[Federal Register Volume 62, Number 189 (Tuesday, September 30, 1997)]
[Rules and Regulations]
[Pages 51021-51030]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-25728]
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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.
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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
[[Page 51022]]
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
[[Page 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 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
[[Page 51024]]
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
[[Page 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 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
[[Page 51026]]
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