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.

Proposed Rules Federal Register

69102 

Vol. 70, No. 218 

Monday, November 14, 2005 

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. 

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the draft guidance document entitled 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: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• 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: 

• FAX: 301–827–6870. 

• 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 email. 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 

Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 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 (§§ 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 useeffectiveness—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 

69104 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

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 

(§§ 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: 

• Physical properties of condoms, 

• Condom slippage and breakage 

during actual use, 

• Plausibility for STD-risk reduction 

attributable to condoms, 

• Evaluations of condom 

effectiveness against STDs by other 

Federal agencies, and 

• 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 FX174 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 μm (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 lotby-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 

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

STD Exposure to and From the Head of the Penis Exposure to Infectious Skin or Mucosa (Excluding the Head of the Penis) 

Group I 

HIV/Aquired Immunodeficiency Syndrome 

(AIDS) 

✓ 

69106 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

1Trichomoniasis 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 

TABLE 1.—STDS AND USUAL ROUTE(S) OF TRANSMISSION—Continued 

STD Exposure to and From the Head of the Penis Exposure to Infectious Skin or Mucosa (Excluding the Head of the Penis) 

Neisseria gonorrhea ✓ 

Chlamydia trachomatis ✓ 

Trichomoniasis ✓ 

Hepatitis B Virus ✓ 

Group II 

Syphilis ✓ ✓ 

Genital HSV ✓ ✓ 

Genital HPV ✓ ✓ 

Chancroid ✓ ✓ 

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 peerreviewed 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 HPVassociated 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 

Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 69107 

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. 

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. 

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 HPVassociated 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 HPVassociated 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 reexposure 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: 

• 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 

• 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 

69108 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

2Neither FDA’s prior labeling recommendations 

nor the agency’s proposed special control guidance 

recommend making specific claims for condom 

effectiveness against chancroid. 

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 crosssectional 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 cervicovaginal, 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 HSV2 acquisition for women but not for men 

(Ref. 17). More recent prospective 

studies showed that condom use was 

associated with a reduced risk of HSV2 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). 

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 

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

69110 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

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 

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

69112 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

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 § 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 

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

69114 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

3Eastern 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. 

4The 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 IndustrySpecific 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.) 

5Mean 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.) 

6ERG 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.) 

7Mean 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.) 

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-theCounter 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. 

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). 

Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 69115 

8ERG 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). 

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

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 onetime 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 firminitiated 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-todate 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. 

69116 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

TABLE 2.—ESTIMATED NUMBER OF

LABEL DESIGNS THAT MAY NEED TO

BE MODIFIED

Component Low-End Estimate 

High-End 

Estimate 

Cartons 475 950 

TABLE 2.—ESTIMATED NUMBER OF

LABEL DESIGNS THAT MAY NEED TO

BE MODIFIED—Continued 

Component Low-End Estimate 

High-End 

Estimate 

Foils 183 367 

TABLE 2.—ESTIMATED NUMBER OF

LABEL DESIGNS THAT MAY NEED TO

BE MODIFIED—Continued 

Component Low-End Estimate 

High-End 

Estimate 

Inserts 144 288 

Total 802 1,605 

TABLE 3.—ESTIMATED RANGE OF COMPLIANCE COSTS BY FUNCTION

Component Range Hours Wage/hour Cost/label Number of labels 

Total 

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 

Manufacturing low 3 $19 .25 802 46,317 

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. 

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

§ 884.5300 Condom. 

(a) Identification. A condom is a 

sheath which completely covers the 

penis with a closely fitting membrane. 

69118 Federal Register / Vol. 70, No. 218 / Monday, November 14, 2005 / Proposed Rules 

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 § 884.1(e) for the 

availability of this guidance document. 

3. Section 884.5310 is revised to read 

as follows: 

§ 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 § 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 

DEPARTMENT OF THE INTERIOR 

Minerals Management Service 

30 CFR Parts 250, 251, and 280 

RIN 1010–AD23 

Oil, Gas, and Sulphur Operations and 

Leasing in the Outer Continental Shelf 

(OCS)—Recovery of Costs Related to 

the Regulation of Oil and Gas 

Activities on the OCS 

AGENCY: Minerals Management Service 

(MMS), Interior. 

ACTION: Proposed rule. 

SUMMARY: MMS is proposing regulations 

which impose new fees to process 

certain plans, applications, and permits. 

The proposed service fees would offset 

MMS’s costs of processing these plans, 

applications, and permits. 

DATES: MMS will consider all comments 

received by January 13, 2006. MMS will 

begin reviewing comments and may not 

fully consider comments received after 

January 13, 2006. 

ADDRESSES: You may submit comments 

on the proposed rule by any of the 

following methods listed below. Please 

use the regulatory identifier number 

(RIN) 1010-AD23 as an identifier in your 

message. See also Public Comment 

Procedures under Procedural Matters. 

• Federal e-Rulemaking Portal: 

http://www.regulations.gov. Follow the 

instructions on the website for 

submitting comments. 

• E-mail MMS at 

rules.comments@mms.gov. Use the RIN 

in the subject line. 

• Fax: 703–787–1546. Identify with 

the RIN. 

• Mail or hand-carry comments to the 

Department of the Interior; Minerals 

Management Service; Attention: Rules 

Processing Team (RPT); 381 Elden 

Street, MS–4024; Herndon, Virginia 

20170–4817. Please reference ‘‘Recovery 

of Costs Related to the Regulation of Oil 

and Gas Activities on the OCS–AD23’’

in your comments. 

You may also send comments on the 

information collection aspects of this 

rule directly to the Office of 

Management and Budget (OMB) via: 

OMB e-mail: 

(OIRA_DOCKET@omb.eop.gov); mail or 

hand carry to the Office of Information 

and Regulatory Affairs, OMB Attention: 

Desk Officer for the Department of the 

Interior (1010–AD23) or by fax (202) 

395–6566. Please also send a copy to 

MMS. 

FOR FURTHER INFORMATION CONTACT: 

Martin Heinze, Program Analyst, Office 

of Planning, Budget and International 

Affairs at (703) 787–1010. 

SUPPLEMENTARY INFORMATION: 

Background 

Federal agencies are generally 

authorized to recover the costs of 

providing services to non-federal 

entities through the provisions of the 

Independent Offices Appropriation Act 

of 1952 (IOAA), 31 U.S.C. 9701. The Act 

requires implementation through 

rulemaking. There are several policy 

documents that provide MMS guidance 

on the process of charging applicants for 

service costs. The governing language 

concerning cost recovery can be found 

in OMB Circular No. A–25 which states 

in part, ‘‘The provisions of this Circular 

cover all federal activities that convey 

benefits to recipients beyond those 

accruing to the general public. * * * 

When a service (or privilege) provides 

special benefits to an identifiable 

recipient, beyond those that accrue to 

the general public, a charge would be 

imposed (to recover the full costs to the 

Federal Government for providing this 

specific benefit, or the market price). 

* * * The general policy is that user 

charges will be instituted through the 

promulgation of regulations.’’ The 

Department of the Interior (DOI) Manual 

mirrors this policy (330 DM 1.3 A.). 

In this rulemaking, ‘‘cost recovery’’

means reimbursement to MMS for its 

costs of performing a service by 

charging a fee to the identifiable 

applicant/beneficiary of the service. 

Further guidance is provided by 

Solicitor’s Opinion M–36987, ‘‘BLM’s 

Authority to Recover Costs of Minerals 

Document Processing’’ (December 5, 

1996). As explained in that Solicitor’s 

Opinion, some costs, such as the costs 

of programmatic environmental studies 

and programmatic environmental 

assessments in support of a general 

agency program are not recoverable 

because they create an ‘‘independent 

public benefit’’ rather than a specific 

benefit to an identifiable recipient. Id. at 

9–10. 

On March 25, 2005, MMS published 

an Advance Notice of Proposed 

Rulemaking (ANPR) in the Federal 

Register titled, ‘‘Recovery of Costs 

Related to the Regulation of Oil and Gas 

Activities on the Outer Continental 

Shelf,’’ (70 FR 15246). (The cost 

recovery fees MMS is addressing in this 

proposed rule are for different activities 

than those addressed in the recently 

promulgated final rule issued on August 

25, 2005 (70 FR 49871)). Through the 

ANPR, MMS alerted the public that we 

seek to recover the costs of processing 

certain permits and applications 

through the rulemaking process. MMS 

believes that cost recovery for the MMSprovided service of reviewing and