Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations 51021

‘‘significant regulatory action’’ under

Executive Order 12866; (2) is not a

‘‘significant rule’’ under DOT

Regulatory Policies and Procedures (44

FR 11034, February 26, 1979); and (3)

will not have a significant economic

impact, positive or negative, on a

substantial number of small entities

under the criteria of the Regulatory

Flexibility Act. A copy of the final

evaluation prepared for this action is

contained in the rules docket. A copy of

it may be obtained by contacting the

rules docket at the location provided

under the caption ADDRESSES.

List of Subjects in 14 CFR Part 39

Air transportation, Aircraft, Aviation

safety, Incorporation by reference,

Safety.

Adoption of the Amendment

Accordingly, pursuant to the

authority delegated to me by the

Administrator, the Federal Aviation

Administration amends part 39 of the

Federal Aviation Regulations (14 CFR

part 39) as follows:

PART 39—AIRWORTHINESS

DIRECTIVES

1. The authority citation for part 39

continues to read as follows:

Authority: 49 USC 106(g), 40113, 44701.

§39.13 [Amended]

2. Section 39.13 is amended by

adding a new airworthiness directive

(AD) to read as follows:

97–20–11 Socata—Groupe Aerospatiale:

Amendment 39–10148; Docket No. 97–

CE–15–AD.

Applicability: Model TBM 700 airplanes

(serial numbers 1 through 109), certificated

in any category, that do not have the main

landing gear (MLG) inboard doors and the

door locking control mechanism removed

(MOD 70–065–32) in accordance with the

Technical Instruction of Modification OPT70

KO59–32, dated December 1995, as

referenced in Socata Service Bulletin (SB)

70–073, Amdt. 1, dated June 1996.

Note 1: This AD applies to each airplane

identified in the preceding applicability

provision, regardless of whether it has been

modified, altered, or repaired in the area

subject to the requirements of this AD. For

airplanes that have been modified, altered, or

repaired so that the performance of the

requirements of this AD is affected, the

owner/operator must request approval for an

alternative method of compliance in

accordance with paragraph (d) of this AD.

The request should include an assessment of

the effect of the modification, alteration, or

repair on the unsafe condition addressed by

this AD; and, if the unsafe condition has not

been eliminated, the request should include

specific proposed actions to address it.

Compliance: Required within the next 100

hours time-in-service after the effective date

of this AD or within the next 6 calendar

months after the effective date of this AD,

whichever occurs first, unless already

accomplished.

To prevent the MLG from failing to extend

because of corroded MLG inboard locking

hinges, which could result in loss of control

of the airplane during landing operations,

accomplish the following:

(a) Remove the MLG inboard doors and the

door locking control mechanism (MOD 70–

065–32) in accordance with the Technical

Instruction of Modification OPT70 KO59–32,

dated December 1995, as referenced in Socata

SB 70–073, Amdt. 1, dated June 1996.

(b) As of the effective date of this AD, no

person may undo MOD 70–065–32 on any

affected airplane, by reinstalling the MLG

inboard doors and the door locking control

mechanism.

(c) Special flight permits may be issued in

accordance with sections 21.197 and 21.199

of the Federal Aviation Regulations (14 CFR

21.197 and 21.199) to operate the airplane to

a location where the requirements of this AD

can be accomplished.

(d) An alternative method of compliance or

adjustment of the compliance time that

provides an equivalent level of safety may be

approved by the Manager, Small Airplane

Directorate, FAA, 1201 Walnut, suite 900,

Kansas City, Missouri 64106. The request

shall be forwarded through an appropriate

FAA Maintenance Inspector, who may add

comments and then send it to the Manager,

Small Airplane Directorate.

Note 2: Information concerning the

existence of approved alternative methods of

compliance with this AD, if any, may be

obtained from the Small Airplane

Directorate.

(e) The removal required by this AD shall

be done in accordance with the Technical

Instruction of Modification OPT70 KO59–32,

dated December 1995, as referenced in Socata

Service Bulletin 70–073, Amdt. 1, dated June

1996. This incorporation by reference was

approved by the Director of the Federal

Register in accordance with 5 U.S.C. 552(a)

and 1 CFR part 51. Copies may be obtained

from Socata—Groupe Aerospatiale, Socata

Product Support, Aeroport Tarbes-OssunLourdes, B P 930, 65009 Tarbes Cedex,

France; or the Product Support Manager

Socata—Groupe Aerospatiale, North Perry

Airport, 7501 Pembroke Road, Pembroke

Pines, Florida 33023. Copies may be

inspected at the FAA, Central Region, Office

of the Regional Counsel, Room 1558, 601 E.

12th Street, Kansas City, Missouri, or at the

Office of the Federal Register, 800 North

Capitol Street NW., suite 700, Washington,

DC.

(f) This amendment (39–10148) becomes

effective on November 13, 1997.

Issued in Kansas City, Missouri, on

September 24, 1997.

Henry A. Armstrong,

Acting Manager, Small Airplane Directorate,

Aircraft Certification Service.

[FR Doc. 97–25832 Filed 9–29–97; 8:45 am]

BILLING CODE 4910–13–U

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96N–0119]

21 CFR Part 801

Natural Rubber-Containing Medical

Devices; User Labeling

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule requiring labeling statements on

medical devices, including device

packaging containing natural rubber that

contacts humans. The rule requires

labeling of medical devices containing

natural rubber latex that contacts

humans to state: ‘‘Caution: This Product

Contains Natural Rubber Latex Which

May Cause Allergic Reactions.’’;

labeling of medical devices containing

dry natural rubber that contacts humans

to state: ‘‘This Product Contains Dry

Natural Rubber.’’; labeling of medical

devices containing natural rubber latex

in their packaging that contacts humans

to state: ‘‘Caution: The Packaging of

This Product Contains Natural Rubber

Latex Which May Cause Allergic

Reactions.’’; labeling of medical devices

containing dry natural rubber in their

packaging that contacts humans to state:

‘‘The Packaging of This Product

Contains Dry Natural Rubber.’’; and that

the claim of hypoallergenicity be

removed from the labeling of medical

devices that contain natural rubber.

These requirements are being

established in response to numerous

reports of severe allergic reactions and

deaths related to a wide range of

medical devices containing natural

rubber.

EFFECTIVE DATE: This final rule is

effective September 30, 1998.

FOR FURTHER INFORMATION CONTACT:

Donald E. Marlowe, Center for Devices

and Radiological Health (HFZ–100),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20850,

301–443–2444, FAX 301–443–2296.

SUPPLEMENTARY INFORMATION:

I. Background

Natural latex is a milky fluid obtained

in commercial quantities primarily from

the Heavea brasiliensis (rubber) tree.

There is often confusion concerning the

terminology used to describe the raw

agricultural materials derived from

rubber-producing plants; products made

from various intermediate forms of the
51022 Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations

raw agricultural material (e.g., natural

rubber latex, dry natural rubber);

formulations of synthetic latex and

synthetic rubber to which natural rubber

has been added; and synthetic rubber

and synthetic latex formulations that do

not contain natural rubber.

‘‘Natural latex,’’ for the purposes of

this rule, is defined as a milky fluid that

consists of extremely small particles of

rubber obtained from plants, principally

from the H. brasiliensis (rubber) tree,

dispersed in an aqueous medium. It

contains a variety of naturally occurring

substances, including cis-1,4-

polyisoprene in a colloidal suspension

(Ref. 1) and plant proteins, which are

believed to be the primary allergen

(Refs. 2, 3, and 4).

‘‘Natural rubber,’’ for the purposes of

this rule, includes all materials made

from or containing natural latex.

Products that contain natural rubber are

made using two commonly employed

manufacturing processes, the natural

rubber latex (NRL) process, and the dry

natural rubber (DNR) process.

The NRL manufacturing process

involves the use of natural latex in a

concentrated colloidal suspension.

Products are formed from natural rubber

latex by dipping, extruding, or coating,

and are typically referred to as

containing or made of ‘‘natural rubber

latex.’’ Examples of products that may

contain natural rubber latex include

medical gloves, catheters, tracheostomy

tubes, and condoms.

The DNR manufacturing process

involves the use of coagulated natural

latex in the form of dried or milled

sheets. Products are formed from dry

natural rubber by compression molding,

extrusion, or by converting the sheets

into a solution for dipping. These

products are typically referred to as

containing or made of dry natural

rubber or ‘‘crepe’’ rubber. Examples of

products that may contain dry natural

rubber include syringe plungers, vial

stoppers, and injection ports on

intravascular tubing.

The phrase, ‘‘contains natural

rubber,’’ as used herein, also includes

products described as made of

‘‘synthetic latex’’ or ‘‘synthetic rubber’’

that include natural rubber in their

formulations. This rule does not apply

to products made from synthetic latex or

synthetic rubber that do not include

natural rubber in their formulations.

FDA has noted an increase in the

number of reports submitted to its

medical device reporting system

regarding sensitivity to natural latex

proteins contained in medical devices,

including deaths following barium

enemas. These deaths were associated

with anaphylactic reactions to the

natural rubber latex cuff on the tip of

barium enema catheters. Scientific

studies and case reports have

documented sensitivity to natural latex

proteins found in a wide range of

medical devices (see Refs. 2 through 23).

Based upon this information, the

agency published a proposed rule on

June 24, 1996 (61 FR 32618), to require

labeling statements on medical devices

containing natural rubber that contact

humans. This final rule is based upon

comments submitted in response to the

June 24, 1996 proposed rule.

II. Highlights of the Final Rule

A. Natural Rubber-Containing Devices;

Labeling

FDA is requiring the labeling for

medical devices containing natural

rubber that contacts humans to include

a statement regarding the presence of

natural rubber. The agency is issuing

this rule because medical devices

composed of natural rubber, or which

contain components formulated from

natural rubber, may pose a significant

health risk to some consumers or health

care providers who are sensitized to

natural latex proteins. A statement in

the labeling of medical devices

identifying the presence of natural

rubber latex is considered to be

necessary for the safe and effective use

of such devices.

‘‘Contacts humans,’’ for the purposes

of this rule, means that the natural

rubber contained in a medical device is

intended to contact or is likely to

contact the user or patient. This

includes contact when the natural

rubber containing device is connected to

the patient by a liquid path or an

enclosed gas path; or the natural rubber

containing device is powdered, and the

powder may carry natural latex proteins

that may contaminate the environment

of the user or patient.

The device may bear one or more of

four labeling statements depending on

the type of natural rubber in the device

and depending on whether the natural

rubber is in the device itself or in its

packaging. The reasoning for requiring

one or more of four separate statements

is discussed more fully in comments 3

and 6 in section III of this document.

Medical devices containing rubber

produced by the NRL process that

contacts humans shall bear labeling

with the following statement in bold

print: ‘‘Caution: This Product Contains

Natural Rubber Latex Which May Cause

Allergic Reactions.’’ Representative

examples of devices that contain NRL

include: Cuffed enema/enterolysis

catheters, latex condoms (with or

without spermicidal lubricant), wound

drains, cuffed airways, latex surgical

gloves, and latex examination gloves.

The agency is also requiring that

medical devices containing rubber

produced by the DNR process that

contacts humans include the following

statement in bold print in their labeling:

‘‘This Product Contains Dry Natural

Rubber.’’ Representative examples of

devices that contain DNR include:

Anesthesia masks, electrode pads,

contraceptive diaphragms, crutch pads

and tips, wheelchair tires, elastic

components of bandages/face masks,

syringe plungers, parenteral drug vial

stoppers, and intravenous injection

ports.

The agency is further requiring

medical devices having packaging that

contains natural rubber that contacts

humans bear labeling with one of the

following statements in bold print:

‘‘Caution: The Packaging of This

Product Contains Natural Rubber Latex

Which May Cause Allergic Reactions.’’

or ‘‘The Packaging of This Product

Contains Dry Natural Rubber.’’, as

appropriate. The purpose of such

statements is to inform individuals who

are sensitive to natural rubber about the

presence of natural rubber in the

packaging of devices that may be, by

themselves, natural rubber-free.

B. Hypoallergenicity

FDA believes that it is also necessary

to prohibit certain labeling statements

on medical devices that contain natural

rubber. FDA believes that the labeling

statement ‘‘hypoallergenic,’’

traditionally used with respect to

medical gloves, cosmetics, and other

products produced for individuals with

chemical allergies, is interpreted by

consumers to mean that the risk of

allergic reactions to any component of

the device would be minimal. This is

not the case with devices that contain

natural rubber. FDA has received

reports of allergic reactions to medical

gloves labeled as ‘‘hypoallergenic.’’

Use of the ‘‘hypoallergenic’’ label has

been based on results of the modified

(human) Draize test. While this test may

be appropriate for detecting

sensitization to residual levels of

processing chemicals, the test does not

detect sensitivity to natural latex

proteins.

Thus, there is no reasonable assurance

that the risk of allergic reactions to

products that contain natural rubber, yet

have reduced levels of processing

chemicals, will be reduced for

individuals who are sensitive to natural

latex proteins. Therefore, the agency

believes that the term ‘‘hypoallergenic’’

on the labeling of a device that contains

natural rubber is misleading in that it
Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations 51023

incorrectly implies that such device

may be used safely by persons sensitive

to natural latex proteins. For these

reasons, FDA is requiring that the

hypoallergenic claim be removed from

the labeling of devices that contain

natural rubber.

C. Effects of This Regulation on

Premarket Submission Requirements

FDA will not require a new

submission under section 510(k) of the

Federal Food, Drug, and Cosmetic Act

(the act) (21 U.S.C. 360(k)) based upon

labeling changes made to comply with

this rule, provided that no other changes

requiring a new 510(k) submission

under 21 CFR 807.81 are made to the

device. Devices subject to an approved

premarket approval application,

however, must submit any change to the

device labeling that is required by this

rule in the next interim report under 21

CFR 814.39(e). Combination products

that have device and drug components

but are regulated under drug premarket

approval provisions shall indicate the

labeling change in a supplement for

changes that may be made before FDA

approval, as required by 21 CFR

314.70(c). Combination products that

have device and biological components,

but that are regulated under the biologic

premarket approval provisions, shall

inform the agency of the labeling change

in the manner described under 21 CFR

601.12.

III. Summary of Comments

The agency received 62 comments, all

of which supported the principle of

natural rubber labeling for the

protection of natural rubber sensitive

individuals. The comments, however,

differed greatly in their specific

approaches.

1. A few comments suggested using

the term ‘‘crepe rubber,’’ instead of ‘‘dry

rubber,’’ and suggested using the term

‘‘synthetic rubber’’ instead of ‘‘synthetic

latex.’’

The agency agrees that ‘‘synthetic

rubber’’ should be used to describe

components of certain natural rubber

products covered by this regulation and

has added that term in the definition of

‘‘natural rubber’’ in § 801.437(b) (21 CFR

801.437(b)). Although the agency has

discussed the meaning of crepe rubber

in the preamble to this regulation, the

agency does not agree that the term

‘‘crepe rubber’’ should be used in place

of ‘‘dry natural rubber’’ in the regulation

because the agency believes the term

‘‘dry natural rubber’’ is the term most

commonly used to describe rubber

manufactured by the DNR process.

2. One comment pointed out that

there are other sources of natural rubber

besides that identified in the preamble

of the proposed rule, the H. brasiliensis

tree.

The agency agrees and has clarified in

the preamble of this regulation that

there are other sources of plant-derived

natural rubber used in the manufacture

of devices that are subject to this rule.

The preamble notes that the H.

brasiliensis tree is the primary source of

commercial natural latex, instead of the

only source.

3. Several comments claimed that

there is no information to suggest that

dry natural rubber has caused allergic

reactions in individuals sensitive to

natural latex proteins; therefore, dry

natural rubber should not be included

in the labeling requirement.

The agency recognizes that there are

lower levels of natural latex proteins in

products produced by the dry natural

rubber process. The agency, however,

does not agree that there is no

information to suggest that dry natural

rubber has caused allergic reactions in

individuals sensitive to natural latex

proteins. To the contrary, there are

numerous reports that levels of natural

latex proteins found in dry rubber can

cause allergic reactions (Refs. 24

through 27). Accordingly, the agency

has concluded that it is in the best

interest of the public health to provide

labeling information that a product

contains dry natural rubber, so that

individuals who are sensitive to the

levels of natural latex proteins found in

dry natural rubber may make an

informed decision regarding the use of

the product.

While the agency believes that

persons who may respond to the levels

of natural latex proteins found in dry

natural rubber need to be informed of

the dry rubber content in a device, the

agency does not believe that those

individuals need to be informed of the

health consequences associated with

dry natural rubber. Because allergy is a

dose-response phenomenon, persons

who may react to natural latex protein

levels found in dry rubber would have

already experienced previous allergic

reactions to the higher levels of natural

latex proteins found in natural rubber

latex products (see Ref. 28). Therefore,

those individuals would generally be

aware that dry natural rubber may cause

them to suffer an allergic reaction.

Accordingly, FDA is requiring that

products that contain only dry rubber

have labeling that informs consumers of

the dry rubber content, but is not

requiring that such products bear

labeling that states the potential health

consequences from the use of the

product. Therefore, FDA is requiring in

the final regulation, § 801.437(e), that

devices that contain dry natural rubber

bear labeling with the following

statement: ‘‘This Product Contains Dry

Natural Rubber.’’

Persons who would not react to the

levels of natural latex proteins found in

dry rubber, but would react to the

higher levels of natural latex proteins

found in natural rubber latex products,

however, may never have been aware of

previous allergic reactions (Ref. 28).

These persons, therefore, need to be

advised of the potential health

consequences of natural rubber latex

products. Accordingly, FDA is requiring

products containing natural rubber latex

to carry labeling that states the potential

health consequences of such products,

as well as a natural rubber latex content

statement. Therefore, FDA is requiring

in the final regulation, § 801.437(d), that

devices containing natural rubber latex

have labeling with the following

statement in bold print: ‘‘Caution: This

Product Contains Natural Rubber Latex

Which May Cause Allergic Reactions.’’

This statement is also required if a

device contains both natural rubber

latex and dry natural rubber that may

contact humans. In this instance, the

single statement will serve to advise a

person who may not be aware that

natural rubber may cause reactions, and

will also advise a person who is aware

of his or her sensitivity to natural rubber

that the product contains an ingredient

that may cause a reaction.

4. Some comments claimed that the

applicability of the labeling statement to

devices that contain natural rubber ‘‘that

may directly or indirectly contact

humans’’ is overly broad. One comment

suggested that the labeling statement be

required only on devices that have an

‘‘intended use’’ that may lead to contact

with humans. Other comments

suggested the statement be limited to

devices which would directly contact

tissues.

The agency does not believe that the

application of the labeling statement to

devices that contain natural rubber ‘‘that

may directly or indirectly contact

humans’’ is overly broad. Latex proteins

may elicit an allergic reaction in

individuals who are sensitive to natural

rubber, even if the proteins are

introduced to the individual through an

indirect route. The agency, however,

recognizes that the term ‘‘indirect

contact’’ may be interpreted more

broadly than the agency intends.

Therefore, in order to avoid confusion,

the agency has modified the regulation

to require the labeling statements only

if the natural rubber contacts humans.

The final regulation, § 801.437(b),

defines the term ‘‘contacts humans’’ to

mean that the natural rubber contained
51024 Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations

in a device is intended to contact or is

likely to contact the user or patient (e.g.,

latex medical gloves or latex enema

tips). This includes contact when the

device that contains natural rubber is

connected to the patient by a liquid path

or an enclosed gas path (e.g.,

intervenous administration sets, or

blood collection or transfusion tubing

with natural rubber injection ports,

injection syringes with natural rubber

plungers, or natural rubber tubing or

connector components used in

anesthesia or endoscopic insufflator

circuits). This also includes contact

when the device that contains natural

rubber is fully or partially coated with

a powder, and such powder may carry

natural rubber proteins that may

contaminate the environment of the user

or patient (e.g., latex tourniquets). This

definition makes it clear that the

labeling statement is required on

devices that have an intended use that

could reasonably be expected to

introduce natural latex proteins to

humans.

5. Several comments suggested that

the natural rubber labeling statement be

expanded to apply to nonmedical

natural rubber latex gloves and other

consumer products that contain natural

rubber. Other comments suggested that

medical devices sold over-the-counter

(OTC) to the consumer be exempt from

the labeling requirements in order to

avoid confusion regarding the natural

rubber-content of other consumer goods

that would not be subject to this

labeling regulation.

The agency disagrees that the

regulation should apply to nonmedical

natural rubber latex gloves and other

consumer products that contain natural

rubber. The regulation of such products

is beyond the scope of this rule. FDA’s

authority under the act to impose

labeling requirements is restricted to

products that meet the definition of

foods, drugs, cosmetics, animal drugs,

biologics, and devices, as those terms

are defined under the act. This rule

applies to devices as defined under

section 201(h) of the act (21 U.S.C.

321(h)). Under section 201(h) of the act,

a device is:

* * * an instrument, apparatus,

implement, machine, contrivance, implant,

in vitro reagent, or other similar or related

article, including any component, part, or

accessory, which is * * * intended for use

in the diagnosis of disease or other

conditions, or in the cure, mitigation,

treatment, or prevention of disease, in man

or other animals * * *, and which does not

achieve any of its principle intended

purposes through chemical action within or

on the body of man or other animals and

which is not dependent upon being

metabolized for the achievement of its

primary intended purposes.

Latex gloves and other products are

subject to this rule, only if they meet the

definition of device under section

201(h) of the act. Latex gloves that are

not used in the cure, mitigation,

treatment or prevention of disease are

not devices within the meaning of

section 201(h) of the act, and, therefore,

are not subject to this rule. Latex

medical gloves that are subject to this

regulation include surgeon’s gloves, as

classified at 21 CFR 878.4460, and

patient examination gloves, as classified

at 21 CFR 880.6250.

FDA also does not agree with the

suggestion that OTC medical devices be

exempted from the labeling

requirements in order to avoid

confusion with natural rubber products

that are not subject to this rule. The

purpose of the labeling requirement is to

provide essential information for

individuals sensitive to natural latex

proteins. An individual who is sensitive

to natural latex proteins is equally likely

to react to an OTC device that contains

natural rubber, as to a prescription

device that contains natural rubber.

Therefore, it is equally important to

provide essential information about

OTC devices that contain natural

rubber, as it is to provide information

about prescription devices that contain

natural rubber. Moreover, the agency

does not believe that labeling, as

required by this rule, on OTC devices,

will cause significant confusion

regarding the natural rubber content of

consumer products that are not devices.

6. Several comments requested

clarification on the applicability of the

requirements to certain devices.

Specifically, the comments asked

whether the rule would apply to:

Bandages with natural rubber in the

adhesive; natural rubber-free devices

packaged in a wrapper using natural

rubber in the adhesive, especially where

the adhesive would contact human

tissue while unwrapping the device;

foods or natural rubber-free devices

handled or applied with natural rubber

latex gloves; covered elastic stretch

bands used to attach an accessory or

component to a device; or, devices

intended to contact only subcutaneous

tissue.

A labeling statement is required for

devices that contain natural rubber

when the natural rubber contacts

humans, as described in § 801.437(b) of

the final rule. Accordingly, devices

intended to contact subcutaneous tissue

would be required to bear the

appropriate statement.

Moreover, bandages with natural

rubber in the adhesive would require

the labeling statement. For this product,

the natural rubber is intended to be

applied directly to the skin. If natural

rubber-containing adhesives in tapes,

bindings, and similar items are intended

to contact, or are likely to contact, the

user or the patient, they are required to

be labeled under this regulation.

Covered elastic bands would not be

considered to be in contact with

humans, provided the covering blocks

the migration of natural rubber proteins

to the patient and user.

FDA does not believe it would be

appropriate to require natural rubber

labeling statements for natural rubberfree devices or foods that may be

handled with latex gloves. As described

previously in comment 5 of this

document, requiring natural rubber

labeling for products, such as foods, that

are not devices is beyond the scope of

this regulation. Moreover, FDA does not

believe that requiring products that are

handled by latex gloves, regardless of

whether such products could be within

the scope of this regulation as devices,

is appropriate if such products do not

contain natural rubber. Requiring

labeling on products that may or may

not come into contact with latex gloves

would confuse consumers and would be

impracticable to implement.

Furthermore, FDA is not aware of any

reports of allergic reactions to rubberfree products that latex gloves have

contacted.

Under the final rule, natural rubbercontaining packaging adhesives that

typically are in areas that hold the flaps

of packaging together would meet the

criteria to subject the product to this

rule only if they contact the patient or

user. However, the agency is not aware

of any evidence or reports of reactions

to packaging adhesives. Given the

pervasiveness of the use of adhesives

that contain some amount of natural

rubber latex, the lack of evidence that

these adhesives cause adverse reactions,

and the ability to open packaging with

adhesives without coming into contact

with the adhesives, the agency

concludes that the adhesives in device

packaging are not intended to contact

humans and are not likely to contact

humans. Therefore, if such adhesives

are the sole source of natural rubber in

the device packaging or the device itself,

a device with such packaging would not

be subject to this rule.

The agency stresses, however, that it

considers device packaging to be an

integral part of a device. Under section

201(h) of the act, a device includes any

components, parts, or accessories. As an

accessory to a device, the packaging is

a device under section 201(h) of the act.

A device that contains natural rubber in
Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations 51025

its packaging, beyond that found in the

adhesive (e.g., a device packaged in a

latex sheath) is likely to contact the user

or patient and must be labeled as

containing natural rubber.

In order to avoid confusion and to

clarify to the consumer whether it is the

device itself or its packaging that

contains natural rubber, however, the

agency believes that a distinct labeling

statement is appropriate for devices that

have packaging that contains natural

rubber that contacts humans.

Accordingly, under § 801.437(f) and (g)

of the final regulation, such devices

shall have labeling with one of the

following statements: ‘‘Caution: The

Packaging of This Product Contains

Natural Rubber Latex Which May Cause

Allergic Reactions.’’ or ‘‘The Packaging

of This Product Contains Dry Natural

Rubber.’’

The agency notes that if one of these

packaging statements is required, it

shall appear regardless of whether there

is a natural rubber statement relating to

the product itself. For example, a device

that contains dry natural rubber that

contacts humans and is also packaged in

dry natural rubber that contacts humans

shall be labeled with both the

statements: ‘‘Caution: The Packaging of

This Product Contains Dry Natural

Rubber.’’ and ‘‘This Product Contains

Dry Natural Rubber.’’

7. Several comments suggested that

the labeling statements be required only

on finished medical devices, and that

device components be exempt.

The agency agrees in part. The

regulation applies to all finished devices

and components that are intended to

contact or are likely to contact the user

or patient. The labeling statement does

not apply to components shipped

directly to a manufacturer or processor

for use in the manufacture of a device

because these components, during the

time before distribution to consumers,

would not be intended to contact, or

likely to contact the user or patient.

Under these circumstances, the parts or

components are not accessible to health

care workers or patients. If, however, a

device component is sold directly to a

consumer, including a patient or health

care worker, and it is intended to

contact or likely to contact a user or

patient, it is required to be labeled

under this regulation, regardless of

whether it must be attached, inserted, or

used in conjunction with other devices.

Replacement parts marketed as

accessories for medical devices that are

intended to contact or likely to contact

a user or patient also require the

labeling statement.

8. One comment suggested that in

vitro diagnostic devices be exempt

because only dry natural rubber is used,

there is usually no patient contact with

the natural rubber components, and

space is very limited for labeling. One

comment suggested that other devices

that do not contact the patient be

exempted, regardless of whether the

natural rubber contacts the tissues of the

health care worker.

The agency believes that in vitro

diagnostic devices should be exempt

only to the extent that the natural rubber

used in vitro diagnostic devices is not

intended to contact or is not likely to

contact the user or the patient. FDA,

however, is requiring labeling for such

devices if they are intended to contact

or are likely to contact health care

workers or other users, as well as the

patient, because all latex-sensitive

persons who use the device need to be

informed of the product’s natural rubber

content.

9. One comment requested an

exemption for the labeling of natural

rubber latex condoms because such

condoms clearly contain latex. The

comment also believed an exemption

should apply to latex condoms because

space for labeling is limited, a warning

regarding allergic reactions may have a

chilling effect on the use by individuals

who are not sensitive to natural rubber,

and the statement may lead to confusion

in differentiating between latex and

natural skin condoms because natural

skin condoms also contain some natural

rubber latex and would require the

statement as well.

The agency disagrees and will require

latex condoms to bear a labeling

statement that the product contains

natural rubber latex that may cause

allergic reactions. Even though

consumers may be aware that the

product contains latex, FDA believes

that the additional information that

natural rubber latex may cause allergic

reactions is essential information to

individuals who are not aware that

natural rubber latex may cause allergic

reactions. The agency believes that there

is sufficient room on condom packaging

for the required statement.

FDA does not believe that the

statement will have a chilling effect on

the use of condoms by individuals who

are not sensitive to natural latex

proteins. The statement, however,

would clearly provide important

information to individuals who are

sensitive to natural latex proteins.

The agency further disagrees with the

suggestion that the labeling statement

would be required on natural skin

condoms, and thereby confuse

consumers with respect to the

differences between latex and natural

skin condoms. Although natural skin

condoms do contain a natural rubber

elastic band, this band is wrapped

within the natural skin sheath, and

there is no evidence to indicate that the

natural rubber ever contacts the user.

Therefore, natural skin condoms that

have a latex component that is not

intended to contact or likely to contact

the user do not require the labeling

statement. Accordingly, the absence of

any latex labeling requirement for

natural skin condoms obviates the

comments concern about confusion that

may result from latex labeling

statements on both latex and natural

skin condoms.

10. Although most comments

supported the requirements of standard

labeling requirements, some comments

suggested that the proposed labeling

statements were overly prescriptive, and

that manufacturers should have wide

latitude in the wording of the statement

provided it contain a general latex

ingredient statement. Other comments

stated that the labeling statements did

not provide sufficient warnings, and

suggested that the agency require a

caution stating that use of the device

may lead to chronic asthma, dermatitis,

or even anaphylactic shock and death.

The agency does not agree with

comments suggesting the labeling

should state possible reactions with

specificity. FDA believes that the

statement advising consumers that a

product may cause an allergic reaction

is specific enough to provide adequate

warning.

The agency also does not believe that

the required labeling statements are

overly prescriptive and that

manufacturers should be given wide

latitude in the wording of labeling

statements. The agency has determined

that requiring standardized statements

for devices containing natural rubber is

the best approach for providing the

essential information in a clear,

consistent, and accurate manner.

FDA realizes that there may be some

circumstances where it may be

appropriate to tailor specific

information concerning a device. If a

manufacturer believes use of statements

that vary from those prescribed by this

regulation is appropriate, § 801.437(i) of

the final regulation provides that the

manufacturer may petition the agency

for an exemption or variance from these

requirements by submitting a citizen

petition under 21 CFR 10.30. Unless the

agency has specifically granted an

exemption or variance, the agency will

consider any variation from the required

statement to be noncompliant, and the

device will be deemed misbranded.

11. Several comments suggested that

the agency recommend the use of
51026 Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations

natural rubber-free devices, or require a

labeling statement that nonnatural

rubber alternatives are available. In

contrast, some comments supported

natural rubber labeling provided that

the label be ‘‘ergonomically equitable’’

(sic) (i.e., not giving natural rubber-free

devices a perceived advantage).

The agency does not recommend the

use of one legally marketed device over

another. Rather the agency is requiring

that labeling for devices that contain

natural rubber provide information

upon which an individual may make an

informed choice regarding the use of the

device. The benefits of devices that

contain natural rubber are well

established, and the agency does not

intend to discourage their use by

persons who are not sensitive to natural

rubber. Therefore, the agency will not

require the labeling statement to

recommend the use of rubber-free

devices.

Furthermore, because the agency is

not requiring a statement that

recommends the use of natural rubberfree devices, the agency does not believe

that this rule gives natural rubber-free

devices an advantage over devices that

contain rubber. Accordingly, the agency

does not believe that further

modifications to the required statements

are necessary to address comments that

suggested the labeling not give the

impression that natural rubber-free

products have an advantage over

products that contain natural rubber.

12. One comment requested

clarification on the labeling of

combination products consisting of

drugs that are packaged in device

container vials with dry natural rubber

stoppers.

This final regulation provides

authority to require natural rubber

labeling on all devices containing

natural rubber, including devices that

are contained within combination

products. As discussed in more detail in

this comment, FDA intends to apply the

natural rubber labeling requirement to

combination products, such as drugs in

device containers that are regulated

currently under drug authorities.

In a final rule that published in the

Federal Register of November 21, 1991

(56 FR 58754), the agency explained

that ‘‘the term combination product

means a product comprised of two or

more different regulated entities, e.g.,

drug, device, or biologic * * *’’ or two

or more different regulated entities that

are produced together as a single entity,

packaged together, or used together to

achieve the intended effect (see 21 CFR

3.2(e)). The fact that a single product

contains two or more regulated entities

does not in itself change the regulatory

status of the individual entities.

Because the entities that comprise a

combination product meet more than

one jurisdictional definition, the agency

may apply one or more sets of

regulatory provisions to the product.

The agency, for example, has applied

both drug and device authorities, and

both biological and device authorities,

to certain combination products. (See

Intercenter Agreement Between the

Center for Drug Evaluation and Research

and the Center for Devices and

Radiological Health (the Drug/Device

Agreement (Ref. 29)), and Intercenter

Agreement Between the Center for

Biologics Evaluation and Research and

the Center for Devices and Radiological

Health (the Biologics/Device Agreement

(Ref. 30)) (hereinafter referred to

collectively as the Intercenter

Agreements).)

Device container vials with dry

natural rubber stoppers, when used in

combination with a drug product, may

be subject to regulation under the

statutes and regulations applicable to

devices. A vial that has a natural rubber

stopper meets the definition of a device

under section 201(h) of the act, in that

such vial is ‘‘an instrument, apparatus,

implement, machine, contrivance,

implant, in vitro reagent, or some other

similar or related article, including any

component, part, or accessory * * *’’

that is intended to cure, mitigate, treat,

or prevent disease, which does not

achieve any of its principal intended

purposes through chemical action

within or on the body of man or other

animals and which is not dependent

upon being metabolized for the

achievement of its primary intended

purposes. The agency regulates these

empty vials, as well as other empty drug

or biologic containers (such as

stoppered vials for use in blood

collection, intravenous containers, and

blood bags), as devices.

When the drug is contained in a vial,

however, the result is a combination

product. The combination status of

devices that serve as containers for

drugs is specifically recognized in the

Drug/Device Agreement. (See Ref. 29, p.

14.) To date, these combination

products have been regulated only

under the drug authorities (Id).

The agency intends to require that all

combination products that contain

natural rubber device components be

labeled in accordance with this

regulation. Although the agency could

require all combination natural rubber

products to comply with the regulation

on its effective date, this regulation will

be applied as follows: Natural rubber

combination products that are currently

listed in the Intercenter Agreements as

being regulated under device labeling

provisions will be required to comply

with this rule on its effective date;

natural rubber combination products

that are listed in the Intercenter

Agreements as being regulated under

drug or biologic labeling provisions,

however, will be subject to this

regulation at the time of the effective

date of this regulation, or at the time the

Intercenter Agreements are amended to

provide that these types of combination

products are subject to this labeling

regulation, whichever is later. FDA will

provide notice in the Federal Register of

the amendments to the Intercenter

Agreements to apply this natural rubber

labeling provision to all combination

products that contain natural rubber

device components.

At this time, the agency anticipates

that the Drug/Device Intercenter

Agreement will be amended to reflect

that prefilled drug vial containers,

transdermal patches, infusion pumps,

and prefilled syringes that presently are

regulated under drug authorities are also

subject to this regulation. The agency

believes, however, that this requirement

will not affect many drug vial

containers, because most drug stoppers

are not being manufactured from dry

natural rubber.

13. A few comments requested

clarification on the applicability of the

requirements to devices already in the

marketplace or intended solely for

export.

This rule is not intended to require

manufacturers to recall any devices

already in interstate commerce.

Therefore, this rule does not apply to

devices initially introduced or initially

delivered for introduction into interstate

commerce before the effective date of

this regulation.

Devices intended solely for export

will not be deemed misbranded for

failure to comply with this regulation

provided that the exporter meets the

criteria of sections 801(e) and 802 of the

act (21 U.S.C. 381(e) and 382).

Nevertheless, FDA encourages the

application of a natural rubber content

statement to all exported devices

containing natural rubber that may

contact humans.

14. A few comments suggested that

devices containing less than a minimum

quantity of natural rubber, the amount

to be determined by the agency, be

exempt from the labeling requirement.

One comment suggested that devices be

labeled with the extractable natural

latex protein content.

The agency agrees in principle,

however, insufficient information

currently exists regarding the minimum
Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations 51027

amount of extractable natural latex

protein that would not elicit an allergic

reaction for this option to be practicable.

Evidence indicates that some persons

are reactive to extremely low levels of

proteins (Ref. 31). The agency is unable

to determine what minimum amount of

natural latex proteins fails to elicit a

reaction in some individuals, and,

therefore, cannot exempt devices

containing less than that minimum.

15. Several comments requested

clarification on the level of packaging

that would require a labeling statement.

Some comments requested additional

flexibility in the placement of the

statement so that the statement may be

put on the device labeling other than the

label, especially where the device label

may be too small to carry such a

statement. Another comment

recommended that the statement be

required not only on the label and in

other labeling, but on the device itself

if the device is dispensed in bulk, as in

the case with natural rubber latex

examination gloves. Other comments

suggested that bulk devices either

remain in the original package in order

to preserve the label, or that the agency

require the user facility to educate and

monitor the use of bulk devices

containing natural rubber. Still another

comment suggested that where bulk

devices are removed to a separate

dispensing container, the dispensing

container also be required to be labeled

with a natural rubber content statement.

FDA believes that the required

labeling statements may be fitted on

small labels. Because of the importance

of the information contained in the

labeling statements for individuals

sensitive to natural latex proteins, the

agency will require the appropriate

statements concerning the natural

rubber content of the products to be

prominently and legibly displayed on

all device labels, and other labeling, and

to appear on the principal display panel

of the device packaging, the outside

package, container or wrapper, and the

immediate device package, container, or

wrapper.

This means, for example, that the

labeling statement for adhesive

bandages that are individually wrapped

and sold in a box would appear on each

individually wrapped bandage, on the

box, and on any individual pieces of

labeling, such as an instructions for use

sheet included in the box. Devices

packaged and sold in bulk dispensing

containers would be required to display

the appropriate statement on the

dispensing container, as it is the

immediate device container or package.

If the packaging of a device contains

natural rubber, the final regulation

requires that a separate statement that

specifically cautions the user that the

natural rubber is contained in the

packaging itself. Statements relating to

the natural rubber content of the

packaging do not have to appear on the

same levels of labeling as the cautionary

statements relating to natural rubber

content in the actual product. The

statements cautioning the user that the

packaging contains natural rubber shall

appear, instead, only on the packaging

that contains the natural rubber, and the

outside package, container, or wrapper.

Placement of cautionary statements in

these locations should warn consumers

adequately of the possible risks of

allergic reactions to the packaging,

while avoiding the potential for

confusion that the actual products

contain natural rubber.

FDA believes that requiring devices to

remain in their original package at the

user site, requiring labeling statements

on dispensers that are sold separately

from the natural rubber containing

devices, and requiring user facilities to

provide education concerning latex

products and to monitor bulk product

use, is impracticable and beyond the

scope of the regulation. Furthermore,

because of the potential manufacturing

difficulties, the agency will not require

devices to be embossed, imprinted, or

otherwise labeled on the individual,

unwrapped device. The agency believes

that the labeling requirements in this

regulation will provide adequate

protection to the users and patients.

16. The vast majority of comments

supported the removal of the

‘‘hypoallergenic’’ claim from the

labeling of medical devices that contain

natural rubber. Those comments that

expressed unease about the removal of

the claim stated that the term does

convey meaningful information to the

user. These comments suggested that an

alternative term be applied, or that the

regulation allow device labeling to state

that the device presents a reduced

potential for sensitizing users to natural

rubber, or that the device contains less

than a specified limit of natural latex

proteins or processing chemicals as

established by the agency. One

comment stated that, until the agency

proves that the tests currently employed

are insufficient to support the

‘‘hypoallergenic’’ claim, the claim

should be allowed.

The agency agrees that the term

‘‘hypoallergenic’’ provides important

information to the consumer who is

sensitive to processing chemicals, but

believes that the term ‘‘hypoallergenic’’

on products containing natural rubber

will mislead consumers to conclude

erroneously that the product may not

cause latex protein allergic reactions.

In the past, manufacturers have

labeled their products ‘‘hypoallergenic’’

on the basis of results of the modified

(human) Draize test. While this test may

be appropriate for detecting sensitivity

to residual levels of processing

chemicals, the test cannot detect the

presence of natural latex proteins.

Furthermore, current manufacturing

processes cannot reduce the levels of

natural latex proteins below that to

which some individuals may react.

The agency disagrees that the

‘‘hypoallergenic’’ label should be

allowed to remain on devices that

contain natural rubber until the agency

proves that the tests currently employed

are insufficient to support the

‘‘hypoallergenic’’ claim, or that claims

should be allowed regarding reduced

levels of latex proteins. The agency has

received reports of allergic reactions to

natural rubber gloves labeled as

hypoallergenic. Given that the modified

(human) Draize Test is not designed to

detect levels of natural latex proteins

that would not induce allergic

responses, and that the agency is not

aware of any current manufacturing

processes that are designed to remove

latex proteins below a level that may

cause adverse reactions, the agency

believes that it has sufficient evidence

that the tests currently employed do not

support the claim ‘‘hypoallergenic’’

with respect to the potential for allergic

reactions to natural latex proteins.

The agency does agree that alternative

statements should be applied to convey

information about devices with reduced

residual chemical levels to consumers

who are sensitive to chemicals. For this

reason, the agency is developing

guidance for manufacturers who want to

make claims relating to latex devices

that have reduced manufacturing

chemical residues. FDA will announce

the availability of this draft guidance

document entitled ‘‘Testing for Skin

Sensitization to Chemicals in Latex

Products’’ in a future issue of the

Federal Register.

17. A few comments stated that the

reference to the draft guidance

document entitled ‘‘Testing for Skin

Sensitization to Chemicals in Latex

Products’’ in the preamble to the June

24, 1996 proposed rule, upon which this

final rule is based, was inappropriate

because the document is still in draft

form, while another comment suggested

the agency reference the draft guidance

document in the regulation itself.

The agency does not believe it is

appropriate to incorporate a draft

guidance document into a regulation.

The agency, however, does believe that
51028 Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations

it is appropriate to use the preambles of

a proposed and final rule relating to

latex devices to inform the public that

the agency is in the process of

developing a guidance document

relating to claims about the sensitizing

potential of manufacturing chemical

residues in latex devices.

18. The vast majority of comments

supported the use of a symbol to

indicate the presence of natural rubber

in a device. These comments stated that

the symbol would promote consumer

recognition and could be used on

devices that have labels that are too

small to fit the full text of the statement.

One comment suggested that the symbol

be stamped on the actual devices,

especially those sold in bulk packages.

Some comments stated that the symbol

should supplement, not replace the text

of the statement. Those comments not

supporting the use of a natural rubber

symbol cautioned that a symbol should

not be used until it is universally

accepted. Another comment suggested

that the agency establish the symbol and

require its use.

The agency agrees that a symbol

would be useful. The agency stresses,

however, that any symbol is intended to

supplement, not replace the required

written labeling statements, and its use

would be voluntary. The agency

appreciates the comments and the

suggested symbol designs that were

submitted, but does not believe that

there is sufficient acceptance of a

symbol to require the use of a symbol

at this time.

19. Several comments stated that the

health benefits of the labeling statement

are potentially so great that the effective

date of the requirement should be less

than 180 days from the date of

publication of this final rule. Other

comments complained that a 180-day

implementation period is not sufficient

to change the labeling on the numerous

devices affected by this rule. These

comments requested at least a 12-month

implementation period. One of these

comments further requested that

implementation be a two-stage process,

and that devices containing dry natural

rubber not be required to carry the

labeling statement until 24 months after

publication of this final rule. Another

comment requested a two-stage

implementation process so that devices

that only indirectly contact humans

would not be required to carry the

labeling statement until 36 months after

publication, or that such devices not be

required to carry any labeling statement.

The agency agrees that the public

health concerns relating to allergic

responses to natural rubber are great.

The agency also acknowledges,

however, that at the time of the

publication of this regulation,

manufacturers have labeling in stock

that does not have the required

statements. In order to minimize the

burden to manufacturers of discarding

labeling that has already been printed,

and to allow sufficient time to reformat

labeling, the agency is providing that

the effective date of this final rule is 1

year after the date of publication. This

effective date will allow most

manufacturers sufficient time, before the

effective date of this rule, to exhaust

their existing supply of labeling stock. If

a manufacturer uses the existing

labeling stock before the effective date

of this rule, however, FDA encourages

manufacturers to add the required

labeling statement at that time.

The agency does not believe that a

two-stage implementation process is

necessary, or that a period of longer

than 1 year is necessary because 1 year

should be adequate time to phase in

new labeling, and reformat the labeling.

Furthermore, the agency believes that a

longer delay in the implementation of

this rule would not be in the interest of

the public health. The comment

suggesting that devices that only

indirectly contact humans not carry any

natural rubber labeling statement is

addressed in comment 4 of this

document.

20. One comment suggested that

manufacturers, distributors, and user

facilities all be responsible for following

the labeling requirements.

The agency agrees with the

underlying concern that the labeling

statement remain on devices. It is only

necessary, however, to require

manufacturers to properly label their

products to ensure that consumers

receive appropriate information

concerning natural rubber products.

Distributors and user facilities may not

alter the device labeling. Any such

alteration may be grounds for a charge

of misbranding a device under sections

201(n) and 502(a), (c), and (f) of the act

(21 U.S.C. 352(a), (c), and (f)).

21. A few comments complained that

the rule could be misinterpreted to

require labeling on all devices

containing any natural rubber

whatsoever. Others stated that the

requirement would have a major impact

on multinational companies, costing at

least $15,000 per device for labeling.

Another comment stated that the agency

underestimated the impact of the rule,

as each manufacturer will need to draft,

review, and relabel primary and

secondary packages of hundreds, if not

thousands of devices.

The agency has clarified the scope of

this regulation in order to minimize the

possibility of misinterpretation. Under

final § 801.437(b), an appropriate

labeling statement is required on

medical devices that contain natural

rubber latex or dry natural rubber that

contacts humans. The agency does not

believe that this rule would require

relabeling for hundreds or thousands of

devices. In fact, the agency has only

identified approximately 70 generic

types of medical devices including

combination products that are subject to

this rule.

Furthermore, FDA does not agree that

this rule will have a major impact on

multinational companies because it

would cost at least $15,000 per device

for labeling. FDA estimates that the cost

to revise the labeling would be between

$1,000 and $2,000 for each type of

device that is relabeled. Moreover, the

cost of implementing this regulation is

further minimized because the 1-year

effective date of this regulation should

allow most manufacturers to exhaust

their current labeling stock prior to

using the labeling that is required under

this regulation.

IV. Paperwork Reduction Act of 1995

The warning statements required by

this regulation are ‘‘public disclosure of

information originally supplied by the

Federal government to the recipient for

the purpose of disclosure to the public

* * *’’ (5 CFR 1320.3(c)(2)).

Accordingly, FDA concludes that the

labeling requirements in this final rule

are not subject to review by the Office

of Management and Budget under the

Paperwork Reduction Act of 1995 (44

U.S.C. 3501–3520).

V. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(11) 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

final rule under Executive Order 12866

and the Regulatory Flexibility Act (5

U.S.C. 601–612), as amended by subtitle

D of the Small Business Regulatory

Fairness Act of 1996 (Pub. L. 104–4).

Executive Order 12866 directs agencies

to assess all costs and benefits of

available regulatory alternatives and,

when regulation is necessary, to select

regulatory approaches that maximize

net benefits (including potential

economic, environmental, public health

and safety, and other advantages;

distributive impacts; and equity). The
Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations 51029

agency believes that this final rule is

consistent with the regulatory

philosophy and principles identified in

the Executive Order. In addition, the

final rule is not a significant regulatory

action as defined by the Executive Order

and so is not subject to review under the

Executive Order.

If a rule has a significant economic

impact on a substantial number of small

entities, the Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact of a rule on small

entities. This rule primarily requires a

labeling change which would not have

a significant economic impact on small

entities. Although this rule will require

a labeling change on a substantial

number of medical devices,

manufacturers will be allowed up to 1

year after the effective date of this

regulation to exhaust their existing

supply of labeling, therefore, most

manufacturers would exhaust their

existing supply of labels. Moreover, the

cost of reformatting the labeling, which

is $1,000 to $2,000 for each different

kind of device, is not significant.

Accordingly, under the Regulatory

Flexibility Act (5 U.S.C. 605(b)), the

agency certifies that the final rule will

not have a significant economic impact

on a substantial number of small

entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

VII. References

The following references have been

placed on display in the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857, and may be seen by interested

persons between 9 a.m. and 4 p.m.,

Monday through Friday.

1. ‘‘Introduction to Latex Compounding

and Processing,’’ The Vanderbilt Latex

Handbook, 3d ed., 1987.

2. Tomazic, V., T. Withrow, B. Fisher, and

S. Dillard, ‘‘Short Analytical Review—LatexAssociated Allergies and Anaphylactic

Reactions,’’ Clinical Immunology

Immunopathology, 64:89–97, 1992.

3. Slater, J., and S. Chabra, ‘‘Latex

Antigens,’’ Journal of Allergy and Clinical

Immunology, 89:673–678, 1992.

4. Hamann, C. P., ‘‘Natural Rubber Latex

Protein Sensitivity in Review,’’ American

Journal of Contact Dermatitis, 4:1, 4–21,

March 1993.

5. Turjanmaa, K., ‘‘Incidence of Immediate

Allergy to Latex Gloves in Hospital

Personnel,’’ Contact Dermatitis, 17:27–275,

1987.

6. Turjanmaa, K., K. Laurila, S. MakinenKiljunen, and T. Reunala, ‘‘Rubber Contact

Urticaria-Allergenic Properties of 19 Brands

of Latex Gloves,’’ Contact Dermatitis, 19:362–

364, 1989.

7. Turjanmaa, K., and T. Reunala,

‘‘Condoms as a Source of Latex Allergen and

Cause of Contact Urticaria,’’ Contact

Dermatitis, 20:360–364, 1989.

8. FDA Medical Alert—Allergenic

Reactions to Latex-Containing Medical

Devices, March 29, 1991.

9. Heese, A., J. Hintzenstern, K-P Peters, H.

Koch, and O. Hornstein, ‘‘Allergic and

Irritant Reactions to Rubber Gloves in

Medical Health Services,’’ Journal of the

American Academy of Dermatology, No. 5

(Part 1): 831–839, November 1991.

10. Hintzenstern, J., A. Heese, H. Koch, KP Peters, and O. Hornstein, ‘‘Frequency,

Spectrum and Occupational Relevance of

Type IV Allergies to Rubber Chemicals,’’

Contact Dermatitis, 24:244–252, 1991.

11. Lahti, A., and K. Turjanmaa, ‘‘Prick and

Use Tests With 6 Globe Brands in Patients

With Immediated Allergy to Rubber

Proteins,’’ Contact Dermatitis, 26:259–262,

1992.

12. Jaeger, D., D. Kleinhans, A. Czuppon,

and X. Baur, ‘‘Latex-Specific Proteins

Causing Immediate-Type Cutaneous, Nasal,

Bronchial, and Systemic Reactions,’’ Journal

of Allergy and Clinical Immunology, 89:759–

768, 1992.

13. Berky, Z., J. Luciano, and W. James,

‘‘Latex Glove Allergy—A Survey of the U.S.

Army Dental Corps,’’ Journal of the American

Medical Association, 268:2695–2697, 1992.

14. Gonzalez, E., ‘‘Latex Hypersensitivity:

A New and Unexpected Problem,’’ Hospital

Practice, pp. 137–151, February 15, 1992.

15. Stehlin, D., ‘‘Latex Allergies: When

Rubber Rubs the Wrong Way,’’ FDA

Consumer, pp. 16–21, September 1992.

16. ACAI (American College of Allergy &

Immunology) Interim Recommendations to

Health Professionals & Organizations

Regarding Latex Allergy Precautions, March

1992.

17. Young, M., M. Meyers, L. McCulloch,

and L. Brown, ‘‘Latex Allergy—A Guideline

for Perioperative Nurses,’’ Association of

Operating Room Nurses Journal, 56:488–502,

1992.

18. Dias, M., I. Conchon, M. Cortes, F.

Pereira, and R. Alonso, ‘‘Anaphylactic

Intraoperative Reaction to Latex,’’ Contact

Dermatitis, 32:305–306, 1995.

19. Safadi, G. S., T. J. Safadi, G. T.

Terezhalmy, J. S. Taylor, J. R. Battisto, and

A. L. Melton, ‘‘Latex Hypersensitivity: Its

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Journal of the American Dental Association,

127:83–88, 1996.

20. Kaczmarek, R. G., B. G. Silverman, T.

P. Gross, R. G. Hamilton, E. Kessler, J. T.

Arrowsmith-Lowe, and R. M. Moore,

‘‘Prevalence of Latex-Specific IgE Antibodies

in Hospital Personnel,’’ Annals of Allergy,

Asthma and Immunology, 76:51–56, 1996.

21. Safadi, G. S., E. C. Corey, J. S. Taylor,

W. O. Wagner, L. C. Pien, and A. L. Melton,

‘‘Latex Hypersensitivity in Emergency

Medical Service Providers,’’ Annals of

Allergy, Asthma and Immunology, 77:39–42,

1996.

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Population,’’ Annals of Allergy, Asthma and

Immunology, 78:41–44, 1997.

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the Center for Devices and Radiological

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Center for Biologics Evaluation and Research

and the Center for Devices and Radiological

Health, October 31, 1991.

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Clinical Immunology, 91:1140–1145, 1993.

List of Subjects in 21 CFR Part 801

Labeling, Medical devices, Reporting

and recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act, and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 801 is

amended as follows:

PART 801—LABELING

1. The authority citation for 21 CFR

part 801 continues to read as follows:

Authority: Secs. 201, 301, 501, 502, 507,

519, 520, 701, 704 of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 321, 331, 351,

352, 357, 360i, 360j, 371, 374).

2. Section 801.437 is added to subpart

H to read as follows:

§ 801.437 User labeling for devices that

contain natural rubber.

(a) Data in the Medical Device

Reporting System and the scientific

literature indicate that some individuals

are at risk of severe anaphylactic

reactions to natural latex proteins. This

labeling regulation is intended to

minimize the risk to individuals

sensitive to natural latex proteins and

protect the public health.

(b) This section applies to all devices

composed of or containing, or having

packaging or components that are

composed of, or contain, natural rubber

that contacts humans. The term ‘‘natural
51030 Federal Register / Vol. 62, No. 189 / Tuesday, September 30, 1997 / Rules and Regulations

rubber’’ includes natural rubber latex,

dry natural rubber, and synthetic latex

or synthetic rubber that contains natural

rubber in its formulation.

(1) The term ‘‘natural rubber latex’’

means rubber that is produced by the

natural rubber latex process that

involves the use of natural latex in a

concentrated colloidal suspension.

Products are formed from natural rubber

latex by dipping, extruding, or coating.

(2) The term ‘‘dry natural rubber’’

means rubber that is produced by the

dry natural rubber process that involves

the use of coagulated natural latex in the

form of dried or milled sheets. Products

are formed from dry natural rubber by

compression molding, extrusion, or by

converting the sheets into a solution for

dipping.

(3) The term ‘‘contacts humans’’

means that the natural rubber contained

in a device is intended to contact or is

likely to contact the user or patient. This

includes contact when the device that

contains natural rubber is connected to

the patient by a liquid path or an

enclosed gas path; or the device

containing the natural rubber is fully or

partially coated with a powder, and

such powder may carry natural rubber

proteins that may contaminate the

environment of the user or patient.

(c) Devices containing natural rubber

shall be labeled as set forth in

paragraphs (d) through (h) of this

section. Each required labeling

statement shall be prominently and

legibly displayed in conformance with

section 502(c) of the Federal Food, Drug,

and Cosmetic Act (the act) (21 U.S.C.

352(c)).

(d) Devices containing natural rubber

latex that contacts humans, as described

in paragraph (b) of this section, shall

bear the following statement in bold

print on the device labeling:

‘‘Caution: This Product Contains Natural

Rubber Latex Which May Cause Allergic

Reactions.’’

This statement shall appear on all

device labels, and other labeling, and

shall appear on the principal display

panel of the device packaging, the

outside package, container or wrapper,

and the immediate device package,

container, or wrapper.

(e) Devices containing dry natural

rubber that contacts humans, as

described in paragraph (b) of this

section, that are not already subject to

paragraph (d) of this section, shall bear

the following statement in bold print on

the device labeling:

‘‘This Product Contains Dry Natural

Rubber.’’

This statement shall appear on all

device labels, and other labeling, and

shall appear on the principal display

panel of the device packaging, the

outside package, container or wrapper,

and the immediate device package,

container, or wrapper.

(f) Devices that have packaging

containing natural rubber latex that

contacts humans, as described in

paragraph (b) of this section, shall bear

the following statement in bold print on

the device labeling:

‘‘Caution: The Packaging of This Product

Contains Natural Rubber Latex Which May

Cause Allergic Reactions.’’

This statement shall appear on the

packaging that contains the natural

rubber, and the outside package,

container, or wrapper.

(g) Devices that have packaging

containing dry natural rubber that

contacts humans, as described in

paragraph (b) of this section, shall bear

the following statement in bold print on

the device labeling:

‘‘The Packaging of This Product Contains

Dry Natural Rubber.’’

This statement shall appear on the

packaging that contains the natural

rubber, and the outside package,

container, or wrapper.

(h) Devices that contain natural

rubber that contacts humans, as

described in paragraph (b) of this

section, shall not contain the term

‘‘hypoallergenic’’ on their labeling.

(i) Any affected person may request

an exemption or variance from the

requirements of this section by

submitting a citizen petition in

accordance with § 10.30 of this chapter.

(j) Any device subject to this section

that is not labeled in accordance with

paragraphs (d) through (h) of this

section and that is initially introduced

or initially delivered for introduction

into interstate commerce after the

effective date of this regulation is

misbranded under sections 201(n) and

502(a), (c), and (f) of the act (21 U.S.C.

321(n) and 352(a), (c), and (f)).

Dated: September 22, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–25728 Filed 9–29–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF STATE

22 CFR Part 41

[Public Notice 2610]

Bureau of Consular Affairs; Visas:

Passports and Visas Not Required for

Certain Nonimmigrants

AGENCY: Bureau of Consular Affairs,

DOS.

ACTION: Interim rule with request for

comments.

SUMMARY: Section 217 of the

Immigration and Nationality Act (INA),

as amended, extends the Visa Waiver

Pilot Program (VWPP) to nationals of all

countries that qualify under the

provisions of the Pilot Program and

which are designated by the Secretary of

State and the Attorney General as

countries whose nationals benefit from

the waiver of the nonimmigrant B–1/B–

2 visa requirement. This interim rule

eliminates probationary entry status in

the pilot program, designates Ireland

(the only country formerly designated as

a participating country with

probationary status) as a permanent

participating country and extends the

VWPP to Slovenia.

DATES: This interim rule is effective

September 30, 1997. Written comments

are invited and must be received on or

before October 30, 1997.

ADDRESSES: Written comments may be

submitted, in duplicate, to the Chief,

Legislation and Regulations Division,

Visa Services, Room L–603C,

Department of State, Washington, D.C.

20520–0106.

FOR FURTHER INFORMATION CONTACT: H.

Edward Odom, Chief, Legislation and

Regulations Division, Visa Office,

Department of State, Washington, D.C.

20522–0113 (202) 663–1203.

SUPPLEMENTARY INFORMATION: This

interim rule amends Part 41, Title 22 of

the Code of Federal Regulations

concerning visas for nonimmigrants

pursuant to section 217 of the

Immigration and Nationality Act, 8

U.S.C. 1187, as amended by Pub. L.

103–415, (108 Stat. 4299, October

25,1994), Pub. L. 103–416, (108 Stat.

4305, October 25, 1994), and Pub. L.

104–208, (110 Stat. 3009–702,

September 30, 1996).

Pub. L. 99–603

Section 313 of the Immigration

Reform and Control Act of 1986 (IRCA),

Pub. L. 99–603, amended the INA by

adding a new section 217 (8 U.S.C.

1187). Section 217 provides for a

nonimmigrant visa waiver pilot program

(VWPP) which waives the

nonimmigrant visa requirement for the

admission of certain aliens into the

United States for a period not to exceed

ninety days. This original provision

authorized the participation of eight

countries in the VWPP to be designated

by the Secretary of State and the

Attorney General, acting jointly from

among countries meeting specific

criteria. These original qualifying

countries included: France; the Federal