[Federal Register Volume 78, Number 76 (Friday, April 19, 2013)]
[Proposed Rules]
[Pages 23508-23515]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-09175]


=======================================================================
-----------------------------------------------------------------------

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 Certain Symbols in Labeling

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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

SUMMARY: The Food and Drug Administration (FDA) is proposing to revise 
medical device and biological product labeling regulations to 
explicitly allow for the inclusion of stand-alone graphical 
representations of information, or symbols, if the symbol has been 
established as part of a standard developed by a nationally or 
internationally recognized standards development organization (SDO) 
(referred to in this document as a ``standardized symbol'') and such 
standardized symbol is part of a standard recognized by FDA for use on 
the labeling of medical devices (or on a subset of medical devices), 
provided that such symbol is explained in a symbols glossary that 
contemporaneously accompanies the medical device. FDA is also proposing 
to revise prescription device labeling regulations to authorize the use 
of the symbol statement ``Rx only'' on the labeling of prescription 
devices.

DATES: Submit electronic or written comments on the proposed rule by 
June 18, 2013. Submit comments on information collection issues under 
the Paperwork Reduction Act of 1995 (the PRA) by May 20, 2013, (see 
section VII). See section IX for the proposed effective date of a final 
rule based on the proposed rule in this document.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0125 and/or Regulatory Information Number (RIN) 0910-AG74, by any of 
the following methods, except that comments on information collection 
issues under the PRA must be submitted to the Office of Information and 
Regulatory Affairs, Office of Management and Budget (OMB) (see section 
VII).

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following way:
     Mail/Hand delivery/Courier (for paper or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency 
name, Docket No. FDA-2013-N-0125, and RIN 0910-AG74 for this 
rulemaking. All comments received may be posted without change to 
http://www.regulations.gov, including any personal information 
provided. For additional information on submitting comments, see 
section VIII.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: 
Michael Ryan, Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New

[[Page 23509]]

Hampshire Ave., Bldg. 66, Rm. 1615, Silver Spring, MD 20993, 301-796-
6283; or
Stephen Ripley, Center for Biologics Evaluation and Research (HFM-17), 
Food and Drug Administration, 1401 Rockville Pike, Suite 200N, 
Rockville, MD 20852, 301-827-6210.

SUPPLEMENTARY INFORMATION: 

I. Background

    Medical device labeling \1\ is intended to clearly communicate 
information to end users, including manufacturer identification, 
intended use, and directions for use. Section 502 of the FD&C Act (21 
U.S.C. 352) requires that industry provide clear and understandable 
labeling for FDA-regulated products. A device is deemed misbranded, 
among other reasons, if its labeling is false or misleading (section 
502(a)), if the required information on the labeling fails to appear in 
terms that are ``likely to be read and understood by the ordinary 
individual under customary conditions of purchase and use'' (section 
502(c)), or if its labeling does not bear ``adequate directions for 
use'' (section 502(f) of the FD&C Act).
---------------------------------------------------------------------------

    \1\ Under section 201(m) of the Federal Food, Drug, and Cosmetic 
Act (the FD&C Act) (21 U.S.C. 321(m)), 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.
---------------------------------------------------------------------------

    FDA has further defined labeling requirements for devices by 
regulation, requiring, in part 801 (21 CFR part 801), that ``[a]ll 
words, statements, and other information required by or under authority 
of the act to appear on the label or labeling shall appear thereon in 
the English language* * *'' (Sec.  801.15(c)(1)). The regulation goes 
on to allow for use of foreign language under certain circumstances, 
but does not mention the use of graphics, pictures, or symbols to 
communicate information. Under the current regulation, graphics, 
pictures, or symbols in labeling that represent required information 
must be accompanied by explanatory English text adjacent to the symbol 
in order to ``appear thereon in the English language.''
    Under Sec.  801.119, labeling for in vitro diagnostic (IVD) devices 
has adequate directions for use if it meets the requirements of Sec.  
809.10 (21 CFR 809.10), which prescribes the statements, declarations, 
and other information that IVD devices must display on their labeling. 
Although Sec.  809.10 does not explicitly authorize the use of symbols, 
the Agency has interpreted this regulation generally to allow graphics, 
pictures, or symbols to meet the labeling requirements of this 
regulation except where this regulation specifies particular labeling 
language.
    The FD&C Act also applies to biological products defined in section 
351(i)(1) of the Public Health Service Act (PHS Act) (42 U.S.C 
262(i).\2\ See, specifically, PHS Act section 351(j) (42 U.S.C. 
262(j)). Accordingly, biological products that are also medical devices 
are subject to the labeling requirements of section 502 of the FD&C Act 
(applicable to any ``word, statement or other information required by 
or under authority of [the FD&C] Act to appear on the label or 
labeling'' of a medical device), as well as the regulations of part 
801, including Sec.  801.15. The part 660 (21 CFR part 660) labeling 
regulations applicable to certain biologic diagnostic substances for 
laboratory tests refer to the labeling requirements of Sec.  809.10. 
See Sec. Sec.  660.2 (for Antibody to Hepatitis B surface Antigen), 
660.28 (for Blood Grouping Reagent), 660.35 (for Reagent Red Blood 
Cells), Sec.  660.45 (for Hepatitis B Surface Antigen), and 660.55 (for 
Anti-Human Globulin).
---------------------------------------------------------------------------

    \2\ ``The term `biological product' means a virus, therapeutic 
serum, toxin, antitoxin, vaccine, blood, blood component or 
derivative, allergenic product, protein (except any chemically 
synthesized polypeptide), or analogous product, or arsphenamine or 
derivative of arsphenamine (or any other trivalent organic arsenic 
compound), applicable to the prevention, treatment, or cure of a 
disease or condition of human beings.'' (42 U.S.C 262(i))
---------------------------------------------------------------------------

    The Food and Drug Administration Modernization Act (FDAMA) added 
section 514(c) to the FD&C Act (21 U.S.C. 360d(c)). This provision 
authorizes FDA to ``recognize all or part of an appropriate standard 
established by a nationally or internationally recognized standard 
development organization,'' for which a person may then submit a 
declaration of conformity in order to meet a premarket submission or 
other requirement under the FD&C Act when the standard applies to and 
satisfies the requirement, including a labeling requirement. Section 
514(c)(2) of the FD&C Act also authorizes 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. Congress noted with 
approval the past work of SDOs, such as the American National Standards 
Institute (ANSI), the International Organization for Standardization 
(ISO), and the International Electrotechnical Commission in the field 
of medical device products from ``[l]ong before the enactment of the 
Medical Device Amendments of 1976'' (S. Rep. No. 43, 105th Cong., 1st 
Sess. 23 (1997)).
    Section 514(c) of the FD&C Act requires FDA to publish in the 
Federal Register the names of all standards to which recognition has 
been given. See the Center for Devices and Radiological Health's 
(CDRH's) public database at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm for the most recent FDA listing of 
recognized consensus standards. In ``Guidance for Industry and FDA 
Staff: CDRH Standard Operating Procedures for the Identification and 
Evaluation of Candidate Consensus Standards for Recognition,'' FDA set 
forth its procedures for recognition of consensus standards. This 
guidance is available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm077322.pdf. Further 
information about the recognition of consensus standards can be found 
in FDA's ``Guidance for Industry and FDA Staff: Frequently Asked 
Questions on Recognition of Consensus Standards,'' available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm075064.pdf. FDA published the initial list of 
recognized consensus standards in the Federal Register of February 25, 
1998 (63 FR 9561).
    Modifications to the initial and previous lists of recognized 
standards--announcing the addition, withdrawal, and revision of such 
standards--are published in the Federal Register. Changes in a 
recognized standard, including changes to a standardized symbol 
recognized in such standard, do not retroactively affect a product's 
clearance or approval status. The most recent modifications to the list 
of recognized standards, including a complete list of the 29 previous 
modifications, was published in the Federal Register on January 15, 
2013 (78 FR 2998). In addition, the Agency maintains hypertext markup 
language and portable document format (PDF) versions of the list of 
``FDA Recognized Consensus Standards.'' Both versions are publicly 
accessible at the Agency's Internet site at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.

[[Page 23510]]

Interested persons should review the supplementary information sheet 
(SIS) published for the standard to understand fully the extent to 
which FDA recognizes the standard.
    While section 503(b)(4) of the FD&C Act (21 U.S.C. 353(b)(4)) 
allows the labels of prescription drug products to contain the symbol 
statement ``Rx only,'' this provision is not applicable to prescription 
devices. In order to give manufacturers, repackers, relabelers, and 
distributors more labeling options for prescription devices, CDRH 
issued the guidance, ``Alternative to Certain Prescription Device 
Labeling Requirements'' on January 21, 2000, which is available at 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085404.htm. It announced CDRH's intent to exercise 
enforcement discretion with respect to the use of the symbol statement 
``Rx only'' on prescription medical device labeling as an alternative 
to the prescription use statement in Sec.  801.109.

II. Proposed Revision to Parts 660, 801, and 809

    FDA is proposing to revise parts 660, 801, and 809 to expressly 
allow for the use in medical device labeling of certain ``stand-alone'' 
symbols (not accompanied by explanatory text adjacent to the symbol) 
contained in a standard that FDA recognizes under its authority under 
section 514(c) of the FD&C Act, as long as a ``symbols glossary'' 
contemporaneously accompanies the device. The term ``symbols glossary'' 
means a compiled listing of each symbol used in the labeling of the 
device and of the meaning of or explanatory text for the symbol. As 
discussed previously, the current regulations do not mention the use of 
symbols. The medical device industry has requested permission to use 
stand-alone symbols in device labeling in order to make the label more 
user-friendly by replacing small, difficult-to-read text with pictorial 
information and to harmonize the labeling requirements of U.S. and 
foreign regulatory bodies.
    Various symbols with accompanying text have been used in health 
product labeling for several years, both on package labels and within 
other labeling documents, such as the instructions for use. The 
proposed rule will continue to allow the use of symbols, including 
standardized symbols, on device labeling when the symbols are 
accompanied by explanatory adjacent text. For IVD devices intended for 
health professional use, CDRH and the Center for Biologics Evaluation 
and Research have interpreted applicable labeling requirements to allow 
the use of certain symbols contained in a standard recognized by FDA in 
labeling without explanatory text adjacent to the symbol. See FDA 
guidance entitled ``Use of Symbols on Labels and in Labeling of In 
Vitro Diagnostic Devices Intended for Professional Use,'' issued 
November 30, 2004. Additionally, CDRH has exercised enforcement 
discretion with respect to the prescription use symbol statement ``Rx 
Only'' (without accompanying explanatory text). See FDA guidance 
entitled ``Alternative to Certain Prescription Device Labeling 
Requirements,'' issued January 21, 2000, available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm072747.htm.
    In the international community, voluntary standards such as ISO 
15223, originally published in 2000, have standardized, commonly-used 
symbols that are often used in U.S. device labeling with adjacent 
explanatory text, and in limited instances, without adjacent text for 
IVD devices.
    In Europe, the widespread use of symbols in medical device labeling 
is in response to the European Commission's 1993 Medical Device 
Directive, which states that any text present on a medical device label 
must be present in all languages so that it can be understood by end 
users in multiple countries. The Medical Device Directive 93/42/EEC 
states in Annex I: ``Where appropriate, this information should take 
the form of symbols. Any symbol or identification colour 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.'' Thus, manufacturers may produce medical 
device labels that include symbols without accompanying text for the 
European market. At present, that same label must be revised to either 
remove the symbol or add accompanying explanatory text, in English, to 
enter the U.S. market. This regulatory difference has created confusion 
and generated industry complaints that manufacturers have to develop 
different labels for each market.
    Under our proposed rule revising parts 660, 801, and 809, FDA seeks 
to harmonize U.S. regulatory requirements with those of the European 
Commission by allowing stand-alone standardized symbols recognized by 
FDA to be used in medical device labeling when a symbols glossary 
contemporaneously accompanies the medical device.
    Based on the process of recognizing consensus standards under 
section 514(c) of the FD&C Act and taking into consideration FDA's 
allowance of symbols on some medical devices for nearly a decade, FDA 
believes that certain symbols contained in national or international 
standards are ``likely to be read and understood by the ordinary 
individual under customary conditions of purchase and use'' (section 
502(c) of the FD&C Act). Thus, FDA is proposing to allow for the use of 
certain stand-alone symbols, contained in standards recognized by FDA, 
on device labeling (including labels) in the United States, so long as 
a symbols glossary contemporaneously accompanies the medical device. 
FDA's Web site will contain up-to-date information on which 
standardized symbols are recognized by FDA. One example of an 
international symbols standard is the Association for the Advancement 
of Medical Instrumentation (AAMI)/ANSI/ISO 15223-1:2012, Medical 
Devices--Symbols to be Used With Medical Device Labels, Labeling and 
Information to be Supplied, Part 1, General Requirements. This standard 
is currently recognized in part by FDA as a standard containing medical 
device-specific symbols that may be used without accompanying text on 
labeling for IVD devices intended for use by health professionals.
    FDA is issuing this regulation to permit the use of stand-alone 
symbols in device labeling under certain circumstances. FDA intends to 
describe its policy for the appropriate use of symbols in device 
labeling in a separate guidance document and to identify the specific 
standardized symbols recognized and the scope of devices affected 
through its standards recognition process. Generally, FDA will consider 
recognizing symbols included in standards if the Agency determines that 
the device user, under customary conditions of purchase and use, will 
understand the meaning of the symbol and the message it was intended to 
convey. (See section 502(c) of the FD&C Act.). This understanding can 
be demonstrated by applying a validation process that complies with an 
appropriate symbol validation standard, such as AAMI/ANSI/ISO 15223-
2:2010 (Part 2), Symbol Development, Selection and Validation. Under 
this process, studies need to demonstrate end-user comprehension of the 
symbol in context and validation data may be submitted to the SDO for 
its review.
    On its own initiative and in response to requests received from the 
public, FDA expects to assess standardized symbols from time to time as 
part of its

[[Page 23511]]

consensus standards recognition process. FDA will consider recognizing 
symbols contained in standards developed by SDOs that follow a process 
where the standard development 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.
    Ordinarily, only standardized symbols that have undergone the SDO's 
written procedures for approval/issuance and validation will be 
recognized. FDA does not intend to recognize symbols that have not been 
validated through SDO procedures nor does FDA intend to recognize 
proprietary symbols. Under FDA's consensus standards recognition 
process, the SDO, not FDA, would review validation data supporting the 
use of each standardized symbol. On the SIS for each standard it 
recognizes, FDA will include a list of device types or categories 
affected by the recognition. This standards recognition process will 
not be changed by the proposed rule.
    It is important to note that any stand-alone symbol that conveys 
information that is required to appear on the labeling of a device 
would be subject to the requirements under the proposed amendment to 
Sec.  801.15(c)(1) that the symbol would have to be recognized by FDA, 
used within any parameters of such recognition, and be explained in a 
symbols glossary that contemporaneously accompanies the device. Under 
section 502(f)(1) of the FD&C Act, device labeling is required to 
provide adequate directions for use to the user of a device. See 
Sec. Sec.  801.5 and 801.109. Therefore, any stand-alone symbol on the 
labeling of a device that conveys directions for use would be subject 
to the symbols glossary requirements under the proposed amendment to 
Sec.  801.15(c)(1).
    FDA is proposing to revise Sec.  801.109(b)(1), as well as Sec.  
801.15(c)(1), to include language that affirmatively permits use of the 
symbol statement ``Rx only,'' without accompanying explanatory text, as 
an alternative to the prescription device label statement ``Caution: 
Federal law restricts this device to sale by or on the order of a 
(licensed healthcare practitioner).'' It is important to note that the 
word ``only'' needs to 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 [rx] symbol in 
the symbol statement ``Rx only'' or the symbol statement ``Rx only'' in 
its entirety may be printed in bold or in regular type.
    The proposed amendments to Sec. Sec.  801.15 and 809.10 would also 
cover biological products regulated as devices. This rule also proposes 
to amend the specific labeling requirements applicable to biological 
products in part 660 to allow for the labeling use of standardized 
symbols that FDA recognizes under its authority under section 514(c) of 
the FD&C Act, as long as there is a ``symbols glossary'' in the 
labeling that contemporaneously accompanies the product. We have also 
proposed changes in part 660 to describe more uniformly the labeling 
requirements applicable to licensed products subject to this part: 
diagnostic substances for laboratory tests.

III. Environmental Impact

    The Agency has 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.

IV. Legal Authority for the Proposed Rule

    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)(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. 
In addition, section 701(a) of the FD&C Act (21 U.S.C. 371(a)) 
authorizes the Agency to issue regulations for the efficient 
enforcement of the FD&C Act.
    A device is misbranded under section 502(a) of the FD&C Act if its 
labeling is false or misleading in any particular. Additionally, 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 prominently placed 
thereon with such conspicuousness (as compared with other words, 
statements, designs, or devices, in the labeling) and in such terms as 
to render it likely to be read and understood by the ordinary 
individual under customary conditions of purchase and use.'' 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 (21 U.S.C. 321(m)), 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.

V. Analysis of Impacts

    FDA has examined the impacts of the proposed 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 Agencies 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). The Agency believes that this proposed rule is not a 
significant regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this rule imposes no new burdens, the Agency 
proposes to certify that the final rule would not have a significant 
economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written

[[Page 23512]]

statement, which includes an assessment of anticipated costs and 
benefits, before proposing ``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 $139 
million, using the most current (2011) Implicit Price Deflator for the 
Gross Domestic Product. FDA does not expect this final rule to result 
in any 1-year expenditure that would meet or exceed this amount.
    Summary: The proposed rule would provide medical device 
manufacturers with the option to use certain stand-alone symbols 
contained in a standard recognized by FDA to communicate information to 
end users as an alternative way to use these standardized symbols on 
device labeling without explanatory adjacent text as long as the device 
is contemporaneously accompanied by an explanatory symbols glossary.
    Medical device manufacturers would only adopt the proposed rule if 
they expect a positive net benefit (estimated benefits minus estimated 
costs). Hence, the rule is expected to provide a non-negative net 
benefit to each adopting manufacturer. Choosing to adopt the rule would 
potentially reduce the costs associated with designing and re-designing 
the labels on medical devices that are currently sold in the United 
States and the European Union. The estimated annual benefits range from 
$8.1 million to $26.1 million at a 3 percent discount rate, and $7.9 
million to $25.6 million at a 7 percent discount rate. Adopting the 
rule would incur one-time administrative costs, which we estimate to 
range from $2.4 million to $9.5 million. Annualized over 20 years, the 
estimated net benefits associated with adopting the proposed rule range 
from $7.8 million to $25.5 million at a 3 percent discount rate, and 
$7.6 million to $24.6 million at a 7 percent discount rate. The costs 
and benefits accrue to the same entities, however, so any firm making 
the change to symbols would, on net, reduce costs.
    FDA also examined the economic implications of the proposed 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 approximately estimated the proposed rule's impact on 
small entities using the percent costs per Universal Products 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 to 48 percent. Because companies can choose to use 
symbols, the Agency concludes that this rule would not have a 
significant adverse impact on any small entities. Furthermore, our 
analysis suggests that companies could reap moderate cost savings via 
switching to using symbols. On average, companies who switch to using 
symbols could expect to receive an average annual cost savings ranging 
from $1,000 to $4,000 per UPC. As a result, it is possible that 
providing medical device manufacturers with the option to use symbols 
may encourage companies, including small entities, to either start 
exporting products or export more products
    The full discussion of the economic impacts (Ref. 1) is available 
in docket FDA-2013-N-0125 and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VI. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule, if finalized, would not contain policies that would 
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, the Agency tentatively concludes that the proposed 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.

VII. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by the OMB under the Paperwork Reduction Act of 
1995 (44 U.S.C. 3501-3520). A description of these provisions is given 
in the Description section of this document with an estimate of the 
annual third-party disclosure burden. 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.
    FDA invites comments on these topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Medical Devices: Use of Certain Symbols in Labeling--
Glossary to Support the Use of Symbols in Labeling.
    Description: FDA is proposing to revise medical device and 
biological product labeling regulations to explicitly allow for the use 
in medical device labeling of certain stand-alone symbols contained in 
a standard that FDA recognizes under its authority under section 514(c) 
of the FD&C Act.
    In particular, FDA will allow the inclusion of certain stand-alone 
graphical representations of information, or symbols, if the symbol has 
been established as part of a standard developed by a nationally or 
internationally recognized SDO and such standardized symbol is part of 
a standard recognized by FDA for use on the labeling of medical 
devices, provided that such symbol is explained in a symbols glossary 
that contemporaneously accompanies the medical device.
    As such the requirement to submit to FDA and disclose to third-
parties a symbols glossary, which means ``a compiled listing of (i) 
each symbol used in the labeling of the device, and (ii) the meaning of 
or explanatory text for the symbol,'' is subject to the PRA.
    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 of 
their devices.
    FDA estimates the burden of this collection of information as 
follows:

[[Page 23513]]



                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Annual
                              Activity                                  Number of      frequency per     Total annual      Hours per       Total hours
                                                                       respondents        response        responses         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--Third Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Annual
                              Activity                                  Number of      frequency per     Total annual      Hours per       Total hours
                                                                       respondents        response        responses         response
--------------------------------------------------------------------------------------------------------------------------------------------------------
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).
    In addition to the proposed third-party disclosure requirements 
referenced previously, this proposed 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 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, subpart B have been approved under 
OMB control number 0910-0231; the collections of information under 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.
    To ensure that comments on information collection are received, OMB 
recommends that written comments be faxed to the Office of Information 
and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-7285, 
or emailed to [email protected]. All comments should be 
identified with the title ``Use of Symbols in Labeling.''
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3407(d)), the Agency has submitted the information collection 
provisions of this proposed rule to OMB for review. These requirements 
will not be effective until FDA obtains OMB approval. FDA will publish 
a notice concerning OMB approval of these requirements in the Federal 
Register.

VIII. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

IX. Proposed Effective Date

    FDA is proposing that any final rule based on this proposal become 
effective 90 days after the date of its publication in the Federal 
Register or at a later date if stated in the final rule.

X. Reference

    The following reference has been placed on display in the Division 
of Dockets Management (see ADDRESSES) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday, and is 
available electronically at http://www.regulations.gov.
    1. Use of Symbols in Medical Device Labeling: Preliminary 
Regulatory Impact Analysis; Initial Regulatory Flexibility Analysis; 
Unfunded Mandates Reform Act Analysis.

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, it is 
proposed that 21 CFR parts 660, 801, and 809 be amended as follows:

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

0
1. The authority citation for 21 CFR 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) introductory text to 
read as follows:


Sec.  660.2  General requirements.

* * * * *
    (c) Labeling. 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 information shall be included. The applicant may 
provide the labeling information referenced in this subsection in the 
form of a symbol, provided that such symbol is either accompanied by 
explanatory text adjacent to the symbol or is contained in a standard 
that FDA recognizes under its authority under section 514(c) of the 
Federal Food, Drug, and Cosmetic Act and is explained in a symbols 
glossary that contemporaneously accompanies the biological product. The 
term ``symbols glossary'' means a compiled listing of each symbol used 
in the labeling of the biological product and of the meaning of or 
explanatory text for the symbol.
* * * * *

[[Page 23514]]

0
3. Amend Sec.  660.28 by revising the introductory text to read as 
follows:


Sec.  660.28  Labeling.

    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. The applicant may provide the 
labeling information referenced in this section in the form of a 
symbol, provided that such symbol is either accompanied by explanatory 
text adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the biological product. The term 
``symbols glossary'' means a compiled listing of each symbol used in 
the labeling of the biological product and of the meaning of or 
explanatory text for the symbol.
* * * * *
0
4. Amend Sec.  660.35 by revising the introductory text to read as 
follows:


Sec.  660.35  Labeling.

    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. The applicant may provide the 
labeling information referenced in this section in the form of a 
symbol, provided that such symbol is either accompanied by explanatory 
text adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the biological product. The term 
``symbols glossary'' means a compiled listing of each symbol used in 
the labeling of the biological product and of the meaning of or 
explanatory text for the symbol.
* * * * *
0
5. Amend Sec.  660.45 by revising the introductory text to read as 
follows:


Sec.  660.45  Labeling.

    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 information shall be included. The applicant may provide the 
labeling information referenced in this section in the form of a 
symbol, provided that such symbol is either accompanied by explanatory 
text adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the biological product. The term 
``symbols glossary'' means a compiled listing of each symbol used in 
the labeling of the biological product and of the meaning of or 
explanatory text for the symbol.
* * * * *
0
6. Amend Sec.  660.55 by revising the introductory text to read as 
follows:


Sec.  660.55  Labeling.

    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, The applicant may provide the 
labeling information referenced in this section in the form of a 
symbol, provided that such symbol is either accompanied by explanatory 
text adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the biological product. The term 
``symbols glossary'' means a compiled listing of each symbol used in 
the labeling of the biological product and of the meaning of or 
explanatory text for the symbol.
* * * * *

PART 801--LABELING

0
7. The authority citation for 21 CFR part 801 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 360i, 360j, 371, 374.

0
8. Amend Sec.  801.15 by revising the section heading and paragraph 
(c)(1) to read as follows:


Sec.  801.15  Medical devices; prominence of required label statements; 
use of symbols in labeling.

* * * * *
    (c)(1) All words, statements, and other information required by or 
under authority of the Federal Food, Drug, and Cosmetic Act to appear 
on the label or labeling of a device shall appear thereon in one or 
more of the following formats:
    (i) The English language;
    (ii) 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 substituted for English;
    (iii) A symbol accompanied by adjacent explanatory English text, or 
text in the predominant language of the Territory, in the case of 
articles distributed solely in Puerto Rico or in a Territory where the 
predominant language is one other than English;
    (iv) A symbol not accompanied by adjacent explanatory text 
contained in a standard that FDA recognizes under its authority under 
section 514(c) of the Federal Food, Drug, and Cosmetic Act provided 
that such symbol is explained in a symbols glossary that 
contemporaneously accompanies the device. FDA may recognize a 
standardized symbol for all devices or only for certain types or 
categories of devices. The term ``symbols glossary'' means a compiled 
listing of each symbol used in the labeling of the device and of the 
meaning of or explanatory text for the symbol;
    (v) The symbol statement ``Rx only'' or ``[rx] only'' may be used 
as provided under Sec.  801.109(b)(1).
* * * * *
0
9. Amend Sec.  801.109 by revising paragraph (b)(1) to read as follows:


Sec.  801.109  Prescription devices.

* * * * *
    (b) * * *
    (1) The symbol statement ``Rx only'' or the statement ``Caution: 
Federal law restricts this device to sale by or on the order of a ----
--------'', the blank to be filled with the word ``physician'', 
``dentist'', ``veterinarian'', or with the descriptive designation of 
any other practitioner licensed by the law of the State in which he 
practices to use or order the use of the device; and
* * * * *

PART 809--IN VITRO DIAGNOSTIC PRODUCTS FOR HUMAN USE

0
10. The authority citation for 21 CFR part 809 continues to read as 
follows:

    Authority: 21 U.S.C. 331, 351, 352, 355, 360b, 360c, 360d, 360h, 
360i, 360j, 371, 372, 374, 381.

0
11. Amend Sec.  809.3 by adding paragraph (c) to read as follows:


Sec.  809.3  Definitions.

* * * * *
    (c) The term ``symbols glossary'' means a compiled listing of each 
symbol used in the labeling of the in vitro diagnostic product and of 
the meaning of or explanatory text for the symbol.
* * * * *
0
12. Amend Sec.  809.10 by revising the paragraph (a) introductory text, 
the first sentence in paragraph (b), and paragraphs (c)(2) introductory 
text, (d) introductory text, (e)(1) introductory text, and (f) 
introductory text to read as follows:

[[Page 23515]]

Sec.  809.10  Labeling for in vitro diagnostic products.

    (a) The label for an in vitro diagnostic product shall state the 
following information, except where such information is not applicable, 
or as otherwise specified in a standard for a particular product class, 
as provided in paragraph (e) of this section, or in the form of a 
symbol, provided that such symbol is either accompanied by explanatory 
text adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the in vitro diagnostic product. FDA 
may recognize a standardized symbol for all devices or only for certain 
types or categories of devices. Section 201(k) of the Federal Food, 
Drug, and Cosmetic Act provides that a requirement made by or under 
authority of this act that any word, statement, or other information 
appear on the label shall not be considered to be complied with unless 
a 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.
* * * * *
    (b) Labeling accompanying each product, e.g., a package insert, 
shall state in one place the following information in the format and 
order specified in this paragraph, except where such information is not 
applicable, or as specified in a standard for a particular product 
class, or where such information is provided in the form of a symbol, 
provided that such symbol is either accompanied by explanatory text 
adjacent to the symbol or is contained in a standard that FDA 
recognizes under its authority under section 514(c) of the Federal 
Food, Drug, and Cosmetic Act and is explained in a symbols glossary 
that contemporaneously accompanies the in vitro diagnostic product. * * 
*
* * * * *
    (c) * * *
    (2) In the case of a shipment or delivery for an investigation that 
is not subject to part 812 (see Sec.  812.2(c)), if the following 
conditions are met, including that, where information required by those 
conditions is provided in the form of a symbol, such symbol must either 
be accompanied by explanatory text adjacent to the symbol or contained 
in a standard that FDA recognizes under its authority under section 
514(c) of the Federal Food, Drug, and Cosmetic Act, and explained in a 
symbols glossary that contemporaneously accompanies the in vitro 
diagnostic product:
* * * * *
    (d) The labeling of general purpose laboratory reagents (e.g., 
hydrochloric acid) and equipment (e.g., test tubes and pipettes) whose 
uses are generally known by persons trained in their use need not bear 
the directions for use required by Sec.  809.10(a) and (b), if their 
labeling meets the requirements of this paragraph, except where such 
information is provided in the form of a symbol, provided that such 
symbol is either accompanied by explanatory text adjacent to the symbol 
or is contained in a standard that FDA recognizes under its authority 
under section 514(c) of the Federal Food, Drug, and Cosmetic Act and is 
explained in a symbols glossary that contemporaneously accompanies the 
reagent or equipment.
* * * * *
    (e)(1) The labeling for analyte specific reagents (e.g., monoclonal 
antibodies, deoxyribonucleic acid (DNA) probes, viral antigens, 
ligands) shall bear the following information, except where such 
information is provided in the form of a symbol, provided that such 
symbol is either accompanied by explanatory text adjacent to the symbol 
or is contained in a standard that FDA recognizes under its authority 
under section 514(c) of the Federal Food, Drug, and Cosmetic Act and is 
explained in a symbols glossary that contemporaneously accompanies the 
reagent:
* * * * *
    (f) The labeling for over-the-counter (OTC) test sample collection 
systems for drugs of abuse testing shall bear the following information 
in language appropriate for the intended users, except where such 
information is provided on labels in the form of a symbol, provided 
that such symbol is either accompanied by explanatory text adjacent to 
the symbol or is contained in a standard that FDA recognizes under its 
authority under section 514(c) of the Federal Food, Drug, and Cosmetic 
Act and is explained in a symbols glossary that contemporaneously 
accompanies the test sample collection system:
* * * * *

    Dated: April 15, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-09175 Filed 4-18-13; 8:45 am]
BILLING CODE 4160-01-P