[Federal Register: November 10, 2008 (Volume 73, Number 218)]
[Rules and Regulations]
[Page 66522-66539]
[DOCID:fr10no08-12]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. FDA-2004-N-0511] (formerly Docket No. 2004N-0556)
RIN 0910-AF21

Obstetrical and Gynecological Devices; Designation of Special
Controls for Male Condoms Made of Natural Rubber Latex

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the
classification regulation for condoms to designate a special control
for male condoms made of natural rubber latex (latex). The special
control for the device is the guidance document entitled ``Class II
Special Controls Guidance Document: Labeling for Natural Rubber Latex
Condoms Classified Under 21 CFR 884.5300.'' The FDA will publish a
notice in the Federal Register announcing the availability of the
special control guidance document no later than the effective date of
this final rule.

DATES: Effective Date: This rule is effective January 9, 2009.
    Compliance Dates: Premarket notification submissions (510(k)s) for
latex condoms filed on or after the effective date of this rule are
expected to comply with the requirement of special controls at the time
that the 510(k) is submitted. Latex condoms cleared for marketing on or
after the effective date of the rule but submitted in 510(k)s filed
before the effective date of the rule are expected to comply with the
requirement of special controls on or before March 10, 2009. Latex
condoms legally marketed before the effective date of this rule are
expected to comply with the requirement of special controls December
10, 2009. Specific information on how the rule will be implemented can
be found in section II.B of this document.

FOR FURTHER INFORMATION CONTACT: Colin M. Pollard, Center for Devices
and Radiological Health (HFZ-470), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20850,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Background
    A. Statutory Framework
    B. Regulatory History of Latex Condoms
    C. Overview of Proposed Rule
    D. Additional Scientific Information Developed After the Completion
of the Proposed Rule and Draft Special Control Guidance
    1. FDA Update of Epidemiology
    2. Latex Condom Label Comprehension Study
II. Summary of the Final Rule
    A. Overview of the Final Rule
    B. Implementation Strategy
    C. Issues Requiring Special Controls
    1. Unintended Pregnancy
    2. Transmission of Sexually Transmitted Infections (STIs)
    3. Incorrect or Inconsistent Use
III. Comments and FDA's Responses
    A. Identification Section of the Classification Regulation
    B. Establishment of a Guidance Document as a Special Control
    C. FDA's Review of Scientific Information
    1. General Comments
    2. Slippage and Breakage
    3. Risk Reduction
    4. Evaluation of Latex Condom Effectiveness
    D. Labeling Recommendations
    1. General
    2. Comprehension
    3. Pregnancy
    4. STIs
    5. Correct and Consistent Use
    6. Risk Reduction
    7. Directions for Use and Precautions
    8. Additional Information
    E. Comments in Response to FDA's Specific Requests
    1. Human Papillomavirus (HPV)
    2. Nonlatex Condoms Without Nonoxynol-9
    F. Implementation
IV. Environmental Impact
V. Analysis of Impacts
    A. Background
    B. Affected Entities and Scope of Effect
    C. Costs of Implementation
    D. Regulatory Flexibility Analysis
VI. Federalism
VII. Paperwork Reduction Act of 1995
VIII. References

I. Background

    In the Federal Register of November 14, 2005 (70 FR 69102), FDA
proposed to amend existing classification regulations to designate a
labeling guidance document as the special control for condoms made of
natural rubber latex (latex condoms), classified under 21 CFR 884.5300,
and latex condoms with spermicidal lubricant containing nonoxynol-9 (N-
9), classified under Sec.  884.5310 (21 CFR 884.5310). As proposed, the
final rule amends Sec.  884.5300 (21 CFR 884.5300) and designates a
guidance document containing labeling recommendations as the special
control for latex condoms. However, FDA continues to review the
comments it received in response to its general and specific requests
for comment on latex condoms with spermicidal lubricant and to evaluate
the controls appropriate for condoms with spermicidal lubricant (Sec.
884.5310). Therefore, FDA is not issuing a final rule on that device at
this time.\1\
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    \1\ On December 19, 2007, FDA published a final rule, codified
at 21 CFR 201.66(c)(5)(ii)(H) and 21 CFR 201.325, that requires that
labeling of OTC vaginal contraceptive/spermicidal drug products
containing N-9 bear the following warnings:
     For vaginal use only
     Not for rectal (anal) use
     Sexually transmitted diseases (STDs) alert: This
product does not protect against HIV/AIDS or other STDs and may
increase the risk of getting HIV from an infected partner
     Do not use if you or your sex partner has HIV/AIDS. If
you do not know if you or your sex partner is infected, choose
another form of birth control.
     When using this product you may get vaginal irritation
(burning, itching, or a rash)
     Stop use and ask a doctor if you or your partner get
burning, itching, a rash or other irritation of the vagina or penis
    Other information in the new labeling includes:
     When used correctly every time you have sex, latex
condoms greatly reduce, but do not eliminate the risk of catching or
spreading HIV, the virus that causes AIDS.
     Studies have raised safety concerns that products
containing the spermicide nonoxynol 9 can irritate the vagina and
rectum. Sometimes this irritation has no symptoms. This irritation
may increase the risk of getting HIV/AIDS from an infected partner.
     You can use nonoxynol 9 for birth control with or
without a diaphragm or condom if you have sex with only one partner
who is not infected with HIV and who has no other sexual partners or
HIV risk factors
     Use a latex condom without nonoxynol 9 if you or your
sex partner has HIV/AIDS, multiple sex partners, or other HIV risk
factors
     Ask a health professional if you have questions about
your best birth control and STD prevention methods.
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    In the following sections of this preamble, FDA addresses the
statutory framework, regulatory history, and scientific information
related to latex condoms; summarizes the final rule; and responds to
the comments on FDA's designation of special controls for the latex
condom.

A. Statutory Framework

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301
et seq.), as amended, including the Medical Device Amendments of 1976
(the 1976

amendments) (Public Law 94-295) and the Safe Medical Devices Act of
1990 (SMDA) (Public Law 101-629), established a comprehensive system
for the regulation of medical devices intended for human use. Section
513 of the act (21 U.S.C. 360c) established three categories (classes)
of devices, depending on the regulatory controls needed to provide
reasonable assurance of their safety and effectiveness. The three
categories of devices are class I (general controls), class II (special
controls), and class III (premarket approval).
    FDA refers to devices that were in commercial distribution before
May 28, 1976 (the date of enactment of the 1976 amendments), as
preamendments devices. Under section 513 of the act, FDA classifies
these devices after the agency takes the following steps: (1) receives
a recommendation from a device classification panel (an FDA advisory
committee); (2) publishes the panel's recommendation for comment, along
with a proposed regulation classifying the device; and (3) publishes a
final regulation classifying the device. FDA has classified most
preamendments devices under these procedures.
    FDA refers to devices that were not in commercial distribution
before May 28, 1976, as postamendments devices. Postamendments devices
are classified automatically by statute (section 513(f) of the act)
into class III without any FDA rulemaking process. These devices remain
in class III unless FDA does one of the following: (1) reclassifies the
device into class I or II; (2) issues an order classifying the device
into class I or II in accordance with section 513(f)(2) of the act; or
(3) issues an order finding the device to be substantially equivalent,
in accordance with section 513(i) of the act, to a legally marketed
device that has been classified into class I or class II or to a
preamendments device of a type that has yet to be initially classified
in accordance with section 513(b). The agency determines whether new
devices are substantially equivalent to predicate devices by means of
premarket notification procedures in section 510(k) of the act (21
U.S.C. 360(k)) and regulations at part 807 (21 CFR part 807).
    Under the 1976 amendments, class II devices were defined as devices
for which there was insufficient information to show that general
controls themselves would provide reasonable assurance of safety and
effectiveness, but for which there was sufficient information to
establish performance standards to provide such assurance. SMDA
broadened the definition of class II devices to mean those devices for
which the general controls by themselves are insufficient to provide
reasonable assurance of safety and effectiveness, but for which there
is sufficient information to establish special controls to provide such
assurance, including performance standards, postmarket surveillance,
patient registries, development and dissemination of guidelines,
recommendations, and any other appropriate actions the agency deems
necessary (section 513(a)(1)(B) of the act).

B. Regulatory History of Latex Condoms \2\
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    \2\ As discussed in the 2005 proposed rule (70 FR 69102 at
69112), the proposal was limited to latex condoms, which represent
the vast majority of condoms marketed in the United States. As
discussed in the proposal, FDA intends to address condoms made from
other materials (natural membrane (skin) or synthetic materials) at
a future date.
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    Prior to enactment of the 1976 amendments, latex condoms were
marketed in the United States for both contraception and prophylaxis,
i.e., reducing the risk of sexually transmitted infections (STIs).\3\
As a preamendments device, the latex condom was classified along with
hundreds of other devices during FDA's original classification
proceedings. Based primarily on the recommendations of experts on the
Obstetrics and Gynecology Device Classification Panel, FDA classified
latex condoms into class II by regulation published in the Federal
Register of February 26, 1980 (45 FR 12710). Condoms were identified as
``* * * a sheath which completely covers the penis with a closely
fitting membrane. The condom is used for contraceptive and for
prophylactic purposes (preventing transmission of venereal disease) * *
*'' (Sec.  884.5300). This classification regulation does not include
condoms with spermicidal lubricant, which are postamendments devices
classified under Sec.  884.5300.
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    \3\ With the exception of a reference to the 2005 proposed
replacement of ``venereal disease'' with ``sexually transmitted
disease,'' FDA is using ``sexually transmitted infection'' or
``STI'' instead of ``sexually transmitted disease'' or ``STD'' in
the final rule and special controls guidance document. This is
discussed in more detail at section III.
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    At the time that latex condoms were classified into class II, the
statutory definition of that class contemplated the establishment of
mandatory performance standards for all class II devices, in accordance
with section 514(b) of the act (21 U.S.C. 360d(b)). Because of the
complex process associated with issuing mandatory performance
standards, the agency did not establish a performance standard for
condoms or virtually any other class II device before the SMDA in 1990
provided additional options for special controls for class II devices.
This rulemaking will for the first time establish a special control for
latex condoms.
    Latex condoms are also subject to the requirement of premarket
notification, a general control requiring a determination of
substantial equivalence before they may be marketed, and other general
controls, including good manufacturing practices (quality system
regulation), registration and listing, adverse event reporting, and the
prohibitions on adulteration and misbranding. This device is also
subject to labeling requirements applicable to all devices, including a
statement of principal intended action(s) and adequate directions for
use as described in part 801 (21 CFR part 801).
    In addition to the general labeling requirements, latex condoms are
subject to specific labeling requirements addressing expiration dating
and latex sensitivity (21 CFR 801.435 and 801.437). FDA established
expiration dating requirements in response to shelf life studies
showing that important latex condom properties can change over time.
The expiration dating regulation addresses the risk of latex condom
deterioration due to product aging and helps ensure that consumers have
information regarding the safe use of latex condoms (62 FR 50501,
September 26, 1997). The latex sensitivity labeling requirements were
added in response to numerous reports of severe allergic reactions and
deaths related to a wide range of medical devices containing natural
rubber (62 FR 51021 at 51029, September 30, 1997).
    In addition to the history of action regarding latex condoms
undertaken under the act, on December 21, 2000, Congress enacted Public
Law 106-554, which required that FDA ``reexamine existing condom
labels'' and ``determine whether the labels are medically accurate
regarding the overall effectiveness or lack of effectiveness of condoms
in preventing sexually transmitted diseases, including [human
papillomavirus].'' In this review, FDA considered the following:
     Physical properties of condoms
     Condom slippage and breakage during actual use
     Plausibility for STI-risk reduction attributable to
condoms
     Evaluations of condom effectiveness against STIs by other
Federal agencies, and
     Clinical studies of condoms' protection against STIs
published in peer-reviewed journals.

    As a result of this review of scientific information and of
existing latex condom labeling, FDA concluded that existing latex
condom labeling was medically accurate in presenting the conclusion
that, as an overall matter, condoms are effective in reducing the risk
of STIs. To help consumers make appropriate choices for their
particular needs, and therefore to ensure the safe and effective use of
condoms, FDA proposed to establish a labeling special control to
address some additional, more nuanced information about condoms and
STIs, as well as to provide information about contraception, and about
appropriate directions and precautions for use of latex condoms. The
present rulemaking grew out of that initiative.

C. Overview of Proposed Rule

    In the Federal Register of November 14, 2005 (70 FR 69102), FDA
issued a proposed rule to amend the classification regulations for
condoms (Sec. Sec.  884.5300 and 884.5310). The proposed regulatory
changes were intended to help ensure that latex condoms were used
safely and effectively by providing labeling conveying a concise,
accurate message that neither exaggerated the degree of protection
provided by latex condoms, nor undervalued overall STI-risk reduction
provided by latex condom use.
    FDA proposed to amend the identification section of the regulations
to change the wording ``venereal disease'' to ``sexually transmitted
diseases.'' FDA also proposed to add classification sections to each of
the regulations, segregating the subset of condoms in each
classification that were made of latex. Finally, FDA proposed to
designate as a special control a guidance document with labeling
recommendations for latex condoms, because the agency believed that
this control, together with general controls, could reasonably assure
the safety and effectiveness of these devices. The draft special
controls guidance recommended labeling to inform consumers about the
extent of protection provided by latex condoms against unintended
pregnancy and against STIs, including labeling that informed consumers
that STIs can be transmitted in various ways, including transmission to
or from the penis and transmission by other types of sexual contact.
The draft guidance recommended that labeling explain that latex condoms
can reduce the risk of STIs, such as gonorrhea and chlamydia, that are
spread to or from the penis by direct contact with the vagina and
genital fluids. It further recommended labeling that indicated that
some STIs, such as genital herpes and human papillomavirus (HPV), may
also be transmitted by contact with infectious skin or mucosa not
covered by the latex condom, and that latex condoms provide less
protection against these STIs.
    FDA proposed to establish the labeling guidance as a special
control, by rulemaking, because it meant that manufacturers would be
required to address the issues identified in the guidance. Unlike a
regular guidance, which imposes no requirements, where a guidance
document has been designated as a special control by a rule,
manufacturers must address the issues identified in the guidance,
either by following the recommendations in the guidance or by some
other means that provides equivalent assurances of safety and
effectiveness. At the same time, establishing a guidance document as a
special control affords greater flexibility than a rule mandating
specific labeling language and can facilitate updating labeling as new
scientific information becomes available because the special control
permits manufacturers to use any labeling that affords equivalent
assurances of safety and effectiveness for latex condoms.
    In response to FDA's requests for comment, more than one hundred
commenters submitted information and comments to the two dockets (one
docket for the proposed rule and one docket for the draft special
controls guidance document). Comments were submitted by consumers,
health professionals, industry, academia, state and Federal government
agencies, as well as professional societies and organizations. The
comments included different points of interest and concern. Many
comments discussed issues involving latex condoms with spermicidal
lubricant containing nonoxynol-9, and as discussed earlier, FDA
continues to review those comments. In some cases, commenters filed
comments to the dockets for both the rule and for the guidance; in
other cases, comments were filed in only one docket. Because of the
intertwined nature of the proposed rule and guidance and because of the
significant overlap in comments, FDA considered all comments in
preparing both the final rule and the intended final special control
guidance document.\4\
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    \4\ The term ``intended final special control guidance
document'' refers to the version of the guidance that is currently
available for reference only at http://www.fda.gov/cdrh/comp/
guidance/1548ref.html, pending approval under the Paperwork
Reduction Act (the PRA). (See Section VII.)
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D. Additional Scientific Information Developed After the Completion of
the Proposed Rule and Draft Special Control Guidance

1. FDA Update of Epidemiology
    In developing the 2005 proposed rule and draft guidance, to assess
the overall effectiveness of latex condoms in preventing transmission
of STIs, FDA evaluated a variety of scientific evidence and information
about condoms and STIs. In particular, FDA considered the physical
properties of a condom, which make it capable of acting as a barrier to
the pathogens that cause STIs; evidence regarding condom slippage and
breakage during actual use; plausibility for STI-risk reduction
attributable to condoms, which draws on information about the different
routes of transmission of different STIs; and evidence from good
quality epidemiological studies published in peer-reviewed journals
evaluating condoms and STI-risk reduction, including evaluations of
condom effectiveness against STIs by other Federal agencies.
    FDA's evaluation divided common STIs into two groups in relation to
their usual routes of sexual transmission. FDA identified as Group I
those STIs that are sexually transmitted solely either to or from the
head of the penis, an area that is covered when a latex condom is used.
Group I STIs include HIV/Acquired Immune Deficiency Syndrome (AIDS),
gonorrhea, chlamydia, trichomoniasis,\5\ and hepatitis B virus (HBV).
FDA identified as Group II those STIs that can be transmitted not only
through contact with the head of the penis, but also through contact
with infected skin outside the area that is covered when a latex condom
is used. Group II STIs include HPV, herpes simplex virus (HSV),
syphilis, and chancroid. Considering the means of transmission of STIs
and the extensive information on the physical characteristics and
performance of condoms, as well as the specific clinical data
available, FDA concluded that there was strong support for the
conclusion that latex condoms reduce the overall risk of transmission

of STIs. FDA also concluded that the degree of risk reduction for
different types of STIs varies with their routes of transmission.
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    \5\ FDA's 2005 proposed rule identified trichomoniasis as a
group I STI based on its route of transmission but did not consider
any significant new information regarding trichomoniasis because
none existed at that time. Neither the prior labeling
recommendations nor the draft special control guidance recommended
making specific claims for condom effectiveness against
trichomoniasis. In formulating this final rule and special control
guidance document, FDA also has found no new information about
condom effectiveness against this specific pathogen, and does not
include specific recommendations for labeling to address it.
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    As discussed in section III.C, FDA's scientific conclusions were
generally supported by the public comments. In preparing this final
rule, moreover, FDA ensured that its scientific basis remains sound.
Using the same approach as in 2005, analyzing systematic reviews\6\
and, when those were not available, analyzing individual clinical
studies for STIs, FDA reviewed more recent epidemiological studies and
analyses published in peer-reviewed publications from December 2004,
the cut-off date for studies considered in developing the proposed
rule, through April 30, 2008. Consistent with its findings in 2005, FDA
confirmed that latex condoms provide effective protection against all
STIs evaluated. FDA findings from its updated review are described in
more detail next.
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    \6\ As stated in the proposed rule (70 FR 69102 at 69107), a
systematic review means a review of a clearly formulated question
that uses systematic and explicit methods to identify, select, and
critically appraise relevant research and to collect and analyze
data from studies that are included with the review.
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Group I STIs

    In the 2005 proposal, FDA concluded that latex condoms, when used
correctly and consistently, are effective in reducing the risk of
transmission of Group I STIs (70 FR 69102 at 69108). No new data
undermine this conclusion and some new studies of particular Group I
STIs provide additional support for it. Therefore, FDA's conclusion
related to the Group I STIs continues to be that latex condoms when
used correctly and consistently are effective in reducing the risk of
transmission of group I STIs.

HIV

    Well-designed studies evaluated prior to the proposed rule show the
effect of consistent condom use on reducing the risk of HIV infection
(70 FR 69102 at 69107 to 69108). One well-designed study conducted a
meta-analysis (where results of all studies selected are pooled and
analyzed) of studies of HIV-discordant subjects (where HIV status is
known at the outset of the study, and an uninfected partner has sex
with an infected partner) and found that condoms were 90 to 95 percent
effective in reducing the incidence of new infections when used
consistently. Another study was a systematic review of longitudinal
studies and found that consistent use of condoms results in at least an
80 percent reduction in HIV incidence.
    No new systematic reviews of condom effectiveness in reducing the
risk of HIV infection have been published since the cut-off for studies
considered in formulating FDA's proposed rule. On the basis described
in the proposed rule, FDA's conclusion remains that consistent and
correct use of latex condoms is highly effective in reducing the risk
of HIV infection.

Gonorrhea and Chlamydia

    Consistent with the FDA conclusions presented in 2005 (70 FR 69102
at 69108), one systematic review presented in 2006 demonstrated that
consistent and correct use of condoms reduces risk of both gonorrhea
and chlamydia in men and women (Ref. 9).

Hepatitis B Virus (HBV)

    As was the case when FDA published its proposed rule, FDA is aware
of no systematic reviews of condom effectiveness against HBV infection.
Nor were any new epidemiological studies of condom use and HBV
infection published during the period of FDA's review for preparation
of this final rule. As discussed in the 2005 proposal (70 FR 69102 at
69108), one cross-sectional study showed that correct and consistent
condom use was significantly associated with lower prevalence of HBV.

Group II STIs

    In the 2005 proposal, FDA concluded that latex condoms, when used
correctly and consistently, are effective in reducing the risk of
transmission of group II STIs. Studies published since December 2004
support, and in the case of HPV, provide additional evidence for, this
conclusion, as discussed below.

HPV

    No new systematic reviews of condoms and HPV infection have been
published since December 2004. At the time of the 2005 proposed rule,
the clinical data regarding the effect of condom use on reducing the
risk of infection with HPV was limited, but two systematic reviews
supported the conclusion that correct and consistent use of latex
condoms can reduce the rates of genital warts and cervical cancer, the
main diseases associated with HPV infection (70 FR 69102 at 69108).
    Since December 2004, several individual studies have addressed
condom use and HPV infection, not only the incidence of HPV-related
disease. Of particular note, a longitudinal study of the association of
condom use and risk of genital HPV infection found that women who
reported consistent condom use for the eight months prior to HPV
testing were less likely to acquire a first-time infection of HPV and
that women who reported 100 percent condom use in the prior eight
months had no cervical squamous intraepithelial lesions detected on
their Pap tests (Ref. 10) (hereinafter referred to as ``2006 Winer et
al. study''). Another study published since the cut-off for the 2005
proposed rule found a higher prevalence of HPV in women who did not use
condoms (Ref. 4). Yet another study published since the 2005 proposed
rule demonstrated an association between prolonged HPV infection and
less consistent condom use (Ref. 7). These newer studies now support
the conclusion that condom use not only reduces the risk of genital
warts and cervical cancer, it also reduces the risk of HPV infection
itself.

Genital Herpes Simplex Virus (HSV)

    No new systematic reviews of condoms and HSV infection have been
published since December 2004. FDA's 2005 conclusions about latex
condom effectiveness were based on the 2002 systematic review showing
that condom use reduced the risk of HSV-2 infection for women (70 FR
69102 at 69108). A more recent prospective study showed effectiveness
of condom use in reducing the risk of HSV infection in men and
replicated effectiveness in women (Ref. 8), supporting the findings of
the 2002 systematic review and FDA's 2005 conclusions.

Syphilis

    As was the case when FDA published its proposed rule, FDA is not
aware of any systematic reviews of condom effectiveness against
syphilis infection. FDA's 2005 conclusions about latex condom
effectiveness were based primarily on the data from two prospective
studies, discussed in the preamble to the proposed rule (70 FR 69102 at
69108), that showed condom use provided significant protection against
syphilis. More recently, one study evaluated risks of STIs, including
syphilis, in female sex workers and found that failure to use a condom
was associated with an increased risk of syphilis (Ref. 6). This
information continues to support the conclusion made in the 2005
proposal that correct and consistent latex condom use reduces the risk
of syphilis.

Chancroid

    Chancroid infection is extremely rare in the United States. In
2006, only 33

new cases were reported in the United States. (Ref. 1). As in 2005,
when FDA published its proposed rule, FDA knows of no systematic review
of condom effectiveness against this STI. No new epidemiological
studies of condom use and chancroid infection have been identified.
Therefore, FDA's conclusions about latex condom effectiveness toward
chancroid remain based on the study discussed in the 2005 proposal that
reported that condom use was associated with a significantly reduced
risk of genital ulcer disease (presumed to be chancroid) among
prostitutes in Kenya (70 FR 69102 at 69108).
    In summary, FDA believes that conclusions from the additional
studies published in peer-reviewed publications from December 2004
through April 30, 2008, are consistent with FDA's 2005 conclusions
about latex condom effectiveness. Newer evidence, such as the
systematic review of the effect of condom use on transmission of
gonorrhea and chlamydia infections (Ref. 9) and the recent
epidemiological studies showing that condom use reduced HPV infection
(Refs. 7 and 10), replicate or strengthen the basis for these
conclusions.
2. Latex Condom Label Comprehension Study
    As described in more detail below, many commenters expressed
concern that FDA's proposed language for latex condom labeling was
confusing, especially in its efforts to describe two tiers of
protection afforded by condoms against STIs. These comments expressed
serious concerns that FDA's latex condom labeling proposal was overly
complex and would ultimately be misunderstood by the consumer. Many
argued that this same confusion and misunderstanding would lead to
unmerited negative impressions of latex condoms and--ultimately--to an
unfounded decrease in latex condom use. One commenter also submitted a
study it had conducted of consumer comprehension of the labeling
proposed in the draft guidance, the results of which supported the
comments that this labeling was not well understood. (This comment and
study are discussed in section III of this document, where FDA
discusses and responds to comments in detail.)
    In light of these important comments on the labeling
recommendations it had proposed, to inform its final rulemaking, FDA
conducted a study to see whether typical consumers understand latex
condom labeling, testing both the current labeling and the labeling
proposed in the 2005 draft guidance document.

FDA Study Objectives

    FDA contracted for a latex condom label comprehension study.
Conducted in November and December 2007, the study was designed to
measure and compare consumer understanding of the labeling recommended
for latex condoms under FDA's 1998 guidance document, ``Latex Condoms
for Men, Information for 510(k) Premarket Notifications: Use of
Consensus Standards for Abbreviated Submissions,'' which is found on
currently marketed latex condoms, and the latex condom labeling
proposed in the 2005 draft special controls guidance. The study
specifically focused on FDA's proposal to include more detailed
information in the labeling about the relative degree of protection
that condoms provide against different STIs.\7\
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    \7\ The study also focused on the new warnings proposed for
condoms with nonoxynol-9 (N-9) in the lubricant; as described in the
introductory paragraph of section I of this preamble, FDA's proposal
to designate a labeling guidance as a special control for those
devices remains open, as FDA is still considering the comments and
other data, including these study results, that are relevant to that
proposal.
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Study Design

    Participants were recruited from six shopping malls, four retail
pharmacies, and three literacy centers in 11 communities throughout the
United States. Eight hundred and forty-four (844) participants between
the ages of 18 and 54 were divided almost evenly to review either the
current or proposed latex condom labeling. Each participant was asked
to respond to a set of questions intended to measure his or her
understanding of the labeling. When responding to the questions,
participants were allowed to look at the labeling provided.
    Quotas were established to attain an equal distribution by sex and
pre-specified proportions of respondents by age and reading ability.
The Rapid Estimate of Adult Literacy in Medicine (REALM) test (Ref. 3)
was used to assess reading level, and a threshold score was chosen,
which divided the group into normal-literacy (ninth grade reading level
and above) and low-literacy (eighth grade reading level and below). Of
the 844 subjects, 430 were classified as normal-literate, 405 as low-
literate, and nine had no REALM score.

FDA Study Results

    Poorer readers and those with less education (two variables not
highly correlated) had lower comprehension scores than those with a
higher reading level. However, there were no differences based on age,
race, ethnicity, income, or the type of neighborhoods where the
respondents resided.
    Participants understood the basic message in both the current and
proposed labeling that latex condoms help protect against transmission
of sexually transmitted infections (>80 percent correct responses).
When comparing equivalent questions between the current and proposed
latex condom labeling, for every comparison with a significant
difference in rates of comprehension, the difference favored the
current latex condom labeling over the proposed latex condom labeling.
Study participants did not understand the more complex messages about
the relative degree of protection provided by condoms against different
STIs (<30 percent correct responses).
    The study was not designed to determine the reasons for the
differences in consumer comprehension of the two labeling versions.
However, FDA's proposed labeling was unarguably lengthier, with
considerably more information than current labeling. Study analysis
suggests that shorter and simpler labeling will more likely result in
better consumer comprehension.

II. Summary of the Final Rule

A. Overview of the Final Rule

    In developing this final rule, FDA considered all of the comments,
as well as its updated review of scientific evidence and results of the
latex condom label comprehension study. FDA concludes that the
scientific evidence today continues to fully support the overall
effectiveness of latex condoms in reducing the risk of transmission of
common STIs. That evidence supports the conclusions that correct and
consistent use of latex condoms reduces the risk of transmission of
HIV/AIDS and other STIs such as gonorrhea that are sexually transmitted
solely by contact with the head of the penis (via genital fluids).
Also, the evidence available today provides even more support than was
available at the time of publication of the proposed rule for the
conclusion that latex condoms are effective in reducing the risk of
transmission of other STIs, such as genital herpes and HPV, that can be
transmitted not only by contact with the head of the penis, the area
covered by a latex condom, but also by contact with infected skin
outside the area covered by the latex condom.
    In developing the final rule and intended final special control
guidance document, FDA not only affirmed the underlying scientific
conclusions, but

also considered whether the labeling statements recommended in the
draft special control guidance document, in particular the statements
addressing the effectiveness of latex condoms against the two groups of
STIs, were adequately clear. Based on comments that criticized the
labeling contained in the draft guidance as, among other things,
``misleading,'' ``overly complex,'' ``difficult to understand,'' and
``negative possibly discouraging use,'' as discussed in section I, FDA
sponsored a latex condom label comprehension study. This study
supported commenters who maintained that the labeling contained in the
draft guidance was too confusing for consumers, and did not effectively
and adequately communicate the effectiveness of latex condoms against
these two groups of STIs.
    Taking account of the comments and other information described in
this preamble, FDA's final rule and intended final special control
guidance remain consistent with the proposal but incorporate some
changes. The final rule, like the proposal, amends the identification
section of Sec.  884.5300 to change the terminology used. As proposed,
the final rule also creates new classification sections distinguishing
condoms made of natural rubber latex from condoms made of other
materials, including natural membrane and synthetic materials. Finally,
as proposed, the final rule designates a guidance document containing
labeling recommendations as the special control for the subset of
condoms made of natural rubber latex, to address issues of safety and
effectiveness discussed below and to convey the basic scientific
conclusions already described. In response to comments and in
consideration of the other information described previously, FDA has
simplified the labeling recommended for latex condoms, including the
labeling statements regarding the degree of protection afforded by
latex condoms against the two groups of STIs. FDA has also updated the
recommended directions for use and precautions to help ensure
consistent and correct use of latex condoms. Finally, FDA has assigned
a new title to the final guidance document designated as a special
control by this rule in order to avoid confusion with the draft
guidance made available in November 2005, which remains available as
the proposed special control for latex condoms with spermicidal
lubricant in association with the pending proposal to amend Sec.
884.5310. (See Section I.)

B. Implementation Strategy

    FDA intends to implement this final rule as described in the
following paragraphs. The general approach remains consistent with what
was set forth in the 2005 proposed rule, but certain time frames have
been extended. Specifically, this final rule will be effective 60 days
after its date of publication, rather than the 30 days anticipated in
the proposed rule. The implementation strategy takes account of the
changed effective date of the final rule, while remaining generally
consistent with the implementation strategy outlined in the proposed
rule.
    The proposed rule anticipated that latex condoms legally marketed
prior to the effective date of a final rule would have 11 months after
the effective date, or a total of 12 months from publication of the
final rule, to meet the requirements of special controls. That proposed
rule also anticipated that latex condoms that were the subject of
pending 510(k) applications on the effective date of any final rule but
cleared subsequently would be expected to comply with the requirement
of special controls for latex condoms no more than 60 days after the
effective date of the final rule.
    For the final rule, FDA intends the following implementation
strategy. Latex condoms that are the subject of premarket notification
submissions (510(k)s) filed on or after the effective date of this rule
are expected to comply with the requirement of special controls
immediately upon the rule taking effect. Therefore, a firm submitting a
510(k) for a latex condom on or after the effective date of this rule
must show that its device meets the recommendations of the special
control guidance (as made available after PRA approval) or in some
other way provides equivalent assurances of safety and effectiveness.
    Latex condoms that are the subject of a 510(k) that is pending on
the effective date of this final rule but are subsequently cleared are
expected to comply with the requirement of special controls by
following the recommendations in the special control guidance (as made
available after PRA approval) or providing equivalent assurances of
safety and effectiveness on or before 120 days after the date of
publication of this final rule.
    Latex condoms that were legally marketed prior to the effective
date of this final rule are expected to comply with the requirement of
special controls by following the recommendations in the special
control guidance (as made available after PRA approval) or providing
equivalent assurances of safety and effectiveness no more than 13
months after the date of publication of this final rule. As in the
proposal, this gives firms marketing these latex condoms 11 months from
the effective date of the final rule to achieve compliance, and a total
period of 13 months from the date of publication of the final rule,
rather than the 12 months from publication defined under the proposal.
FDA believes that this period will allow for the production of new
labeling to meet the requirement of special controls without leading to
product shortages, while promoting the regulatory purpose of ensuring
that this new labeling is available to consumers in a timely fashion.

C. Issues Requiring Special Controls

    In the 2005 proposed rule, FDA identified several issues associated
with the use of latex condoms that required special controls to help
provide a reasonable assurance of safety and effectiveness. The issues
included the risks of unintended pregnancy and of STI transmission, and
the issue of incorrect or inconsistent use, which undermines the
effectiveness of the latex condom in protecting against unintended
pregnancy and STI transmission.
    In the final rule, FDA is designating a guidance document with
labeling recommendations as the required special control for latex
condoms to address the issues of safety and effectiveness associated
with these devices--the risks of unintended pregnancy and of STIs, and
the issue of incorrect or inconsistent use.
1. Unintended Pregnancy
    One of the principal intended actions of latex condoms is
contraception. Latex condoms can greatly reduce the risk of unintended
pregnancy, but cannot eliminate it. The special controls guidance
recommends that the labeling indicate that latex condoms are intended
to prevent pregnancy. Labeling should also indicate that latex condoms
do not completely eliminate the risk of pregnancy. The guidance also
recommends that the package insert contain contraceptive effectiveness
information comparing pregnancy rates for latex condoms to rates for
other contraceptive options available in the United States including
drugs, devices, and methods of permanent sterilization, as well as a
statement that consumers who have questions about contraceptive
options, particularly because of health reasons for avoiding pregnancy,
should contact a health care provider.

2. Transmission of Sexually Transmitted Infections (STIs)
    The other principal intended action of latex condoms is protection
against the transmission of STIs. The intended final special controls
guidance recommends that labeling state that latex condoms are intended
to prevent HIV infection (AIDS) and other STIs. In addition, the
labeling should include a statement that condoms do not completely
eliminate the risk of STIs. Labeling should indicate that latex condoms
reduce the risk of STIs by providing a barrier against the source of
infection. Labeling should indicate that latex condoms are most
effective at reducing transmission of STIs such as HIV infection (AIDS)
and gonorrhea that are spread by contact with the head of the penis, an
area covered when the condom is used. Labeling should also indicate
that condoms are less effective against STIs such as HPV and herpes
that can also be spread by contact with infected skin that is not
covered by the latex condom.
    The intended final guidance also recommends labeling that indicates
that a health care provider should be contacted if a consumer believes
they may have an STI. The intended final special controls guidance
further recommends that labeling indicate that for more information on
latex condoms or STIs, a health care provider or public health agency
should be contacted.
3. Incorrect or Inconsistent Use
    In order to get the most protection from a latex condom, latex
condoms must be used correctly every time a consumer has sex. To
promote correct use, the intended final special controls guidance
recommends that labeling include directions for use and precautions
against incorrect use. To promote consistent use, the intended final
special controls guidance recommends that labeling state that to get
the most protection from a latex condom, a condom be used correctly
every time the consumer has sex.

III. Comments and FDA's Responses

    More than 100 commenters submitted information and comments to the
two dockets for the proposed rule and draft special controls guidance
document. The commenters included consumers, health professionals,
industry, academia, State and Federal agencies, professional societies,
and organizations. Because of the intertwined nature of the documents
and the significant duplication of comments between the dockets for the
proposed rule and draft special controls guidance document, FDA is
summarizing and responding to the comments to both dockets in this
preamble.
    In general, the comments stated that FDA had properly described the
science regarding latex condom effectiveness, on which FDA based its
proposed special control labeling recommendations. None of the comments
questioned the importance of accurate latex condom labels. Many
comments indicated that consumers deserve to understand how and why
condoms work. However, as previously noted, a substantial number of
comments stated that the specific labeling recommendations in the draft
guidance document were too complex to be effective in conveying this
important information to consumers, and could inadvertently lead to
misimpression regarding the safety and effectiveness of condoms,
particularly for use in reducing the risk of STIs.
    In issuing the final rule designating the revised guidance document
as a special control, FDA is affirming the safety and effectiveness of
condoms for contraception, as well as for reducing the risk of
transmission of STIs, including those most common in the United States.
In response to comments, and in light of the consumer comprehension
studies provided in those comments and described previously, FDA has
revised the recommended labeling messages contained in the intended
final special control guidance document to simplify them and better
communicate the essential information they contain. Following is a
summary of the specific comments and the agency's responses.

A. Identification Section of the Classification Regulation

    (Comment 1) One comment stated that FDA should substitute
``sexually transmitted infections'' wherever it was using ``sexually
transmitted diseases.'' This comment pointed out that the purpose of
the latex condom is to prevent the infection; the diseases are the
clinical sequellae of the infection.
    (Response) FDA agrees with this comment, and notes that the term
``sexually transmitted infection'' has gained currency in the clinical
community. Accordingly, FDA have revised the language in Sec.  884.5300
and the labeling recommendations in the special controls guidance
document to use ``sexually transmitted infection'' or ``STI.''

B. Establishment of a Guidance Document as a Special Control

    (Comment 2) One commenter disagreed with the decision by FDA to
issue labeling guidelines under special controls guidance rather than
mandating through regulation specific new language on all condom
labeling to address the concerns FDA has identified. The commenter did
not agree with giving flexibility to manufacturers on the wording used.
    (Response) FDA believes a special control guidance will provide an
appropriate level of control over labeling. Unlike a regular guidance,
which imposes no requirements, where a guidance document has been
designated as a special control by a rule, manufacturers must address
the issues identified in the guidance, either by following the
recommendations in the guidance or by some other means that provides
equivalent assurances of safety and effectiveness. If a manufacturer
proposes to use a means other than the labeling recommendations set
forth in the intended final special control guidance, the manufacturer
will need to establish equivalent assurance of safety and effectiveness
of the alternative.

C. FDA's Review of Scientific Information

    The 2005 proposed rule included a summary of FDA's review of the
medical accuracy of latex condom labeling, which included an extensive
review of the scientific information related to condoms. As discussed
in the proposal, FDA considered the physical properties of condoms,
condom slippage and breakage during actual use, the plausibility for
STI-reduction attributable to condoms, evaluations of condom protection
against STIs by other Federal agencies, and clinical data regarding
condom protection against STIs. The follow sections discuss the
comments and FDA's responses related to this review.
1. General Comments
    (Comment 3) Many of the comments commended the proposed rule and
draft special controls guidance document as well grounded in the
scientific and medical evidence and consistent with the findings from
clinical studies in the available literature.
    (Response) FDA agrees. In addition to the studies on which the 2005
proposal was based, as described previously, peer-reviewed
epidemiological studies published subsequently have also supported the
conclusion that latex condom use reduces the risk of STIs.
2. Slippage and Breakage
    (Comment 4) One comment challenged FDA's estimate of the rates of
condom slippage and breakage in actual use and expressed concerns that

some ``key points'' were missing, including the experience of the user.
More specifically, the commenter ``would have preferred that most
slippage and breakage fall within the 2-4% range with experienced users
toward the 2% and lower range and inexperienced users at the higher 4%
range and above.'' This comment also disagreed with FDA's statement
that condom slippage and breakage data support the conclusion that
condoms reduce the risk of STI transmission and stated ``[s]lippage and
breakage data does not support the conclusion that condoms help, rather
the opposite.'' The commenter stated that the labeling recommendations
should reflect that even with perfect use, an individual can become
infected when slippage and breakage occurs.
    (Response) FDA disagrees that the slippage and breakage data do not
support the conclusion that condoms reduce the risk of STI
transmission. FDA notes that rates of slippage and breakage during use
have been measured for many different commercially available latex
condoms, typically ranging between 0.5-2% (70 FR 69102 at 69105). FDA
believes that these low rates of condom slippage and breakage, when
taken together with studies of condom properties discussed in the
proposed rule (see 70 FR 69102 at 69104 to 69105), support the
conclusion that latex condoms, when used consistently and correctly,
provide a reliable barrier to STI pathogens. FDA concurs with the
commenter's point that even with correct and consistent use, slippage
and breakage can occur. FDA does not believe, however, that additional
wording is necessary to underscore this point regarding perfect use.
FDA believes that the labeling recommendations as crafted accurately
reflect the overall conclusion that when used correctly and
consistently, latex condoms reduce the risk of STI transmission but do
not completely eliminate it.
3. Risk Reduction
    (Comment 5) One comment suggested that FDA's analysis overlooked
infectivity. This comment recommended changes to the FDA conclusion
about condom effectiveness to reflect this.
    (Response) FDA does not believe that discussion of infectivity
would benefit consumers in making safe and effective use of latex
condoms. While the infectivity of the pathogen is among the factors
that affect the baseline risk of acquiring a specific STI, even the
most infective STI pathogen cannot penetrate an intact latex condom.
Infectivity of the pathogen thus only impacts the net risk of infection
despite condom use where the latex condom does not present a barrier to
interrupt the potential path of transmission--either because the
infected skin is outside the area covered by the condom, or because the
condom has failed (a rare event with correct use). In its intended
final labeling recommendations, FDA has already described that condoms
derive their effectiveness from providing a barrier to the source of
infection and that condoms are less effective against STIs that are
transmitted by contact with infected skin outside the area covered by
the condom (as well as by contact with the head of the penis).
Recommended labeling also emphasizes the importance of correct and
consistent use to maximize the protection provided by a latex condom,
but acknowledges that use of condoms does not completely eliminate the
risk of STI transmission. As labeling does not quantify the amount of
risk reduction for specific STIs, FDA does not believe that addition of
discussion of infectivity would provide useful information beyond the
expression of limits and of conditions to optimize benefit already
provided.
    (Comment 6) One comment challenged FDA's conclusions regarding the
degree of risk reduction afforded by latex condoms when the population
evaluated in epidemiologic studies from which data were obtained
consisted of commercial sex workers (CSWs). This comment stated that
``One must use caution when generalizing prostitute studies to the
general population.''
    (Response) The commenter did not provide additional details or
support for his statement, but referenced an epidemiologic study (70 FR
69102 at 69117, reference 31, Kjaer, S.K., E.I. Svare, A.M. Worm, et
al.). The authors of that study noted that CSWs are likely to have
become sexually active at a younger age compared to other populations,
and speculated that early and multiple STIs in this population might
lead to a more robust immunologic response among chronically infected
compared to other populations. Importantly, however, the authors noted
that this latter theory is unproven.
    Conducting studies outside the United States, in places and
populations where the disease prevalence is high, makes it possible to
obtain valid outcomes data from studies that are reasonably sized and
would likely be impossible to conduct in lower risk populations in the
United States. Despite differences between the study populations and
typical U.S. users, FDA believes conclusions from such studies are
relevant, because the following fundamental elements that the studies
address are identical in the study population and in the expected U.S.
user population: (1) Primary study endpoint (presence of infection);
(2) pathogen (individual STI); (3) route of transmission (sexual); and
(4) prophylaxis (latex condom).
4. Evaluation of Latex Condom Effectiveness
    (Comment 7) One comment strongly criticized the June 2000 Workshop
convened by the National Institutes of Health (NIH) with other Federal
public health agencies and outside experts (70 FR 69102 at 69106), its
deliberative process, and the conclusions that were issued afterwards.
This comment stated that available evidence today actually supports a
stronger statement regarding latex condom effectiveness for STI
prevention, especially those STIs transmitted by contact with genital
fluids.
    (Response) FDA agrees that there is more evidence today on the
effectiveness of latex condoms against acquisition of various STIs than
was available when the June 2000 workshop was held. This includes
additional data that further support the longstanding public health
message that latex condoms are highly effective against HIV/AIDS. As
described previously in section I, it also encompasses new data now
showing that condoms protect against HPV infection as well as the
clinical sequellae of HPV infection, genital warts and cervical cancer.
    (Comment 8) One comment stated that FDA's labeling proposal was
misleading regarding condom use lowering the risk of HPV infection and
disease. It cited a 1999 letter from Dr. Richard Klausner, then
director of the National Cancer Institute, to the U.S. House of
Representatives Commerce Committee stating ``the conclusion that
condoms are ineffective against HPV infection is based on the results
of several long term studies that have failed to show that barrier
contraceptives prevent cervical HPV infection, dysplasia or cancer,''
as well as the summary report of the June 2000 Workshop on condom
effectiveness.
    (Response) As discussed in section I, many studies described in the
published literature since 2000, including two systematic reviews
(discussed in the 2005 proposed rule, 70 FR 69102 at 69108), support
the conclusion that correct and consistent latex condom use can reduce
the rates of cervical dysplasia and genital warts, diseases associated
with HPV infection.

Moreover, as discussed in section I.D.1, since December 2004, several
individual studies have addressed condom use and HPV infection and
demonstrated that use of latex condoms reduces the risk of HPV
infection itself. The letter from Dr. Klausner and the HPV conclusions
of the June 2000 Workshop report have been superseded by the evidence.
    (Comment 9) Another comment stated that FDA's summary of the
evidence is misleading where it states ``[The Centers for Disease
Control and Prevention's] report cited three studies (not included in
the June 2000 Workshop report) that showed a statistically significant
reduction in risk of HPV infection attributable to condoms, but noted
that most studies did not show this effect'' (70 FR 69102 at 69107).
This comment stated that only one of the three reports identified
demonstrated true risk reduction; the other two were not statistically
significant because their confidence interval touched on 1.0.
    (Response) As noted by the comment, two of the three studies
regarding the effect of condom use on HPV infection that were cited had
a confidence value with an upper bound of 1.0. FDA's 2005 draft
guidance reflected the limited evidence then available regarding the
effect of condom use on HPV infection itself, by recommending
statements based on the evidence regarding the effect of latex condom
use on clinical consequences of HPV infection, cervical cancer and
genital warts, which came from studies other than those addressed by
the comment. As described in section I.D. of this document, moreover,
subsequent to publication of the proposed rule, additional studies of
HPV infection have published that have shown statistically significant
reduction in HPV infection.
    The best-designed study to date evaluating whether latex condoms
reduce the risk of HPV infection is the 2006 Winer et al. study
published after the 2005 proposed rule was issued (Ref. 10). Compared
to previous studies on condoms and HPV infection, the 2006 Winer et al.
study had a prospective, longitudinal design which provided critical
information on the temporal relationship between condom use and HPV
infection. Another asset in this study design is that study subjects
provided information on condom use every 2 weeks in order to improve
the precision of reported condom use. Also, data were collected using
electronic diaries, a method that may yield more truthful reporting on
condom use behavior than through ace-to-face interviews. Study
inclusion criteria limited participation to women who first had
intercourse with a male partner within two weeks before enrollment or
during the study. This ensured that HPV infections detected during the
study were truly ``incident,'' that is, truly occurred during the
course of the study in a previously uninfected woman. Incident HPV
infection, or lack of infection, was then evaluated as it related to
100 percent, 50 to 99 percent, 5 to 49 percent or <5 percent condom
use. The adjusted hazard ratio for incident HPV for women whose
partners had used condoms 100 percent of the time over the 8 months of
the study compared to women whose partners used condoms <5 percent of
the time was 0.3, 95 percent confidence interval 0.1 to 0.6 with p-
value 0.003. This result is statistically significant. The conclusion
of the study was that ``among newly sexually active women, consistent
condom use by their partners appears to reduce the risk of cervical and
vulvovaginal HPV infection.''
    FDA believes that the results of the 2006 Winer et al. support the
conclusion that consistent latex condom use reduces the risk of
cervical and vulvovaginal HPV infection, which is stronger than the
conclusion in the 2004 CDC Report to Congress that ``condoms may
provide some protection in preventing transmission of HPV infections
but that protection is partial at best.''

D. Labeling Recommendations

    As discussed earlier, in the 2005 proposed rule, FDA identified
several issues associated with the use of latex condoms that required
special controls to help provide a reasonable assurance of safety and
effectiveness. The issues included the risks of unintended pregnancy
and of STI transmission, and the issue of incorrect or inconsistent
use. FDA proposed to designate a guidance document with labeling
recommendations as the required special control for latex condoms, to
address the issues of safety and effectiveness associated with these
devices. The following sections discuss the comments and FDA's
responses related to the labeling recommendations of the special
controls guidance document.
1. General
    (Comment 10) Many comments expressed concerns that FDA had allowed
``politics'' to influence FDA policy. For example, one comment stated
that the proposed rule appeared to ``bring politics and morality into
what should be a science based process.'' Many commenters shared a
concern that the proposed labeling would ``discourage'' the use of
condoms and undermine the public's confidence in condoms.
    (Response) As discussed in the 2005 proposal, FDA's efforts to
improve latex condom labeling and thereby help ensure the safety and
effectiveness of condoms grew out of a statutorily mandated review of
existing latex condom labeling to determine whether it was medically
accurate with respect to the overall effectiveness or lack of
effectiveness of condoms in preventing transmission of STIs, including
HPV. FDA concluded that latex condoms help protect against all STIs,
but better against some than others. More accurate information about
the effectiveness of latex condom use with respect to STI transmission
can lead to better choices by individuals who seek to protect
themselves against these infections and potentially to reduced transfer
of STIs. The final rule and intended final special control guidance are
based on FDA's scientific evaluation of all available evidence.
2. Comprehension
    (Comment 11) Many comments stated that, although consistent with
the evidence, the FDA proposal for latex condom labeling was overly
complex and confusing, especially in regards to STIs transmitted
through skin to skin contact. Some comments were concerned that the
labeling might discourage condom use due to confusion or
misunderstanding.
    Other comments stated that latex condom labeling needs to be clear
and positive. Many comments strongly encouraged FDA to re evaluate its
labeling proposal with the objectives of keeping it simple, clear,
correct, and specific.
    (Response) The labeling recommendations of the draft guidance
reflected an attempt to strike a balance between providing more
information for the consumer and creating a complex message that might
be misunderstood. These and other comments about label comprehension
prompted FDA to sponsor a label comprehension study of both current
labeling and the labeling recommendations included in the draft
guidance. The results of the FDA-sponsored label comprehension study
were discussed in section I and contributed to FDA's simplification of
the labeling recommended in the intended final special control
guidance.
    (Comment 12) One commenter submitted the results from its own label
comprehension study, conducted in January 2006, to evaluate how well
the general public understood FDA's proposed latex condom labeling.
This study, using a paper-and-pencil

questionnaire, surveyed a convenience sample of 247 men and women
between 18 and 30 years of age in Austin, Texas. The study concluded
that it is important for condom labeling to provide clear and specific
information to users on risk reduction provided by condoms for
pregnancy and various sexually transmitted diseases. In general, survey
respondents preferred statements that are easy to understand and
provide detailed and specific information.
    (Response) FDA acknowledges the value of this label comprehension
study. However, the use of a small convenience sample, drawn from a
highly educated university town, may have limited validity and may also
be difficult to generalize because it lacks geographic and educational
diversity. These limitations contributed to FDA's decision to conduct
its own study. As described previously, in consideration of this study
and the numerous comments regarding the complexity and potential for
misunderstanding of labeling, as well as FDA's own labeling study, the
intended final special controls guidance document contains
substantially simplified labeling recommendations.
    (Comment 13) Many comments shared the view that FDA would be
``misleading and misinforming millions of Americans if the label is
changed * * *.'' One commenter expressed concern that ``the addition of
extensive labels to condom packaging may constitute `red flags' to
consumers intending to have sex, and that those flags may increase sex
without the protection of condoms.''
    (Response) FDA's labeling initiative should in no way be construed
to mean that condoms do not work. As explained in the preamble to the
proposed rule and updated and reaffirmed here, scientific evidence
supports the conclusion that latex condoms are effective in reducing
the risk of pregnancy and the overall risk of STI transmission,
although latex condoms are more effective with regard to some STIs than
others. In fact, as described earlier, the data supporting overall
latex condom effectiveness in reducing STI transmission are stronger
today than ever. In light of comments and consumer comprehension data,
FDA has made revisions to the labeling to clarify the wording and
reflect this overall conclusion.
    (Comment 14) Many comments stated that the FDA proposal lacked
balance, with far more emphasis than necessary on what a condom cannot
do and not enough emphasis on the benefits of condom use. One comment
stated that ``[g]iven that many persons prefer sex without condoms and
the new labeling clarifying that condoms may not be as effective as
desired or imagined, many people may chose [sic] to simply have sex,
forego the condom, and take their risks.'' In contrast, two comments
stated that the FDA condom labeling proposal overstated condom
effectiveness, and lacked sufficient balance with too little scientific
detail. These two comments stated that the proposal alternates between
complexity that makes it difficult to understand and scientific
imprecision.
    (Response) After consideration of the many comments on this and
related risk messaging principles, and based on the results of its
label comprehension study, FDA concluded that the labeling in its draft
special controls guidance document created an unacceptable level of
confusion and misunderstanding. FDA also concluded, consistent with
findings from its label comprehension study, that putting more
scientific words and phrases into the limited space available for latex
condom labeling would only lead to more consumer confusion. The latex
condom labeling now recommended in the intended final special control
guidance document has focused the message of latex condom intended use
and simplified the message on differential effectiveness.
    (Comment 15) Some comments acknowledged a need for a two tier
message regarding the degree of protection afforded by condoms for
different STIs, but stated that the message needed to remain simple.
Some comments stated the key message is that although condoms provide
less protection against STDs such as genital herpes and human
papillomavirus, they do provide some protection.
    (Response) FDA acknowledges the challenge of crafting a latex
condom message that ensures that consumers not only understand the
significant overall clinical benefits of latex condom use, but also
understand the differing levels of protection against the various STIs.
FDA continues to believe that it is important for condom labeling to
provide information about differential effectiveness against STIs.
Clearer information about differential risks and benefits of condom use
can lead to better choices by individuals who seek to protect
themselves by using condoms. In its intended final special controls
guidance, FDA has refined the latex condom effectiveness message to
convey this information more clearly.
3. Pregnancy
    (Comment 16) One comment stated that the FDA proposed labeling for
intended use was incomplete because it did not address protection
against pregnancy.
    (Response) FDA agrees with this comment and the intended final
special controls guidance includes pregnancy protection in the primary
statement of intended action.
    (Comment 17) Several comments commended FDA for recommending
inclusion of a table in the labeling with comparative efficacy rates
for different barrier contraceptive options. Many comments suggested
updating the table and presenting efficacy data on all contraceptive
options. Other comments suggested including rates for both `typical
use' and `perfect use' so consumers could see the beneficial effect of
correct and consistent latex condom use. A few comments suggested that
effectiveness be presented as success rates, not failure rates. One
comment stated that FDA should not require such a table because it is
not useful, would be confusing, and would tend to discourage condom
use.
    (Response) FDA agrees with the many comments in favor of including
information on comparative contraceptive effectiveness. The intended
final guidance recommends inclusion of up-to-date contraceptive
effectiveness information comparing the percentage of women
experiencing unintended pregnancy during 1 year of use of latex condoms
with rates experienced during 1 year of use of other contraceptive
options available in the United States including drugs, devices, and
methods of permanent sterilization. The guidance recommends at minimum
inclusion of typical use rates, but this does not preclude inclusion of
perfect use rates. To permit manufacturers flexibility to fit
contraceptive effectiveness information in their labeling and
accommodate new data as it becomes available, the guidance no longer
provides a specific recommended table format.
    Regarding whether contraceptive effectiveness information should be
expressed as ``success'' or ``failure,'' FDA notes that contraceptive
studies evaluate pregnancy as the primary outcome measure. The
statistical hypothesis and analysis is built around the pregnancy rate,
and this is not easily transposed to a ``success'' rate. Therefore, FDA
continues to recommend that these data be presented as pregnancy rates
associated with the use of condoms or other methods, but does not
mandate that the term ``failure'' be used in labeling.
    The agency believes that providing contraceptive effectiveness
information will not confuse consumers or

discourage condom use. Rather, FDA believes that this information will
help consumers to determine whether latex condoms, available without a
prescription, will sufficiently address their contraceptive needs, or
whether they should seek other options, including those that may
require consulting a health care provider. In keeping with this
purpose, the intended final guidance also recommends that contraceptive
effectiveness information be accompanied by a statement advising
consumers to consult a health care provider if they have any questions
about contraception, particularly because of health reasons for
avoiding pregnancy.
4. STIs
    (Comment 18) One comment stated that the labeling in the draft
guidance that described the differential effectiveness of condoms
against Group I and Group II STIs should include a complete list of the
STIs in each group.
    (Response) FDA declines to recommend that labeling addressing the
degree of STI protection contain a complete list of STIs falling within
each group. Based on the results from FDA's label comprehension study,
which indicated that the message on this point in the draft guidance
was not well understood, the agency is concerned that including such a
list might be more confusing than helpful. FDA's intended final special
controls guidance recommends a simplified message on this point, which
includes examples of each type of STI, and also directs consumers to
consult a health care provider or public health agency for more
information on condoms or STIs.
    (Comment 19) Several commenters expressed concern that latex condom
labeling should not lose sight of the primary message that condoms are
highly effective against HIV infection, the most serious of all STIs.
Some of these comments also emphasized the importance of distinguishing
between condom attributes and user behavior, i.e., to emphasize the
protective benefit if used properly.
    (Response) None of the new studies reviewed by FDA since
publication of the 2005 proposed rule uncovered any new information to
detract from FDA's earlier finding that condoms are effective against
HIV/AIDS, arguably the most serious STI because of its devastating
consequences. Consistent with this evidence, FDA's intended final
special controls guidance recommends labeling that specifically
reflects the conclusion that condoms are effective against HIV/AIDS.
Recommended labeling also indicates that to get the most protection
from latex condoms, consumers should use them correctly every time they
have sex.
5. Correct and Consistent Use
    (Comment 20) One comment emphasized that user behavior concepts
such as correct use and consistent use are true for almost all devices
and drugs but do not belong in the statement of intended action. This
comment went on to state that precautions to ensure correct and
consistent use are important considerations for optimizing
effectiveness and should be placed elsewhere on the labeling. This
comment also noted that stating that condoms do not eliminate risk is
redundant with the statement that condoms help to reduce risk and is
therefore unnecessary.
    (Response) FDA agrees with this comment in part. FDA's intended
final guidance recommends a simple statement of intended action, that
latex condoms are intended to prevent pregnancy, HIV/AIDS, and other
STIs. Because information about optimal use conditions and their effect
on risk reduction also deserves labeling prominence, the intended final
special control guidance recommends that a statement emphasizing the
importance of correct and consistent use be included in a section on
the retail package entitled ``Important Information.'' In addition, the
guidance recommends specific directions and precautions to help ensure
such use. With regard to the question of redundancy, FDA believes that
it is useful and appropriate that condom labeling explicitly reflect
the results of scientific studies, which indicate that risk reduction
from condoms is not 100 percent, and therefore continues to recommend a
specific statement that condoms do not completely eliminate the risk of
pregnancy and STIs.
    (Comment 21) One commenter stated that FDA's recommended language
for the rear panel of the condom retail package was not accurate
because it did not contain the statement that condoms must be used
consistently and correctly to provide benefit. This commenter
recommended that a new section be included in condom labeling titled
``Consequences of Incorrect and Inconsistent Condom Use,'' which would
include the statement ``With the exception of genital herpes and HIV,
we have no clinical studies that show any risk reduction from
inconsistent condom use * * *.'' Elsewhere the same commenter noted
that none of the studies in HIV sero-discordant couples asked about
correct use. Another commenter made a related point, stating ``Although
`correct and consistent use' appears almost 15 times [in the preamble
to the proposed rule] almost all condom use studies with an STI outcome
actually only measured consistent condom use. The word `correct' should
be struck from the [rulemaking] document when it occurs in this
context.''
    (Response) These comments do not disagree with FDA's view that
condom labeling should communicate that correct and consistent use are
important to obtain the maximum benefit from a latex condom. FDA agrees
that the correctness of condom use is more difficult to evaluate in an
epidemiologic study than whether or not the condom was used for every
act of intercourse. Nevertheless, FDA believes that condom
effectiveness is in part a function of correct use, and therefore that
labeling should communicate the importance of correct use to achieve
best results.
    In the intended final special control guidance, both correct and
consistent use are addressed in the section called ``Important
Information'' on the rear panel of the recommended labeling, with a
recommended statement which reads: ``To get the most protection from a
latex condom, use one correctly every time you have sex.'' In addition,
the recommended labeling contains directions for use and precautions to
help ensure correct and consistent use, including the reminder to use a
new condom for each act of sex. The intended final special control
guidance also recommends labeling addressing the degree of STI
protection afforded by condoms, which describes that the reduction in
risk of STIs afforded by latex condoms results from their ability to
provide a barrier against the source of infection, and elaborates on
the difference in effectiveness against STIs that are spread by contact
with the head of the penis (an area that a condom covers) and those
also spread by contact with infected skin not covered by the condom.
FDA believes it is understood in this discussion of how condoms achieve
their effect that the condom must in fact be used to be effective. FDA
believes that the recommended labeling appropriately and accurately
communicates the importance of using latex condoms correctly and
consistently to obtain their benefits.
6. Risk Reduction
    (Comment 22) One comment stated that FDA should substitute ``risk
reduction'' for words such as ``prevent/prevention'' and ``protect/
protection'' to avoid the perception that risk reduction is total
(i.e., 100 percent).

    (Response) In the intended final special control guidance, FDA
recommends an initial statement of the intended action of condoms,
which includes an example stating that ``Latex condoms are intended to
prevent pregnancy, HIV/AIDS, and other sexually transmitted
infections.'' The agency believes that this is an example of an
appropriate, plain language statement of the intended action of a latex
condom. FDA agrees, however, that it is important that consumers
appreciate that risk reduction offered by condoms is not complete. In
language recommended for inclusion on the rear panel of the retail
package in a box entitled ``Important Information,'' the intended final
guidance recommends a statement, ``Latex condoms do not completely
eliminate the risks of pregnancy and sexually transmitted infections.''
The guidance also recommends the ``Important Information'' include a
statement characterizing latex condoms as reducing the risk of STI
transmission. Although the recommended wording is not identical to the
language suggested by the commenter, FDA believes that the recommended
labeling clearly conveys that use of a latex condom does not guarantee
complete elimination of risks of pregnancy or STIs. Consistent with
these statements on the outer package, the recommended package insert
also contains a section called ``Degree of STI Protection'' which
describes the relative risk reduction that can be expected for STIs
that differ in the way that they are transmitted.
    (Comment 23) One comment stated that FDA should recommend latex
condom labeling to include a data table showing the amount of risk
reduction afforded by condoms for the common STIs. This comment
indicated that the table should include estimates for ``perfect use''
and ``typical use,'' further suggesting that ``typical use'' is a
synonym for ``inconsistent use.'' Another comment recommended that
latex condom labeling should give information on differential
effectiveness in quantitative terms. That is, labeling should present
the amount of risk reduction provided by latex condom use, numerically
for each STI.
    (Response) FDA disagrees with these comments because the data are
not sufficiently developed to provide meaningful numbers to consumers.
    (Comment 24) One comment recommended the statement ``For STIs
however such as gonorrhea/chlamydia, which are much more infectious
[than HIV], incorrect or inconsistent condom use can very quickly lead
to an infection'' be included in a new section called ``Consequences of
Incorrect and Inconsistent Condom Use.''
    (Response) FDA does not agree the previous statement should be
included in condom labeling because we are not aware of scientific
studies supporting the conclusion that ``incorrect or inconsistent
condom use can very quickly lead to an infection'' for certain STIs.
The temporal relationship between incorrect or inconsistent condom use
and infection has not been measured systematically (with the exception
of the 2006 Winer et al. study who evaluated ``always,''
``inconsistent,'' and ``almost never'' condom use and incident HPV
infection). We agree with the commenter's implicit premise that, to get
the most protection from a latex condom, one should use a condom
correctly every time one has sex and the recommended labeling reflects
this accordingly.
    (Comment 25) Two comments stated that latex condom labeling should
discuss the difference between the degree of risk reduction afforded by
a latex condom when used correctly during a single act of penile-
vaginal intercourse compared with degree of risk reduction accumulated
during typical use over time during many acts of penile-vaginal
intercourse. The comments stated that the degree of risk reduction is
higher during a single act compared to cumulative risk reduction over
many acts of intercourse.
    (Response) Although FDA agrees in principle with the concept that
risk is lower during a single event compared to overall risk from
multiple possible exposures, it is important to note that all of the
studies evaluated by FDA looked at cumulative risk over many possible
exposures. None of the studies FDA reviewed evaluated latex condom
effectiveness against STIs during a single act of intercourse between
an uninfected person and an infected partner. FDA does not believe that
adding a discussion of hypothetical risk reduction during a single use
would improve the latex condom label.
    (Comment 26) Several comments stated that the latex condom labeling
recommendations in the draft guidance document focused on penile-
vaginal sex and do not specifically address oral sex or anal sex. Some
commenters suggested that labeling should be revised to specifically
indicate that condoms help prevent transmission of STIs between the
penis and mouth or rectum. Other comments stated that FDA's draft
guidance generically refers to sexual contact without stating that
scientific data are only available on risk reduction provided by a
condom during penile-vaginal intercourse. One comment suggested that
the rule and guidance document need to be ``clear * * * that we are
talking about the use of the male latex condom as used in vaginal
intercourse.'' Another indicated that FDA should view condom use ``for
everything but penile-vaginal sex [as] `off-label'.''
    (Response) Like the draft guidance, the labeling recommendations in
the final guidance document do not specifically address oral or anal
sex. This is not a change from the current labeling of condoms and is
reflective of the lack of premarket clearance or approval submissions
requesting an indication for use specifically for oral or anal sex.
Although most of the reliable epidemiological data about latex condoms
and STIs come from studies conducted in populations who engage in
penile-vaginal intercourse, a meta-analysis evaluated a number of
studies that tested behavioral interventions designed to increase
condom use during all forms of sexual contact and concluded that there
was an overall decrease in STIs from increased condom use (Ref. 2).
Other scientific information about the basis of latex condom
effectiveness against STIs--which indicates that latex condoms reduce
the transmission of STIs to which they provide a physical barrier--is
applicable to sexual contact between the penis and mouth or rectum. FDA
believes the labeling recommendations reflect the information
available.
7. Directions for Use and Precautions
    (Comment 27) One comment stated that the directions for use in the
FDA proposal are outdated and include steps for which there is no
underlying reason, e.g., squeeze air out of condom tip. This comment
pointed to a simplified set of five steps for correct condom use,
developed by the Information and Knowledge for Optimal Health (INFO)
Project, Johns Hopkins Bloomberg School of Public Health (Ref. 5).
    (Response) FDA reviewed the five-step directions for use of condoms
recommended by the INFO Project, and some of its approach was adopted
in the intended final special control guidance. FDA also included some
of its own general recommendations for developing medical device
patient labeling, such as recommendations for the use of diagrams.
    (Comment 28) One comment suggested modification of the storage
precaution, from ``Store condoms in a cool, dry place'' to ``Avoid
condom exposure to direct sunlight or storage for prolonged periods at
temperatures above 100 F.''

    (Response) FDA agrees in principle with this comment and has
adopted it in the following slightly revised format in the intended
final special controls guidance: ``Avoid exposure of the condom to
direct sunlight. Store latex condoms in a cool, dry place (below
100[deg] F).'' FDA notes that the model language in the guidance may be
varied so long as it provides appropriate directions for use and
precautions that contribute to ensuring safety and effectiveness of the
specific condom in question.
    (Comment 29) One comment requested that the directions for use in
the labeling be in boldface font.
    (Response) FDA does not agree with this comment. Highlighting
techniques, such as bold, are used to emphasize important words or
phrases, or for headings. Bolding all the directions for use would
overdo this highlighting technique, and could decrease the impact of
the directions.
    (Comment 30) Another comment stated that the directions for use
should include another bullet explaining how to properly dispose of a
latex condom.
    (Response) FDA agrees with this comment and has added a
recommendation in the intended final special controls guidance to
include in the directions for use a direction on how to properly
dispose of a latex condom.
8. Additional Information
    (Comment 31) One comment stated that latex condom labeling should
include a recommendation that sexually active persons seek advice from
a health care professional and that sexually active persons be
vaccinated against HBV and HPV.
    (Response) FDA's intended final special controls guidance
recommends that latex condom labeling include advice to consumers to
contact a health care provider if the consumer believes that he/she may
have an STI, as well as directing consumers to contact a health care
provider or public health agency for more information on latex condoms
or STIs. FDA believes this labeling, which is similar to the first
element suggested by the comment, is appropriate in light of the
recognition that condoms reduce, but do not eliminate, the risk of
STIs. Consumers who believe they are infected with an STI and are using
condoms to reduce the risk that they will transmit that STI to their
partner should also seek advice from a health care practitioner,
because treatment options may be available that will not only benefit
the infected person, but will also help to further reduce (or
eliminate) the risk of STI transmission. Advising consumers who may
already be infected with an STI to complement condom use with seeking
advice from a health care practitioner thus helps to ensure the safe
and effective use of condoms for STI prevention. Similarly, FDA's
recommendation that labeling alert consumers to contact a health care
provider or public health agency for more information on latex condoms
or STIs complements the labeling recommendations regarding the degree
of protection against different types of STIs. This labeling will help
ensure safe and effective use of condoms by alerting consumers to
additional resources that can expand on the basic information regarding
STI transmission provided by the labeling and also help the consumer
evaluate their individual circumstances.
    However, FDA believes that it would be inappropriate for latex
condom labeling to advise all sexually active persons to be vaccinated
against HPV and HBV in part because these vaccines are not universally
indicated for ``all sexually active individuals.'' For example, the
currently available HPV vaccine is not approved for use in men. The HBV
vaccine is indicated only for populations at risk for HBV. A
recommendation to be vaccinated against HPV and/or HBV should be
offered by a health care professional after consultation with the
individual.
    (Comment 32) One comment recommended that FDA should work with NIH,
CDC, and other research colleagues to monitor the impact of the new
labeling and to learn how to better reduce the adverse consequences of
sex.
    (Response) This comment did not address the substance of the
rulemaking or labeling recommendations. If important new evidence
becomes available, FDA may reconsider its approach in light of that
evidence.
    (Comment 33) A few comments commended FDA for its labeling proposal
but warned that it should avoid additional educational information
about social behaviors or public health programs. These comments stated
that this kind of information is not appropriate for latex condom
labeling. Another comment asked that references to pregnancy and HIV
programs be placed in the labeling.
    (Response) FDA believes that the purpose of latex condom labeling
is to adequately identify the product and its intended action, with
information about the product, including adequate directions for use
and any other necessary cautions or warnings, to ensure safe and
effective use. As discussed earlier, FDA is including as recommended
labeling a statement that consumers should consult a health care
practitioner or public health authorities for more information about
condoms or STIs. This labeling complements the recommended labeling
regarding the degree of protection against different types of STIs,
which FDA's label comprehension study and numerous comments indicated
needed to be kept simple in order to be well understood. By alerting
consumers to additional resources that can expand on the basic
information regarding STI transmission provided by the labeling, and
also help the consumer evaluate their individual circumstances, the
recommended labeling regarding contacting a health care practitioner or
public health agency will help to ensure the safe and effective use of
latex condoms.

E. Comments in Response to FDA's Specific Requests

    FDA's 2005 proposed rule included specific requests for comments.
Several of the specific requests related to latex condoms with
spermicidal lubricant containing N-9. As discussed in the introductory
paragraph of section I, FDA continues to review the comments it
received related to that device. FDA also specifically requested
comments on whether its labeling recommendations should include more
detailed information on the prevention of genital HPV infection and
information on different approaches for prevention of cervical cancer
(FDA responded to one comment related to this request in section
III.D.8). Finally, FDA specifically requested comment on potential
special controls for nonlatex condoms without N-9. FDA received the
following comments in response to FDA's requests.
1. Human Papillomavirus (HPV)
    (Comment 34) In response to FDA's specific request related to HPV,
one commenter stated that ``[c]ondoms can reduce the transmission of
seminal fluid carrying the human papillomavirus. Therefore, decreasing
the direct effect of these fluids on the cervix may be helpful in
decreasing the risk of cervical dysplasia and neoplasia. It would be
appropriate for labels to indicate that HPV still can be acquired
through direct skin contact in areas not protected by the condom.''
    (Response) FDA's labeling recommendations in the intended final
special controls guidance document are consistent with this comment.
FDA's labeling recommendation is that the package insert indicate that
latex condoms reduce the risk of transmitting STIs by providing a
barrier against the source of infection but also include statements
that ``Latex condoms are less

effective against STIs, such as Human Papillomavirus (HPV) and herpes.
These STIs can also be spread by contact with infected skin that is not
covered by the condom.''
2. Nonlatex Condoms Without Nonoxynol-9
    (Comment 35) One comment indicated that consumers should be aware
that latex condoms might cause an allergic reaction and the use of a
nonlatex condom might reduce this risk. The comment noted that
``special controls beyond evidence-based labeling do not appear to be
warranted.'' Another comment recommended that FDA require that
packaging between latex condoms, latex condoms with N-9, natural
membrane condoms, and novelty condoms look ``clearly different.''
    (Response) FDA appreciates the information submitted and intends to
consider these comments when FDA evaluates the regulatory approach to
these devices.

F. Implementation

    (Comment 36) One comment stated that the 1-year period proposed for
implementing new condom labeling for latex condoms legally marketed
before the effective date of this final rule is unrealistically short.
This comment said it will take approximately 24 months, not 12 months,
to implement all the required changes because the draft labeling may
necessitate changes to packaging with its requisite capital equipment
changes.
    (Response) In the final guidance, FDA has shortened the statement
of intended action to be placed on the individual foil packet (primary
package). As a result of this change, a different size foil package for
the individual condom should not be needed. FDA has also shortened the
recommended statements to be included in the package insert and made
more clear the flexibility permitted to manufacturers to determine how
to present certain elements, such as contraceptive effectiveness
information. Therefore, FDA does not believe that capital equipment
changes will be needed to implement this special control. In addition,
as discussed in section II, latex condoms legally marketed before the
effective date of this final rule will be expected to comply with the
requirement of special controls within 11 months after the effective
date, as was proposed. However, the effective date of this final rule
will be 60 days after publication, not 30 days as anticipated, so
manufacturers will have a total of 13 months after publication to
comply with the requirement of special controls.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.34(b) 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.

V. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs 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 final rule is not an economically significant regulatory action
under the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. FDA does not believe that the final rule will have a
significant economic impact on a substantial number of small entities,
but recognizes the uncertainty of its estimates. In the proposed rule
the agency solicited but did not receive specific comments on its
estimates and methodology of analysis of the impact of the rule on
small businesses.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written 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 $130 million, using the most current (2007) 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.

A. Background

    The purpose of this final rule is to amend the classification
regulation for condoms to designate a labeling guidance as a special
control for latex condoms. As discussed earlier in this preamble, latex
condoms are currently classified into class II in accordance with
section 513 of the act. The special controls guidance identifies
particular issues associated with these devices and recommends labeling
to address those issues. The benefit of this final rule is that
establishing the labeling guidance as a special control ensures that
manufacturers will provide consumers with the information they need to
make an informed decision regarding the use of latex condoms and to use
them safely and effectively. The labeling guidance helps ensure that
information provided to consumers does not undervalue the overall STI-
risk reduction provided by latex condom use, but does not exaggerate
the effectiveness of latex condoms against certain types of STIs. More
specific information about the effectiveness of latex condoms with
respect to pregnancy and STI transmission, as well as clearer
directions for use and precautions about how to obtain the maximum
benefit from latex condoms, can lead to better choices by individuals
who seek to protect themselves against unintended pregnancy and STIs.
Establishing a rule designating as a special control a guidance
document that contains labeling recommendations, rather than
establishing a labeling regulation, provides both the agency and
manufacturers greater flexibility and will result in providing
consumers with any new or enhanced information more quickly. The agency
believes this special control will, together with the general controls,
provide reasonable assurance of the safety and effectiveness of these
devices.

B. Affected Entities and Scope of Effect

    The final rule will affect persons responsible for the labeling of
latex condoms, which, in most cases, will be manufacturers of condoms,
including repackagers. Manufacturers of latex condoms, including
repackagers, will need to address the issues identified in the special
controls guidance document. A firm need only show that its device meets
the recommendations of the guidance document or in some other way
provides equivalent assurances of safety and effectiveness. To meet the
recommendations of the special controls guidance document, wording on
the retail package, including the principal display panel, the primary
condom package (individual foil), and package insert will most likely
need changes to conform to the guidance document.

    Agency records show there are approximately 35 entities that
manufacture or repackage latex condoms affected by this final rule. FDA
does not track the number of different product and package combinations
(stockkeeping units (SKUs)) on the market. Based on data FDA received
from industry, FDA estimates that currently there are between 500 and
1,000 SKUs on the market that will need labeling changes. If the
products are sold with a retail package, the wording on each of these
SKUs will need to be changed. Because manufacturers can often use the
same individual foil and package inserts across their product lines,
the number of versions of foil and insert labeling that require changes
will be less than the number of SKUs.
    Based on the agency's experience with the industry and anecdotal
information from manufacturer and retail Web sites, FDA estimates that
there will be a total of 802 to 1,605 labeling changes to retail
packages, individual foils, and package inserts. FDA assumed that 95
percent of the SKUs (475 to 950) are marketed with 3 levels of labeling
(a retail package, individual foil, and package insert), and the
remaining 5 percent have 2 levels (a foil and package insert). For the
SKUs with three levels of labeling, FDA further assumed that for every
3 retail package redesigns there would be 1 foil label redesign, and
for every 4 retail package redesigns, there would be 1 package insert
redesign. FDA based these assumptions on FDA's knowledge that a single
condom type is often sold in several retail packages containing
different numbers of condoms, in which case retail packages would be
different for each SKU but package inserts and foil labels would be
shared by multiple SKUs. The distribution of the different labeling
that would need to be redesigned is listed in Table 1 of this document
and includes 475 to 950 retail packages, 183 to 367 foils, and 144 to
288 inserts. (Sample calculation: (500 x 0.95 / 3) + (500 x 0.05) foils
and (500 x 0.95 / 4) + (500 x 0.05) inserts.)

C. Costs of Implementation

    Frequent package changes or redesigns are standard business
practice in the consumer healthcare products market. Manufacturers with
products intended for retail sales will have established routines for
product relabeling and employees with the technical expertise to
implement labeling changes. The cost to relabel a product can be broken
into three basic components: regulatory, graphics, and manufacturing.
The regulatory component includes determining what changes are
necessary, drafting the wording for the new labeling, and coordinating
the review and revisions. The graphics component includes preparing the
layouts, proofs, and printing. Finally, the manufacturing component
includes incorporating the new labeling into the manufacturing system,
discarding old labeling inventory, and making any changes to the
packaging line to accommodate the new labeling, if necessary.
    The final rule designates a special controls guidance document that
recommends changes to wording and some additional text. Many of the
labeling recommendations are similar to statements in existing condom
labeling, but are being updated to reflect current information. These
changes should not require major changes in the design or layout of
existing labeling and FDA believes that the changes can be incorporated
without having to increase the dimensions of any of the labeling. As
discussed elsewhere in the preamble, FDA received one comment that
suggested that manufacturers might need to increase package size to
accommodate the proposed wording. After conducting a label
comprehension study and considering other comments and information, FDA
shortened and reworded the recommended labeling. In addition, the
intended final special controls guidance does not specify a particular
format for the contraceptive effectiveness information. The agency
believes that with the changes to the wording and increased flexibility
in presentation, we have addressed these concerns.
    The itemized cost estimates used in this analysis were derived from
a study performed for FDA by Eastern Research Group, Inc. (ERG), an
economic consulting firm, to estimate the economic impact of the 1999
Over-the-Counter Human Drug Labeling Requirements final rule (64 FR
13254, March 17, 1999).\8\ Because the packaging requirements for latex
condoms are similar to those of many over-the-counter (OTC) drugs, the
cost to redesign and print the labeling for OTC drugs is an appropriate
proxy for the estimated costs to redesign and print condom labeling.
For this analysis, cost estimates were adjusted to account for
inflation using the producer price index (PPI) for finished consumer
goods, and current wage rates specific to the medical device industry
were substituted for the wages used by ERG in the original OTC drug
labeling impact study.\9\
---------------------------------------------------------------------------

    \8\ Eastern Research Group, Inc., Cost Impacts of the Over-the-
Counter Pharmaceutical Labeling Rule (March 1999). Contract number
223-94-8031, Docket No. 96N-0420, OTC Volume 28 FR, Division of
Dockets Management.
    \9\ The ERG cost estimates were based on estimates made in 1998.
The annual PPI for finished consumer goods rose by 27.5 percent
between 1998 and 2007 (from 130.7 to 166.6, http://www.bls.gov).
Wage estimates are from the Bureau of Labor Statistics, May 2007
National Industry-Specific Occupational Employment and Wage
Estimates, NAICS 339100--Medical Equipment and Supplies
Manufacturing (http://www.bls.gov).
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    FDA estimates that the regulatory component of each labeling
redesign would require between 8 to 16 hours per SKU. Using a wage rate
of $44.17, the incremental cost of the one-time regulatory component
cost to redesign would be $353 to $707 per labeling redesign (8 to 16
hours x $44.17/hour).\10\ The one-time cost of the graphic component
was estimated to be $640 per labeling redesign.\11\ The one-time cost
of the manufacturing component, which included the incorporation of the
new labeling into the manufacturing system and discarding the remaining
inventory of the old labeling, was estimated to require between 3 and 5
hours per label. Using the wage rate of $21.84 for a production
employee, this cost would range from about $66 to $109 per label (3 (to
5) hours x 21.84/hour).\12\ The value of the old labeling inventory
would vary greatly depending on the type and complexity of the
labeling, the average sales per SKU, and the length of the
implementation period granted. Based on the ERG study, with a 13-month
implementation period FDA estimates that the one-time inventory loss
would range from $478 to $1,913 per foil or package insert and from
$1,435 to $5,738 per carton.\13\
---------------------------------------------------------------------------

    \10\ Mean hourly wage for a compliance officer, SOC 13-1041, in
NAICS 339100 is $31.55, which was increased by 40 percent to account
for employee benefits and equals $44.17 (http://www.bls.gov).
    \11\ ERG estimated the cost at $500 per redesign. Adjusting for
inflation, the cost would be $638 ($500 x 1.275) and was rounded to
$640. (See footnotes 7 and 8).
    \12\ Mean hourly wage for the average production worker is
$13.75, SOC 51-0000, in NAICS 339100, which was increased by 40
percent to account for employee benefits and equals $19.25 (http://
www.bls.gov).
    \13\ ERG estimated that when there was no implementation period
granted, the average inventory loss for OTC drug container labels
ranged from $1,500 to $6,000 for small to medium sized OTC drug
firms. With a 14-month implementation period that loss decreased by
3/4. The value of carton inventory was estimated to be about 3 times
greater than container labels. Allowing for inflation (see footnote
6) the 0-month estimates are approximately $1,913 and $7,650,
respectively (e.g., $1,500 x 1.275).
---------------------------------------------------------------------------

    FDA believes that by providing manufacturers with a 13-month period
to achieve compliance for those latex condoms that are legally marketed
before the rule is effective, there will be

enough time for them to sell their existing product inventory and have
enough newly labeled inventory on hand to meet demand without a
disruption in supply. The total estimated incremental one-time costs to
the industry for each component of a labeling redesign was calculated
by multiplying the cost per label by the number of labels affected and
are presented in table 2 of this document. Because of the uncertainty
of the estimates, only the lowest and highest estimated costs are
presented rather than reporting the intermediate values that would be
obtained using other pairings of high with low values in the ranges
estimated. The total one-time incremental cost to the industry was
estimated to be between $1.7 million and $9.0 million. The cost to
individual firms to comply with this rule would vary greatly depending
on the number of products they produced, how the products were
packaged, and the sales volume. As stated earlier in this document,
frequent labeling changes are a cost of doing business in the consumer
healthcare products market and firms would have the skills necessary to
comply with this rule. Because the steps followed for a firm-initiated
change are the same as for regulatory change, the labeling
recommendations could be incorporated at the time a firm is
implementing a firm-initiated labeling change for little additional
cost, and thus, the economic impact will be mitigated by the number of
firm-initiated labeling changes made during the implementation period.
In addition, because most labeling equipment can handle different
labeling sizes and types and because there are a large number of
companies available that can provide contract labeling services, FDA
does not believe that any manufacturer would incur major costs such as
the need to purchase new labeling or packaging equipment as a result of
this rule.

D. Regulatory Flexibility Analysis

    There are about 12 domestic entities that manufacture or repackage
condoms. The Small Business Administration (SBA) has established
criteria to identify small entities in given industries using the North
American Industry Classification System Code (NAICS). The NAICS for
manufacturing latex condoms is 326299 (All Other Rubber Product
Manufacturing). Firms in this industry are considered small if they
have fewer than 500 employees. Ten of the 12 domestic entities affected
by this rule are small as defined by SBA.
    The one-time cost to relabel, including the inventory loss, will
range from about $3,000 to $9,000 per unique product SKU. When the SKUs
differ only by the quantity per carton the one-time cost per SKU are
even less, ranging from about $2,100 to $6,400 because the foil and
insert labels are the same.
    As discussed earlier in this document, while the cost to the
industry to revise latex condom labeling is small, FDA lacks sufficient
specific information on the distribution of costs and characterization
of the industry to certify that this rule would not have a significant
economic impact on a substantial number of small entities. Thus, while
FDA does not believe that this final rule will have a significant
effect on a substantial number of small entities, FDA recognizes the
uncertainty of the estimates.

Table 1.--Estimated Number of Label Designs That May Need To Be Modified
------------------------------------------------------------------------
        Component            Low-End Estimate        High-End Estimate
------------------------------------------------------------------------
Cartons                   475                     950
------------------------------------------------------------------------
Foils                     183                     367
------------------------------------------------------------------------
Inserts                   144                     288
------------------------------------------------------------------------
Total                     802                     1,605
------------------------------------------------------------------------

                            Table 2.--Estimated Range of Compliance Costs By Function
----------------------------------------------------------------------------------------------------------------
                                                                                Total
     Component          Range      Hours    Wage/Hour    Cost/Label   Number of  -------------------------------
                                                                        Labels          Low            High
----------------------------------------------------------------------------------------------------------------
Regulatory           Low                8       $44.17  ...........          802        $283,395  ..............
                    ----------------------                          --------------------------------------------
                     High              16  ...........  ...........        1,605  ..............      $1,134,286
----------------------------------------------------------------------------------------------------------------
Graphic              Low         ........  ...........         $640          802        $513,280  ..............
                    ----------------------                          --------------------------------------------
                     High        ........  ...........  ...........        1,605  ..............      $1,027,200
----------------------------------------------------------------------------------------------------------------
Manufacturing        Low                3       $21.84  ...........          802         $52,547  ..............
                    ----------------------                          --------------------------------------------
                     High               5  ...........  ...........        1,605  ..............        $175,266
----------------------------------------------------------------------------------------------------------------
Inventory--foil &    Low         ........  ...........         $478          327        $156,306  ..............
 insert
                    ----------------------             ---------------------------------------------------------
                     High        ........  ...........       $1,913          655  ..............      $1,253,015
----------------------------------------------------------------------------------------------------------------
Inventory--carton    Low         ........  ...........       $1,435          475        $681,625  ..............
                    ----------------------             ---------------------------------------------------------
                     High        ........  ...........       $5,738          950  ..............      $5,451,100
----------------------------------------------------------------------------------------------------------------
Total Costs                                                                           $1,687,153      $9,040,867
----------------------------------------------------------------------------------------------------------------

VI. Federalism

    FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. Section 4(a) of the Executive order
requires agencies to ``construe * * * a Federal statute to preempt
State law only where the statute contains an express preemption
provision or there is some other clear evidence that the Congress
intended preemption of State law, or where the exercise of State
authority conflicts with the exercise of Federal authority under the
Federal statute.'' Federal law includes an express preemption provision
that preempts certain state requirements ``different or in addition
to'' certain federal requirements applicable to devices. 21 U.S.C.
360k; Medtronic v. Lohr, 518 U.S. 470 (1996); Riegel v. Medtronic, 128
S.Ct. 999 (2008). In this rulemaking, FDA has determined that general
controls by themselves are insufficient to provide reasonable assurance
of the safety and effectiveness of the device, and that there is
sufficient information to establish special controls to provide such
assurance. FDA has therefore imposed a special control to address the
risks of unintended pregnancy, transmission of sexually transmitted
infections, and incorrect or inconsistent use. This special control
creates ``requirements'' for specific medical devices under 21 U.S.C.
360k, even though product sponsors have some flexibility in how they
meet those requirements. Papike v. Tambrands, Inc., 107 F.3d 737, 740-
42 (9th Cir. 1997).
    In addition, as with any Federal requirement, if a State law
requirement makes compliance with both Federal law and State law
impossible, or would frustrate Federal objectives, the State
requirement would be preempted. See Geier v. American Honda Co., 529
U.S. 861 (2000); English v. General Electric Co., 496 U.S. 72, 79
(1990); Florida Lime & Avocado Growers, Inc., 373 U.S. 132, 142-43
(1963); Hines v. Davidowitz, 312 U.S. 52, 67 (1941).
    The preemptive effects are the result of existing law set forth in
the statute as interpreted in decisions of the United States Supreme
Court. FDA therefore has not sought separate comment on the preemptive
effect of this action because it is not seeking independently to
preempt state law beyond the effects of 21 U.S.C. 360k or existing case
law.

VII. Paperwork Reduction Act of 1995

    This final rule contains no collections of information, but
designates as a special control a guidance document that contains
collections of information that are subject to review by the Office of
Management and Budget (OMB) under the PRA (44 U.S.C. 3501-3520).
Elsewhere in this issue of the Federal Register, FDA is publishing a
notice announcing the submission to OMB of the proposed information
collection provisions of that guidance document, Class II Special
Controls Guidance Document: Labeling for Natural Rubber Latex Condoms
Classified Under 21 CFR 884.5300, which contains further information
about the paperwork burden for that guidance. Prior to 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 the guidance designated as a
special control by this final rule and announcing the availability of
the final guidance as approved. 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.

VIII. References

    The following references have 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.
(FDA has verified the Web site addresses, but FDA is not responsible
for subsequent changes to the Web sites after this document publishes
in the Federal Register.)
    1. Centers for Disease Control and Prevention ``Table 41.
Chancroid--Reported Cases and Rates by State/Area Listed in
Alphabetical Order: United States and Outlying Areas, 2002-2006''
[Last accessed 5/15/2008 at: http://www.cdc.gov/std/stats/tables/
table41.htm]
    2. Crepaz, N., A.K. Horn, S.M. Rama, T. Griffin, J.B. Deluca,
M.M. Mullins, S.O. Aral, The HIV/Aids Prevention Research Synthesis
Team, ``The Efficacy of Behavioral Interventions in Reducing HIV
Risk Sex Behaviors and Incident Sexually Transmitted Disease in
Black and Hispanic Sexually Transmitted Disease Clinic Patients in
the United States: A Meta-Analytic Review,'' Sexually Transmitted
Diseases, June 2007; 34(6): 319-332.
    3. Davis, T.C., S.W. Long, R.H. Jackson, E.J. Mayeaux, R.B.
George, P.W. Murphy, M.A. Crouch, ``Rapid Estimate of Adult Literacy
in Medicine: A Shortened Screening Instrument,'' Family Medicine
1993; 25:391-5.
    4. del Amo, J., C. Gonzalez, J. Losana, P. Clavo, L. Munoz, J.
Ballesteros, A. Garcia-Saiz, M.J. Belza, M. Ortiz, B. Menendez, J.
del Romero, F. Bolumar, ``Influence of Age and Geographical Origin
in the Prevalence of High Risk Human Papillomavirus in Migrant
Female Sex Workers in Spain, Sexually Transmitted Infections 2005
February; 81(1):79-84.
    5. Johns Hopkins Bloomberg School of Public Health, Information
and Knowledge for Optimal Health (INFO) Project, http://
www.infoforhealth.org/globalhandbook/book/fph_chapter13/fph_
chap13_how_to_use.shtml.
    6. Ruan, Y., X. Cao, H-Z. Qian, L. Zhang, G. Qin, Z. Jiang, et
al. ``Syphilis Among Female Sex Workers in Southwestern China:
Potential for HIV Transmission,'' Sexually Transmitted Diseases,
December 2006, vol. 33, No. 12, p.719-723.
    7. Shew, M.L., J.D. Fortenberry, W. Tu, B.E. Juliar, B.E.
Batteiger, B. Qadadri, D.R. Brown, ``Association of Condom Use,
Sexual Behaviors, and Sexually Transmitted Infections With the
Duration of Genital Human Papillomavirus Infection Among Adolescent
Women,'' Archives of Pediatrics and Adolescent Medicine, 2006
February; 160(2):151-6.
    8. Wald, A., A.G. Langenberg, E. Krantz, J.M. Douglas Jr., H.H.
Handsfield, R.P. DiCarlo, A.A. Adimora, A.E. Izu, R.A. Morrow, L.
Corey, ``The Relationship Between Condom Use and Herpes Simplex
Virus Acquisition,'' Annals of Internal Medicine, 2005 November
15;143(10):707-13.
    9. Warner, L., K.M. Stone, M. Macaluso, J.W. Buehler, H.D.
Austin, ``Condom Use and Risk of Gonorrhea and Chlamydia: A
Systematic Review of Design and Measurement Factors Assessed in
Epidemiologic Studies,'' Sexually Transmitted Diseases, 2006
January; 33(1):36-51.
    10. Winer, R.L., J.P. Hughes, Q. Feng, S. O'Reilly, N.B. Kiviat,
K.K. Holmes, L.A. Koutsky, ``Condom Use and the Risk of Genital
Human Papillomavirus Infection in Young Women,'' The New England
Journal of Medicine, 2006 June 22;354(25):2645-54.

List of Subjects in 21 CFR Part 884

    Medical devices.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
884 is amended as follows:

PART 884--OBSTETRICAL AND GYNECOLOGICAL DEVICES

0
1. The authority citation for 21 CFR part 884 continues to read as
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
2. Section 884.5300 is revised to read as follows:

Sec.  884.5300   Condom.

    (a) Identification. A condom is a sheath which completely covers
the penis with a closely fitting membrane. The condom is used for
contraceptive and for prophylactic purposes (preventing transmission of
sexually transmitted infections). The device may also be used to
collect semen to aid in the diagnosis of infertility.