symbols is expected to lower the marginal cost of producing
exports, medical device manufacturers, including small entities, may be
able to increase their production either by starting to export products
or by exporting more products.
    The full analysis of economic impacts is available in the docket
for this final rule (FDA-2013-N-0125) and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm (Ref.
6).

VI. Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The title,
description, and respondent description of the information collection
provisions are provided in the following paragraphs with an estimate of
the annual reporting and third-party disclosure burdens. Included in
the estimate is the time for reviewing instructions, searching existing
data sources, gathering and maintaining the data needed, and completing
and reviewing each collection of information.
    Title: Medical Devices: Use of Symbols in Labeling--Glossary to
Support the Use of Symbols in Labeling.
    Description: FDA is issuing a final rule revising medical device
and certain biological product labeling regulations by explicitly
allowing for the optional use in medical device labeling of stand-alone
symbols established in an SDO-developed standard.
    In particular, FDA will allow the use of stand-alone graphical
representations of information, or symbols in the labeling for the
medical devices, if the symbols are established in a standard developed
by an SDO as long as: (1) The standard is recognized by FDA under its
authority under section 514(c) of the FD&C Act and the symbol is used
according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition, or alternatively, (2) if the symbol
is not included in a standard recognized by FDA under section 514(c) of
the FD&C Act or the symbol is in a standard recognized by FDA but is
not used according to the specifications for use of the symbol set out
in the FDA section 514(c) recognition, the device manufacturer
otherwise determines that the symbol is likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use and uses the symbol according to the specifications
for use of the symbol set forth in the SDO-developed standard. In
addition, in either case, the symbol must be explained in a written or
electronic symbols glossary that is included in the labeling for the
medical device. Furthermore, the labeling on or within the package
containing the device must bear a prominent and conspicuous statement
identifying the location of the glossary that is written in English or,
in the case of articles distributed solely in Puerto Rico or in a
Territory where the predominant language is one other than English, the
predominant language may be used. The use of such symbols must also
comply with other applicable labeling requirements of the FD&C Act,
such as section 502(a) and section 502(f). The final rule also allows
the use of the symbol statement ``Rx Only'' or ``[rx] only.''
    Description of Respondents: The likely respondents for this
collection of information are domestic and foreign device manufacturers
who plan to use stand-alone symbols on the labels and/or labeling for
their devices marketed in the United States.

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Number of
                              Activity                                  Number of      responses  per   Total  annual   Average  burden    Total hours
                                                                       respondents       respondent       responses      per  response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Glossary...........................................................           3,000                1            3,000                1            3,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                                               Table 2--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Number of
                              Activity                                  Number of       disclosures     Total  annual   Average  burden    Total hours
                                                                       respondents    per  respondent    disclosures    per  disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Glossary...........................................................           3,000                1            3,000                4           12,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    The estimated burden is based on the data in a similar collection
for recommended glossary and educational outreach approved under OMB
control number 0910-0553 (Use of Symbols on Labels and in Labeling of
In Vitro Diagnostic Devices Intended for Professional Use). As such,
the PRA also covers the requirements of this final rule to submit the
symbols glossary to FDA in otherwise required submissions during the
premarket review process and to disclose it to third parties in
otherwise required device labeling, which means adding to such
submission or labeling a compiled listing of each SDO-established
symbol used in the labeling for the device; the title and designation
number of the SDO-developed standard containing the symbol; and the
title of the symbol and its reference number, if any, in the standard;
and the meaning or explanatory text for the symbol as provided in the
FDA recognition or, if FDA has not recognized the standard or portion
of the standard in which the symbol is located or the symbol is used
not in accordance with the specifications for use of the symbol set out
in the FDA section 514(c) recognition, the explanatory text as provided
in the standard. We assume that the additional requirement of
identifying in the symbols glossary the SDO-developed standard
establishing the symbol and its reference number if any, not included
in proposed rule,

results in no significant additional cost burden.
    The information collection provisions in this final rule have been
submitted to OMB (control number 0910-0740) for review as required by
section 3507(d) of the Paperwork Reduction Act of 1995.
    Before the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. 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 control number.
    This final rule refers to previously approved collections of
information found in FDA regulations. These collections of information
are subject to review by OMB under the Paperwork Reduction Act of 1995
(44 U.S.C. 3501-3520). The collections of information in 21 CFR part
812 have been approved under OMB control number 0910-0078; the
collections of information in 21 CFR part 807, subpart E have been
approved under OMB control number 0910-0120; the collections of
information in 21 CFR part 814, subparts A through E have been approved
under OMB control number 0910-0231; the collections of information in
21 CFR part 801 and Sec.  809.10 have been approved under OMB control
number 0910-0485; and the collections of information in Sec. Sec.
660.2, 660.28, 660.35, 660.45, and 660.55 have been approved under OMB
control number 0910-0338.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

VIII. Effective Date

    This rule is effective on September 13, 2016.

IX. Federalism

    We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, we conclude that the rule
does not contain policies that have federalism implications as defined
in the Executive order and, consequently, a federalism summary impact
statement is not required.

X. References

    The following references are on display in the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, and are available for viewing by
interested persons between 9 a.m. and 4 p.m., Monday through Friday;
they are also available electronically at http://www.regulations.gov.
FDA has verified the Web site addresses, as of the date this document
publishes in the Federal Register, but Web sites are subject to change
over time.

1. Frequently Asked Questions on Recognition of Consensus Standards;
Guidance for Industry and FDA Staff, September 2007, available at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm074973.htm.
2. The National Technology Transfer and Advancement Act of 1995
(Pub. L. 104-113), section 12(d), 110 Stat. 783.
3. Office of Management and Budget, OMB Circular A-119 (63 FR 8546,
February 19, 1998) (Final Revision).
4. Use of Symbols on Labels and in Labeling of In Vitro Diagnostic
Devices Intended for Professional Use; Guidance for Industry and FDA
Staff, FDA, November 2004, available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085404.htm.
5. Alternative to Certain Prescription Device Labeling Requirements;
Guidance for Industry, FDA, January 2000, available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm072747.htm.
6. Use of Symbols in Medical Device Labeling: Final Regulatory
Impact Analysis; Final Regulatory Flexibility Analysis; Unfunded
Mandates Reform Act Analysis; available at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/ucm350746.htm.

List of Subjects

21 CFR Part 660

    Biologics, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 801

    Labeling, Medical devices, Reporting and recordkeeping
requirements.

21 CFR Part 809

    Labeling, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321 et seq., as amended), the Public Health Service Act, and
under authority delegated to the Commissioner of Food and Drugs, 21 CFR
parts 660, 801, and 809 are amended as follows:

PART 660--ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR
LABORATORY TESTS

0
1. The authority citation for part 660 continues to read as follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372; 42 U.S.C. 216, 262, 263, 263a, 264.

0
2. Amend Sec.  660.2 by revising paragraph (c) to read as follows:

Sec.  660.2  General requirements.

* * * * *
    (c) Labeling. (1) In addition to the items required by other
applicable labeling provisions of this subchapter, the following shall
also be included:
    (i) Indication of the source of the product immediately following
the proper name on both the final container and package label, e.g.,
human, guinea pig.
    (ii) Name of the test method(s) recommended for the product on the
package label and on the final container label when capable of bearing
a full label (see Sec.  610.60(a) of this chapter).
    (iii) A warning on the package label and on the final container
label if capable of bearing a full label (see Sec.  610.60(a) of this
chapter) indicating that the product and antigen if supplied, shall be
handled as if capable of transmitting hepatitis.
    (iv) If the product is dried, the final container label shall
indicate ``Reconstitution date: ___'' and a statement indicating the
period within which the product may be used after reconstitution.
    (v) The package shall include a package enclosure providing:
    (A) Adequate instructions for use;
    (B) A description of all recommended test methods; and
    (C) Warnings as to possible hazards, including hepatitis, in
handling the product and any ancillary reagents and materials
accompanying the product.
    (2) The applicant may provide the labeling information referenced
in paragraph (c)(1) of this section in the form of:
    (i) A symbol accompanied by explanatory text adjacent to the
symbol;
    (ii) A symbol not accompanied by adjacent explanatory text that:
    (A) Is contained in a standard that FDA recognizes under its
authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act;
    (B) Is used according to the specifications for use of the symbol
set

forth in FDA's section 514(c) recognition; and
    (C) Is explained in a paper or electronic symbols glossary that is
included in the labeling for the device and the labeling on or within
the package containing the device bears a prominent and conspicuous
statement identifying the location of the symbols glossary that is
written in English or, in the case of articles distributed solely in
Puerto Rico or in a Territory where the predominant language is one
other than English, the predominant language may be used; or
    (iii) A symbol not accompanied by adjacent explanatory text that:
    (A) Is established in a standard developed by a standards
development organization (SDO);
    (B) Is not contained in a standard that is recognized by FDA under
its authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act or is contained in a standard that is recognized by FDA but is not
used according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition;
    (C) Is determined by the manufacturer to be likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use in compliance with section 502(c) of the Federal Food,
Drug, and Cosmetic Act;
    (D) Is used according to the specifications for use of the symbol
set forth in the SDO-developed standard; and
    (E) Is explained in a paper or electronic symbols glossary that is
included in the labeling for the device and the labeling on or within
the package containing the device bears a prominent and conspicuous
statement identifying the location of the symbols glossary that is
written in English or, in the case of articles distributed solely in
Puerto Rico or in a Territory where the predominant language is one
other than English, the predominant language may be used.
    (3) The use of symbols to provide the labeling information
referenced in paragraph (c)(1) of this section which do not meet the
requirements of paragraph (c)(2) of this section renders a device
misbranded under section 502(c) of the Federal Food, Drug, and Cosmetic
Act.
    (4) For purposes of paragraph (c)(2) of this section:
    (i) An SDO is an organization that is nationally or internationally
recognized and that follows a process for standard development that is
transparent, (i.e., open to public scrutiny), where the participation
is balanced, where an appeals process is included, where the standard
is not in conflict with any statute, regulation, or policy under which
FDA operates, and where the standard is national or international in
scope.
    (ii) The term ``symbols glossary'' means a compiled listing of:
    (A) Each SDO-established symbol used in the labeling for the
device;
    (B) The title and designation number of the SDO-developed standard
containing the symbol;
    (C) The title of the symbol and its reference number, if any, in
the standard; and
    (D) The meaning or explanatory text for the symbol as provided in
the FDA recognition or, if FDA has not recognized the standard or
portion of the standard in which the symbol is located or the symbol is
not used according to the specifications for use of the symbol set
forth in FDA's section 514(c) recognition, the explanatory text as
provided in the standard.
* * * * *

0
3. Amend Sec.  660.20 by revising paragraph (a) to read as follows:

Sec.  660.20  Blood Grouping Reagent.

    (a) Proper name and definition. The proper name of this product
shall be Blood Grouping Reagent and it shall consist of an antibody-
containing fluid containing one or more of the blood grouping
antibodies listed in Sec.  660.28(a)(4).
* * * * *

0
4. Revise Sec.  660.28 to read as follows:

Sec.  660.28  Labeling.

    (a) In addition to the applicable labeling requirements of
Sec. Sec.  610.62 through 610.65 and Sec.  809.10 of this chapter, and
in lieu of the requirements in Sec. Sec.  610.60 and 610.61 of this
chapter, the following requirements shall be met:
    (1) Final container label--(i) Color coding. The final container
label of all Blood Grouping Reagents shall be completely white, except
that all or a portion of the final container label of the following
Blood Grouping Reagents may be color coded with the specified color
which shall be a visual match to a specific color sample designated by
the Director, Center for Biologics Evaluation and Research. Printing on
all final container labels shall be in solid black. A logo or company
name may be placed on the final container label; however, the logo or
company name shall be located along the bottom or end of the label,
outside the main panel.

------------------------------------------------------------------------
           Blood grouping reagent                Color of label paper
------------------------------------------------------------------------
Anti-A.....................................  Blue.
Anti-B.....................................  Yellow.
Slide and rapid tube test blood grouping
 reagents only:
    Anti-C.................................  Pink.
    Anti-D.................................  Gray.
    Anti-E.................................  Brown.
    Anti-CDE...............................  Orange.
    Anti-c.....................  Lavender.
    Anti-e.................................  Green.
------------------------------------------------------------------------

    (ii) Required information. The proper name ``Blood Grouping
Reagent'' need not appear on the final container label provided the
final container is distributed in a package and the package label bears
the proper name. The final container label shall bear the following
information:
    (A) Name of the antibody or antibodies present as set forth in
paragraph (a)(4) of this section.
    (B) Name, address (including ZIP code), and license number of the
manufacturer.
    (C) Lot number, including sublot designations.
    (D) Expiration date.
    (E) Source of product if other than human plasma or serum.
    (F) Test method(s) recommended.
    (G) Recommended storage temperature in degrees Celsius.
    (H) Volume of product if a liquid, or equivalent volume for a dried
product if it is to be reconstituted.
    (I) If a dried product, to remind users to record the
reconstitution date on the label, the statement ``RECONSTITUTION DATE
___. EXPIRES 1 YEAR AFTER RECONSTITUTION DATE.''
    (iii) Lettering size. The type size for the specificity of the
antibody designation on the labels of a final container with a capacity
of less than 5 milliliters shall be not less than 12 point. The type
size for the specificity of the antibody designations on the label of a
container with a capacity of 5 milliliters or more shall be not less
than 18 point.
    (iv) Visual inspection. When the label has been affixed to the
final container, a sufficient area of the container shall remain
uncovered for its full length or no less than 5 millimeters of the
lower circumference to permit inspection of the contents. The label on
a final product container for antibodies Anti-c, Anti-k, or Anti-s
shall display a bar immediately over the specificity letter used in the
name, i.e., Anti-c, Anti-k, or Anti-s.
    (2) Package label. The following information shall appear either on
the package label or on the final container label if it is visible
within the package.

    (i) Proper name of the product.
    (ii) Name of the antibody or antibodies present as set forth in
paragraph (a)(4) of this section.
    (iii) Name, address (including ZIP Code), and license number of the
manufacturer.
    (iv) Lot number, including sublot designations.
    (v) Expiration date.
    (vi) Preservative used and its concentration.
    (vii) Number of containers, if more than one.
    (viii) Volume or equivalent volume for dried products when
reconstituted, and precautions for adequate mixing when reconstituting.
    (ix) Recommended storage temperature in degrees Celsius.
    (x) Source of the product if other than human serum or plasma.
    (xi) Reference to enclosed package insert.
    (xii) If a dried product, a statement indicating the period within
which the product may be used after reconstitution.
    (xiii) The statement: ``FOR IN VITRO DIAGNOSTIC USE.''
    (xiv) The statement: ``MEETS FDA POTENCY REQUIREMENTS.''
    (xv) If human blood was used in manufacturing the product, the
statement: ``CAUTION: ALL BLOOD PRODUCTS SHOULD BE TREATED AS
POTENTIALLY INFECTIOUS. SOURCE MATERIAL FROM WHICH THIS PRODUCT WAS
DERIVED WAS FOUND NEGATIVE WHEN TESTED IN ACCORDANCE WITH CURRENT FDA
REQUIRED TESTS. NO KNOWN TEST METHODS CAN OFFER ASSURANCE THAT PRODUCTS
DERIVED FROM HUMAN BLOOD WILL NOT TRANSMIT INFECTIOUS AGENTS.''
    (xvi) A statement of an observable indication of an alteration of
the product, e.g., turbidity, color change, precipitate, that may
indicate possible deterioration of the product.
    (3) Package insert. Each final container of Blood Grouping Reagent
shall be accompanied by a package insert meeting the requirements of
Sec.  809.10. If two or more final containers requiring identical
package inserts are placed in a single package, only one package insert
per package is required.
    (4) Names of antibodies.

               Blood Group Designation for Container Label
------------------------------------------------------------------------

------------------------------------------------------------------------
Anti-A                               Anti-Jk\b\
Anti-A1                              Anti-Js\a\
Anti-A, B                            Anti-Js\b\
Anti-A and B                         Anti-K
Anti-B                               Anti-k
Anti-C                               Anti-Kp\a\
Anti-C\w\                            Anti-Kp\b\
Anti- c                  Anti-Le\a\
Anti-CD                              Anti-Le\b\
Anti-CDE                             Anti-Lu\a\
Anti-Co\b\                           Anti-Lu\b\
Anti-D                               Anti-M
Anti-DE                              Anti-M\g\
Anti-Di\a\                           Anti-N
Anti-E                               Anti-P1
Anti-e                               Anti-S
Anti-Fy\a\                           Anti-s
Anti-Fy\b\                           Anti-U
Anti-I                               Anti-Wr\a\
Anti-Jk\a\                           Anti-Xg\a\
------------------------------------------------------------------------

    (b) The applicant may provide the labeling information referenced
in paragraph (a) of this section in the form of:
    (1) A symbol accompanied by explanatory text adjacent to the
symbol;
    (2) A symbol not accompanied by adjacent explanatory text that:
    (i) Is contained in a standard that FDA recognizes under its
authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act;
    (ii) Is used according to the specifications for use of the symbol
set forth in FDA's section 514(c) recognition; and
    (iii) Is explained in a paper or electronic symbols glossary that
is included in the labeling for the device and the labeling on or
within the package containing the device bears a prominent and
conspicuous statement identifying the location of the symbols glossary
that is written in English or, in the case of articles distributed
solely in Puerto Rico or in a Territory where the predominant language
is one other than English, the predominant language may be used; or
    (3) A symbol not accompanied by adjacent explanatory text that:
    (i) Is established in a standard developed by a standards
development organization (SDO);
    (ii) Is not contained in a standard that is recognized by FDA under
its authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act or is contained in a standard that is recognized by FDA but is not
used according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition;
    (iii) Is determined by the manufacturer to be likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use in compliance with section 502(c) of the Federal Food,
Drug, and Cosmetic Act;
    (iv) Is used according to the specifications for use of the symbol
set forth in the SDO-developed standard; and
    (v) Is explained in a paper or electronic symbols glossary that is
included in the labeling for the device and the labeling on or within
the package containing the device bears a prominent and conspicuous
statement identifying the location of the symbols glossary that is
written in English or, in the case of articles distributed solely in
Puerto Rico or in a Territory where the predominant language is one
other than English, the predominant language may be used.
    (c) The use of symbols in device labeling to provide the labeling
information referenced in paragraph (a) of this section which do not
meet the requirements in paragraph (b) of this section renders a device
misbranded under section 502(c) of the Federal Food, Drug, and Cosmetic
Act.
    (d) For purposes of paragraph (b) of this section:
    (1) An SDO is an organization that is nationally or internationally
recognized and that follows a process for standard development that is
transparent, (i.e., open to public scrutiny), where the participation
is balanced, where an appeals process is included, where the standard
is not in conflict with any statute, regulation, or policy under which
FDA operates, and where the standard is national or international in
scope.
    (2) The term ``symbols glossary'' means a compiled listing of:
    (i) Each SDO-established symbol used in the labeling for the
device;
    (ii) The title and designation number of the SDO-developed standard
containing the symbol;
    (iii) The title of the symbol and its reference number, if any, in
the standard; and
    (iv) The meaning or explanatory text for the symbol as provided in
the FDA recognition or, if FDA has not recognized the standard or
portion of the standard in which the symbol is located or the symbol is
not used according to the specifications for use of the symbol set
forth in FDA's section 514(c) recognition, the explanatory text as
provided in the standard.

0
5. Revise Sec.  660.35 to read as follows:

Sec.  660.35  Labeling.

    (a) In addition to the items required by Sec.  809.10 of this
chapter and other applicable labeling provisions of this chapter, the
following information shall be included in the labeling:
    (1)(i) A logo or company name may be placed on the final container
label, however, the logo or company name

shall be located along the bottom or end of the label, outside of the
main panel.
    (ii) If washing the cells is required by the manufacturer, the
container label shall include appropriate instructions; if the cells
should not be washed before use, e.g., if washing will adversely affect
the product, the package insert shall explain.
    (2) The container label of Group O cells shall state:
    ``FOR USE IN DETECTION OF UNEXPECTED ANTIBODIES'' or ``FOR USE IN
IDENTIFICATION OF UNEXPECTED ANTIBODIES'' or ``NOT FOR USE IN DETECTION
OR IDENTIFICATION OF UNEXPECTED ANTIBODIES''.
    (3) Except as provided in this section, the container and package
labels shall state the percentage of red blood cells in the suspension
either as a discrete figure with a variance of more than [+/-] 1
percentage unit or as a range the extremes of which differ by no more
than 2 percentage units. If the stated red blood cell concentration is
less than 2 percent, the variance shall be no more than [+/-] 0.5
percentage unit.
    (4) The words ``pooled cells'' shall appear on the container and
package labels of products prepared from pooled cells. The package
label or package insert shall state that pooled cells are not
recommended for pre-transfusion tests, done in lieu of a major
crossmatch, to detect unexpected antibodies in patients' samples.
    (5) The package insert of a pooled product intended for detection
of unexpected antibodies shall identify the number of donors
contributing to the pool. Products designed exclusively for ABO Serum
Grouping and umbilical cord cells need not identify the number of
donors in the pool.
    (6) When the product is a multicontainer product, e.g., a cell
panel, the container label and package label shall be assigned the same
identifying lot number, and shall also bear a number or symbol to
distinguish one container from another. Such number or symbol shall
also appear on the antigenic constitution matrix.
    (7) The package label or package insert shall state the blood group
antigens that have been tested for and found present or absent on the
cells of each donor, or refer to such information in an accompanying
antigenic constitution matrix. Cells for ABO Serum Grouping are exempt
from this requirement. The package insert or antigen constitution
matrix shall list each of the antigens tested with only one source of
antibody.
    (8) The package label or package insert shall bear the cautionary
statement: ``The reactivity of the product may decrease during the
dating period.''
    (9) The package insert of a product intended for the detection or
identification of unexpected antibodies shall note that the rate at
which antigen reactivity (e.g., agglutinability) is lost is partially
dependent upon individual donor characteristics that are neither
controlled nor predicted by the manufacturer.
    (10) The package insert shall provide adequate directions for use.
    (11) The package insert shall bear the statement:
    ``CAUTION: ALL BLOOD PRODUCTS SHOULD BE TREATED AS POTENTIALLY
INFECTIOUS. SOURCE MATERIAL FROM WHICH THIS PRODUCT WAS DERIVED WAS
FOUND NEGATIVE WHEN TESTED IN ACCORDANCE WITH CURRENT FDA REQUIRED
TESTS. NO KNOWN TEST METHODS CAN OFFER ASSURANCE THAT PRODUCTS DERIVED
FROM HUMAN BLOOD WILL NOT TRANSMIT INFECTIOUS AGENTS.''
    (12) The package insert or the antigenic constitution matrix for
each lot of product shall specify the date of manufacture or the length
of the dating period.
    (13) Manufacturers shall identify with a permanent donor code in
the product labeling each donor of peripheral blood used for detection
or identification of unexpected antibodies.
    (b) The applicant may provide the labeling information referenced
in paragraph (a) of this section in the form of:
    (1) A symbol accompanied by explanatory text adjacent to the
symbol;
    (2) A symbol not accompanied by adjacent explanatory text that:
    (i) Is contained in a standard that FDA recognizes under its
authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act;
    (ii) Is used according to the specifications for use of the symbol
set forth in FDA's section 514(c) recognition; and
    (iii) Is explained in a paper or electronic symbols glossary that
is included in the labeling for the device and the labeling on or
within the package containing the device bears a prominent and
conspicuous statement identifying the location of the symbols glossary
that is written in English or, in the case of articles distributed
solely in Puerto Rico or in a Territory where the predominant language
is one other than English, the predominant language may be used; or
    (3) A symbol not accompanied by adjacent explanatory text that:
    (i) Is established in a standard developed by a standards
development organization (SDO);
    (ii) Is not contained in a standard that is recognized by FDA under
its authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act or is contained in a standard that is recognized by FDA but is not
used according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition;
    (iii) Is determined by the manufacturer to be likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use in compliance with section 502(c) of the Federal Food,
Drug, and Cosmetic Act;
    (iv) Is used according to the specifications for use of the symbol
set forth in the SDO-developed standard; and
    (v) Is explained in a paper or electronic symbols glossary that is
included in the labeling for the device and the labeling on or within
the package containing the device bears a prominent and conspicuous
statement identifying the location of the symbols glossary that is
written in English or, in the case of articles distributed solely in
Puerto Rico or in a Territory where the predominant language is one
other than English, the predominant language may be used.
    (c) The use of symbols in device labeling to provide the labeling
information referenced in paragraph (a) of this section which do not
meet the requirements of paragraph (b) of this section renders a device
misbranded under section 502(c) of the Federal Food, Drug, and Cosmetic
Act.
    (d) For purposes of paragraph (b) of this section:
    (1) An SDO is an organization that is nationally or internationally
recognized and that follows a process for standard development that is
transparent, (i.e., open to public scrutiny), where the participation
is balanced, where an appeals process is included, where the standard
is not in conflict with any statute, regulation, or policy under which
FDA operates, and where the standard is national or international in
scope.
    (2) The term ``symbols glossary'' means a compiled listing of:
    (i) Each SDO-established symbol used in the labeling for the
device;
    (ii) The title and designation number of the SDO-developed standard
containing the symbol;
    (iii) The title of the symbol and its reference number, if any, in
the standard; and

    (iv) The meaning or explanatory text for the symbol as provided in
the FDA recognition or, if FDA has not recognized the standard or
portion of the standard in which the symbol is located or the symbol is
not used according to the specifications for use of the symbol set
forth in FDA's section 514(c) recognition, the explanatory text as
provided in the standard.

0
6. Revise Sec.  660.45 to read as follows:

Sec.  660.45  Labeling.

    (a) In addition to the requirements of Sec. Sec.  610.60, 610.61,
and 809.10 of this chapter, the labeling shall bear the following:
    (1) The ``d and y'' antigen subtype and the source of the product
to follow immediately the proper name on both the final container label
and the package label. If the product is intended to identify
antibodies to the ``r and w'' antigen subtype, the antigen subtype
designation shall include the ``r and w'' antigen subtype.
    (2) The name of the test method(s) recommended for use of the
product on the package label and on the final container label, when
capable of bearing a full label (see Sec.  610.60(a) of this chapter).
    (3) A warning on the package label and on the final container label
stating that the product is capable of transmitting hepatitis and
should be handled accordingly.
    (4) The package shall include a package insert providing:
    (i) Detailed instructions for use,
    (ii) An adequate description of all recommended test methods, and
    (iii) Warnings as to possible hazards, including hepatitis
transmitted in handling the product and any ancillary reagents and
materials accompanying the product.
    (b) The applicant may provide the labeling information referenced
in paragraph (a) of this section in the form of:
    (1) A symbol accompanied by explanatory text adjacent to the
symbol;
    (2) A symbol not accompanied by adjacent explanatory text that:
    (i) Is contained in a standard that FDA recognizes under its
authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act;
    (ii) Is used according to the specifications for use of the symbol
set forth in FDA's section 514(c) recognition; and
    (iii) Is explained in a paper or electronic symbols glossary that
is included in the labeling for the device and the labeling on or
within the package containing the device bears a prominent and
conspicuous statement identifying the location of the symbols glossary
that is written in English or, in the case of articles distributed
solely in Puerto Rico or in a Territory where the predominant language
is one other than English, the predominant language may be used; or
    (3) A symbol not accompanied by adjacent explanatory text that:
    (i) Is established in a standard developed by a standards
development organization (SDO);
    (ii) Is not contained in a standard that is recognized by FDA under
its authority in section 514(c) of the Federal Food, Drug, and Cosmetic
Act or is contained in a standard that is recognized by FDA but is not
used according to the specifications for use of the symbol set forth in
FDA's section 514(c) recognition;
    (iii) Is determined by the manufacturer to be likely to be read and
understood by the ordinary individual under customary conditions of
purchase and use in compliance with section 502(c) of the Federal Food,
Drug, and Cosmetic Act;
    (iv) Is used according to the specifications for use of the symbol
set forth in the SDO-developed standard; and
    (v) Is explained in a paper or electronic symbols glossary that is
included in the labeling for the device and the labeling on or within
the package containing the device bears a prominent and conspicuous
statement identifying the location of the symbols glossary that is
written in English or, in the case of articles distributed solely in
Puerto Rico or in a Territory where the predominant language is one
other than English, the predominant language may be used.