Natural Rubber-Containing Medical Devices; User Labeling

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

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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

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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 Sec. 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, Sec. 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, Sec. 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, Sec. 801.437(b),

defines the term ``contacts humans'' to mean that the natural rubber

contained

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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

Sec. 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 rubber-free 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 rubber-free

products that latex gloves have contacted.

Under the final rule, natural rubber-containing 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

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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 Sec. 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, Sec. 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

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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 rubber-free 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

[[Page 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

[[Page 51028]]

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

Sec. 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

[[Page 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--Latex-Associated 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. Makinen-Kiljunen, 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, K-P 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

Prevalence Among Dental Professionals,'' 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.

22. Kibby, T., and M. Akl, ``Prevalence of Latex Sensitization

in a Hospital Employee Population,'' Annals of Allergy, Asthma and

Immunology, 78:41-44, 1997.

23. Marzulli, F. N., and H. I. Maibach, ``The Use of Graded

Concentrations in Studying Skin Sensitizers: Experimental Contact

Sensitization in Man,'' Food, Cosmetics, and Toxicology, 12:219-227,

1974.

24. Lear, J. T., and J. S. C. English, ``Anaphylaxis After

Hepatitis B Vaccination,'' Lancet, 345:1249, 1995.

25. Towse, A., M. O'Brien, F. J. Twarog, J. Braimon, and A. C.

Moses, ``Local Reaction Secondary to Insulin Injection,'' Diabetes

Care, 18:1195-1197, 1995.

26. MacCracken, J., P. Stenger, and T. Jackson, ``Latex Allergy

in Diabetic Patients,'' Diabetes Care, 19:184, 1996.

27. Jones, J. M., G. L. Sussman, and D. H. Beezhold, ``Latex

Allergen Levels of Injectable Collagen Stored in Syringes With

Rubber Plungers,'' Urology, 47:898-902, 1996.

28. ``Hypersensitivity Type I,'' Immunology, pp. 19.1-19.18;

edited by I. M. Roitt, J. Brostoff, and D. K. Male, Grower Medical

Publishing, Ltd., London, 1985.

29. Intercenter Agreement Between the Center for Drug Evaluation

and Research and the Center for Devices and Radiological Health,

October 31, 1991.

30. Intercenter Agreement Between the Center for Biologics

Evaluation and Research and the Center for Devices and Radiological

Health, October 31, 1991.

31. Kelly, K. J., K. Viswanath, M. Zacharisen, A. Resnick, and

J. N. Fink, ``Skin and Serologic Testing in the Diagnosis of Latex

Allergy,'' Journal of Allergy and 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:

Sec. 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

[[Page 51030]]

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 Sec. 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