[Federal Register Volume 61, Number 122 (Monday, June 24, 1996)]
[Proposed Rules]
[Pages 32618-32621]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-15990]
[[Page 32617]]
_______________________________________________________________________
Part VII
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 801
Latex-Containing Devices; User Labeling; Proposed Rule
Federal Register / Vol. 61, No. 122 / Monday, June 24, 1996 /
Proposed Rules
=======================================================================
-----------------------------------------------------------------------
[[Page 32618]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 96N-0119]
RIN 0910-AA34
21 CFR Part 801
Latex-containing Devices; User Labeling
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the regulations to require all medical devices containing natural
rubber latex that may directly or indirectly contact living human
tissue to be labeled with a statement identifying the product as one
which contains natural rubber latex and which may cause allergic
reactions. The agency is also amending the regulation to require that
hypoallergenicity claims be removed from latex medical gloves and other
natural rubber latex medical devices because the modified human Draize
test currently used to support hypoallergenicity claims addresses only
chemical sensitivity, and it is inappropriate for determining protein
sensitivity in humans. These requirements are being proposed in
response to numerous reports that have been received of severe allergic
reactions to a wide range of medical devices containing natural rubber
latex.
DATES: Comments by September 23, 1996. FDA is proposing that the final
regulation based on this proposal be effective 180 days after the date
of its publication in the Federal Register.
ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: Donald E. Marlowe, Center for Devices
and Radiological Health (HFZ-100), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-443-2444.
SUPPLEMENTARY INFORMATION:
I. Background
Natural rubber latex is a milky fluid produced by the Heavea
brasiliensis (rubber) tree. There is often confusion concerning the
terminology used to describe the raw agricultural material derived from
the rubber tree and the chemical nomenclature that refers to emulsions
of synthetic rubbers and plastics to which natural rubber latex has
been added.
Latex, either natural or synthetic, is a colloidal dispersion of a
polymeric material in a liquid system mostly aqueous in nature (Ref.
1). ``Natural rubber latex,'' for the purpose of this proposed rule,
means a milky fluid that consists of extremely small particles of
rubber, obtained from the H. brasiliensis (rubber) tree, dispersed in
an aqueous medium. It contains a variety of naturally occurring
substances, including carbohydrates, lipids, phospholipids, proteins,
minerals, small amounts of complex organic material, water, and cis-1,4
polyisoprene, in a colloidal suspension.
The phrase ``natural rubber latex'' refers to the raw material used
in the manufacture of both natural rubber latex products and dry
natural rubber products. These products are formed by two commonly
employed manufacturing processes. One of these is the natural rubber
latex manufacturing process (NRL process), which involves the use of
natural latex in a concentrated liquid form. Products are formed from
NRL processing by dipping, extruding, or coating, and are typically
referred to as containing or made of ``natural rubber latex.'' Examples
of devices manufactured by the NRL process include medical gloves,
catheters, and condoms.
The dry natural rubber manufacturing process (DNR process) involves
the use of coagulated natural latex in dried or milled sheets. Products
are formed from the DNR process 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 rubber.''
Examples of devices or device components containing dry rubber include
syringes with dry rubber plungers, vial stoppers, and intravascular
injection ports.
The phrase, ``contains natural rubber latex,'' as used herein,
encompasses products made by either process, as well as products
described as made of ``synthetic latex'' that include natural rubber
latex in their formulations. This proposed rule would not apply to
products made from synthetic latex, which do not include natural rubber
latex in their formulation.
Since 1988, FDA has noted an increase in the number of reports
submitted to its Medical Device Reporting (MDR) system regarding
sensitivity to natural rubber latex proteins contained in medical
devices. In May of 1990, FDA became aware of deaths associated with
barium enema procedures. Further investigation of the problem revealed
that these deaths were associated with anaphylactic reactions to the
natural latex cuff on the tip of the barium enema catheters. In several
hundred reports of adverse reactions to natural rubber latex that the
agency has received since October 1988, 16 have involved deaths from
anaphylactic shock. Furthermore, several scientific journals have
reported incidents of sensitivity to natural rubber latex proteins in a
wide range of medical devices. (See Refs. 2 through 18.)
Section 701(a) of the Federal Food, Drug, and Cosmetic Act (the
act) (21 U.S.C. 371(a)) authorizes FDA to issue substantive binding
regulations for the efficient enforcement of the act. (Weinberger v.
Hynson, Westcott & Dunning, Inc., 412 U.S. 609 (1973); see also
Weinberger v. Bentex Pharmaceuticals, Inc., 412 U.S. 645, 653 (1973);
National Ass'n of Pharmaceutical Manufacturers v. FDA, 637 F.2d 877 (2d
Cir. 1981); National Confectioners Ass'n v. Califano, 569 F.2d 690
(D.C. Cir. 1978); National Nutritional Foods Ass'n v. Weinberger, 512
F.2d 688 (2d Cir.), cert. denied, 423 U.S. 825 (1975).)
Section 502(a) of the act (21 U.S.C. 352(a)) provides that a device
is misbranded ``If its labeling is false or misleading in any
particular.'' Section 201(n) of the act (21 U.S.C. 321(n)) provides
that, in determining whether labeling of a regulated article (such as a
device) is misleading
* * * there shall be taken into account * * * not only
representations made or suggested by statement, word, design,
device, or any combination thereof, but also the extent to which the
labeling * * * fails to reveal facts material in light of such
representations * * * with respect to consequences which may result
from the use of the article to which the labeling * * * relates
under the conditions of use prescribed in the labeling or
advertising thereof or under such conditions of use as are customary
or usual.
The courts have upheld FDA's authority to prevent false or
misleading labeling by issuing regulations requiring label warnings and
other affirmative disclosures. (See, e.g., Cosmetic, Toiletry, and
Fragrance Association v. Schmidt, 409 F. Supp. 57 (D.D.C. 1976), aff'd
without opinion, Civil No. 75-1715 (D.C. Cir. August 19, 1977), even in
the absence of a proven cause-and-effect relationship between product
usage and harm; Council for Responsible Nutrition v. Goyan, Civil No.
80-1124 (D.D.C August 1, 1980).)
Section 502(f)(1) of the act provides that a device is also
misbranded unless its labeling bears adequate directions for use.
Adequate directions for use means
[[Page 32619]]
adequate directions under which a layperson can use a device safely and
for the purpose for which it was intended. (See 21 CFR 801.5 and
801.6.)
II. Latex Labeling
FDA is proposing that medical devices containing natural rubber
latex that may directly or indirectly contact living human tissue be
labeled with a statement identifying the product as one which contains
natural rubber latex, which may cause allergic reactions. Direct
contact with living human tissue occurs when a natural rubber latex-
containing medical device touches the skin, mucous, or serosal
surfaces. Examples of indirect contact with living human tissue by a
natural rubber latex-containing medical device include, but are not
limited to, the following: Contact with natural rubber latex proteins
that have become suspended in liquid, which can occur when injections
are given through a natural rubber latex-containing injection port or a
syringe with a natural rubber latex-containing plunger; contact with
natural rubber latex protein that is airborne, often in conjunction
with the use of glove dusting powder; and contact with natural latex
residues that have been transferred to nonrubber latex-containing
medical devices, or other objects or surfaces. Devices affected by this
proposed rule would be required to be labeled with one of the following
statements: ``This product contains natural rubber latex which may
cause allergic reactions in some individuals''; ``This product has
components that contain natural rubber latex which may cause allergic
reactions in some individuals''; or ``This product is made from natural
rubber latex which may cause allergic reactions in some individuals''.
The agency has provided three labeling options so that
manufacturers may choose the language most appropriate for their
products. The agency invites comments regarding whether FDA should
require a single, uniform, labeling statement for all natural latex-
containing medical devices, and the agency will consider comments
recommending alternative language for the proposed labeling statements.
Representative examples of natural rubber latex-containing medical
devices which would require such labels include, but are not limited to
the following: Cuffed-barium enema tips and enteroclysis catheters;
contraceptive devices such as condoms with or without spermicidal
lubricant, cervical caps, diaphragms and accessories, and therapeutic
douche apparati; airway and respiratory devices such as oxygen
cannulas, nasopharyngeal airways, tracheal tubes and inflatable cuffs,
tracheobronchial suction catheters, breathing bags and mouthpieces;
dental and surgical equipment such as dental dams, orthodontic
appliances and headgear, anaesthetic gas masks, epistaxis balloons, and
endotracheal tubes; and frequently used hospital equipment such as
urinary catheters and accessories, blood pressure cuffs, intravascular
equipment with latex injection ports, electrode pads, tourniquets,
enema bags, hot or cold water bottles, rubber sheets, stomach and
intestinal tubes, hemodialysis equipment, wound drains, adhesive tape,
elastic bandages, and medical gloves.
Medical gloves include surgeon's gloves, as classified at 21 CFR
878.4460, and patient examination gloves, as classified at 21 CFR
880.6250. Some medical gloves are made of materials that may not
contain natural rubber latex in their formulations and, therefore,
would not be subject to this proposal. It should be further noted that
the term ``medical gloves'' is used to distinguish them from nonmedical
gloves that are not regulated by FDA. Nonmedical gloves, commonly
referred to as utility, industrial, protective, or general purpose
gloves, are not medical devices if they are not intended and/or labeled
for a medical purpose, such as prevention of disease. Such products
would not be subject to this proposed rule.
This rule is being proposed because medical devices that are
composed of natural rubber latex, or which contain components
formulated from natural latex, pose a significant health risk to some
health care consumers and providers. A statement on the label of
medical devices identifying the presence of natural latex, and its
risks, is considered to be necessary for the safe and effective use of
such devices. The primary purpose of such a statement is to inform
health care professionals and consumers about the presence and risks of
natural rubber latex, and to ensure a safe medical environment for
persons who have been identified as sensitive to natural rubber latex.
The agency believes that a statement on the labeling of the devices
stating that the product contains natural rubber latex, and that the
presence of natural rubber latex may cause allergic reactions, is
essential. The omission of such information from the labeling of such a
device would constitute an omission of a material fact, and would
render the device misbranded within the meaning of section 502(a) of
the act (21 U.S.C. 352(a)). Moreover, because users need to be aware of
safety problems that may be caused by natural rubber latex, FDA
believes that a device containing natural rubber latex, which is not
labeled with information regarding the presence of natural rubber latex
and its potential risks, fails to bear adequate directions for use, and
is, therefore, also misbranded under section 502(f)(1) of the act.
Section 502(c) of the act provides that a device is misbranded
``[i]f any word, statement, or other information required by or under
authority of this Act to appear on the label or labeling is not
prominently placed thereon with such conspicuousness (as compared with
other words, statements, designs, or devices, in the labeling) and in
such terms as to render it likely to be read and understood by the
ordinary individual under customary conditions of purchase and use.''
Accordingly, the proposed regulation would require the rubber latex
sensitivity statement to be displayed prominently and conspicuously on
the device labeling. If the labeling statement is not prominently
displayed, the product would be deemed misbranded under section 502(c)
of the act.
Accordingly, under the proposed rule, any natural rubber latex-
containing medical device that is not labeled as required, and that is
initially introduced or initially delivered for introduction into
interstate commerce after the effective date of the final rule, would
be misbranded under sections 201(n) and 502(a), (c), and (f)(1) of the
act.
FDA believes that it is also necessary to prohibit certain labeling
statements on devices that contain natural rubber latex. FDA has
received reports of sensitivity to medical gloves labeled as
``hypoallergenic.'' FDA believes that this term, traditionally used
with cosmetics, erroneously implies that the user of products labeled
as hypoallergenic is assured that the risk of an allergic reaction to
the chemicals or other materials in the products would be minimal. In
the past, use of the ``hypoallergenic'' label has been based on 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 accurately detect the presence or absence of natural
latex protein levels. Furthermore, current manufacturing processes
cannot remove from devices the natural latex proteins below the level
to which some individuals may be sensitive. Thus the risk of allergic
reaction remains.
Therefore, the agency believes that the presence of the term
``hypoallergenic''
[[Page 32620]]
on the labeling of a natural rubber latex-containing device is false
and misleading because it incorrectly implies that the product labeled
as ``hypoallergenic'' may be used safely by latex sensitive persons.
FDA also believes that products with such labeling fail to bear
adequate directions for use because they do not state that rubber
latex-containing products labeled as hypoallergenic may still cause
allergic reactions. For these reasons, FDA is proposing that the
hypoallergenic claim be removed from the labeling of natural rubber
latex-containing medical devices. Accordingly, under the proposed rule,
FDA would consider natural rubber latex-containing medical devices
labeled as hypoallergenic that are initially introduced or delivered
for introduction after the effective date of the final rule, to be
misbranded under section 502(a) and (f)(1) of the act. Although
manufacturers would no longer be permitted to label their rubber latex-
containing devices as ``hypoallergenic,'' persons wishing to make
claims regarding the sensitizing potential of manufacturing chemical
residues (MTB's, thiurams, and carbamates) in finished latex products
should contact the Division of Small Manufacturers Assistance (1-800-
638-2041) and request a copy of the guidance document entitled
``Testing for Skin Sensitization to Chemicals in Latex Products.''
FDA does not intend to require a new submission under section
510(k) of the act (21 U.S.C. 360) (510(k) submission) based upon
labeling changes made to comply with this proposed regulation, provided
that no other changes requiring a new 510(k) submission under 21 CFR
807.81 are made to the device. FDA does not intend to require
manufacturers of devices subject to an approved premarket approval
(PMA) application to submit a PMA supplement under 21 CFR 814.39(d),
for any change to the product labeling that would be required by this
regulation. FDA intends, instead, to require manufacturers to submit an
annual report under 21 CFR 814.39(e) for such changes.
III. Request for Comments
FDA recognizes that this regulation applies to an array of devices
that vary widely in their manufacture and use. FDA welcomes comments on
all aspects of the regulation, but particularly invites comments on the
following areas:
1. Some of the devices to which this regulation applies may be sold
in bulk packages which are then divided up and used individually. How
can FDA best ensure that the message that the regulation is intended to
convey reaches the ultimate user?
2. It has been suggested that the message could be conveyed by
using a symbol, especially on smaller devices. FDA invites comments on
whether using a symbol would be useful, and, if so, what would be an
appropriate symbol?
IV. Exemptions and Variances
Affected persons may request an exemption or variance from the
requirements of this regulation, if they believe that full compliance
with the regulation is not necessary for the safe and effective use of
the device. Requests for exemption or variance must be submitted in
accordance with the requirements for a citizen petition set forth in 21
CFR 10.30.
V. Environmental Impact
The agency has determined under 21 CFR 25.24(e)(2) that this action
is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required.
VI. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).
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 agency believes that
this rule is consistent with the regulatory philosophy and principles
identified in the Executive Order. In addition, the proposed rule is
not a significant regulatory action as defined by the Executive Order
and so is not subject to review under the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. This proposed rule primarily requires a labeling
change which would not have a significant economic impact on small
entities, because the 180 days before the final rule based upon this
proposal would become effective will allow most manufacturers to
exhaust their existing supply of labels. Therefore, under the
Regulatory Flexibility Act, no further analysis is required.
VII. Paperwork Reduction Act of 1995
FDA tentatively concludes that the labeling requirements in this
proposed rule are not subject to review by the Office of Management and
Budget because they do not constitute a ``collection of information''
under the Paperwork Reduction Act of 1995 (Pub. L. 104-13). Rather, the
proposed warning statements 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)).
VIII. Comments
Interested persons may submit written comments regarding this
proposed rule, by September 23, 1996, to the Dockets Management Branch
(address above). Two copies of any comments are to be submitted, except
that individuals may submit one copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments may be seen in the office above between 9
a.m. and 4 p.m., Monday through Friday.
IX. References
The following references have been placed on display in the Dockets
Management Branch (address above) 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 edition, 1987.
2. Turjanmaa, K., ``Incidence of Immediate Allergy to Latex
Gloves in Hospital Personnel,'' Contact Dermatitis, 17: 27-275,
1987.
3. 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.
4. Turjanmaa, K. and T. Reunala, ``Condoms as a Source of Latex
Allergen and Cause of Contact Urticaria,'' Contact Dermatitis, 20:
360-364, 1989.
5. FDA medical alert--allergenic reactions to latex-containing
medical devices, March 29, 1991.
6. 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.
7. 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.
8. Tomazic, V., T. Withrow, B. Fisher, and S. Dillard, ``Short
Analytical Review-Latex-
[[Page 32621]]
Associated Allergies and Anaphylactic Reactions,'' Clinical
Immunology and Immunopathology, 64: 89-97, 1992.
9. Slater, J. and S. Chhabra, ``Latex Antigens,'' Journal of
Allergy and Clinical Immunology, 89: 673-678, 1992.
10. 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.
11. 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.
12. Berky, Z., J. Luciano, and W. James, ``Latex Glove Allergy--
A Survey of the US Army Dental Corps,'' Journal of the American
Medical Association, 268: 2695-2697, 1992.
13. Gonzalez, E., ``Latex Hypersensitivity: A New and Unexpected
Problem,'' Hospital Practice, pp. 137-151, February 15, 1996.
14. Stehlin, D., ``Latex Allergies: When Rubber Rubs the Wrong
Way,'' FDA Consumer, pp. 16-21, September 1992.
15. ACAI (American College of Allergy & Immunology), Interim
Recommendations to Health Professionals & Organizations Regarding
Latex Allergy Precautions, March, 1992.
16. Young, M., M. Meyers, L. McCulloch, and L. Brown, ``Latex
Allergy-A guideline for perioperative nurses,'' AORN Journal, 56:
488-502, 1992.
17. Hamann, C. P., ``Natural Rubber Latex Protein Sensitivity in
Review,'' American Journal of Contact Dermatitis, 4:1. March 1993,
4-21.
18. 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.
19. USDHHS/PHS/FDA/CDRH, Regulatory Requirements for Medical
Gloves--A Workshop Manual, FDA 93-4257, as amended May, 1993.
List of Subjects in 21 CFR Part 801
Labeling, Medical devices, and 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. New Sec. 801.437 is added to subpart H to read as follows:
Sec. 801.437 User labeling for rubber latex-containing medical
devices.
(a) This section applies to all medical device products composed of
or containing, or having components which are composed of or contain,
natural rubber latex that may directly or indirectly contact living
human tissue. The term ``natural rubber latex'' includes natural rubber
latex, dry rubber, and synthetic latex which contains natural rubber
latex in its formulation.
(b) Data in the Medical Device Reporting System and scientific
literature indicate that some individuals may be at risk of a severe
anaphylactic reaction to natural rubber latex proteins. In order to
protect the public health and minimize the risk to rubber latex
sensitive individuals, medical devices containing natural rubber latex
shall be labeled as set forth in paragraphs (c) and (d) of this
section.
(c) Natural rubber latex-containing medical devices shall
prominently and legibly bear one of the following statements on the
device labeling, in conformance with section 502(c) of the act: ``This
product contains natural rubber latex which may cause allergic
reactions in some individuals''; ``This product has components that
contain natural rubber latex which may cause allergic reactions in some
individuals''; or ``This product is made from natural rubber latex
which may cause allergic reactions in some individuals''.
(d) Because the natural rubber latex proteins to which some
individuals are sensitive cannot be completely removed from latex
gloves, the term ``hypoallergenic'' is inappropriate. Therefore, rubber
latex gloves and other natural rubber latex-containing medical devices
shall not contain the term ``hypoallergenic'' on their labeling.
(e) 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.
(f) Any device subject to this section that is not labeled in
accordance with paragraphs (c) and (d) of this section, and that is
initially introduced or initially delivered for introduction into
interstate commerce after the effective date of this final regulation,
is misbranded under sections 201(n) and 502(a) and (f)(1) of the act.
Any such device that is not labeled in accordance with paragraph (c) of
this section, is also misbranded under section 502(c) of the act.
Dated: June 17, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-15990 Filed 6-21-96; 8:45 am]
BILLING CODE 4160-01-F