[Federal Register Volume 70, Number 218 (Monday, November 14, 2005)]
[Proposed Rules]
[Pages 69102-69118]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-22611]


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Proposed Rules
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains notices to the public of 
the proposed issuance of rules and regulations. The purpose of these 
notices is to give interested persons an opportunity to participate in 
the rule making prior to the adoption of the final rules.

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Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / 
Proposed Rules

[[Page 69102]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. 2004N-0556]
RIN 0910-AF21


Obstetrical and Gynecological Devices; Designation of Special 
Control for Condom and Condom With Spermicidal Lubricant

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the classification regulations for condoms and condoms with spermicidal 
lubricant containing nonoxynol-9 (condoms with spermicidal lubricant) 
to designate a special control for natural rubber latex (latex) condoms 
with and without spermicidal lubricant. FDA is proposing the draft 
guidance document entitled ``Class II Special Controls Guidance 
Document: Labeling for Male Condoms Made of Natural Rubber Latex,'' as 
the special control that the agency believes will help provide a 
reasonable assurance of the safety and effectiveness of the devices. 
Elsewhere in this issue of the Federal Register, FDA is announcing a 
notice of availability of the draft special controls guidance document 
for public comment.

DATES: Submit written or electronic comments on the proposed rule by 
February 13, 2006. See section IV.C of this document for the proposed 
effective and compliance dates of a final rule based on this proposal.

ADDRESSES: You may submit comments, identified by Docket No. 2004N-0556 
and/RIN number 0910-AF21, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
    <bullet> Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
    <bullet> FAX: 301-827-6870.
    <bullet> Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and Docket No. and Regulatory Information Number (RIN) (if a RIN number 
has been assigned) for this rulemaking. All comments received may be 
posted without change to http://www.fda.gov/ohrms/dockets/default.htm, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: 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: The preamble to this proposed rule provides 
an extensive scientific discussion addressing the medical accuracy of 
condom labeling, as required by Public Law 106-554. This discussion 
provides the basis for the labeling recommendations that FDA proposes, 
through this rulemaking, to designate as a special control for latex 
condoms. (FDA intends to address condoms made from other materials at a 
future date and solicits comments on possible special controls for such 
condoms in section VIII of this document.) After reviewing public 
comments, FDA intends to issue a final rule designating the guidance 
document as the special control for latex condoms with and without 
spermicidal lubricant.

I. Statutory and Regulatory Background

    The Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 301 
et seq.), as amended by the Medical Device Amendments of 1976 (the 1976 
amendments) (Public Law 94-295), the Safe Medical Devices Act of 1990 
(SMDA) (Public Law 101-629), the Food and Drug Administration 
Modernization Act (Public Law 105-115), and the Medical Device User Fee 
and Modernization Act (Public Law 107-250), 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, defined by 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).
    Under section 513 of the act, FDA refers to devices that were in 
commercial distribution before May 28, 1976 (the date of enactment of 
the 1976 amendments), as preamendments devices. 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.
    Devices that were not in commercial distribution before May 28, 
1976, generally referred to as postamendments devices, are classified 
automatically by statute (section 513(f) of the act) into class III 
without any FDA rulemaking

[[Page 69103]]

process. Those devices remain in class III until FDA does 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. 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).
    In addition to the act, as amended, and its implementing 
regulations, 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].'' Under this mandate, FDA undertook a review of the 
medical accuracy of condom labeling, which included an extensive review 
of the scientific information related to condoms. This review is 
discussed in the following paragraphs. The draft special controls 
guidance document includes labeling recommendations based on this FDA 
review.

II. Regulatory History of the Devices

A. Condoms

    Condoms were marketed in the United States for both contraceptive 
and prophylactic (preventing transmission of sexually transmitted 
diseases (STDs)) use prior to the enactment of the 1976 amendments. As 
a preamendments device, the condom was classified along with hundreds 
of other devices during FDA's original classification proceedings. 
Based primarily on the clinical expertise and experience of experts on 
the Obstetrics and Gynecology Device Classification Panel, FDA 
classified 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) * * 
* '' (21 CFR 884.5300). This classification regulation includes latex 
condoms.
    At the time that 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 SMDA provided 
additional options for special controls for class II devices in 1990. 
The present rulemaking proposes to designate a special control for 
latex condoms.
    Condoms are also subject to general controls, which include 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 (Sec. Sec.  801.435 and 801.437). FDA established 
expiration dating requirements in response to information that showed 
that the effectiveness of latex condoms as a barrier to sexually 
transmitted diseases, including human immunodeficiency virus (HIV), is 
dependent upon the integrity of the latex material. The expiration 
dating regulation addresses the risk of 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).

B. Condoms With Spermicidal Lubricant

    Condoms with spermicidal lubricant (containing nonoxynol-9) were 
classified by statute into class III because they were not in 
commercial distribution before May 28, 1976 (enactment of the 1976 
amendments). In 1982, in response to a reclassification petition, the 
Center for Devices and Radiological Health (CDRH) reclassified condoms 
with the spermicide nonoxynol-9 (N-9) in the lubricant from class III 
to class II. The purpose of N-9 in the lubricant was to provide 
additional contraceptive protection in the event that semen were to 
leak or seep into the vagina. At the time of this reclassification, N-9 
was already available as an over-the-counter vaginal drug product, used 
alone or with a cervical cap or diaphragm.
    The petition for reclassification of condoms with N-9 in the 
lubricant contained evidence demonstrating that N-9 on the condom 
reduces sperm motility, a key factor in fertilization. Although the 
petition did not include clinical data to establish the degree of 
contraceptive protection provided by the N-9 in addition to that 
provided by the condom, FDA believed that the condom with spermicidal 
lubricant might provide an increase in use-effectiveness--the level of 
effectiveness attained by typical users, including those who either 
fail to use the product correctly or do not use it each time during 
sexual intercourse--and recognized that clinical studies of the device 
would be difficult to conduct and may not provide evidence justifying 
the effort of collecting it (47 FR 18670, April 30, 1982).
    To address the limitation of the data, in the agency's 
reclassification order, FDA stipulated that the labeling for condoms 
with spermicidal lubricant bear the following contraceptive 
effectiveness provision:
    This product combines a latex condom and a spermicidal 
lubricant. The spermicide, nonoxynol-9, reduces the number of active 
sperm, thereby decreasing the risk of pregnancy if you lose your 
erection before withdrawal and some semen spill outside the

[[Page 69104]]

condom. However, the extent of decreased risk has not been 
established. This condom should not be used as a substitute for the 
combined use of a vaginal spermicide and a condom.
    In the preamble to the final rule that codified the 
reclassification, FDA explained that condoms with spermicidal lubricant 
were reclassified into class II, provided that the labeling included 
the contraceptive effectiveness provision and an expiration date 
statement (47 FR 49021, October 29, 1982). To date, all legally 
marketed condoms with spermicidal lubricant have included the 
contraceptive effectiveness provision in the proposed labeling 
contained in the premarket notification (510(k)) submission that formed 
the basis for their clearance by CDRH. The condom with spermicidal 
lubricant is identified as ``a sheath which completely covers the penis 
with a closely fitting membrane with a lubricant that contains a 
spermicidal agent, N-9. This condom is used for contraceptive and 
prophylactic purposes (preventing transmission of venereal disease)'' 
(21 CFR 884.5310).
    Condoms with spermicidal lubricant were reclassified into class II, 
mandatory performance standards. As discussed earlier in this document, 
however, 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 1990, when the enactment of SMDA provided additional options for 
special controls. Consistent with current statutory authority, the 
present rulemaking proposes to designate a special control for latex 
condoms with spermicidal lubricant, as well as latex condoms without 
spermicidal lubricant. Condoms with spermicidal lubricant are also 
subject to general controls, including good manufacturing practices 
(quality system regulation), establishment registration and device 
listing, adverse event reporting, and the prohibitions on adulteration 
and misbranding.
    This device is also subject to the labeling requirements applicable 
to all devices, including a statement of principal intended action(s) 
and adequate directions for use, as described in part 801. In addition 
to these general labeling requirements, latex condoms with spermicidal 
lubricant are also subject to the same labeling requirements addressing 
expiration dating and latex sensitivity as condoms without spermicidal 
lubricant (Sec. Sec.  801.435 and 801.437).

III. Review of the Medical Accuracy of Condom Labeling

    In re-examining condom labeling as directed by Public Law 106-554, 
and in the development of the draft special controls guidance document, 
FDA considered the following:
    <bullet> Physical properties of condoms,
    <bullet> Condom slippage and breakage during actual use,
    <bullet> Plausibility for STD-risk reduction attributable to 
condoms,
    <bullet> Evaluations of condom effectiveness against STDs by other 
Federal agencies, and
    <bullet> Clinical data regarding condom protection against STDs.
    Taken together, the information FDA considered and its analysis 
support the conclusion that condoms reduce the overall risk of STD 
transmission, although the degree of risk reduction for different types 
of STDs varies with their routes of transmission.
    During the course of its reexamination of the medical accuracy of 
condom labeling, FDA also considered information on N-9 (section III.F 
of this document) and recent studies on contraception (section III.G of 
this document). The following sections summarize FDA's review.

A. Physical Properties of Condoms

    Condoms are designed to work in accordance with a straightforward 
premise--condoms provide a physical barrier to sperm and to STD 
pathogens, and thus can reduce the likelihood of conception or STD 
transmission, which depend on the passage of those agents. (In the case 
of condoms containing N-9 in the lubricant, with respect to 
contraception, this physical barrier is supplemented by a spermicide.) 
To assess this premise, and in particular to determine what condom 
labels should communicate, FDA considered several sources of 
information about the physical properties of condoms.
1. Condom Barrier Property (Viral Penetration Assay)
    To test the hypothesis that a condom inherently acts as a barrier 
to passage of very tiny particles, Lytle et al., conducted an in vitro 
study of nine different brands of latex condoms commercially available 
in the United States (470 samples), with and without spermicidal 
lubricant containing N-9. This study, later characterized as a viral 
penetration assay, used the bacteriophage [PHgr]X174 as a surrogate for 
a pathogenic human virus (Ref. 1). This surrogate bacteriophage is only 
27 nanometers (nm) in size, and is smaller than any pathogens that 
cause STDs. (By way of comparison, most bacteria are 1,000 nm or 
larger; HIV and herpes simplex virus (HSV) are on the order of 100 nm, 
and human papillomavirus (HPV) is about 53 nm. The test bacteriophage 
is also much smaller than sperm, which are 5-10 microm (cell body), 
i.e., 5,000-10,000 nm.) Of the 470 condoms tested, 12, or 2.6 percent, 
exhibited some viral penetration. Only two of the 470 condoms (0.43 
percent) exhibited significant viral penetration.
    This study showed that latex condoms are highly effective at 
preventing passage of even the smallest infectious agents. This 
supports the conclusion expressed later in this document that condoms 
are effective in reducing transmission of any STD to which they provide 
a mechanical barrier, namely, any STD that is spread to or from the 
penis, the area covered by the condom.
2. Presence/Absence of Holes (Water Leak Test)
    Another physical property important to condom performance is the 
presence or absence of tiny pinholes that might occur in some condoms, 
even under optimal manufacturing conditions, but which are too small to 
see without magnification. As the viral penetration assay (Ref. 1) 
illustrated, passage of a virus or bacterium requires concomitant 
passage of the fluid medium in which the pathogens are suspended. 
Consequently, to operate as effective barriers, condoms should not have 
holes, even tiny holes, that might permit passage of fluid. The notion 
that condoms should not have holes is intuitive, and condom 
manufacturers have for years used tests for detection of tiny holes in 
the condom as a product release quality control measure, on a lot-by-
lot basis. Likewise, FDA has pursued legal actions against 
manufacturers of condoms that have holes. See, e.g., Dean Rubber 
Manufacturing Co. v. United States, 356 F.2d 161 (8th Cir. 1966) 
(condoms labeled for prevention of venereal disease were adulterated 
where some had tiny pinholes, detectable through water leak test).
    One way to test for the presence of tiny pinholes is by a standard 
water leak test that requires filling the condom with 300 milliliters 
(ml) of water and inspecting for leakage. Current consensus standards 
(American Society for Testing Materials (ASTM) D 3492 and International 
Standards Organization (ISO) 4074) address test methodology and 
acceptance criteria, and the agency has recognized both of these 
standards in accordance with section 514(c) of the act. (Interested 
parties can search for FDA-recognized

[[Page 69105]]

standards by accessing the following Web site: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/search.cfm.)
    The agency believes that condom test methods and acceptance 
criteria regarding barrier properties specified in either of these two 
recognized standards are appropriate for use by manufacturers in the 
implementation of good manufacturing practices (GMPs) under the quality 
system regulations (21 CFR part 820) for their condom manufacturing 
operations. During inspections to monitor compliance with the quality 
system regulation, FDA confirms that condoms manufactured for the U.S. 
market are subject to appropriate acceptance testing to demonstrate 
compliance with their performance specifications, including testing to 
address the detection of pinholes. FDA also performs a check of all 
imported condom shipments, using the water leak test described 
previously in this document, to determine whether they meet an 
acceptable quality level.
3. Air Burst Properties
    Besides being made of material that inherently serves as a barrier 
to sperm and microscopic STD pathogens, and being manufactured through 
processes that minimize the occurrence of tiny holes in finished 
product, other physical properties of a condom important to its 
effectiveness include air burst properties, such as burst pressure and 
burst volume. Such properties have previously been correlated with 
breakage during use (Ref. 2). In developing standards that specify 
minimum values that manufacturers use as specifications for their 
condoms, FDA and standards development organizations considered data 
from studies of air burst testing combined with data from 
manufacturers' experience with this test methodology. On April 5, 1994, 
FDA issued a letter to condom manufacturers requesting that they adopt 
ISO air burst testing as part of their finished device testing to 
provide increased assurance of protection from sexually transmitted 
diseases, including HIV. Following the issuance of this letter and 
FDA's recognition of the ISO, ASTM, and similar standards, 
manufacturers of latex condoms legally distributed in the United States 
have established and implemented air burst test requirements as part of 
their GMP procedures.
4. Packaging and Shelf Life
    In collaboration with the Centers for Disease Control and 
Prevention (CDC) and state level health departments, FDA sponsored a 
large, multi-year shelf-life study testing the physical properties of 
marketed condoms over time under a variety of test conditions during 
the 1990s (Ref. 3). This study also highlighted the importance of 
quality packaging of the condom to prevent product deterioration. Using 
the results of this study, FDA issued a new labeling regulation in 1997 
to address expiration dating for condoms made from natural rubber latex 
and the shelf life testing that must support it (Sec.  801.435). A 
similar provision is now contained in the international standard for 
latex condoms (ISO 4074).

B. Condom Slippage and Breakage During Actual Use

    Because condoms must be in place and intact to form an effective 
barrier and thus help prevent pregnancy and provide protection against 
STD transmission, condoms should be designed to avoid slippage and 
breakage during actual use. As discussed later in this document, the 
National Institutes of Health (NIH) convened a workshop on condom 
effectiveness against STDs in June 2000 (the June 2000 Workshop). The 
June 2000 Workshop panelists looked at the question of condom slippage 
and breakage during use. The report from the June 2000 Workshop, based 
on the best available studies at the time, concluded that the condom 
breakage rate during use ranges from 0.4 percent to 2.3 percent, with a 
comparable rate for condom slippage (Ref. 4). Key factors affecting 
breakage include lack of experience, use of lubricant, and condom size. 
Since the June 2000 Workshop, we are aware of three additional, 
prospective studies that are consistent with these findings (Refs. 5, 
6, and 7).
    These data, when considered together with condom barrier properties 
and plausibility information (discussed in the following paragraphs), 
also support the conclusion that condoms reduce the risk of STD 
transmission, although, as discussed in the following section, the 
degree of risk reduction varies depending on the route of transmission 
of the STD. As discussed later in this document, this finding is also 
supported by review of studies on condom use and STD risk reduction.

C. Plausibility for STD Risk Reduction Attributable to Condoms

    FDA evaluated the plausibility of attributing STD risk reduction to 
regular condom use by integrating the preceding information about the 
condom's barrier properties with information about general condom 
design (e.g., how the condom is donned and how it covers the penis) and 
about the clinical microbiology of STD pathogens and how they are 
transmitted. Specifically, STD transmission requires contact between a 
pathogen source from an infected individual (e.g., semen, mucus, or 
lesion) and a recipient site of an uninfected partner (e.g., vaginal or 
cervical mucosa of a woman, the urethra of a man, genital skin of 
either a man or a woman). For the reasons explained in the following 
paragraphs, the agency concludes that condoms can limit this contact, 
and that they thus reduce the overall risk of STD transmission.
    In the evaluation to determine the overall effectiveness of condoms 
in preventing STD transmission, it is critical to recognize that 
individual STDs vary with respect to routes of transmission (e.g., via 
penile fluid or exposure to infectious skin) and infectivity (e.g., how 
many viral or bacterial particles must be transmitted for infection to 
occur). Based on these factors, FDA evaluated the extent to which a 
condom, which only covers the shaft and head of the penis, can provide 
an effective physical barrier to transmission of different STDs. To 
determine whether and to what extent it is reasonable, based on 
available information, to expect a condom to protect against different 
STDs, FDA considered nine STDs, including those most common in the 
United States, and their routes of sexual transmission. Table 1 of this 
document lists each STD considered and its usual route(s) of sexual 
transmission.

            Table 1.--STDs and Usual Route(s) of Transmission
------------------------------------------------------------------------
                                                  Exposure to Infectious
                           Exposure to and From       Skin or Mucosa
          STD             the Head of the Penis   (Excluding the Head of
                                                        the Penis)
------------------------------------------------------------------------
Group I
------------------------------------------------------------------------
HIV/Aquired              [check]                  ......................
 Immunodeficiency
 Syndrome (AIDS)

[[Page 69106]]

 
Neisseria gonorrhea      [check]                  ......................
Chlamydia trachomatis    [check]                  ......................
Trichomoniasis           [check]                  ......................
Hepatitis B Virus        [check]                  ......................
------------------------------------------------------------------------
Group II
------------------------------------------------------------------------
Syphilis                 [check]                  [check]
Genital HSV              [check]                  [check]
Genital HPV              [check]                  [check]
Chancroid                [check]                  [check]
------------------------------------------------------------------------

    Regarding the potential for STD risk reduction attributable to 
condom use, FDA concluded that the potential for condoms to help 
prevent STDs that are transmitted from or to the penis (table 1, group 
I) is greater than the potential risk reduction for STDs that are also 
transmitted by contact with infectious skin or mucosa not covered by 
the condom (table 1, group II). This risk reduction is a result of the 
condom's ability to serve as a barrier to help prevent contact between 
the genital fluids and the potentially susceptible mucosa. For STDs 
transmitted from or to the penis, a condom will provide a physical 
barrier that helps to prevent STD pathogens contained in penile fluid 
from reaching the cervico-vaginal or ano-rectal mucosa, thereby 
reducing the risk of transmission from males with STDs that meet these 
conditions. It also protects a man's urethra from STD pathogens 
contained in his partner's secretions. STDs that meet these conditions 
include HIV, gonorrhea, chlamydia, trichomoniasis, Hepatitis B, and are 
listed in group I, in table 1 of this document.
    For group II STDs, under its plausibility analysis, FDA concludes 
that while condoms are likely to provide some risk reduction, the 
degree of risk reduction may not be as great as that expected for group 
I STDs. This is because, for group II STDs, the condom provides a 
barrier in some, but not all, situations that may lead to transmission. 
Protection against group II STDs depends on the site of the sore/ulcer 
or infection. Condoms can only protect against transmission when the 
ulcers or infections are covered or when susceptible sites are 
protected by the condom.
     In summary, considering the means of transmission of STDs and the 
extensive information on the physical characteristics and performance 
of condoms, FDA believes there is strong support for the conclusion 
that condoms are effective in reducing the overall risk of STD 
transmission. The extent of risk reduction varies between two general 
groups of STDs. Risk reduction is greater for those transmitted 
exclusively through contact with the penis. Risk reduction is not as 
great for those that may be transmitted both through such contact and 
through contact with infectious skin or mucosa not covered by the 
condom.

D. Evaluations of Condom Protection Against STDs by Other Federal 
Agencies

    FDA also reviewed evaluations by other federal public health 
agencies regarding condoms and the protection they provide against 
sexually transmitted diseases.
1. The June 2000 Workshop: Scientific Evidence on Condom Effectiveness
    In June 2000, the National Institutes of Health (NIH) convened a 
workshop with other federal public health agencies and outside expert 
panelists. The June 2000 Workshop entitled ``Scientific Evidence on 
Condom Effectiveness for Sexually Transmitted Disease (STD) 
Prevention'' involved other federal agencies, including FDA, CDC, and 
the U.S. Agency for International Development. The report issuing from 
the June 2000 Workshop was based on consideration of approximately 138 
papers, the majority of which were published before December 1999, 
mostly in peer-reviewed journals (http://www.niaid.nih.gov/dmid/stds/condomreport.pdf). (FDA has verified the Web site address, but we are 
not responsible for subsequent changes to the Web site after this 
document publishes in the Federal Register.) During its deliberations, 
the June 2000 Workshop panelists considered whether condoms can prevent 
infection by eight different STDs and came to the following 
conclusions:
    HIV/AIDS: Workshop findings reaffirmed that condoms are highly 
effective against HIV transmission. From review of a meta-analysis of 
HIV discordant couples (Ref. 8), it was noted that correct and 
consistent condom use decreased the risk of HIV/AIDS transmission by 
approximately 85 percent. Panelists noted that many of the HIV/AIDS 
studies they reviewed employed better study methodologies than studies 
of other STDs. For example, HIV/AIDS studies were prospective, measured 
exposure for discordant couples (i.e., one partner is infected and the 
other is not infected), and were more likely to measure the effect of 
correct and consistent condom use. The primary outcome measure for 
these studies was typically condom effectiveness against transmission 
of HIV. Such study design features represent a relative strength of the 
HIV/AIDS condom literature compared with condom literature for other 
STDs.
    Gonorrhea: Studies reviewed showed that correct and consistent 
condom use would reduce the risk of gonorrhea for men. However, the 
report stated that limitations in study methodology did not allow an 
assessment of the degree of protection in women.
    Genital HPV: The report issuing from the Workshop concluded that 
most of the reviewed studies did not obtain sufficient information on 
condom use to allow careful evaluation of the association between 
condom use and HPV infection or disease. The report also concluded that 
there was no epidemiologic evidence that condom use reduced the risk of 
HPV infection, but that condom use might afford some protection in 
reducing the risk of HPV-associated diseases, including warts in men 
and cervical neoplasia (cervical cancer precursors and invasive cancer) 
in women.
    Chlamydia, Syphilis, Genital HSV, Chancroid, and Trichomoniasis:\1\ 
The

[[Page 69107]]

report stated that the scientific literature did not allow an accurate 
assessment of the degree of potential protection offered against these 
STDs by correct and consistent condom use.
---------------------------------------------------------------------------

    \1\ Trichomoniasis was addressed by the June 2000 Workshop 
organized by NIH, the report of which is cited in Ref. 4, as well as 
in a CDC fact sheet discussed later in this document (http://www.cdc.gov/nchstp/od/latex.htm). (FDA has verified the Web site 
address, but we are not responsible for subsequent changes to the 
Web site after this document publishes in the Federal Register.) FDA 
has similarly included this STD in table 1 as a group I STD on the 
basis of its route of transmission. This rulemaking does not 
consider any additional information regarding trichomoniasis, 
however, because there is no significant new information on this 
STD. Neither FDA's prior labeling recommendations nor its proposed 
special control guidance recommend making specific claims for condom 
effectiveness against trichomoniasis.
---------------------------------------------------------------------------

    Although the panel acknowledged the available laboratory data on 
physical performance of condoms, as well as data from clinical studies 
on condom use patterns and condom slippage and breakage during use, 
neither these factors nor the plausibility of condom protection against 
the various STDs were considered in the summary conclusions on STD risk 
reduction described previously in this document, which reflected solely 
the assessment of clinical studies. As already explained, FDA's 
approach in the present rulemaking has considered all of these factors, 
in addition to the clinical data.
    The June 2000 Workshop Summary also included an FDA analysis that 
looked at how different possible condom failure modes can affect the 
expected volume of semen exposure. Workshop panelists concluded that 
this analysis showed that, even in the event of condom breakage, 
leakage or slippage, condom use would still result in greatly reduced 
exposures because the amount of semen is reduced by orders of magnitude 
when compared to not using a condom at all.
2. CDC Fact Sheet ``Male Latex Condoms and Sexually Transmitted 
Diseases''
    In December 2002, CDC developed a fact sheet for public health 
personnel entitled ``Male Latex Condoms and Sexually Transmitted 
Diseases,'' with information on condom protection against HIV/AIDS, 
gonorrhea, chlamydia, trichomoniasis, HSV, syphilis, chancroid, and HPV 
(http://www.cdc.gov/nchstp/od/latex.htm). (FDA has verified the Web 
site address, but we are not responsible for subsequent changes to the 
Web site after this document publishes in the Federal Register.) CDC's 
fact sheet addressed the same eight STDs considered by the June 2000 
Workshop. The CDC Fact Sheet was based on laboratory studies, the 
theoretical basis for protection for condoms to reduce risk for STDs, 
and results of clinical studies. Based on review of these items, the 
fact sheet concluded:
    Latex condoms, when used consistently and correctly, are highly 
effective in preventing transmission of HIV, the virus that causes 
AIDS. In addition, correct and consistent use of latex condoms can 
reduce the risk of other sexually transmitted diseases (STDs), 
including discharge and genital ulcer diseases. While the effect of 
condoms in preventing human papillomavirus (HPV) infection is 
unknown, condom use has been associated with a lower rate of 
cervical cancer, an HPV-associated disease.
3. CDC Report to Congress entitled ``Prevention of Genital Human 
Papillomavirus Infection''
    CDC included a systematic literature review of condoms and HPV and 
HPV-associated diseases in its January 2004 report to Congress entitled 
``Prevention of Genital Human Papillomavirus Infection.'' This report 
describes the epidemiology of genital HPV infection and its 
transmission, and summarizes strategies to prevent infections with 
genital HPV and HPV-associated diseases. The 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 (Refs. 31, 32, 33). The report stated that ``all published 
epidemiologic studies have significant methodologic limitations which 
make the effect of condoms in prevention of HPV infection unknown.'' 
The report continued:
    Given these observations, as well as the facts that laboratory 
studies show that latex condoms provide a barrier to HPV and that 
most genital HPV in men is located on areas of the skin covered by a 
condom, the cumulative body of available scientific evidence 
suggests that condoms may provide some protection in preventing 
transmission of HPV infections but that protection is partial at 
best. The available scientific evidence is not sufficient to 
recommend condoms as a primary prevention strategy for the 
prevention of genital HPV infection. There is evidence that the use 
of condoms may reduce the risk of cervical cancer.
    The summary section of the report addressed strategies to prevent 
HPV infection and stated ``[w]hile available scientific evidence 
suggests that the effect of condoms in preventing HPV is unknown, 
condom use has been associated with lower rates of the HPV-associated 
diseases of genital warts and cervical cancer.'' The CDC report offered 
two possible explanations about how condoms might reduce the risk of 
genital warts and cervical cancer when the effect of condoms in 
preventing HPV infection is unknown. Condom use could reduce the 
quantity of HPV transmitted or the likelihood of re-exposure to HPV, 
thereby decreasing the risk of developing clinical disease. Another 
possible explanation offered by CDC is that condom use reduces the risk 
of exposure to a possible cofactor for cervical cancer, such as 
chlamydia or genital herpes, thereby reducing the risk of developing 
cervical cancer (Ref. 9). The summary section went on to state that 
``[r]egular cervical cancer screening for all sexually active women and 
treatment of precancerous lesions remains the key strategy to prevent 
cervical cancer.''

E. Systematic Reviews Regarding Condom Protection Against STDs

    The agency also analyzed the following sources of clinical data 
regarding condom protection against STDs:
    <bullet> Systematic reviews (meaning reviews 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) for STDs where such reviews were available; and
    <bullet> Individual clinical studies for STDs where systematic 
reviews were not identified.
    In the following analysis of clinical studies regarding condom 
protection against STDs, the STDs have been grouped according to 
plausibility for risk reduction attributable to condom use, discussed 
previously. The STDs transmitted primarily to or from the head of the 
penis (HIV, gonorrhea, chlamydia, and HBV) are discussed first (group I 
STDs). STDs that are also transmitted by exposure to infectious skin or 
mucosa excluding the head of the penis are discussed second (group II 
STDs). FDA believes this body of literature illustrates both the 
limitations and the benefits of condom use for protection against STDs.
1. Group I
    HIV: In a recent meta-analysis (Ref. 10), Weller and Davis selected 
14 clinical studies for final analysis based on exemplary study design. 
These prospective cohort studies of discordant heterosexual couples 
showed that correct and consistent use of condoms resulted in an 
overall 80 percent reduction in HIV incidence. Other reviews (Ref. 11) 
also have shown risk reduction against HIV associated with correct and 
consistent condom use. Consistent with the NIH Workshop findings, these 
reviews support the conclusion that correct and consistent

[[Page 69108]]

condom use is highly effective in reducing the transmission of HIV 
infection.
    Gonorrhea: FDA is aware of one systematic review of the condom 
literature regarding protection against gonorrhea. This systematic 
review of 42 epidemiological studies reported in 2004 evaluated condom 
effectiveness for preventing gonorrhea, chlamydia, and pelvic 
inflammatory disease and found that in the vast majority of studies 
condom use was associated with a reduced risk of gonorrhea in women and 
men (Ref. 12).
    Chlamydia: FDA is aware of one systematic review of the condom 
literature regarding protection against chlamydia (Ref. 12). The 2004 
epidemiology review cited in the previous discussion of gonorrhea found 
that the vast majority of studies showed that correct and consistent 
condom use reduces the risk of chlamydia for both men and women.
    This information also supports the conclusion that correct and 
consistent condom use can reduce the risk of chlamydia in both men and 
women.
    Hepatitis B: FDA is not aware of any systematic reviews of the 
condom literature regarding protection against Hepatitis-B (HBV). 
Although data are limited, FDA identified one study that addressed this 
issue. This was a cross-sectional study (Ref.13), that showed that 
correct and consistent condom use was significantly associated with 
lower prevalence of HBV.
    In summary, the previously discussed information shows that 
condoms, when used correctly and consistently, can be effective in 
reducing the risk of transmission of group I STDs, which are 
transmitted by exposure of the cervico-vaginal, urethral, or rectal 
mucosa to penile fluids or cervico-vaginal secretions.
2. Group II
    Syphilis: FDA is not aware of any systematic reviews of the condom 
literature regarding protection against syphilis. However, FDA 
identified two prospective studies that have examined this question. A 
prospective cohort analysis of female ``sex workers'' in Bolivia (Ref. 
14), showed that condom use was associated with a 61 percent reduction 
in the risk of syphilis. A secondary analysis of a prospective study 
(Ref. 15) also found a significant protective effect for condoms 
against syphilis transmission. Although data are limited, this 
information also supports the conclusion that correct and consistent 
condom use can reduce the risk of syphilis.
    Genital Herpes: FDA is aware of one systematic review of the condom 
literature regarding protection against herpes. A literature review 
published in 2002 (Ref. 16) found that condom use appeared to reduce 
the risk of HSV-2 infection for women; an important study, cited in 
that review, was a prospective study among discordant couples that 
found condom use during more than 25 percent of sex acts was associated 
with protection against HSV-2 acquisition for women but not for men 
(Ref. 17). More recent prospective studies showed that condom use was 
associated with a reduced risk of HSV-2 for men and women (Refs. 18 and 
19).
    HPV: Genital HPV is a common infection in sexually active persons. 
Certain strains of genital HPV cause genital warts, while others are 
asymptomatic. The majority of genital HPV infections spontaneously 
regress and do not lead to clinical disease. Less commonly, genital HPV 
infection is persistent and leads to cellular abnormalities of the 
cervix that may progress to cervical cancer (Ref. 34).
    FDA is aware of two systematic reviews of the scientific literature 
on HPV infection and condom use. The previously described 2004 CDC 
Report to Congress concluded that ``* * * the effect of condoms in 
preventing HPV infection is unknown, [but] condom use has been 
associated with lower rates of the HPV-associated diseases of genital 
warts and cervical cancer'' (Ref. 9). CDC concluded that the available 
scientific evidence is not sufficient to recommend condoms as a primary 
prevention strategy for the prevention of genital HPV infection, but 
that it does indicate that use of condoms may reduce the risk of 
cervical cancer. A separate review of 20 studies in 2002 found that, 
while condoms may not prevent HPV infection, they can reduce the risk 
of genital warts, cervical intraepithelial neoplasia II or III, and 
invasive cervical cancer (Ref. 20). This supports the conclusion that 
condoms can reduce the risk of genital warts, cervical intraepithelial 
neoplasia II or III, and invasive cervical cancer, which are caused by 
HPV.
    Chancroid: FDA was unable to identify any systematic review 
articles on whether condom use reduces the risk of chancroid. Although 
data are limited, FDA is aware of one prospective cohort study (Ref. 
21) of condom use for prevention of genital ulcer disease (presumed to 
be chancroid) that was conducted among prostitutes in Kenya. This study 
reported that condom use was associated with a significantly reduced 
risk of genital ulcer disease. It is important to note that the 
incidence of chancroid in the United States is extremely low.\2\ In 
1999, only 143 new cases were reported to the CDC (Ref. 22).
---------------------------------------------------------------------------

    \2\ Neither FDA's prior labeling recommendations nor the 
agency's proposed special control guidance recommend making specific 
claims for condom effectiveness against chancroid.
---------------------------------------------------------------------------

    In summary, the previously discussed information suggests that 
condoms, when used correctly and consistently, can be effective in 
reducing the risk of transmission of group II STDs. The degree of risk 
reduction would be expected to be less than that for group I STDs.

F. Nonoxynol-9 (N-9)

    Because N-9 kills HIV in vitro, some researchers in the early 1990s 
hypothesized that N-9 might help prevent or reduce the risk of HIV 
transmission in humans. This benefit, however, has not been 
demonstrated and was never included on the labeling of either drugs or 
devices, including condoms lubricated with N-9. Further, recent 
clinical data demonstrate that N-9 does not protect against HIV 
transmission, and frequent use can cause vaginal irritation, which may 
increase the risk of transmission of HIV from infected partners.
    A study of ``sex workers'' in South Africa, Benin, Cote d'Ivoire, 
and Thailand who used a vaginal N-9 gel formulation reported higher HIV 
incidence than women who used a placebo formulation (without N-9) (Ref. 
23). The study did not control for covariates such as condom use or 
anal sex, but 16 percent of women converted from HIV negative to HIV 
positive in the N-9 gel arm, compared to 12 percent of women who 
converted from HIV negative to HIV positive in the placebo group 
(p=.047). The study also showed that for the 32 percent of participants 
who reported use of a mean of more than 3.5 applications of vaginal gel 
per working day, the risk of HIV-1 infection in N-9 users was almost 
twice that in women who used the placebo gel. Researchers found that 
women who used N-9 had more vaginal lesions and vaginal lesions with 
epithelial breach, which might have facilitated the HIV transmission 
through the vaginal mucosa.
    On June 25, 2002, the United Nation's World Health Organization 
(WHO) issued a report from a meeting it held in October 2001 to assess 
the available scientific information regarding the safety and 
effectiveness of N-9 when used for contraceptive purposes and to 
provide advice to Member States on the use of N-9. (Ref. 24). The WHO 
report concluded that there was no published

[[Page 69109]]

scientific evidence that N-9-lubricated condoms provide any additional 
protection against pregnancy or STDs compared with condoms lubricated 
with other products . In view of this finding and because adverse 
effects due to the addition of N-9 to condoms were possible, the WHO 
recommendation to the Member States was that condoms lubricated with N-
9 should no longer be promoted for use in their condom distribution 
programs. However, the WHO report also concluded that ``* * * it is 
better to use N-9-lubricated condoms than no condoms.''
    Prompted by this information, FDA conducted an exhaustive review of 
available literature on N-9 related to STD transmission for the purpose 
of evaluating over-the-counter (OTC) vaginal contraceptive drug 
products containing N-9. Based on this review, FDA concluded that N-9 
does not protect against HIV/AIDS and other STDs. Furthermore, FDA 
identified potential new risks regarding HIV/AIDS associated with N-9 
use. On January 16, 2003, FDA published a notice of proposed rulemaking 
that proposed to add warnings on the labeling for over-the-counter 
vaginal contraceptive drug products that contain N-9 (68 FR 2254, 
January 16, 2003) to address this information. FDA believes that, with 
the additional warnings, consumers can safely use these OTC drug 
products for their intended use as contraceptives. The preamble for 
this proposed drug labeling rule discusses in detail FDA's scientific 
review and conclusions regarding N-9 and STD transmission, which the 
agency likewise considered in its present evaluation.
    The study of ``sex workers'' discussed previously in this document 
and others discussed in the preamble to the proposed labeling rule for 
vaginal contraceptive drugs containing N-9 were conducted using N-9 
drug products, not latex condoms containing N-9 in the lubricant. FDA 
is aware of only one study specifically examining the effect on STD 
risk of N-9 in condom lubricant (Ref. 25). The study found no 
additional protective effect for gonorrhea and chlamydia. In addition, 
FDA believes the literature regarding N-9 vaginal contraceptive drug 
products establishes that N-9 does not protect against HIV/AIDS or 
other STDs, and also indicates that vaginal irritation can result from 
exposure to N-9, including in amounts similar to that found on N-9 
lubricated condoms. That literature also indicates that such irritation 
presents a potential increased risk of HIV/AIDS transmission if a user 
is subsequently exposed to genital secretions from an infected partner.
    In addition to the information regarding vaginal irritation and 
subsequent increased risk of HIV transmission associated with N-9 use, 
recent scientific studies also provide evidence indicating that N-9 
damages rectal tissue and may increase transmission of infectious 
agents through the rectum. In animal studies comparing N-9 rectal 
lubricant against lubricant that is N-9 free, shortened time until 
infection occurred in animals pretreated with the N-9 product (Ref. 
26).
    Histologic abnormalities were more common on rectal biopsy 
following N-9 use compared to placebo lubricant (89 percent vs. 69 
percent) (Ref. 27). In a different study, rectal lavage following 
application of N-9 gel showed sheets of exfoliated epithelium 15 
minutes following product application. No sheets of cells were observed 
15 minutes following application of the control product. Finally, no 
sheets of cells were noted 8 to 12 hours following application of 
either product (Ref. 28).
    FDA is not aware of studies that have been conducted expressly to 
determine whether use of N-9 during anal intercourse increases the risk 
of HIV acquisition in humans. However, FDA believes that the evidence 
described previously in this document regarding the increased 
likelihood of HIV acquisition attributable to vaginal N-9 exposure, 
combined with the evidence of anal tissue disruption from N-9, suggests 
a similar risk in that context.

G. Contraception

    As stated earlier in this document, condoms are also used to help 
prevent unintended pregnancy. The effectiveness of condoms as a 
contraceptive has been well established for years, as indicated in 
FDA's 1980 classification regulation and reaffirmed by recently 
published contraceptive studies on commercially available condoms 
(Refs. 5, 6, 29, and 30). These studies show that the typical use 
pregnancy rate after 6 month's reliance on condoms is 5.4 percent to 
7.9 percent. These studies also show that correct and consistent use 
can significantly lower the failure (pregnancy) rate. Many of the same 
caveats that apply to use of a condom for STD risk reduction are 
equally important to condom use for preventing unintended pregnancy, 
e.g., correct and consistent use and factors that affect slippage and 
breakage (experience, lubrication, condom size). Attention to these 
factors is important to maximize condom protection.

IV. Proposed Rule

    FDA reviewed the previously stated information as part of our 
reexamination of condom labeling directed by Public Law 106-554. In 
light of the agency's findings from our review, FDA is proposing to 
amend the classification regulations for condoms. The proposed 
regulatory changes, discussed in the following paragraphs, are intended 
to help ensure that condoms are used safely and effectively by 
providing labeling conveying a concise, accurate message that neither 
exaggerates the degree of overall protection provided by condoms, nor 
undervalues overall STD risk reduction provided by condom use.

A. Overview of Regulatory Changes

    First, FDA is proposing to amend the identification sections of the 
classification regulations for condoms with and without spermicidal 
lubricant to change the wording ``venereal disease'' to ``sexually 
transmitted diseases,'' to reflect current medical terminology. These 
identification sections will continue to encompass condoms made of all 
materials, including natural membrane (skin) and synthetics, as well as 
latex. Second, FDA is proposing to add classification sections to each 
of the regulations, segregating the subset of condoms in each 
classification that are made of latex. Finally, FDA is proposing to 
designate a special controls guidance document with labeling 
recommendations for latex condoms.
    As previously noted, latex condoms with and without spermicidal 
lubricant were classified into class II prior to the effective date of 
the SMDA provisions that broadened the definition of class II devices 
to establish special controls beyond mandatory performance standards. 
Developing a special controls guidance document as the means to provide 
reasonable assurance of the safety and effectiveness of condoms was not 
a regulatory option at the time of their original classification. Under 
the authority provided by SMDA, FDA is now able to propose the 
designation of a guidance document as a special control the agency 
believes will, together with the general controls, reasonably assure 
the safety and effectiveness of these devices. FDA has developed a 
draft special controls guidance entitled ``Class II Special Controls 
Guidance Document: Labeling for Male Condoms Made of Natural Rubber 
Latex.'' This draft guidance document describes means by which latex 
condoms with and without spermicidal lubricant may comply with the 
requirement of special controls for

[[Page 69110]]

class II devices. The draft guidance document identifies the issues 
associated with these devices and recommends addressing these issues 
through labeling.
    The current voluntary guidance recommendations for condom labeling 
do not address some of the important information FDA has identified in 
this proposed rule. In particular, current labeling does not provide 
specific information about the reduced protection condoms offer against 
transmission of certain STDs, such as HPV, that can be transmitted 
through contact with infected skin outside the area covered by the 
condom. In addition, current labeling does not provide specific 
information about the potential risks associated with the use of the 
spermicidal lubricant nonoxynol-9 (N-9) in condoms. FDA believes that 
providing consumers with this additional information on condom labeling 
can improve the safe and effective use of condoms. More accurate 
information about the risks and benefits of condom use with respect to 
STD transmission can lead to better choices by individuals who seek to 
protect themselves against these infections and potentially to reduced 
transfer of STDs.
    The labeling recommendations in the draft guidance are intended to 
provide information to users of latex condoms with and without 
spermicidal lubricant. The draft special controls guidance recommends 
labeling to inform users about the extent of protection provided by 
condoms against unintended pregnancy and against various types of STDs, 
as well as information about possible risks associated with exposure to 
N-9 contained in the spermicidal lubricant of some condoms. The 
labeling recommendations provide important information for condom users 
to assist them in determining whether latex condoms are appropriate for 
their needs and, if so, to determine whether a condom with or without 
N-9 lubricant is most suitable. Many of the labeling recommendations 
are similar to statements in existing condom labeling, but are being 
updated to reflect current information. The labeling recommendations 
related to N-9 are more comprehensive than existing labeling.
     FDA believes that this draft guidance is an appropriate special 
control to help provide reasonable assurance of the safety and 
effectiveness of latex condoms and latex condoms with spermicidal 
lubricant containing N-9. The following section discusses the issues 
requiring special controls and how FDA's proposed special control 
guidance document, announced elsewhere in this issue of the Federal 
Register, recommends addressing them.

B. Issues Requiring Special Controls

    From its general knowledge of condoms and its specific review of 
the scientific evidence regarding the overall effectiveness of condoms 
in preventing STD transmission, FDA has identified several issues 
associated with the use of latex condoms that require special controls 
to provide reasonable assurance of safety and effectiveness. As 
addressed in more detail in the following paragraphs, the draft 
guidance document provides labeling recommendations that address the 
risks of unintended pregnancy and of STD transmission, the issue of 
incorrect and inconsistent use (which undermines the effectiveness of 
the condom in protecting against unintended pregnancy and STD 
transmission), and the risks and limited benefits presented by N-9, 
which is used in latex condoms with spermicidal lubricant.
1. Unintended Pregnancy
    One of the principal intended uses of latex condoms is 
contraception. Although latex condoms can greatly reduce the risk of 
unintended pregnancy, they cannot eliminate this risk. In addition, as 
discussed elsewhere in this document, N-9, which is used in the 
lubricant of some condoms, kills sperm, but the degree of additional 
contraceptive protection that it adds to the condom has not been 
measured.
    The draft special controls guidance document recommends that the 
labeling indicate that, when used correctly, latex condoms can greatly 
reduce, but do not eliminate, the likelihood of pregnancy. The draft 
guidance also recommends that the labeling include a comparative 
contraceptive effectiveness table with pregnancy rates for barrier 
contraceptives. This table is provided in the draft guidance and is 
intended to enable contraceptive users to compare alternatives and make 
appropriate choices.
    The draft special controls guidance document also includes a 
recommendation that the labeling for latex condoms with N-9 state that 
the pregnancy protection that N-9 provides has not been measured. If 
the proposed rule designating a special control and the accompanying 
guidance become final, the new statement will supersede the provision 
originally included in the order reclassifying latex condoms with N-9 
from class III to class II (47 FR 49201).
2. Transmission of STDs
    The other principal intended use of latex condoms is protection 
against the transmission of STDs. In developing the special control, 
FDA examined the plausibility of STD risk reduction and other 
scientific evidence, explained previously in section III of this 
document. This body of evidence indicates that as an overall matter, 
latex condoms are effective at reducing the risk of STD transmission, 
but that differences exist in the level of risk reduction provided by 
latex condoms with respect to two general groups of STDs, distinguished 
by their means of transmission.
    Consistent with FDA's findings in the scientific review described 
previously in this document, the draft special controls guidance 
provides specific labeling recommendations addressing the risks of STD 
transmission by explaining the effectiveness of latex condoms with 
regard to this use. The draft guidance recommends that the labeling 
explain that latex condoms can greatly reduce, but not eliminate, the 
risk of acquiring or transmitting (catching or spreading) HIV. The 
guidance also recommends labeling to inform users that STDs can be 
transmitted in various ways, including transmission to or from the 
penis and transmission by other types of sexual contact. The guidance 
recommends labeling to explain that latex condoms can reduce the risk 
of STDs that are spread to or from the penis by direct contact with the 
vagina and genital fluids, such as gonorrhea and chlamydia.
     It further recommends labeling that indicates that some STDs, such 
as genital herpes and HPV, may also be transmitted by contact with 
infectious skin or mucosa not covered by the condom, and that condoms 
provide less protection against these STDs. Labeling should clarify 
that, even for these STDs, however, there may be some benefits from 
correct and consistent use, such as a lower risk of catching or 
spreading herpes infection and a lower risk of developing some HPV-
related diseases, such as genital warts and cervical cancer.
    The guidance for condom labeling does not recommend including 
information about other ways to prevent the transmission of STDs or to 
reduce the adverse clinical outcomes associated with these infections. 
There is important additional public health information about 
strategies to prevent transmission of HPV and to reduce serious 
clinical outcomes. These strategies include abstinence for men

[[Page 69111]]

and women and regular cervical screening for women. However, the agency 
believes its primary role in this area is its jurisdiction over 
labeling for latex condoms and that its main goal must be to ensure 
that such labeling supports the safe and effective use of latex condoms 
by users who have chosen latex condoms for protection. At this time, 
the agency has concluded that it would not be useful to include in 
condom labeling additional educational information about social 
behaviors or public health programs that can reduce the risk and 
consequences of STD transmission. Additional information in condom 
labeling may confuse condom purchasers or cause them to overlook 
important messages. However, providing this information through other 
mechanisms not under FDA's jurisdiction may be beneficial.
    FDA believes the message it has crafted in its labeling 
recommendations is a balanced recognition of the benefits and limits of 
condoms for reducing STDs. The guidance does recommend that condom 
users consult health care professionals or seek additional information 
about STDs from reputable governmental agencies. FDA's recommended 
labeling is also likely to be a springboard for new initiatives to 
inform and educate public health officials, health educators, and--in 
the end--potential condom users. FDA fully expects to partner with 
Federal, State, and local public health officials to help develop such 
informational and educational materials.
    Later in this proposal, FDA is specifically requesting comments 
from the public about the value of adding additional information to 
condom labeling about other ways to prevent the spread of HPV and the 
clinical outcomes that may develop from that infection.
3. Incorrect or Inconsistent Use
    In order for latex condoms to achieve a protective effect against 
the risks identified above, they must be used correctly and 
consistently. Incorrect use can undermine the effectiveness of the 
condom against the likelihood of unintended pregnancy and risks of STD 
transmission. Inconsistent use, for example, not using a condom with 
every act of intercourse, can also diminish the effectiveness of the 
condom against the risks of unintended pregnancy and STD transmission.
    The draft special controls guidance document recommends that the 
labeling include appropriate precautions to help reduce the incorrect 
and inconsistent use of latex condoms. The draft guidance recommends 
specific precautions on using, storing, and lubricating latex condoms.
4. Issues Associated With N-9 in Condoms With Spermicidal Lubricant
    As discussed previously in this document, since 1982, condoms with 
N-9 in the lubricant have been required to bear a statement addressing 
the contraceptive effectiveness of N-9 in order to be classified under 
Sec.  884.5310. No claims relating N-9 to the effectiveness of condoms 
in preventing STD transmission have been permitted on condom labeling. 
Subsequently, new information has been developed that demonstrates that 
there are risks associated with N-9 that may outweigh its benefits as a 
spermicidal lubricant for certain users and that confirms that N-9 
provides no benefit for STD prevention.
    Specifically, as explained in the previous sections, based on its 
review of the available scientific evidence, FDA concludes that N-9 
kills sperm; however, the additional pregnancy protection provided by 
N-9 has not been measured. This limited contraceptive benefit clearly 
does not apply when a condom is used for anal sex. Furthermore, N-9 on 
the condom does not protect against HIV/AIDS or other STDs. FDA also 
concludes that N-9 can irritate the vagina, which may increase the risk 
of HIV/AIDS transmission from an infected partner. Additionally, 
clinical data demonstrate that N-9 can irritate the cells lining the 
rectum, a finding that, in combination with other information about the 
transmissibility of HIV, indicates that N-9 may increase the risk of 
HIV transmission from an infected partner when used for anal sex. Given 
these factors, for some users, risks associated with N-9 may outweigh 
the benefits of using a condom containing N-9 in the spermicidal 
lubricant. The recommended labeling in the draft special controls 
guidance instructs such users to choose a latex condom without N-9.
    From discussions with condom manufacturers, FDA's understanding is 
that a large proportion of couples using condoms with N-9 are using 
them primarily for contraceptive protection and are at low risk for 
HIV/AIDS infection. To provide reasonable assurance of safe and 
effective use, however, users need to know about the increased risk of 
HIV acquisition from an infected partner that might be associated with 
exposure to N-9, including exposure resulting from use of condoms 
containing N-9 in the lubricant, as well as understand the scope of 
benefits provided by latex condoms lubricated with N-9. Through the 
proposed designation of the special controls guidance document, FDA 
seeks to provide decisionmaking information and cautions that should 
permit users to determine whether a latex condom with spermicidal 
lubricant is appropriate for their needs.
    Specifically, FDA's draft special controls guidance document 
recommends that the labeling for latex condoms with spermicidal 
lubricant state that the product contains the spermicide N-9, which 
kills sperm, but that the pregnancy protection provided by N-9 has not 
been measured. The draft guidance also recommends that the labeling 
state that the N-9 lubricant on the condom does not protect against 
HIV/AIDS or other STDs. Including this information permits potential 
users of condoms with N-9 to evaluate the benefits that this particular 
type of condom may offer, particularly in relation to other latex 
condoms. As discussed in FDA's proposed rule on OTC vaginal 
contraceptive drug products containing N-9, information currently 
available to the general public creates the misperception that N-9 
might help decrease the risk of becoming infected with HIV and other 
STDs (68 FR 2254). Addressing the lack of STD protection provided by N-
9 is therefore necessary to help assure safe and effective use of 
condoms with N-9 because the public may mistakenly believe that N-9 
does provide this benefit.
    In addition, the draft special controls guidance document 
recommends that condom labeling inform users that use of N-9 can 
irritate the vagina and that this may increase the risk of getting HIV/
AIDS from an infected partner. Labeling should also inform users that 
if they or their partner have HIV/AIDS, or if their infection status is 
unknown, they should choose a latex condom without N-9. In addition, 
given that use of N-9, which is intended solely for contraceptive 
effect, offers no benefit for anal intercourse, and that rectal use of 
N-9 may increase the risk of HIV/AIDS transmission, the proposed 
labeling warns that N-9 can irritate the rectum and that condoms with 
N-9 should not be used for anal sex.
    FDA believes that the designation of this special control, which 
addresses the information developed since the 1982 reclassification of 
condoms with spermicidal lubricant into class II, together with general 
controls, should reasonably assure the safety and effectiveness of 
these devices. Crafting labeling for these devices does present unique 
difficulties, however. Unlike OTC vaginal contraceptive drugs

[[Page 69112]]

containing N-9, latex condoms (both with and without N-9) are intended 
for STD prevention as well as contraception. While the N-9 lubricant 
provided on some condoms is intended to support only the contraceptive 
use of the condom, this N-9 lubricant component may also 
unintentionally increase the risk of transmission of HIV if a person 
were exposed to an infected partner's secretions after first being 
exposed to the N-9 lubricant on the condom. For example, this increased 
risk scenario could occur if a person had sex using a condom with N-9 
and then subsequently had sex with an infected partner who did not use 
any condom. At the same time, for reasons explained in the prior 
sections, latex condoms with N-9 are effective barrier devices, and it 
is this barrier effectiveness that is the source of their protection 
against HIV/AIDS and other STDs.
     For these reasons, the proposed labeling in the draft special 
controls guidance document indicates that latex condoms (both with and 
without spermicidal lubricant containing N-9), when used correctly 
every time you have sex, greatly reduce, but do not eliminate, the risk 
of catching or spreading HIV, while also indicating that persons who 
may be at risk of HIV exposure should choose latex condoms without N-9. 
We welcome comments on this labeling and on any means of improving it 
to minimize confusion. In addition, in section VIII of this document, 
FDA specifically requests comments on whether this special control is 
sufficient to provide a reasonable assurance of the safety and 
effectiveness of latex condoms with spermicidal lubricant containing N-
9, or whether there are other special controls that FDA should 
consider. FDA also requests comments on whether special controls alone 
are sufficient to provide a reasonable assurance of the safety and 
effectiveness of latex condoms with spermicidal lubricant containing N-
9 or whether the risks of N-9 outweigh the potential contraceptive 
benefits the spermicide adds to the barrier protection of condoms.
    At this time, FDA is not proposing to designate a special control 
for any condoms made of natural membrane (skin) or synthetic materials. 
Discussions with the condom industry indicate that condoms made from 
natural rubber latex represent nearly 98 percent of the U.S. retail 
market for condoms. The agency understands that all condoms distributed 
by public health and other organizations are also made from natural 
rubber latex, based on the agency's discussions with manufacturers. The 
agency believes, therefore, that the recommendations in the draft 
special controls guidance document address the vast majority of condoms 
distributed in the United States. However, at a future date, FDA also 
intends to address condoms made from other materials that are not 
specifically addressed by this guidance. Until FDA provides further 
specific guidance for these products, manufacturers of synthetic 
condoms may consult Part C of FDA's guidance document entitled 
``Testing Guidance for Male Condoms Made From New Material (June 25, 
1995),'' available at: http://www.fda.gov/cdrh/ode/oderp455.html, and 
manufacturers of natural membrane condoms may consult the guidance 
document entitled ``Guidance for Industry-Uniform Contraceptive 
Labeling (July 23, 1998),'' available at: http://www.fda.gov/cdrh/ode/contrlab.html.
    FDA believes, however, that most of the recommendations contained 
in the draft special controls guidance document for latex condoms 
regarding labeling to address N-9 are also applicable to nonlatex 
condoms containing N-9, and encourages manufacturers to follow those 
aspects, as noted in the draft guidance itself. We also specifically 
solicit comment in section VIII of this document on whether the 
recommendations in the proposed draft guidance that address issues 
related to N-9 should be proposed as a special control for all condoms 
with spermicidal lubricant, regardless of material.

C. Implementation and Proposed Effective and Compliance Dates

    After reviewing public comments on this proposed rule and draft 
guidance document, FDA intends to finalize the guidance document and to 
issue a final rule for condoms with and without spermicidal lubricant, 
which will make that guidance document effective as the special control 
for latex condoms with and without spermicidal lubricant. FDA proposes 
to implement any such final rule as follows. We propose that any final 
rule based on this proposal become effective 30 days after the date of 
its publication in the Federal Register. We propose that latex condoms 
cleared for marketing on or after this effective date (but submitted in 
510(k)s filed before the effective date) comply with the requirement of 
special controls by following the recommendations in the special 
control or providing equivalent assurances of safety and effectiveness 
no more than 60 days after the effective date of any final rule based 
on this proposal. Premarket notification submissions (510(k)s) for new 
latex condoms with or without spermicidal lubricant, filed after the 
effective date of any final rule based on this proposal, must address 
the issues covered in the special controls guidance document when the 
510(k) is submitted. However, the firm submitting a 510(k) needs only 
to show that its device meets the recommendations of the guidance or in 
some other way provides equivalent assurances of safety and 
effectiveness.
    FDA proposes that latex condoms legally marketed before the 
effective date of any final rule resulting from this proposal comply 
with the requirement of special controls by following the 
recommendations in the special controls guidance document or in some 
other way providing equivalent assurances of safety and effectiveness 
within 12 months after the date of publication of the final rule based 
on this proposal in the Federal Register (11 months after the effective 
date of the final rule based on this proposal). If the issues requiring 
special controls are addressed by labeling as recommended in the 
special controls guidance document, no new premarket notification 
(510(k)) or other report need be filed to address the changes made. 
(However, if a manufacturer chooses to satisfy the requirement of 
special controls by making other changes to the device that trigger the 
submission of a new 510(k) in accordance with Sec.  807.81(a)(3), a new 
submission will be required.)
    This dual compliance date proposal is intended to allow depletion 
of stocks of condoms with existing labeling, as well as production of 
condoms with new labeling. Based on discussion with major 
manufacturers, we believe that the majority of latex condoms reach 
final users well within 12 months of leaving manufacturer control. We 
welcome comment on our estimate and on the proposed implementation 
strategy in general.

V. 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.

VI. Analysis of Impacts

    FDA has examined the impacts of the proposed 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

[[Page 69113]]

benefits of available regulatory alternatives and, when regulation is 
necessary, to select regulatory approaches that maximize net benefits 
(including potential economic, environmental, public health and safety, 
and other advantages; distributive impacts; and equity). The agency 
believes that this proposed rule is consistent with the principles 
identified in Executive Order 12866. The Office of Management and 
Budget (OMB) has determined that this proposed rule is a significant 
regulatory action as defined by the Executive order and so is subject 
to OMB review.
    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 proposed rule will 
have a significant economic impact on a substantial number of small 
entities, but recognizes the uncertainty of its estimates. Because the 
agency acknowledges that many affected entities are small entities, the 
analysis presented below, along with this preamble, constitutes the 
agency's Initial Regulatory Flexibility Analysis, and the agency 
specifically solicits comments on its estimates and analysis of the 
impact of the rule on those small entities.
    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 $115 million, using the most current (2003) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

A. Background

    The purpose of this proposed rule is to amend the classification 
regulations for condoms and condoms with spermicidal lubricant to 
designate a labeling guidance as a special control for latex condoms 
within either classification. (FDA intends to address condoms made from 
other materials at a future date.) As discussed earlier in this 
preamble, condoms and condoms with spermicidal lubricant have been 
previously classified into class II in accordance with section 513 of 
the act. The draft special controls guidance identifies particular 
issues associated with these devices and recommends labeling to address 
those issues. The current voluntary guidance recommendations for condom 
labeling do not address some of the important risk information FDA has 
identified in this proposed rule. In particular, current labeling does 
not provide specific information about the reduced protection condoms 
offer against transmission of certain STDs, such as HPV, that can be 
transmitted through contact with infected skin outside the area covered 
by the condom. In addition, current labeling does not provide specific 
information about the potential risks associated with the use of the 
spermicidal lubricant nonoxynol-9 (N-9) in condoms. FDA believes that 
providing consumers with this additional information on condom labeling 
can improve the safe and effective use of condoms. More accurate 
information about the risks and benefits of condom use with respect to 
STD transmission can lead to better choices by individuals who seek to 
protect themselves against these infections and potentially to reduced 
transfer of STDs.
    Other options the agency considered. One option the agency 
considered was to publish its conclusions as a regular guidance 
document, rather than as a special controls guidance document. This 
approach would have made the information available to the public 
through agency publication, but it would not have required that 
manufacturers address the labeling issues FDA has identified. Unlike a 
regular guidance, which imposes no requirements, a special controls 
guidance requires that manufacturers 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. Although FDA believes that many manufacturers would 
incorporate significant portions of the new recommendations 
voluntarily, as they have in the past with respect to other 
recommendations for condom labeling, FDA concluded that a purely 
voluntary approach did not ensure sufficient compliance or consistency 
to adequately convey this important information to the public.
    The agency also considered rulemaking that would mandate specific 
new language on all condom labeling to address the concerns FDA has 
identified. The agency rejected this option because a labeling rule 
deprives manufacturers of any flexibility with respect to the way they 
provide the information to consumers and because a labeling rule is 
difficult to change or amend as new scientific information becomes 
available to update the public health message.
    The benefit of the option the agency has chosen is that 
establishing the labeling guidance as a special control means that 
manufacturers will be required to address the concerns identified in 
the guidance, although they will not be bound to use the particular 
language FDA is recommending. Since the passage of the Safe Medical 
Devices Act of 1990, FDA has been permitted to establish ``special 
controls'' as a way to ensure that a manufacturer of a Class II device 
will be able to establish the safety and effectiveness of that device. 
In addition to all the general controls that apply to all classes of 
devices (such as adverse event reporting and good manufacturing 
practices), a ``special control'' provides an additional and necessary 
level of assurance that the risks associated with a Class II device can 
be addressed by the manufacturer.
    Special control guidances have become one of the most important 
ways that FDA ensures the safety and effectiveness of Class II medical 
devices. While a special control guidance remains a ``guidance'' 
because there is no requirement to comply with the specific 
recommendations the guidance sets forth, the special control guidance 
places an obligation upon the manufacturer to address the issues and 
concerns identified in that guidance. As a practical matter, most 
manufacturers do follow the recommendations in a special controls 
guidance because it is frequently the least burdensome way for that 
manufacturer to make sure that his Class II product will meet the 
necessary standards of safety and effectiveness. However, the 
manufacturer can address the issues identified in the guidance by 
following the recommendations in the guidance or by some other means 
that provides equivalent assurances of safety and effectiveness. In 
this way, issuing a special controls labeling guidance for condoms 
ensures that manufacturers will provide consumers with the information 
they need to make an informed decision regarding the use of condoms. 
The special control guidance helps ensure that information provided to 
consumers does not exaggerate the degree of overall protection provided 
by condoms, nor undervalues the overall STD risk reduction provided by 
condom use. The agency believes this special control will, together 
with the general controls, provide reasonable assurance of the safety 
and effectiveness of those devices.

[[Page 69114]]

B. Affected Entities and Scope of Effect

    The proposed rule would affect the persons responsible for the 
labeling of latex condoms, which, in most cases, would be manufacturers 
of the vast majority of condoms, including repackagers. If a final rule 
is issued, manufacturers of condoms, including repackagers, will need 
to address the issues identified in the special controls guidance 
document. The 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 would most likely 
need changes to conform to the guidance document.
    Agency records show that approximately 35 entities that manufacture 
or repackage latex condoms would be affected by this proposed rule. FDA 
does not track the number of different product and package combinations 
or stockkeeping units (SKUs) on the market. Based on data we received 
from industry, we estimate that currently there are between 500 and 
1,000 SKUs on the market that would need labeling changes. If the 
products are sold with a retail package, the wording on each of these 
SKUs would 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 this labeling that would require changes 
would 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, we estimate that 
there would be a total of 802 to 1,605 labeling changes to retail 
packages, individual foils, and package inserts. We 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, we further assumed that for every 
three retail package redesigns there would be one foil label redesign, 
and for every four retail package redesigns, there would be one package 
insert redesign. We based these assumptions on our 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 2 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 proposed 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. 
The labeling recommendations related to N-9 are more comprehensive than 
existing labeling. In general, these changes should not require major 
changes in the design or layout of existing labeling and we believe 
that, in most cases, the changes could be incorporated without having 
to increase the dimensions of any of the labeling.
    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).\3\ Because the packaging requirements for 
condoms are similar to those of many OTC drugs, we believe 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.\4\ We request specific comment on the values and methodology 
used to estimate the costs in the following paragraphs.
---------------------------------------------------------------------------

    \3\ 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.
    \4\ The ERG cost estimates were based on estimates made in 1998. 
The annual PPI for finished consumer goods rose by 9.6 percent 
between 1998 and 2003 (from 130.7 to 143.3) http://www.cdc.gov/nchstp/dstd/Stats_trends/trends2000.pdf, extracted July 7, 2004. 
Wage estimates are from the Bureau of Labor Statistics, May 2003 
National Industry-Specific Occupational Employment and Wage 
Estimates, NAICS 339100--Medical Equipment and Supplies 
Manufacturing, (http://stats.bls.gov/oes/2003/may/naics4_339100.htm), extracted July 7, 2004. (FDA has verified the Web site 
addresses, but we are not responsible for subsequent changes to the 
Web site after this document publishes in the Federal Register.)
---------------------------------------------------------------------------

    We estimate that the regulatory component of each labeling redesign 
would require between 8 to 16 hours per SKU. Using a wage rate of 
$43.69,\5\ the incremental cost of the one-time regulatory component 
cost to redesign would be $350 to $700 per labeling redesign (8 (to 16) 
hours x $43.69/hour). The one-time cost of the graphic component was 
estimated to be $550 per labeling redesign.\6\ 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 $19.25 for a production 
employee,\7\ this cost would range from about $58 to $96 per label (3 
(to 5) hours x 19.25/hour).

[[Page 69115]]

 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 12-month implementation period we estimate that the one-
time inventory loss would range from $410 to $1,650 per foil or package 
insert and from $1,250 to $4,950 per carton.\8\
---------------------------------------------------------------------------

    \5\ Mean hourly wage for a compliance officer, SOC 13-1041, in 
NAICS 339100 is $31.21, which was increased by 40 percent to account 
for employee benefits and equals $43.69 (http://stats.bls.gov/oes/2003/may/naics4_339100.htm). (FDA has verified the Web site 
addresses, but we are not responsible for subsequent changes to the 
Web site after this document publishes in the Federal Register.)
    \6\ ERG estimated the cost at $500 per redesign. Adjusting for 
inflation, the cost would be $548 ($500 x 1.096) and was rounded to 
$550. (See footnotes 3 and 4.)
    \7\ 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://stats.bls.gov/oes/2003/may/naics4_339100.htm). (FDA has verified 
the Web site addresses, but we are not responsible for subsequent 
changes to the Web site after this document publishes in the Federal 
Register.)
    \8\ 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 12-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 
4) the 0-month estimates are approximately $1,650 and $6,575, 
respectively (e.g., $1,500 x 1.096).
---------------------------------------------------------------------------

    FDA believes that by providing a 12-month implementation period, 
manufacturers would have enough time 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 3 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 $1.5 and $7.9 million.
    The cost to individual firms to comply with this proposed 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 proposed 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, if this rule became final, the 
economic impact of this proposed rule would 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, we 
do 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.
    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 proposed rule are small as defined by SBA.
    The size of a firm alone, however, would not be a determinant 
factor on the economic impact of this proposed rule. The relative 
impact per SKU would be less for products with a high volume of sales 
because the one-time costs are spread over a larger number of units. 
The cost of actual replacement labeling should also be lower for 
products with high volume sales. Our experience with the device 
industry in general, as well as with the latex condom industry in 
particular, indicates that a small-sized company is just as likely as a 
large-sized one to have products with high sales volume and to have the 
same or a greater number of SKUs.
    The agency considered three alternatives before choosing to issue 
this proposed rule. They included the options of issuing a guidance 
that would not be designated as a special control, issuing a labeling 
regulation mandating exact wording, and the option chosen, issuing a 
proposed rule that designates a special controls guidance document with 
labeling recommendations. We rejected the issuance of a guidance 
document alone because it would not provide enough assurance that 
consumers would receive the information regarding the issues of latex 
condoms with or without N-9 and thus would not provide sufficient 
assurance of safety and effectiveness. We rejected the option of a 
labeling rule with specified wording because it would not provide 
manufacturers with any flexibility in addressing these issues today and 
would not, in the future, permit flexibility in addressing new 
scientific information relevant to these issues.
    We chose to issue a proposed rule that designates a special 
controls guidance document because it requires that the device either 
meet the recommendations or in some other way provide equivalent 
measures of safety and effectiveness. This approach protects the public 
health by ensuring that manufacturers address the issues related to 
latex condoms with or without N-9, while, at the same time, it affords 
manufacturers some flexibility in implementing the mitigation measures 
outlined in the special controls labeling guidance document.
    We also considered different implementation periods before 
proposing a 12-month implementation period. The agency believes that 
consumers should have the most up-to-date information and that this 
labeling will lead to better understanding of the health risks and 
benefits of the product. We believe that allowing for a longer 
implementation period unnecessarily postpones consumer's access to the 
information. However, an implementation period shorter than 12 months 
would increase the costs imposed by the rule, and it would be difficult 
for those manufacturers producing many SKUs to accomplish the task 
within a shorter time frame because of the large number of label 
designs that would need to be changed. We have learned through industry 
and trade association comments submitted in response to proposed OTC 
drug rules that the OTC drug industry can accommodate a 12-month 
implementation period without undue economic hardship and believe that 
the condom industry can accommodate a similar implementation period 
without undue economic effects on the industry or harmful effects on 
the costs or supply of condoms.
    As discussed earlier in this document, while we believe the cost to 
revise latex condom labeling is small, we lack sufficient specific 
information on the 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 proposal will have a significant effect on a 
substantial number of small entities, we recognize the uncertainty of 
our estimates. We request specific comments regarding the assumptions 
and methodology used in this analysis. FDA intends to consider all 
comments and data received and will reassess the economic impact of 
this proposed rule in the preamble to the final rule.

[[Page 69116]]



Table 2.--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 3.--Estimated Range of Compliance Costs by Function
----------------------------------------------------------------------------------------------------------------
                                                                                            Total
 Component    Range      Hours      Wage/hour    Cost/label     Number of   ------------------------------------
                                                                 labels           Low               High
----------------------------------------------------------------------------------------------------------------
Regulatory   low          8          $43.69     ...........      802           $280,315     ....................
            ---------------------                           ----------------------------------------------------
             high        16       ............  ...........    1,605         .............         $1,121,952
----------------------------------------------------------------------------------------------------------------
Graphic      low      ..........  ............    $550           802            441,100     ....................
            ---------------------                           ----------------------------------------------------
             high     ..........  ............  ...........    1,605         .............            882,750
----------------------------------------------------------------------------------------------------------------
Manufacturi  low          3          $19.25     ...........      802             46,317     ....................
 ng
            ---------------------                           ----------------------------------------------------
             high         5       ............  ...........    1,605         .............            154,480
----------------------------------------------------------------------------------------------------------------
Inventory    foil     ..........  ............  ...........  ..............  .............
              and
              insert
            ---------
             low      ..........  ............    $410           327            134,070
            ----------------------------------------------------------------------------------------------------
             high     ..........  $1,650           655       ..............   1,080,750
            ----------------------------------------------------------------------------------------------------
             carton   ..........  ............  ...........  ..............  .............  ....................
            ---------
             low      ..........  ............  $1,250           475            593,750     ....................
            ----------------------------------------------------------------------------------------------------
             high     ..........  ............  $4,950           950         .............          4,702,500
----------------------------------------------------------------------------------------------------------------
Total Cost                                                                   $1,495,552            $7,942,432
----------------------------------------------------------------------------------------------------------------

VII. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by OMB under the 
Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520) is not 
required.
    FDA also tentatively concludes that the special controls guidance 
document identified by this rule contains new information collection 
provisions that are subject to review and clearance by OMB under the 
PRA. Elsewhere in this issue of the Federal Register, FDA is publishing 
a notice announcing the availability of the draft guidance document 
entitled ``Class II Special Controls Guidance Document: Labeling for 
Male Condoms Made of Natural Rubber Latex''; the notice contains an 
analysis of the paperwork burden for the draft guidance.

VIII. Specific Request for Comments

    FDA welcomes comments on all aspects of the proposed regulation, 
but particularly invites comments on the following issues:
    As discussed in more detail in section IV of this document, FDA 
specifically requests comments on whether its labeling recommendations 
for condoms should include more detailed information on the prevention 
of genital HPV infection, and information on different approaches for 
prevention of cervical cancer.
    In addition, as discussed in section IV of this document, FDA 
specifically requests comments on whether this special control is 
sufficient to provide a reasonable assurance of the safety and 
effectiveness of latex condoms with spermicidal lubricant containing N-
9, or whether there are other special controls that FDA should 
consider. FDA also requests comments on whether special controls alone 
are sufficient to provide a reasonable assurance of the safety and 
effectiveness of latex condoms with spermicidal lubricant containing N-
9 or whether the risks of N-9 outweigh the potential contraceptive 
benefits the spermicide adds to the barrier protection of condoms.
    Finally, as discussed in section IV of this document, the current 
special control proposal applies only to latex condoms. FDA 
acknowledges, however, that concerns regarding N-9 in condoms with 
spermicidal lubricant would appear to be very similar for all condoms, 
nonlatex as well as latex. For purposes of making a future proposal, 
FDA solicits comment on possible special controls for nonlatex 
(including both skin and synthetic) condoms containing N-9. FDA 
solicits comments on whether the guidance currently proposed as a 
special control only for latex condoms, insofar as it addresses risks 
associated with N-9, should be proposed as that special control. FDA 
also welcomes comments suggesting alternative special controls for 
nonlatex condoms with N-9. Moreover, FDA also welcomes comments on 
potential special controls for nonlatex condoms without N-9.

[[Page 69117]]

IX. General Request for Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

X. 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 we are not responsible 
for subsequent changes to the Web site after this document publishes in 
the Federal Register.)
    1. Lytle, C. D., L. B. Routson, G. B. Seaborn, et al., ``An In 
Vitro Evaluation of Condoms as Barriers to a Small Virus,'' Sexually 
Transmitted Diseases, 1997: 24:3:161-164.
    2. Steiner, M. J., R. Foldesy, D. Cole, et al., ``Study to 
Determine the Correlation Between Condom Breakage in Human Use and 
Laboratory Test Results,'' Contraception, 1992:46:3:279-288.
    3. Free, M. J., V. Srisamang, J. Vail, et al., ``Latex Rubber 
Condoms: Predicting and Extending Shelf Life,'' Contraception, 
1996:53:4:221-229.
    4. National Institute of Allergy and Infectious Diseases, 
Workshop Summary: Scientific Evidence on Condom Effectiveness for 
Sexually Transmitted Disease (STD) Prevention, July 2001.
    5. Walsh, T. L., R. G. Frezieres, K. Peacock, et al., 
``Evaluation of the Efficacy of a Nonlatex Condom: Results From a 
Randomized, Controlled Clinical Trial,'' Perspectives on Sexual and 
Reproductive Health, 2003:35:2:79-86.
    6. Steiner, M. J., R. Dominik, R. W. Rountree, et al., 
``Contraceptive Effectiveness of Polyurethane Condom and a Latex 
Condom: A Randomized Controlled Trial,'' Obstetrics and Gynecology, 
2003:101:3:539-547. see 69117
    7. Potter, W. D. and M. de Villemeur, ``Clinical Breakage, 
Slippage and Acceptability of a New Commercial Polyurethane Condom: 
A Randomized, Controlled Study,'' Contraception, 2003:68:1:39-45.
    8. Davis, K. R. and S. C. Weller, ``The Effectiveness of Condoms 
in Reducing Heterosexual Transmission of HIV,'' Family Planning 
Perspectives, 1999: 31:6:272-279.
    9. Centers for Disease Control and Prevention, Department of 
Health and Human Services, Report to Congress: Prevention of Genital 
Human Papillomavirus Infection, 18, January 2004.
    10. Weller, S. and K. Davis, ``Condom Effectiveness in Reducing 
Heterosexual HIV Transmission (Cochrane Review),'' In: The Cochrane 
Library Issue 3, 2002, Oxford: Update Software.
    11. Pinkerton, S. D., P. R. Abramson, Effectiveness of Condoms 
in Preventing HIV Transmission, Social Science and Medicine, 1997, 
May; 44(9):1303-12.
    12. Warner, D. L., K. M. Stone, and J. W. Buchler, Using 
Epidemiology to Understand Condom Effectiveness for Preventing 
Gonorrhea, Chlamydia, and Pelvic Inflammatory Disease [abstract 
P116], 2004, National STD Prevention Conference, March 8 to 11, 
2004, Philadelphia, PA.
    13. Sanchez, J., E. Gotuzzo, J. Escamilla, et al., ``Sexually 
Transmitted Infections in Female Sex Workers: Reduced by Condom Use 
but Not Limited by a Periodic Examination Program,'' Sexually 
Transmitted Diseases, 1998:25:2:82-89.
    14. Levine, W. C., R. Revollo, V. Kaune, et al., ``Decline in 
Sexually Transmitted Disease Prevalence in Female Bolivian Sex 
Workers: Impact of an HIV Prevention Project,'' AIDS, 1998 Oct 
1;12(14):1899-1906.
    15. Ahmed, S., T. Lutalo, M. Wawer, et al., ``HIV Incidence and 
Sexually Transmitted Disease Prevalence Associated with Condom Use: 
A Population Study in Rakai, Uganda,'' AIDS, 2001 Nov 9; 
15(16):2171-9.
    16. Casper, C. and A. Wald, ``Condom Use and the Prevention of 
Genital Herpes Acquisition,'' Herpes, 2002:9:1:10-4.
    17. Wald A., A. G. M. Langenberg, K. Link, et al., ``Effect of 
Condoms or Reducing the Transmission of Herpes Simplex Virus Type 2 
From Men to Women,'' Journal of American Medical Association, 
2001:285:3100-3106.
    18. Wald A., A. Langenberg, E. Kexel, et al., ``Condoms protect 
Men and Women Against Herpes Simplex Virus Type 2 (HSV-2) 
Acquisition [abstract B9E]. Presented at the 2002 National STD 
Prevention Conference,'' March 4-7, San Diego, CA.
    19. Gottlieb, S. L., J. M. Douglas , M. Foster, et al., 
``Incidence of Herpes Simplex Virus Type 2 Infection in Five 
Sexually Transmitted Disease Clinics and the Effect of HIV/STD Risk 
Reduction Counseling,'' Journal of Infectious Diseases, 
2004:190:1059-1067.
    20. Manhart, L. E. and L. A. Koutsky, ``Do condoms prevent 
genital HPV infection, external genital warts, or cervical 
neoplasia? A meta analysis,'' Sexually Transmitted Diseases, 
2002:29:11:725-735.
    21. Cameron, D. W., E. N. Ngugi, A. R. Ronald, et al., ``Condom 
Use Prevents Genital Ulcers in Women Working as Prostitutes,'' 
Sexually Transmitted Diseases, 1991:18:3:188-191.
    22. Centers for Disease Control and Prevention, Tracking the 
Hidden Epidemics 2000, Trends in STDs in the United States, 
Chancroid (http://www.cdc/gov/nchstp/dstd/Stats_Trends/Trends2000.pdf).
    23. Van Damme, L., G. Ramjee, M. Alary, et al., ``Effectiveness 
of COL-1492, a Nonoxynol-9 Vaginal Gel, on HIV-1 Transmission in 
Female Sex Workers: A Randomized Controlled Trial,'' The Lancet, 
2002: 360; 9338: 971-977.
    24. WHO/CONRAD Technical Consultation on Nonoxynol-9: Summary 
Report, World Health Organization, Geneva, 9-10 October, 2001, pp. 
1- 27
    25. Roddy R. E., M. Cordero, K. A. Ryan, et al., ``A Randomized 
Controlled Trial Comparing Nonoxynol-9 Lubricated Condoms With 
Silicone Lubricated Condoms for Prophylaxis,'' Sexually Transmitted 
Infections, 1998: 74:116-119.
    26. Phillips, D., ``Nonoxynol-9 Enhances Rectal Infection by 
Herpes Simplex Virus in Mice,'' Contraception, 1998:57:341-348.
    27. Tabet, S. R., C. Surawicz, S. Horton, et al., ``Safety and 
Toxicity of Nonoxynol-9 Gel as a Rectal Microbicide,'' Sexually 
Transmitted Diseases, 1999:26:10:564-571.
    28. Phillips, D. ``Nonoxynol-9 Causes Rapid Exfoliation of 
Sheets of Rectal Epithelium,'' Contraception, 2000: 62:3:149-154.
    29. Frezieres, R. G., T. L. Walsh, A. L. Nelson, et al., 
``Evaluation of the Efficacy of a Polyurethane Condom: Results From 
a Randomized, Controlled Clinical Trial,'' Family Planning 
Perspectives, 1999:31:2:81-87.
    30. Gallo, M. F., D. A. Grimes, and K. F. Schulz, ``Nonlatex vs. 
Latex Male Condoms for Contraception: A Systematic Review of 
Randomized Clinical Trials,'' Contraception, 2003:68:5:319-236.
    31. Kjaer, S. K., E. I. Svare, A. M. Worm, et al., ``Human 
Papillomavirus Infection in Danish Female Sex Workers: Decreasing 
Prevalence With Age Despite Continuously High Sexual Activity,'' 
Sexually Transmitted Diseases, 2000: 27(8):438-445.
    32. Kotloff K. L., S. S. Wasserman, K. Russ, et al., ``Detection 
of Genital Human Papillomavirus and Associated Cytologic 
Abnormalities Among College Women,'' Sexually Transmitted Diseases, 
1998:25(5):243-250.
    33. Mayaud P., D. K. Gill, H. A. Weiss, et al., ``The 
Interrelation of HIV, Cervical Human Papillomavirus, and Neoplasia 
Among Antenatal Clinic Attenders in Tanzania,'' Sexually Transmitted 
Infections, 2001:77(4):248-254.
    34. 11th Report on Carcinogens, National Toxicology Program, 
January 31, 2005, (FactSheet).

List of Subjects in 21 CFR Part 884

    Medical devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 884 be amended as follows:

PART 884--OBSTETRICAL AND GYNECOLOGICAL DEVICES

    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.
    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.

[[Page 69118]]

 The condom is used for contraceptive and for prophylactic purposes 
(preventing transmission of sexually transmitted diseases). The device 
may also be used to collect semen to aid in the diagnosis of 
infertility.
    (b) Classification. (1) Class II (special controls) for condoms 
made of materials other than natural rubber latex, including natural 
membrane (skin) or synthetic.
    (2) Class II (special controls) for natural rubber latex condoms. 
The guidance document entitled ``Class II Special Controls Guidance 
Document: Labeling for Male Condoms Made of Natural Rubber Latex'' will 
serve as the special control. See Sec.  884.1(e) for the availability 
of this guidance document.
    3. Section 884.5310 is revised to read as follows:


Sec.  884.5310   Condom with spermicidal lubricant.

    (a) Identification. A condom with spermicidal lubricant is a sheath 
which completely covers the penis with a closely fitting membrane with 
a lubricant that contains a spermicidal agent, nonoxynol-9. This condom 
is used for contraceptive and for prophylactic purposes (preventing 
transmission of sexually transmitted diseases).
    (b) Classification. (1) Class II (special controls) for condoms 
made of materials other than natural rubber latex, including natural 
membrane (skin) or synthetic.
    (2) Class II (special controls) for natural rubber latex condoms. 
The guidance document entitled ``Class II Special Controls Guidance 
Document: Labeling for Male Condoms Made of Natural Rubber Latex'' will 
serve as the special control. See Sec.  884.1(e) for the availability 
of this guidance document.

    Dated: June 21, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-22611 Filed 11-10-05; 8:45 am]
BILLING CODE 4160-01-S