Obstetrical and Gynecological Devices; Designation of Special Controls for Male Condoms Made of Natural Rubber Latex, 66522-66539 [E8-26825]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 73, Number 218 (Monday, November 10, 2008)]
[Rules and Regulations]
[Pages 66522-66539]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-26825]


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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, 301-594-1180.

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

[[Page 66523]]

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.

[[Page 66524]]

    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 https://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

[[Page 66525]]

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

[[Page 66526]]

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

[[Page 66527]]

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.

[[Page 66528]]

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

[[Page 66529]]

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.

[[Page 66530]]

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 comme