[Federal Register Volume 64, Number 146 (Friday, July 30, 1999)]
[Proposed Rules]
[Pages 41710-41743]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-19191]



[[Page 41709]]

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Part V





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Parts 801, 878, and 880



Surgeon's and Patient Examination Gloves; Reclassification and Medical 
Glove Guidance Manual Availability; Proposed Rule and Notice

  Federal Register / Vol. 64, No. 146 / Friday, July 30, 1999 / 
Proposed Rules  

[[Page 41710]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 801, 878, and 880

[Docket No. 98N-0313]
RIN 0910-AB74


Surgeon's and Patient Examination Gloves; Reclassification

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY:  The Food and Drug Administration (FDA) is proposing 
regulations to reclassify all surgeon's and patient examination gloves 
as class II medical devices because it believes that general controls 
are insufficient to provide a reasonable assurance of safety and 
effectiveness. The reclassified gloves, including those made of natural 
rubber latex (NRL) or synthetic material, will be regulated in four 
categories: Powdered surgeon's gloves, powder-free surgeon's gloves, 
powdered patient examination gloves, and powder-free patient 
examination gloves. The proposed special controls are in the form of a 
proposed guidance document entitled ``Medical Glove Guidance Manual,'' 
which includes recommended protein and glove powder limits, and new 
label caution statements including protein and powder labeling 
requirements. FDA is also proposing to require expiration dating. This 
proposed rule is intended to reduce the adverse health effects from 
allergic and foreign body reactions caused by the natural latex (NL) 
protein allergens and glove powder found on surgeon's and patient 
examination gloves and to reduce the adverse health effects from 
defects in the barrier integrity and quality of surgeon's and patient 
examination gloves.
DATES: Written comments by October 28, 1999. Written comments on the 
information collection requirements should be submitted by August 30, 
1999.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit written comments on the information 
collection requirements to the Office of Information and Regulatory 
Affairs, Office of Management and Budget (OMB), New Executive Office 
Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn.: Wendy 
Taylor, Desk Officer for FDA.

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, 301-827-4777.

SUPPLEMENTARY INFORMATION:

I. Background

    Surgeon's and patient examination gloves are intended to provide an 
effective barrier against potentially infectious materials and other 
contaminants. However, the use of surgeon's and patient examination 
gloves has been associated with a number of adverse health effects in 
patients and users, including allergic reactions, foreign body 
reactions, and irritation.
    NL is a milky fluid that consists of extremely small particles of 
rubber obtained from plants, principally from the Heavea brasiliensis 
(rubber) tree, dispersed in an aqueous medium. NL contains a variety of 
naturally occurring substances, including plant proteins, which are 
believed to be the primary allergens associated with NL allergy. NL is 
employed in the natural rubber latex manufacturing process. Products 
made by the natural rubber latex manufacturing process, such as medical 
gloves, are referred to as containing or made of NRL. For a more 
complete description of the NRL manufacturing process and further 
definition of related terms, see the final rule entitled ``Natural 
Rubber-Containing Medical Devices; User Labeling,'' published on 
September 30, 1997 (62 FR 51021), and codified in part 801 (21 CFR part 
801) at Sec. 801.437.
    Glove powder is defined as the total particulate matter on a 
finished glove, including donning and dusting powder, as well as 
former-release (or mold-release) compounds and manufacturing debris. 
The main component of donning and dusting powder is most commonly 
cornstarch.
    Health care workers, comprised of physicians, dentists, 
pharmacists, nurses, technologists, technicians, and phlebotomists, use 
millions of NRL gloves during procedures involving millions of 
patients; this makes NRL gloves a significant source of exposure to NL 
allergens (Ref. 1).
    Studies of health care workers, blood donors, and ambulatory 
surgical patients have demonstrated an appreciable prevalence of NL 
sensitivity (Refs. 2 to 8). FDA has received 330 reports of adverse 
events attributed to NL allergy occurring in patients and health care 
workers, which suggests that allergic reaction to NRL products in 
health care settings manifests itself in a variety of symptoms ranging 
from dermatitis to anaphylaxis (Ref. 9). The general population is 
directly exposed to NRL from a variety of sources, including consumer 
products such as industrial gloves and NRL balloons, as well as medical 
devices such as barrier contraceptives and NRL gloves.
    FDA has significant concerns about the role of glove powder as a 
carrier of airborne allergens, because NL allergens have been shown to 
bind to cornstarch. A number of published clinical and experimental 
studies support this conclusion (Refs. 10 to 14). In addition to the 
role of glove powder as a carrier of airborne allergens, FDA is also 
aware that glove powder contributes to a number of other adverse health 
effects. As particulate matter, it can cause foreign body reactions, 
resulting in inflammation, granulomas and adhesions of peritoneal 
tissues after surgery (Refs. 15 to 19). Glove powder may serve as an 
absorbent or adsorbent for unbound chemicals that may be irritants or 
chemical contact sensitizers. In addition, glove powder from nonsterile 
patient examination gloves may also support microbial growth and act as 
a carrier for endotoxins (Ref. 20). These multiple concerns of adverse 
health effects associated with particulate matter from the surface of 
medical gloves constitute compelling reasons for FDA to reduce the 
amount of powder on all gloves, as well as to ensure that both powdered 
gloves and powder-free alternatives are clearly labeled so users and 
consumers may make informed choices. Although data is not currently 
available to quantify a maximum allowable level of glove powder, 
decreased exposure to glove powder will decrease the prevalence of 
adverse health effects. Therefore, FDA is recommending a powder level 
it believes is achievable by industry.
    In June 1997, the National Institute of Occupational Safety and 
Health (NIOSH) issued a safety alert recommending the use of powder-
free, reduced protein content NRL or synthetic gloves as a means to 
reduce exposure to NL allergens, specifically via the airborne route of 
exposure (Ref. 21). While FDA agrees with the goal of reducing exposure 
to airborne allergens, FDA is concerned that efforts to produce powder-
free gloves with satisfactory donning properties may require additional 
manufacturing processes that, if not appropriately controlled, have 
deleterious effects on physical properties, performance, and shelf-life 
of the gloves (Refs. 22 and 23).

[[Page 41711]]

II. Statutory Authority

    The Federal Food, Drug, and Cosmetic Act (the act), as amended by 
the Medical Device Amendments of 1976 (the 1976 amendments) (Public Law 
94-295), the Safe Medical Devices Act of 1990 (SMDA) (Public Law 101-
629), and the Food and Drug Administration Modernization Act of 1997 
(FDAMA) (Public Law 105-115), established a comprehensive system for 
the regulation of medical devices intended for human use. Section 513 
of the act (21 U.S.C. 360c) established three categories (classes) of 
devices, depending on the regulatory controls needed to provide a 
reasonable assurance of their safety and effectiveness.
    The three categories of devices are class I (general controls), 
class II (special controls), and class III (premarket approval). The 
effect of classifying a device into class I is to require that the 
device meet only the general controls that are applicable to all 
devices. The effect of classifying a device into class II is to require 
the device to meet special controls as well as general controls, which 
together provide reasonable assurance of the safety and effectiveness 
of the device. Class II devices are devices which cannot be classified 
in class I because general controls by themselves are insufficient to 
provide reasonable assurance of safety and effectiveness and for which 
there is sufficient information to establish special controls to 
provide such assurance, including the issuance of performance 
standards, postmarket surveillance, patient registries, and guidelines 
(see section 513(a)(1)(B) of the act). The effect of classifying a 
device into class III is to require each manufacturer of the device to 
submit to FDA a premarket approval application (PMA) that includes 
information concerning safety and effectiveness of the device.
    Under section 513 of the act, devices that were in commercial 
distribution before May 28, 1976 (the date of enactment of the 
amendments), generally referred to as preamendments devices, are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    A device that is first offered in commercial distribution after May 
28, 1976, generally referred to as a postamendments device, and which 
FDA determines to be substantially equivalent to a device classified 
under this scheme, is classified into the same class as the device to 
which it is substantially equivalent. The agency determines whether new 
devices are substantially equivalent to previously offered devices by 
means of premarket notification procedures in section 510(k) of the act 
(21 U.S.C. 360(k)) and part 807 of the regulations (21 CFR part 807). A 
device that was not in commercial distribution prior to May 28, 1976, 
and that has not been found by FDA to be substantially equivalent to a 
legally marketed device, is classified automatically by statute 
(section 513(f) of the act) into class III, without any FDA rulemaking 
proceeding.
    Reclassification of classified preamendments devices is governed by 
section 513(e) of the act (21 U.S.C. 360c(e)). This section provides 
that FDA may, by rulemaking, reclassify a device (in a proceeding that 
parallels the initial classification proceeding) based upon ``new 
information.'' The reclassification can be initiated by FDA or by the 
petition of an interested person. The term ``new information,'' as used 
in section 513(e) of the act, includes information developed as a 
result of the reevaluation of the data before the agency when the 
device was originally classified, as well as information not presented, 
not available, or not developed at that time. (See, e.g., Holland 
Rantos v. United States Department of Health, Education, and Welfare, 
587 F.2d 1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 
(6th Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).)
    Reevaluation of the data previously before the agency is an 
appropriate basis for subsequent regulatory action where the 
reevaluation is made in light of changes in ``medical science.'' (See 
Upjohn v. Finch, supra, 422 F.2d at 951.) However, regardless of 
whether data before the agency are past or new data, the ``new 
information'' on which any reclassification is based is required to 
consist of ``valid scientific evidence,'' as defined in section 
513(a)(3) of the act (21 U.S.C. 360c(a)(3)) and 21 CFR 860.7(c)(2). FDA 
relies upon ``valid scientific evidence'' in the classification process 
to determine the level of regulation for devices. For the purpose of 
reclassification, the valid scientific evidence upon which the agency 
relies must be publicly available. Publicly available information 
excludes trade secret and/or confidential commercial information.
    On November 21, 1997, the President signed into law FDAMA. Section 
206 of FDAMA added a new section 510(m) (21 U.S.C. 360(m)) to the act. 
Section 510(m)(2) of the act provides that FDA may, on its own 
initiative or upon petition of an interested person, exempt a class II 
device from the requirement of premarket notification in section 510(k) 
of the act, if FDA determines that a 510(k) submission is not necessary 
to provide reasonable assurance of the safety and effectiveness of the 
device. Such an exemption would permit manufacturers to introduce the 
generic type of device into commercial distribution without first 
submitting a premarket notification to FDA.
    Section 701(a) of 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 ``[I]f 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)).
    FDA may impose testing requirements in a labeling regulation issued 
under its general rulemaking authority. (See, e.g.,

[[Page 41712]]

American Frozen Food Inst. v. Mathews, 413 F. Supp. 548 (D.D.C. 1976), 
aff'd per curiam sub nom. American Frozen Food Inst. v. Califano, 555 
F.2d 1059 (D.C. Cir. 1977); see also National Nutritional Foods Ass'n 
v. Weinberger, supra.) Thus, FDA may require that all manufacturers use 
the same conditions to test aging to ensure that the expiration date 
reflects the period of time a product can be used safely. Similar 
requirements are imposed in Sec. 801.430(f) for absorbency testing for 
menstrual tampons, and in Sec. 801.420(c)(4) on hearing aid 
manufacturers and distributors who must determine and state technical 
data values for hearing aid labeling in accordance with specified test 
procedures. The hearing aid regulation has been upheld. (American 
Speech and Hearing Ass'n v. Califano, Medical Devices Report (CCH) No. 
77-1327 Secs. 15004, 15007 (D.D.C. August 23, 1977) aff'd No. 77-1327 
(D.C. Cir. Dec. 19, 1977).) Food regulations issued under section 
701(a) of the act also impose many such specific testing requirements 
(see e.g., 21 CFR 113.40 (tests for low-acid canned foods); 21 CFR 
155.190(b)(2)(i) (test for determining drained weight of canned 
tomatos); 21 CFR 161.190 (method for determining color designation of 
tuna).

III. Powder and Protein Concerns

    Although FDA has been concerned about airborne NL allergens 
associated with the use of powdered medical gloves and has undertaken 
continued efforts to address these concerns, recent heightened 
awareness within the health care community and State and Federal 
Government agencies of adverse health effects has prompted this 
proposed action.
    Over the past 3 years, FDA has received requests to ban the use of 
all glove powders. These requests have been based on a number of 
clinical and experimental studies reporting that cornstarch on surgical 
gloves can reduce tissue resistance to infection, enhance the 
development of infection, cause formation of granulomas and adhesions, 
act as a carrier of NL protein from NRL products, and serve as a 
potential source of occupational asthma. Although a ban of all powdered 
medical gloves has been requested by petitioners and would reduce the 
problem of airborne powder, it would not completely address the problem 
of NL allergy and would potentially leave a significant and important 
need for high quality barrier products unmet.
    One of the concerns regarding glove powder, in general, is its 
capability, as particulate material, to cause foreign body reaction, 
resulting in inflammation, granulomas and adhesions of peritoneal 
tissues after surgery (Refs. 15 to 19). Although cornstarch was 
considered to be absorbable by United States Pharmacopeia (USP), 
changes in the sterilization processes have reduced absorbability 
significantly (Ref. 15). Cornstarch represents a growth source for 
bacteria, and it is also a carrier of endotoxin, which can play a role 
in enhancing both delayed and immediate hypersensitivity (Ref. 20). 
Clinical experience suggests that powder on NRL gloves, in addition to 
its role in Type I allergy, may also be a contributing factor in the 
development of irritant dermatitis and Type IV allergy. Irritant skin 
reactions have been observed in association with frequent exposure to 
glove powder. Compromised skin barrier properties resulting from such 
reactions may permit penetration of allergens and other substances into 
the skin, thereby increasing chances for the development of both Type I 
and Type IV allergy (Ref. 24).
    In addition, a significant concern, specific to NL gloves, exists 
regarding the role of glove powder as a carrier of airborne NL 
allergens. A number of respiratory problems and episodes of bronchial 
spasms in hospital employees and patients, reported since the mid 
1980's, were ascribed to inhalation of airborne NL allergens in 
settings with heavy use of powdered gloves (Refs. 25 to 30). The 
implication of glove powder in the previous clinical reports was based 
on medical histories of individuals presenting with symptoms, on 
positive skin tests, positive tests for the presence of antibodies to 
NL allergens in blood and, in some cases, on positive inhalation 
challenge tests. A number of published clinical and experimental 
studies support this conclusion.
    Binding of NL proteins to cornstarch was demonstrated in recent 
laboratory studies, which support a causal relationship between 
asthmatic reactions in individuals with NL allergy and the exposure to 
airborne particles from NL products (Refs. 10 and 11). The level of 
exposure and the severity of the reactions depend on both the amount of 
powder and the amount of NL protein allergens on the finished products. 
Measurements of airborne particle levels in environments where NL 
gloves were used frequently demonstrated that the level of airborne 
allergen is directly related to the frequency of powdered NL glove 
usage in particular areas and to the level of allergen and/or powder on 
the gloves used (Refs. 12 and 14).
    Direct evidence that NL protein allergens, bound to the glove 
powder particles, provoke respiratory allergic reactions and asthma-
like attacks has been documented by the bronchial provocation tests 
with powders on NL gloves. The bronchial provocation tests were 
performed by having allergic individuals inhale the extracts from 
powder-free surgeon's gloves, from powdered surgeon's gloves, and from 
cornstarch powder not exposed to NL. The studies indicated that 
cornstarch powder not exposed to NL did not cause any reaction in 
sensitized subjects, while nebulized powdered NL surgeon's glove 
extract, and to some extent, nebulized powder-free glove extract 
induced bronchoconstriction in tested subjects (Ref. 31).
    However, the scientific data to define the quantitative 
relationship between respiratory allergic reactions and powder level on 
NL gloves are not available at this time. Such data and the specific 
dose-response relationship would be difficult to establish, because 
allergenicity of the airborne glove powder depends on the amount of 
powder and also on the amount of powder-bound allergenic proteins. 
Standardized methods for measuring the amount of powder-bound proteins 
or allergens and the amount of inhaled powder are not available.
    NL protein has been widely reported as a cause of Type I 
sensitivity in individuals who have been exposed to NL devices (Refs. 2 
to 8). Repeated exposure to NL protein is considered to increase the 
probability that an individual will become sensitized. Total water-
extractable protein on the finished NL product is considered an 
indirect measure of the potential allergenicity. Because several NL 
proteins have already been identified as allergenic and others may be 
identified in the future, exclusion of any proteins from the evaluation 
may result in an inaccurate determination of potential allergenicity. 
The total water-extractable protein level measured using the standard 
American Society for Testing and Materials (ASTM) D 5712 method was 
found to correlate well with currently used allergen measurement 
methods. Most importantly, a total water-extractable protein level 
correlates also with the skin prick test, which is a direct measure of 
allergic response in sensitized individuals (Ref. 32). Since May 1991, 
FDA has advised manufacturers of NL devices to reduce the water-
extractable protein on their NL devices. This reduction is now 
addressed in the Quality System (QS) Regulation at 21 CFR 820.3(p) and 
820.70(h).

[[Page 41713]]

    Initially, a labeling claim for a protein level was not accepted in 
a 510(k) submission because a standard test method for measuring water-
extractable protein in NL did not exist. In 1995, with the help of 
industry and FDA, ASTM published the ``ASTM Standard Test Method for 
Analysis of Protein in Natural Rubber and its Products, D 5712-95.'' 
FDA subsequently issued a document entitled ``Interim Guidance On 
Protein Content Labeling Claim For Latex Medical Gloves,'' which is 
based on this test method. Manufacturers were allowed to use this 
guidance to submit a 510(k) submission for NL gloves identifying the 
level of water-extractable protein for the device. FDA is now proposing 
that a recommended limit on water-extractable protein per glove and the 
actual protein level appear on the label.
    The amount of powder required for satisfactory donning of gloves 
has not been quantified, and the level of glove powder used varies 
greatly. Limited laboratory data from measurements of a number of 
surgeon's and patient examination gloves demonstrated that powder 
levels ranged from 70 to 375 milligrams (mg) per glove for surgeon's 
gloves and from 50 to 426 mg per glove for patient examination gloves 
(Ref. 31). Because of the multiple concerns regarding adverse health 
effects associated with particulate matter from the surface of 
surgeon's and patient examination gloves, FDA is now proposing that a 
recommended limit on glove powder and the actual level of glove powder 
appear on the label. FDA recognizes there is a correlation between 
powder level and ease of glove donning and that powder level is 
correlated with adverse health effects. For this reason, FDA is 
encouraging industry to find the balance between donning requirements 
and reducing the risks of adverse health effects.
    Lowering the powder level and the amount of protein on surgeon's 
and patient examination gloves will reduce exposure to NL allergens and 
benefit both allergic individuals and those at risk to develop allergy. 
In addition, the reduction of glove powder levels will help reduce 
exposure to particulate materials responsible for foreign body 
reactions. However, the reduction of powder and protein levels must be 
accomplished by methods that do not compromise the availability of or 
barrier properties of surgeon's and patient examination gloves.

IV. Barrier and Other Quality Issues

    In the Federal Register of October 21, 1980 (45 FR 69723), FDA 
issued a final rule classifying the patient examination glove into 
class I and exempting manufacturers of the device from compliance with 
premarket notification procedures under section 510(k) of the act and 
certain requirements of the current good manufacturing practice (CGMP) 
regulation. FDA granted the exemptions in the 1980 regulation because, 
at that time, no adverse experiences had been related to patient 
examination gloves. Furthermore, the role of the gloves as a protective 
barrier against human immunodeficiency virus (HIV) transmission was not 
recognized and the concomitant risks associated with glove failure were 
not well understood.
    In the Federal Register of January 19, 1982 (47 FR 2810 at 2852), 
FDA proposed that the surgeon's glove be classified into class II 
because of concerns about tissue compatibility and the risk of 
infection if the devices were not properly sterilized. Comments offered 
in response to the proposed classification stated that those problems 
could be addressed through general controls, including labeling and 
CGMP adherence, and recommended that the device be classified into 
class I because of the history of its safe and effective use. In the 
Federal Register of June 24, 1988 (53 FR 23856), FDA issued a final 
rule classifying the surgeon's glove into class I without exemptions. 
Manufacturers and importers of surgeon's gloves have been required to 
comply with the premarket notification and CGMP regulations since the 
initial classification of the device.
    Over the years, many issues regarding surgeon's and patient 
examination gloves have been brought to the attention of FDA. The 
acquired immune deficiency syndrome (AIDS) epidemic resulted in an 
elevated reliance on medical gloves as a barrier against blood-borne 
viral transmission. The increased demand for gloves soon outstripped 
the domestic supply. Foreign glove manufacturers began to meet the 
demand for additional gloves. Many manufacturers with little or no 
medical glove manufacturing experience began operations, resulting in 
large quantities of gloves of uncertain quality entering the U.S. 
market.
    Following the advent of AIDS as a major public health concern and 
recommendations from the Centers for Disease Control and Prevention 
(CDC) that health care workers use appropriate barrier precautions to 
prevent exposure to the HIV virus, FDA recognized the need for greater 
assurance that cross-contamination between patients and health care 
workers be prevented. Accordingly, in the Federal Register of January 
13, 1989 (54 FR 1602), FDA revoked the exemption for patient 
examination gloves from certain CGMP requirements in order to assure 
that manufacturers provide an acceptable manufacturing quality level. 
FDA similarly revoked the exemption from premarket notification 
requirements for patient examination gloves. On December 12, 1990 (55 
FR 51254), FDA published regulations describing certain circumstances 
under which surgeon's and patient examination gloves would be 
considered adulterated, and establishing the sampling plans and test 
methods the agency would use to determine whether gloves were 
adulterated (Sec. 800.20 (21 CFR 800.20)). Subsequently, FDA initiated 
inspections of glove manufacturers to assure conformance with the 
acceptable quality levels (AQL) identified in that regulation.
    FDA has sought to address many concerns regarding the quality and 
barrier integrity of medical gloves. Certain processes or conditions 
can often contribute to degradation of the barrier. NL degrades if it 
is not correctly formulated and processed. Proper formulation includes 
the use of stabilizers, antiozonants, and antioxidants to reduce 
degradation. Improper curing can also cause thin spots on the glove 
surface, which may lead to early barrier failure.
    Gloves composed of synthetic polymer, such as nitrile, are produced 
by essentially the same processes as NL. The same accelerators, 
antioxidants, and stabilizers are used to reduce degradation. Thus, 
improper formulation and processing may also lead to rapid degradation 
of synthetic gloves.
    Storage conditions can also cause degradation of the polymers, 
whether natural or synthetic. These storage conditions include the 
temperature at which the material is held, the humidity of their 
environment, and any radiation (for example, sunlight or fluorescent 
lights) to which the material may be exposed.
    Additionally, chlorination is widely used to reduce the tackiness 
of NL gloves and thus eliminate the need for donning powder. 
Chlorination works by degrading the surface of the gloves. Therefore, 
chlorination must be carefully controlled in order to prevent 
destruction of the glove barrier. Improperly chlorinated gloves rapidly 
degrade, and breaks in the latex film may occur in a matter of months.
    Another concern has been the presence of minute defects known as 
pinholes, which directly affect the barrier integrity of the gloves. 
FDA studies of micro-photographs of

[[Page 41714]]

defective NL devices have shown that dust, dirt, rust, paint chips, 
charred starch, insect parts, and other debris may cause pinholes. 
Therefore, appropriate environmental and processing controls, as 
required by the QS regulation, are needed. Manufacturers also need to 
control other causes of pinholes such as former vibration, air bubbles 
in the dipping tanks, dirty formers, incorrect formulation, and 
excessive curing temperatures.
    If gloves have pinholes, breaks or tears, viruses can potentially 
penetrate the glove wall, eliminating or reducing the gloves' 
effectiveness as a barrier. On April 6 and 7, 1989, the University of 
Maryland, in conjunction with FDA, held a conference entitled ``Latex 
as a Barrier Material,'' which reiterated the value of NL as a barrier 
film and generated continued support towards more research in this area 
by industry and FDA.
    Although manufacturers have data to show that their gloves meet 
their company AQL for defects when the gloves are shipped, for some 
manufacturers, the same gloves which passed the manufacturer's tests 
are sometimes rejected at the port of entry in the United States 
because the gloves fail the FDA water leak test at that point. This 
test result disparity, whether due to degradation or for other reasons, 
is a primary reason why, upon importation, the gloves of some 
manufacturers have been detained without physical examination. 
Manufacturers should assure, by means of stability testing, that their 
surgeon's and patient examination gloves will continue to meet the 
manufacturers' specifications over the expected life of the gloves.
    FDA is aware that microbial growth on gloves also can be a problem. 
The QS regulation requires manufacturers to control processing, 
shipping and storage environment, and contamination when these can 
adversely affect the product. Therefore, processing controls should 
include: Using only cornstarch with an acceptable bioburden, properly 
storing the cornstarch until it is used, applying cornstarch by 
established procedures, cooling the cornstarch slurry and/or using an 
antimicrobial in the cornstarch slurry tanks, checking finished gloves 
on a sampling basis to assure that excessive cornstarch is not applied, 
keeping the finished gloves clean, establishing and meeting a dryness 
specification for finished gloves, and protecting finished gloves from 
adverse environmental conditions.
    Although synthetic materials have improved in recent years, NL 
gloves may be superior to some synthetic gloves in regard to barrier 
properties (Ref. 34). Both NL and synthetic surgeon's and patient 
examination gloves provide protection against microorganisms; however, 
it has been demonstrated that compared to vinyl, NL has more effective 
and durable barrier qualities (Refs. 35 and 36).
    There are other safety and performance issues related to gloves and 
other barrier devices that are currently being considered by industry 
and FDA. These issues include puncture resistance, tear resistance, 
reliability, and biocidal claims.

V. The Proposed Rule

    Based upon new information that was not presented, not available, 
or not developed when FDA originally classified surgeon's and patient 
examination gloves, FDA has reevaluated its classification in light of 
changes in the medical science discussed in sections III and IV of this 
document. The new, publicly available, valid scientific evidence 
demonstrates that these gloves should not remain as class I devices 
because of: (1) Barrier integrity concerns; (2) degradation of quality 
during storage; (3) contamination concerns; and (4) concerns about 
exposure to NL allergens and the role of glove powder as a carrier of 
airborne NL allergens, and the inability of general controls to address 
these concerns. The agency believes that general controls are no longer 
sufficient to provide reasonable assurance of the gloves' safety and 
effectiveness and, therefore, FDA is proposing that these gloves be 
reclassified into class II.
    Surgeon's and patient examination gloves are intended for use as an 
effective barrier against potentially infectious materials and other 
contaminants. Risk to the user or patient may result from lack of 
barrier integrity from degradation, pinholes, breaks, tears, or loss of 
quality during storage, potentially causing penetration of the glove 
wall by viruses or other infectious materials. When glove powder comes 
into contact with compromised human tissue, risk to the user or patient 
may result from foreign body reactions caused by NL allergens bound to 
the glove powder. Allergic reactions may also be caused by inhalation 
of NL allergens bound to the glove powder. Reducing the degree of risk 
to acceptable levels depends on effective maintenance of the barrier 
properties of the gloves and on reducing exposure to NL allergens, 
particularly exposure to airborne NL allergens. The highest risk 
products are those with large amounts of glove powder and NL protein 
and those products with poor barrier properties.
    In order to enable users to distinguish between powdered and 
powder-free gloves and to choose the glove type appropriate for their 
needs, FDA proposes to reclassify surgeon's gloves into two separate 
classifications, based on powder level: Powdered surgeon's gloves, and 
powder-free surgeon's gloves. FDA similarly proposes to reclassify 
patient examination gloves into two categories: Powdered patient 
examination gloves, and powder-free patient examination gloves.
    FDA is proposing that these gloves be subject to two special 
controls: A guidance document entitled, ``Medical Glove Guidance 
Manual,'' and new user labeling requirements. FDA believes that the 
proposed guidance document and user labeling requirements are necessary 
to provide reasonable assurance of the safe and effective use of the 
devices. The guidance is currently being issued in draft as a Level 1 
guidance consistent with the good guidance practices (GGP's) FDA 
adopted for the development, issuance, and use of guidance documents 
(62 FR 8961, February 27, 1997). Elsewhere in this issue of the Federal 
Register, FDA is announcing the availability of the guidance in draft 
form, to provide an opportunity for comment.
    The proposed guidance document recommends that manufacturers of 
powdered surgeon's and patient examination gloves limit the amount of 
powder to no more than 120 mg of powder per glove, regardless of glove 
size. In order to limit total exposure to the user, a ``per glove'' 
measurement (mg per glove) is used instead of the ``per unit'' dose (mg 
per gram (g) of glove material). Under the proposed labeling 
requirements, manufacturers of all powdered gloves would be required to 
include the actual level of glove powder on the label. FDA believes 
that the recommended limit should be sufficient for proper donning of 
gloves, but would reduce exposure to airborne glove powder particles. 
In addition to the role of glove powder as a carrier of airborne 
allergens, FDA is also aware that glove powder contributes to a number 
of other adverse health effects. As particulate matter, it can cause 
foreign body reactions, resulting in inflammation, granulomas and 
adhesions of peritoneal tissues after surgery (Refs. 15 to 19). Glove 
powder may serve as an absorbent or adsorbent for unbound chemicals 
that may be irritants or chemical contact sensitizers.
    The proposed guidance document further recommends that 
manufacturers of powder-free surgeon's and patient

[[Page 41715]]

examination gloves limit the amount of total trace (residual) powder to 
no more than 2-mg particulate weight (based on the ASTM test standard D 
6124-97) per glove, regardless of glove size. Previously, this limit 
was recommended to manufacturers who wanted to market gloves with a 
powder-free labeling claim. A number of premarket notification 
submissions based on this claim already have been cleared for market.
    The proposed guidance document also recommends that manufacturers 
of NL surgeon's and patient examination gloves limit the amount of 
water-extractable protein on the gloves to no more than 1,200 
micrograms (g) of protein per glove, regardless of glove size. 
In order to limit total exposure to the user, a ``per glove 
measurement'' (mg per glove) is used instead of a ``per unit'' dose (mg 
per g of glove material). Under the proposed labeling requirements, 
labeling on all NL gloves would be required to include the level of 
water-extractable protein measured, as recommended in the guidance, by 
the currently recognized ASTM D 5712 modified Lowry method. The lowest 
acceptable amount of water-extractable protein that may be stated in 
the labeling will be limited by the sensitivity of the current ASTM D 
5712 test method to 50 g of protein per g of natural rubber 
product (which translates to 300 g per glove for a 6 g glove, 
i.e., 6 x 50 = 300). FDA believes that without a more sensitive 
standard method, lower claims would be misleading.
    The proposed labeling requirements are a special control intended 
to provide guidance to users of surgeon's and patient examination 
gloves. They would require manufacturers to provide new caution 
statements, which would include both the FDA recommended limit for 
glove powder and protein levels, as well as the actual glove powder and 
protein levels present in the manufacturer's gloves. The labeling 
special control provides essential decisionmaking information for 
health professionals, patients, and lay users. The information required 
under the proposed regulations would assist health care professionals, 
patients and lay users to select a lower risk device by providing 
information about protein and glove powder levels.
    The proposed caution statements would be required to appear on all 
device labels and other labeling, including the principal display panel 
of the device packaging, the outside package, container or wrapper, and 
the immediate device package, container or wrapper. The proposed 
caution statements for powdered and powder-free NL gloves (surgeon's 
and patient examination) would supersede the caution statements in 
Sec. 801.437(d) for devices containing NRL currently required in the 
regulation published in the Federal Register of September 30, 1997 
(effective September 30, 1998).
    Labeling for powdered surgeon's and patient examination gloves 
containing NL that contacts humans would be required to bear the 
following statement:
    ``Caution: This product contains natural rubber latex which may 
cause allergic reactions. FDA recommends that this product contain 
no more than 120 mg powder and 1,200 g extractable protein 
per glove. This product contains no more than [insert level] mg 
powder and no more than [insert level] g extractable 
protein per glove.''
    Labeling for powder-free surgeon's and patient examination gloves 
containing NL that contacts humans would be required to bear the 
following statement:
     ``Caution: This product contains natural rubber latex which may 
cause allergic reactions. FDA recommends that this product contain 
no more than 1,200 g extractable protein per glove. This 
product contains no more than [insert level] g extractable 
protein per glove.''
    FDA is also proposing new labeling requirements for powdered gloves 
made of synthetic material. FDA proposes that labeling for those gloves 
bear the following statement:
     ``Caution: Glove powder is associated with adverse reactions. 
FDA recommends that this product contain no more than 120 mg powder 
per glove. This product contains no more than [insert level] mg 
powder per glove.''
FDA is proposing no new labeling for powder-free surgeon's gloves and 
patient examination gloves made of synthetic materials.
    FDA is also proposing to require expiration dating on the labeling 
of all powdered surgeon's and patient examination gloves and powder-
free surgeon's and patient examination gloves. Previously, expiration 
dating has not been required for surgeon's or patient examination 
gloves, although it is customary for surgeon's gloves to bear an 
expiration date for sterility. A few glove manufacturers have 
voluntarily used expiration dates based on real-time data to support 
the integrity of the gloves throughout the shelf-life period.
    In view of the quality concerns discussed in section IV of this 
document, especially those relating to degradation of barrier integrity 
over time, FDA believes that expiration dating is necessary to allow 
users to correctly store and use stock of gloves, and to allow users to 
avoid gloves that may have degraded. Users must be aware of the 
potential for degradation of gloves in order to safely use such 
products to provide a barrier from infectious agents. Accordingly, FDA 
believes that shelf life is a fact material to the consequences of use 
of surgeon's and patient examination gloves. Therefore, FDA is now 
proposing that all surgeon's and patient examination gloves be required 
to bear an expiration date on their primary and retail packaging and 
shipping carton. The expiration date should consist of the month and 
year for which data exists to support the shelf-life of the gloves. The 
time period upon which the expiration date is based starts with the 
date of manufacture.
    This expiration date must be based on testing conducted according 
to a validated stability study protocol to determine the shelf-life of 
the gloves. The stability study protocol should employ tests commonly 
used by industry to demonstrate the physical and mechanical integrity 
of the gloves over their claimed shelf-life.
    Manufacturers will not be required to provide new section 510(k) of 
the act submissions to demonstrate the shelf-life of gloves. However, 
for each distinct glove design, the records of study protocols and test 
data must be retained for a period equivalent to the design and 
expected life of the gloves, and must be made available for inspection 
by FDA personnel.
    Expiration dates for sterile surgeon's or patient examination 
gloves should either be based on the shelf-life determined by stability 
studies as outlined in the proposed rule, or on the sterility shelf-
life, whichever is shorter. Only one expiration date should appear on 
each product.
    FDA does not intend to require a new submission under section 
510(k) of the act based upon labeling changes or reductions in glove 
powder or NL protein made to comply with any final regulation based 
upon this proposed regulation, provided that no other changes requiring 
a new 510(k) submission under Sec. 807.81 are made to the device.
    Section 510(m) of the act allows FDA to exempt a class II device 
from the requirement of premarket notification in section 510(k) of the 
act. FDA does not intend to exempt powdered or powder-free surgeon's or 
patient examination gloves from premarket notification because of FDA's 
concerns regarding the effective maintenance of barrier properties and 
adverse health effects associated with NL allergens, glove powder and 
residual chemical sensitizers and irritants.
    This proposed rule would not impose requirements on glove users or 
user facilities. Therefore, it would not affect

[[Page 41716]]

the authority of the Secretary of Labor, under the Occupational Safety 
and Health Act (OSH act), to enforce regulations, standards, or other 
directives issued under the OSH act.

VI. Specific Request for Comments

    FDA recognizes that this regulation affects surgeon's and patient 
examination gloves in different ways, depending on glove powder level. 
FDA also recognizes that manufacturing processes for powdered and 
powder-free gloves vary. FDA welcomes comments on all aspects of the 
proposed regulation, but particularly invites comments on the following 
issues:
    1. FDA requests comments on the timeframe for implementation of the 
proposed rule considering the need for changes in production, 
technology, and labeling, as well as the immediate need to address 
adverse health concerns associated with medical gloves. Although FDA 
prefers a 1-year effective date, FDA is proposing a 2-year effective 
date based on indications from industry that the necessary changes 
could not be made in 1 year and that a shortage of medical gloves could 
result.
    2. In the proposed guidance document, FDA recommends a limit of no 
more than 120 mg powder per powdered glove, regardless of size, as the 
maximum level in order to reduce exposure to particulates and airborne 
allergens. FDA requests comments on the recommended limit with regard 
to the minimum level of powder needed for adequate donning of gloves.
    3. FDA requests comments on the feasibility and desirability of 
additional labeling requiring manufacturers to state the primary 
ingredients in glove powder in the product labeling.
    4. In the proposed guidance document, FDA is recommending no more 
than 2 mg powder per glove, regardless of size, as the recommended 
powder level for those surgeon's and patient examination gloves labeled 
``powder-free.'' FDA requests comments on the proposed limit. FDA is 
also seeking comments on the possible impact of this powder limit on 
barrier properties and shelf-life of NL gloves.
    5. FDA is also considering a future requirement that all surgeon's 
and patient examination gloves marketed in the United States be powder-
free. FDA requests comments as to whether a continued need for powdered 
gloves exists, and, if so, the reason for this need.
    6. FDA considered restrictions on the sale (advertising), 
distribution, and use of powdered surgeon's and patient examination 
gloves. FDA is seeking comments on the feasibility of such 
restrictions.
    7. In the proposed guidance document, FDA is recommending an upper 
limit of no more than 1,200 g protein per NL glove, regardless 
of size, as the maximum level for NL surgeon's and patient examination 
gloves. FDA is seeking comments on the proposed recommended limit.
    8. FDA's objectives in this proposed rulemaking are to reduce 
adverse health effects from allergic reactions and foreign body 
reactions by controlling the levels of water-extractable protein and 
glove powder on NL gloves. FDA requests comments as to whether there 
are feasible alternative approaches to achieve these objectives. If 
other alternatives or data submitted present feasible methods to 
protect the public health or suggest that different powder or protein 
levels are adequate to protect the public health, FDA may incorporate 
such data or approaches in a final rule.
    9. FDA also invites comments on the issue of whether the 
recommended limits on powder and protein proposed in this rule should 
be recommended limits or required limits.
    10. FDA considered allowing manufacturers to establish an initial 
tentative shelf-life up to a certain duration based on accelerated 
aging data, provided that manufacturers initiate concurrent real-time 
shelf-life studies to confirm and extend the tentative shelf-life. FDA 
has been unable, however, to determine whether any validated stability 
study protocols exist employing accelerated aging methodologies. The 
agency invites comments or information on the availability of 
accelerated aging stability study protocols which are predictive of 
glove shelf-life. If convincing information concerning such protocols 
is available, FDA may incorporate such an approach in a final rule.
    11. FDA considered requiring the use of a special air handling 
system at the point of use for those facilities using powdered 
surgeon's and patient examination gloves with powder levels over 120 mg 
per glove, regardless of glove size. FDA is seeking comments on the 
appropriateness of this restriction.
    12. FDA seeks comments as to whether a provision permitting 
affected persons to request exemptions or variances from the labeling 
requirements or restrictions on distribution and use proposed in this 
rule should be added.

VII. General Request for Comments

    Interested persons may submit written comments regarding this 
proposed rule by October 28, 1999, to the Dockets Management Branch 
(address above). Comments regarding the information collection 
provisions should be submitted by August 30, 1999, to the Office of 
Information and Regulatory Affairs, Office of Management and Budget 
(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.

VIII. Access to Special Control

    The availability of the special control entitled ``Medical Glove 
Guidance Manual'' is being announced elsewhere in this issue of the 
Federal Register. A copy of the ``Medical Glove Guidance Manual'' may 
be seen by interested persons in the Dockets Management Branch (address 
above) between 9 a.m. and 4 p.m., Monday through Friday.
    Persons interested in obtaining a copy of the guidance may also do 
so using the World Wide Web (WWW). FDA's Center for Devices and 
Radiological Health (CDRH), maintains an entry on the WWW for easy 
access to information including text, graphics, and files that may be 
downloaded to a PC with access to the Web. The CDRH home page is 
updated on a regular basis and includes the draft ``Medical Glove 
Guidance Manual;'' device safety alerts; Federal Register reprints; 
information on premarket submissions (including lists of approved 
applications and manufacturers' addresses); small manufacturers' 
assistance; and information on video conferencing and electronic 
submissions, mammography matters, and other device-oriented 
information. The CDRH home page may be accessed at ``http://
www.fda.gov/cdrh''.
    Submit written requests for single copies of the draft guidance to 
the Division of Small Manufacturers Assistance, Center for Devices and 
Radiological Health (HFZ-220), Food and Drug Administration, 1350 
Piccard Dr., Rockville, MD 20850. Send two self-addressed adhesive 
labels to assist that office in processing your request, or fax your 
request to 301-443-8818.
    To receive the directions via fax machine on receiving the proposed 
guidance document, call CDRH Facts-on-Demand system at 800-399-0381, or 
301-827-0111 from a touch-tone telephone. At the first voice prompt, 
press 1 to access the Division of Small Manufacturers Assistance (DSMA) 
Fax, at the second voice prompt, press 2, and then enter the document 
number 852

[[Page 41717]]

followed by the pound sign (#). Then follow the remaining voice prompts 
to complete your request.

IX. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, under the Regulatory Flexibility Act (5 U.S.C. 601-612), 
and under the Unfunded Mandates Reform Act (Public Law 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). Unless the agency 
certifies that the rule is not expected to have 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 economic impact of a rule on small 
entities. Section 202 of the Unfunded Mandates Reform Act requires that 
agencies prepare an assessment of anticipated costs and benefits before 
proposing any rule that may result in an expenditure by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100 million in any one year (adjusted annually for inflation).
    The agency believes that this proposed rule is consistent with the 
principles set out in the Executive Order and in these two statutes. 
The rule is an economically significant regulatory action as defined by 
the Executive Order. With respect to the Regulatory Flexibility Act, 
FDA does not believe that this proposal will have a significant effect 
on a substantial number of small entities, but recognizes the 
uncertainty of its estimates. Therefore, the agency has prepared an 
IRFA. FDA is not required to conduct a cost-benefit analysis according 
to the Unfunded Mandates Reform Act, because the rule will not impose 
any mandates on State, local, or tribal governments, or the private 
sector, that will result in an annual expenditure of $100 million or 
more.
    Furthermore, in accordance with the Small Business Regulatory 
Enforcement Fairness Act of 1995 (Public Law 104-121), it has been 
determined that this proposed rule would be a major rule for the 
purpose of congressional review.

A. Objectives of the Proposed Regulations

    The objectives of this proposed regulation are to reduce the 
adverse health effects from allergic and foreign body reactions caused 
by the NL protein allergens and glove powder found on surgeon's and 
patient examination gloves, and from defects in the barrier integrity 
and quality of surgeon's and patient examination gloves. The rule will 
accomplish these objectives by encouraging manufacturers to limit both 
the level of water-extractable protein allowed on gloves and the level 
of powder packaged with the gloves, and by requiring the inclusion of 
caution statements and the actual level of protein and powder in the 
labeling of the gloves. In addition, labeling will include expiration 
dates to ensure that the gloves provide adequate barrier protection and 
that all medical gloves meet quality standards specified in the special 
control guidance referenced elsewhere in this preamble. FDA believes 
that by reducing the amount of powder dispersed, these special controls 
will reduce the incidence and severity of the allergic reactions caused 
by NL proteins without compromising the barrier performance of these 
products.

B. Risks of NL Protein Allergic Reactions

    FDA recognizes that no systemic epidemiological data exist to 
identify the risk of airborne NL protein allergens. However, several 
sources indicate that a proportion of the U.S. population have 
developed NL sensitivity (Refs. 1 to 8) due to increased exposure to NL 
proteins. The increased use of NL gloves with unlimited powder and 
protein levels in recent years is believed to contribute to these 
adverse events.
    FDA's Adverse Experience Reporting System received a total of 330 
NL allergy Medical Device Reports (MDR's) associated with medical 
gloves for the 12-month period of August 15, 1996, through August 15, 
1997 (Ref. 9). These reports included reactions of 435 affected 
persons. Despite the lack of representative sampling and the 
unconfirmed nature of these reports, FDA believes these data may 
provide a reasonable measure of the magnitude of existing risk. Table 1 
classifies these reports by type and severity of reaction and shows the 
results by number of affected patients.

   Table 1.--Number of Patients Reporting to FDA Natural Rubber Latex Allergies Reactions Associated with Medical Gloves Between August 15, 1996, and
                                                                     August 15, 1997
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                        Type of Allergic Reaction1
                                                 -------------------------------------------------------------------------------------------------------
                                                                                                                                  Respiratory Requiring
                                                                             Systemic Topical (i.e.,    Systemic Respiratory      Aggressive Treatment
                                                        Local Topical         rash not in area with       (e.g., wheezing,         (e.g., anaphylaxis,
                                                                                 direct contact)        shortness of breath)        hospitalization)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Patients Reporting Reaction                                  20                        21                       294                       100
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\Includes 40 patients with unclassified reactions that were distributed by proportion of reported reactions.

    FDA has long been aware that MDR's received by the agency may 
account for as little as one percent of the actual events (Ref. 37). If 
true, the reports received for allergic reactions associated with 
medical gloves could represent as many as 43,500 allergic incidents 
during the 12-month period. Because patients may often fail to connect 
an allergic incident to use of gloves, FDA believes that this estimate 
better reflects the true number of incidents associated with medical 
gloves. Given that approximately 22.0 billion gloves (Ref. 38) were 
used and 2.16 billion patient visits occurred during that period (Ref. 
39), the projected baseline rate of annual allergic reaction incidents 
to the total population (0.0001626) at current protein/powder levels 
does not seem unreasonable.
    Despite the widespread under-reporting cited in the General 
Accounting Office (GAO) report, FDA believes that those allergic 
reactions that require the most aggressive treatment would be subject 
to less under-reporting. For this analysis, FDA has assumed that MDR's 
for patients with severe allergic reactions are under-reported by 33 
percent, and the other three categories are proportionally

[[Page 41718]]

increased to account for the total under-reporting (Table 2). 
Specifically, FDA believes that the 100 reported incidents of 
respiratory allergic reactions requiring aggressive treatment (from 
Table 1) represent only 150 actual such incidents; not 1,000 as would 
be indicated by MDR underreporting. The difference of 850 expected 
incidents were distributed to the remaining three categories to result 
in 43,500 total incidents. Table 2 also shows the proportion of each 
category of reactions reporting long-term and short-term effects, based 
on reported lost work-time due to recovery. As expected, only 6 percent 
of all topical local reactions were considered long-term, while almost 
half of the serious systemic reports were long-term. As discussed in 
the benefits section (section IX.F of this document), FDA has assumed, 
based on discussions with clinicians, that short-term impacts have a 
duration of 1 day and long-term impacts a duration of 2 months.
    Table 2 also presents FDA's estimated annual number of each type of 
allergic reaction. Although no mortalities were reported in the MDR's 
for this period, anaphylaxis carries a risk of mortality that FDA 
statisticians place at up to 2 percent, even in health care settings. 
Because not all reported serious systemic respiratory reactions were 
anaphylaxis, FDA assigned a probability of 0.002 to the adjusted 
reports to account for potential fatalities due to anaphylactic shock 
caused by NL allergens. (This assumes that only 10 percent of all 
respiratory reactions that require aggressive treatment were due to 
anaphylaxis.) Given the estimated under-reporting rate, this implies an 
annual risk of 0.3 mortalities. FDA expects that by encouraging lower 
protein and powder levels for medical gloves, the proportion of 
allergic reactions to NL protein allergens will be reduced.

   Table 2.--Estimated Number of Patients Experiencing Natural Rubber Latex Allergic Reaction Associated With Medical Gloves From August 15, 1996, to
                                        August 15, 1997, and Proportion Experiencing Short- and Long-Term Effects
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Type of Allergic Reaction
                                                     ---------------------------------------------------------------------------------------------------
                                                                                                                     Respiratory Requiring Aggressive
                                                                                                   Systemic                      Treatment
                                                         Local Topical     Systemic Topical       Respiratory    ---------------------------------------
                                                                                                                    Other Reactions        Mortality
--------------------------------------------------------------------------------------------------------------------------------------------------------
Estimated Number of Patients Experiencing Reaction          2,588               2,717              38,045                 149.7                 0.3
Proportion Exhibiting Short-Term Effects (duration            94%                 74%                 73%                 51%                  NA
 of 1 day)
Proportion Exhibiting Long-Term Effects (duration of           6%                 26%                 27%                 49%                  NA
 2 months)
--------------------------------------------------------------------------------------------------------------------------------------------------------

C. Costs of the Proposed Regulation

    This section develops estimates of the costs of compliance with the 
proposed rule by comparing the expected costs of using surgeon's and 
patient examination gloves after the rule is in effect to the costs 
that would have been incurred in the absence of the rule. Regulatory 
costs occur in four categories. First, the proposed regulation is 
expected to accelerate the trend of the glove market towards more 
costly, powder-free products. Second, higher average glove purchase 
prices will result from the increased cost of gloves with recommended 
levels of powder and NL proteins compared to the cost of gloves with 
unregulated levels of powder and NL proteins. Third manufacturers will 
be required to conduct shelf-life testing on gloves in order to support 
expiration dates. Fourth, increased labeling costs will result from the 
addition of protein and powder levels and/or expiration dating to each 
package of surgeon's and patient examination gloves. Because many of 
the estimates are derived from uncertain projections based on limited 
data, sensitivity analyses are presented for the most critical 
variables and assumptions.

D. Baseline Conditions

    1. Annual Number of Gloves
    To measure the incremental costs of the regulation against a 
baseline of nonregulation, FDA first projected future glove sales. An 
estimated 22.0 billion surgeon's and patient examination gloves were 
used in the United States in 1997, more than an 11-fold increase from 
the approximately 2.0 billion gloves used in 1987 (Ref. 38). The major 
contributors to this growth were the recognition of the potential risk 
from AIDS infection and the publication of Occupational Safety and 
Health Administration (OSHA) regulations requiring barrier protection 
for patients and employees exposed to blood borne pathogens (Ref. 40).
    FDA assumed that the demand for surgeon's and patient examination 
gloves will continue to grow as a result of expected increases in 
employment within the health services industry (Standard Industrial 
Classification (SIC) 80). The Bureau of Labor Statistics has suggested 
that employment within this industry may continue to grow at an annual 
rate of 3.9 percent (Ref. 41). Assuming that annual glove use per 
employee remains at current levels of approximately 10 pairs per day, 
the agency projected that the annual demand for gloves will increase 
over the next 10 years at an approximate rate of 3.9 percent per year 
(see Table 3). As expected growth in employment or patient health 
service visits may also predict future glove use. FDA tested this 
assumption by forecasting alternative rates of growth in the 
sensitivity analyses presented in section IX.G of this document.
    About 65 percent of the current glove market consists of powdered 
gloves (Ref. 38), but both health service facilities and glove 
manufacturers agree that the market share of powdered gloves is 
decreasing rapidly as facilities gain awareness of the potential 
adverse health effects associated with NL protein allergens. 
Manufacturers, however, explain that powdered gloves will not soon 
disappear, because new chlorinators and production lines associated 
with powder-free glove production take at least 18 months to

[[Page 41719]]

install and because powdered gloves are still desired by a proportion 
of customers. However, manufacturers have estimated that even in the 
absence of this regulation, the market share of powder-free gloves 
could reach as high as 60 percent within 18 months (Ref. 38). For this 
analysis, FDA assumed that, even in the absence of regulation, the 
market share for powdered gloves would decrease from the current 65 
percent down to 20 percent within 4 years. Concurrently, the market 
share for powder-free gloves would increase from 35 percent up to 80 
percent over the same period (see Table 3).
    Next, FDA estimated that gloves manufactured with synthetic 
materials (referred to as synthetic gloves), which are available in 
both powdered and powder-free varieties, account for approximately 10 
percent of the current market. Most synthetic gloves are manufactured 
of vinyl, but other polymers are also used. Synthetic gloves are 
generally believed to provide less acceptable barrier protection after 
extended use and reduced tactile sensitivity compared to NL. FDA 
assumed that, in the absence of regulation, this market share would 
increase slightly each year, accounting for 20 percent of the market 
within 5 years. Table 3 includes the projected market shares for each 
glove type.
    Because these projections contain considerable uncertainty, FDA 
analyzed several alternative assumptions in the sensitivity analysis 
section presented in section IX.G of this document. These scenarios 
assume that, in the absence of this rule, the anticipated baseline 
market adjustments would take either 10 years, or would not occur at 
all.

[[Page 41720]]



                                   Table 3.--Surgeon's and Patient Examination Glove Market Shares--Baseline Estimate
--------------------------------------------------------------------------------------------------------------------------------------------------------
                     All Surgeon's and                      Synthetic Gloves                                   Natural Rubber Latex Gloves
                          Patient      -----------------------------------------------------------------------------------------------------------------
                        Examination
        Year               Gloves                              Number of                                                Number of
                    ------------------- Number for Powder-      Powdered       Total (billion)   Number of Powder-       Powdered       Total (billion)
                      Number of Gloves    Free (billion)       (billion)                           Free (billion)       (billion)
                         (billion)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Current                       22.00               0.77               1.43               2.20               6.93              12.87              19.80
1                             22.86               1.37               1.37               2.74              10.06              10.06              20.12
2                             23.75               1.99               1.33               3.32              12.25               8.17              20.42
3                             24.68               2.76               1.18               3.95              14.51               6.22              20.73
4                             25.64               3.69               0.92               4.61              16.82               4.20              21.02
5                             26.64               4.26               1.07               5.33              17.05               4.26              21.31
6                             27.68               4.43               1.11               5.54              17.71               4.43              22.14
7                             28.76               4.60               1.15               5.75              18.40               4.60              23.00
8                             29.88               4.78               1.20               5.98              19.12               4.78              23.90
9                             31.04               4.97               1.24               6.21              19.87               4.97              24.83
10                            32.25               5.16               1.29               6.45              20.64               5.16              25.80
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 41721]]

2. Baseline Glove Cost
    There are an estimated 198 current marketers of surgeon's and 
patient examination gloves in the United States, 10 of which are 
domestic manufacturers. Approximately 95 percent of all gloves 
purchased in the United States are imported. Although individual 
marketers of surgeon's and patient examination gloves operate in a 
highly competitive industry and face highly elastic demand curves, the 
aggregate market demand for the gloves is assumed to be price 
inelastic, because of workplace regulations that require gloves as 
barrier protection (Ref. 42). Demand is inelastic if the percentage 
increase in price exceeds the percentage decrease in quantity sold. 
Consequently, most glove manufacturing cost increases would be passed 
on to health care facilities in the form of industry wide price 
increases. Although over 95 percent of the manufacturing facilities are 
located overseas and the world wide demand for gloves is high, the 
United States market dominates global sales. According to Malaysian 
manufacturers (Ref. 38), about 80 percent of their gloves are for U.S. 
customers.
    Current prices of powdered NL gloves average $3.90 per 100, while 
powder-free NL gloves average $5.80 per 100 (Ref. 38). Prices were 
reported as averages of both surgeon's and patient examination gloves. 
The price difference of $1.90 per 100, or almost $.02 per pair, is 
attributable to a number of factors, but the predominant reason is the 
increased cost of removing former-release powder and/or applying other 
lubricants to produce powder-free gloves. The estimated cost for 
synthetic gloves is $4.15 per 100 for powdered and $5.03 per 100 for 
powder-free. Vinyl gloves account for 90 percent of the synthetic glove 
market, with the remaining gloves manufactured from polymers and other 
materials.
    The nation's annual expenditures for surgeon's and patient 
examination gloves are currently estimated at over $1.0 billion. Even 
in the absence of regulation, FDA expects that these outlays would 
increase to $1.1 billion within 1 year and $1.7 billion within 10 
years.

E. Estimation of Compliance Costs

    The net costs of compliance with the proposed regulation is the 
difference between glove-related costs with and without the regulation. 
As noted earlier, industry comments suggest that even in the absence of 
this regulation, the market share of powder-free gloves is expected to 
increase from 35 percent to about 80 percent over a 4-year period. With 
regulation, this trend will be accelerated. Although the market effects 
of the rule cannot be known with certainty, FDA estimates that powder-
free gloves will achieve the 80 percent market share 2 years earlier, 
or within 2 years of the rule's implementation. In addition, 
manufacturers would experience increased costs due to the 
recommendation to limit the level of protein to 1,200 g per glove and 
the level of powder on NL and synthetic powdered gloves to 120 mg per 
glove. These costs would be passed through to health care facilities in 
the form of higher prices. Finally, each package of NL gloves must 
include labeling that includes protein and powder levels and expiration 
dating, and shelf-life testing must support this labeling.
1. Accelerated Market Share for Powder-Free and Synthetic Gloves
    Figure 1 illustrates FDA's forecast that powder-free gloves would 
gain 80 percent of the surgeon's and patient examination glove market 
share within 4 years without regulation and within 2 years with 
regulation. Manufacturers have indicated (Ref. 38) that if U.S. 
facilities are willing to bear the market price for powder-free gloves, 
the powder-free supply to other parts of the world could be shifted to 
meet U.S. demand and powder-free market shares could reach as high as 
60 percent within 18 months. FDA forecasts that the proposed 
regulations will accelerate this trend by reinforcing incentives for 
facilities to use powder-free gloves. The shaded area of the chart 
measures the expected substitution of powder-free for powdered gloves 
caused by facilities choosing to increase use of powder-free gloves in 
response to regulatory controls. In addition, FDA projects that the 
synthetic market share will rise from 10 to 20 percent within 5 years 
without regulation, but within 2 years with regulation. The expected 
market shares with the proposed regulation in place are shown in Table 
4.
    FDA also examined the potential of this regulation to result in 
domestic shortages of latex gloves and concluded that there would be 
minimal disruption to the U.S. market, as it constitutes such a major 
proportion of global sales (up to 80 percent (Ref. 38)). If other 
countries do not restrict glove powder, it is possible that the number 
of powder-free gloves sold in those markets would fall in the short-
term, while producers adjusted to the demand shift. FDA solicits public 
comment on how manufacturers would respond to these altered market 
forces.

[[Page 41722]]



                                     Table 4.--Surgeon's and Patient Examination Glove Market Shares with Regulation
--------------------------------------------------------------------------------------------------------------------------------------------------------
                       Surgeon's and                        Synthetic Gloves                                   Natural Rubber Latex Gloves
                          Patient      -----------------------------------------------------------------------------------------------------------------
                        Examination
        Year               Gloves                              Number of                                                Number of
                    ------------------- Number of Powder-       Powdered       Total (billion)   Number of Powder-       Powdered       Total (billion)
                        Total Number      Free (billion)       (billion)                           Free (billion)       (billion)
                         (billion)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Current                       22.00               0.77               1.43               2.20               6.93              12.87              19.80
1                             22.86               1.37               1.37               2.74              10.06              10.06              20.12
2                             23.75               2.47               1.33               3.80              12.97               6.98              19.95
3                             24.68               3.95               0.99               4.94              15.79               3.95              19.74
4                             25.64               4.10               1.03               5.13              16.41               4.10              20.51
5                             26.64               4.26               1.07               5.33              17.05               4.26              21.31
6                             27.68               4.43               1.11               5.54              17.71               4.43              22.14
7                             28.76               4.60               1.15               5.75              18.40               4.60              23.00
8                             29.88               4.78               1.20               5.98              19.12               4.78              23.90
9                             31.04               4.97               1.24               6.21              19.87               4.97              24.83
10                            32.25               5.16               1.29               6.45              20.64               5.16              25.80
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 41723]]

    Because the regulation would not be implemented until 2 years after 
publication of the final rule (as shown in Figure 1), no costs would be 
incurred in the first year. Moreover, there would be no market share-
associated costs expected after the fourth year, because, by that time, 
there would be no difference in the respective market shares of 
powdered and powder-free gloves. Based on these assumptions, the 
accelerated increase in the powder-free market share results in 
increased regulatory costs of $18.9 million in the second year and 
$37.3 million in the third year. In the fourth year following 
implementation of the rule, costs would fall by $2.9 million due to the 
increased use of lower cost synthetic gloves. As shown in Table 5, the 
average annualized costs (at a 7 percent discount rate over a 10-year 
period) attributable to the accelerated market share for powder-free 
gloves are calculated at $6.4 million.

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[[Page 41725]]

2. Increased Costs for Powdered Gloves
    Limiting the amount of protein and powder permitted on gloves would 
increase the production cost and therefore raise the purchase price of 
gloves to health care facilities. Although the limits are only 
recommended, both the actual and recommended levels of protein and 
powder must be included on the product label. Thus, FDA believes it 
likely that most glove manufacturers will meet the recommended levels. 
According to tests conducted by FDA, current powder levels on powdered 
gloves vary between 50 mg and 426 mg per glove. For this analysis, FDA 
assumed that a typical powdered NL or synthetic glove contains 260 mg 
of powder (based on the observed distribution). Current glove protein 
levels vary widely.
    Several manufacturers indicated that even minimal recommendations 
on powder and protein would result in cost increases of as much as five 
percent. These increases would be due to the increased testing and 
validation required to ensure that gloves did not exceed limits, the 
slower production times resulting from more controlled processes, the 
increased inventory damage when stripping gloves from molds, the 
increased controls for slurry mixtures, the increased time spent 
cleaning or replacing filters and other equipment, and the other costs 
associated with more careful controls for the entire manufacturing 
process. Manufacturers stated that limiting powder is more a question 
of adding controls in the production process than adding new production 
lines or facilities. Equipment such as slurries and tumblers are 
currently in place, and controls are likely to consist of simply 
weighing finished gloves or weighing the slurry filters. However, these 
costs are expected to result in increased contract prices for U.S. 
health facilities, because there are no substitute products for medical 
gloves.
    To calculate the costs of alternative permissible powder limits, 
FDA estimated an average cost function where the cost of reducing each 
mg of powder increases as the proportion of powder remaining on the 
manufactured glove decreases. Because current powdered NL gloves cost 
$3.90 per 100 and powder-free gloves cost $5.80 per 100, FDA calculated 
that the $1.90 cost of removing the average 260 mg of powder per 100 
gloves is about $0.0073 per mg ($1.90/260 mg). If the cost function 
were linear, the incremental cost of reducing powder levels by 140 mg 
(i.e., from the current average 260 mg of powder to the recommended 
level of 120 mg) would be calculated as $0.0073 times 140, or $1.022 
per 100 gloves. However, FDA believes that the relationship is unlikely 
to be linear as several manufacturers indicated that significant 
control costs would be needed to achieve even modest reductions in 
powder levels, after which average costs would rise slowly and then 
more steeply as powder concentrations approach zero. Such a functional 
form is typical of many manufacturing processes and illustrated by the 
solid sigmoid curve shown in Figure 2 (Refs. 44 and 45). A cost 
equation fitting this illustrated functional form is:
    Y = 0.00365 + 0.0292(X - 0.5)3
    Where:
    Y equals the cost per mg removed per 100 gloves, and
    X equals the proportion of powder removed.
    Figure 2 includes the estimated cost function for removing powder 
from synthetic gloves as the hashed line. The expected costs per mg 
removed are less than for NL gloves because the current price 
difference between powder-free and powdered synthetic gloves ($0.88 per 
100) is less than the difference for NL gloves ($1.90 per 100).
    On the assumption that these equations approximate the actual 
relationships, FDA estimates that the cost of limiting powder to 120 mg 
per 100 NL gloves is about $0.003652 per mg removed, or about $0.511 
per 100 NL gloves. For synthetic gloves, the estimated costs are 
$0.001693 per mg removed, or about $0.237 per 100 synthetic gloves. As 
shown in Figure 3, the control costs rise sharply for limits below 120 
mg. For example, a proposed powder limit of 100 mg per NL and synthetic 
glove would result in costs over 15 percent greater than the proposed 
120 mg limit. Because of the control processes required, FDA assumes 
that the previous estimates would also account for the cost of limiting 
protein levels for NL gloves.
    Table 5 shows these estimated costs over a 10-year period. Because 
the regulation is expected to be implemented 2 years after publication 
of the final rule, no increased powdered glove costs are incurred in 
the first year. In year 2, the higher prices for powdered NL gloves 
result in increased costs of $35.7 million. In year 3, these costs fall 
to $20.2 million. Thereafter, the yearly incremental compliance costs 
associated with NL glove powder and protein limits vary between $21.0 
and $26.4 million. The average annualized contribution of this cost 
category (at a 7 percent discount rate over 10 years) equals $21.4 
million.
    Within 2 years, higher costs for powdered synthetic gloves will 
equal $3.1 million. The yearly incremental compliance cost for powdered 
synthetic gloves is expected to decrease to $2.3 million in year 3, and 
then increase slightly each year throughout the evaluation period. The 
average annualized contribution of this cost category (at a 7 percent 
discount rate over 10 years) equals $2.4 million.

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                                                     Table 5.--Compliance Costs Over 10-Year Period
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                              Cost of        Increased        Cost of       Cost of Shelf-Life Testing
                                            Accelerated    Powdered NRL      Synthetic   --------------------------------  Labeling Cost   Total Cost ($
                  Year                     Market Share      Gloves ($       Gloves ($     Test Cost ($   Lost Inventory    ($ million)      million)
                                            ($ million)      million)        million)        million)       ($ million)
--------------------------------------------------------------------------------------------------------------------------------------------------------
1                                               0.0             0.0             0.0             0.0             0.0             0.0             0.0
2                                              18.9            35.7             3.1             1.6             3.0             1.6            63.9
3                                              37.3            20.2             2.3             1.2             1.3             0.6            62.9
4                                               2.9            21.0             2.4             1.2             1.1             0.5            23.3
5                                               0.0            21.8             2.5             1.3             1.4             0.7            27.7
6                                               0.0            22.6             2.6             1.3             1.2             0.5            28.2
7                                               0.0            23.5             2.7             1.5             1.1             0.6            29.4
8                                               0.0            24.4             2.8             1.5             1.6             0.8            31.1
9                                               0.0            25.5             2.9             1.4             1.3             0.6            31.7
10                                              0.0            26.4            43.1             1.5             1.3             0.6            32.9
Total                                          53.3           221.0            24.6            12.5            13.3             6.5           331.2
Average Annualized (7 percent discount          6.4            21.4             2.4             1.2             1.3             0.7            33.4
 rate)
--------------------------------------------------------------------------------------------------------------------------------------------------------

3. Costs of Shelf-life Testing and Inventory Loss
    The proposed regulation will require manufacturers of patient 
examination and surgical gloves to develop and affix labeling to their 
products that will include expiration dating. To ensure that medical 
gloves will maintain adequate barrier protection for the entire stated 
period, manufacturers will likely conduct real-time shelf-life testing 
of gloves. The compliance costs of this testing includes both the 
actual cost of conducting laboratory tests, and the lost revenues of 
inventory lost due to sampling.
    a. Shelf-life testing. FDA contracted with the Eastern Research 
Group (ERG), an economic consulting firm, to contact domestic and 
foreign glove manufacturers and research laboratories to determine the 
expected unit costs of shelf-life testing, and to determine current 
levels of industry compliance. ERG developed a cost model that 
estimated compliance costs according to the size of the manufacturer 
(Ref. 45a).
    ERG estimated that the expected marketing life for each glove model 
is approximately 3 years. During this period, stability testing is 
likely to occur at 6-month, 1-year, 2-year, and 3-year intervals. The 
actual tests were assumed to consist of a combination of real-time and 
accelerated tests. Overall, the estimated costs of a shelf-life test 
was found to approximate $265 for foreign tests and $865 for domestic 
tests. (The difference in testing costs are attributable to the lower 
purchasing power parity per capita in foreign countries that produce 
medical gloves.)
    As explained in Ref. 45a, almost 3,000 separate glove models are 
currently produced by 198 separate manufacturers. Only 160 models are 
marketed by the 10 domestic manufacturers. Given the expected growth in 
the demand for gloves, and the shift to powder-free and synthetic glove 
models, the estimated costs of shelf-life testing varies with FDA's 
projected number of future glove models. It was assumed that new models 
would have two shelf-life tests during the year of introduction while 
models already marketed would have one annual shelf-life test. Finally, 
ERG and industry sources estimated the current level of shelf-life 
testing based on both domestic/foreign and size characteristics.
    Based on these assumptions, the greatest increase in shelf-life 
testing is expected during year 2, with over 6,000 additional tests due 
to this proposed regulation. The total cost of conducting these tests 
equals $1.6 million, of which $0.1 million is incurred by domestic 
glove manufacturers. Amortizing the annual testing costs by 7 percent 
over 10 years, the average annualized costs of conducting the required 
shelf-life tests equals $1.2 million.
    b. Inventory losses. As part of these tests, manufacturers will be 
required to set inventory aside from which test samples will be 
selected. ERG, with discussions with laboratories and manufacturers, 
has determined that small glove manufacturers would be likely to set 
10,000 gloves per model aside for shelf-life testing while large 
manufacturers would set 30,000 gloves per model. Given the industry 
characteristics as discussed in Ref. 45a, this implies that over 115 
million gloves would be set aside in year 2. In addition, the relative 
market shares of synthetic, NL, powdered and powder-free gloves is 
expected to change over time which will affect the average lost revenue 
per sample. FDA analyzed the impact of this future inventory loss and 
found that during year 2 of the evaluation period, the value of lost 
inventory for testing is expected to equal over $3.0 million for the 
entire industry. The average annualized cost of this lost inventory (as 
shown in Table 5) at 7 percent over 10 years equals $1.3 million.
    4. Costs of Labeling. ERG also developed estimates of the costs of 
developing the proposed enhanced labeling for gloves. These estimates 
included the costs of artwork, design, regulatory review, production 
and application, as shown in Ref. 45a. Overall, the average cost of 
developing a label for a foreign medical glove model was estimated to 
equal $411, while a domestic model would cost $1,444. The number of 
domestic and foreign glove models expected to be introduced throughout 
the 10-year evaluation period and the market characteristics as 
discussed in Ref. 45a, indicate that the costs of labeling will equal 
$1.4 million in year 2. These yearly costs will then decrease to as low 
as $0.3 million by the 10th year. The average annualized cost of 
developing and producing labeling for medical gloves attributable to 
this proposed regulation is estimated to equal $0.7 million, as shown 
in Table 5.
5. Total Incremental Costs
    Figure 4 presents the estimated annual expenditures imposed by the 
proposed rule. Overall, costs of $63.9 million are expected in year 2. 
These costs decreased to $62.9 million in year 3, and then decrease to 
$23.3 million in the third year. Costs are expected to

[[Page 41729]]

increase slightly for each subsequent year. Most of the incremental 
costs, as shown in Table 5, are due to increases in glove costs 
(powdered NL and synthetic gloves with limited powder levels). The 
estimated average annualized cost over a 10-year period (at a 7 percent 
discount rate) is $33.4 million.

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F. Benefits of the Proposed Regulations

1. Expected Risk Reduction
    As discussed previously, the estimated annual proportion of the 
population (0.0001626) that experiences allergic reactions associated 
with medical gloves is assumed to be related to the prevalence of 
environmental protein and powder. Consequently, reducing protein and 
powder levels would reduce the proportion of the population expected to 
experience an allergic reaction. Decreases would be expected in NL 
sensitization as well as allergic reactions.
    To estimate this relationship, FDA assumed that the proportion of 
the population affected would vary directly with the total quantity of 
environmental protein/powder. The annual level of environmental 
protein/powder was calculated from the expected annual number of 
powdered NL gloves multiplied by the average level of powder per glove. 
The current market share of powdered NL gloves (Table 3) and the 
current average level of glove powder (260 mg) yield an aggregate 
estimate of 3.346 billion g of protein/powder. This quantity of 
protein/powder is associated with allergic reactions in 0.0001626 of 
the population, or 0.000049 reactions per billion g. If the 
relationship between the number of reactions and the quantity of 
protein/powder were linear, the model implies a 30 percent reduction in 
allergic prevalence for each billion g of powder reduction. 
Alternatively, the function relationship may take other forms, and FDA 
suspects that the increasing number of reports of allergic reactions to 
NL in recent years likely indicates a nonlinear relationship. Figure 5 
presents a polynomial projection that FDA tentatively adopts as a 
plausible estimate for this analysis. The equation of the function 
illustrated in Figure 5 is:
    Y = (0.0000143)X2
    Where:
    Y equals the proportion of the population with NL allergic 
reactions, and
    X equals the level of environmental protein/powder (in billions of 
g).
    Although the exact relationship is speculative, FDA believes that 
an exponential relationship as shown in Figure 5 is most likely. As 
shown in section IX.G of this document, the agency's sensitivity 
analysis indicates that due to the rising baseline projection, this 
polynomial projection yields smaller benefits than a linear model.
    Table 6 shows the expected number of allergic reactions associated 
with protein/powder levels with and without the proposed regulation. 
The protein/powder amounts are derived from the expected numbers of 
powdered NL gloves shown in Tables 3 and 4, the current average glove 
powder level (260 mg per glove), and the new recommended glove powder 
level (120 mg per glove). Powdered synthetic gloves do not affect this 
relationship because no NL proteins are associated with those products. 
Table 6 shows that in the absence of the proposed regulation, the 
expected increased market share of powder-free gloves would reduce the 
number of annual allergic reactions attributable to medical gloves from 
43,500 to only 4,800 within 4 years. With the proposed regulation in 
place, the expected number of allergic reactions would decrease to only 
900 within 3 years, and consistently remain several thousand fewer than 
those expected without regulations.
2. Benefits
    To estimate the potential benefits of the proposed rule, the number 
of reduced expected allergic reactions shown in Table 6 were 
distributed in proportion to the categories shown in Table 2. Assuming 
that the decreased number of reactions would not modify the severity 
distribution as reported in the MDR's (as adjusted to account for 
under-reporting), the proposed regulation would reduce annual allergic 
reactions by 15,100 within 2 years. The characteristics of these second 
year avoided reactions are shown in the first four columns of Table 7.

[[Page 41733]]



                                                     Table 6.--Expected Number of Allergic Reactions
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                  In the Absence of Regulation1                                   With Regulation2
                    ------------------------------------------------------------------------------------------------------------------   Difference in
                         Number of                                                Number of                                                 Allergic
        Year          Powdered Natural   Level of Powder    Estimated Number   Powdered Natural   Level of Powder    Estimated Number    Reactions with
                        Rubber Latex       (billion g)        of Allergic        Rubber Latex       (billion g)        of Allergic      Regulation (000)
                      Gloves (billion)                      Reactions (000)    Gloves (billion)                      Reactions (000)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Current                       12.87               3.35              43.5           - NA -             - NA -             - NA -             - NA -
1                             10.06               2.62              26.9               10.06               2.62              26.9                0.0
2                              8.17               2.13              17.9                6.98               0.84               2.8              (15.1)
3                              6.22               1.62              10.4                3.95               0.47               0.9               (9.5)
4                              4.20               1.09               4.8                4.10               0.49               1.0               (3.8)
5                              4.26               1.11               5.0                4.26               0.51               1.1               (3.9)
6                              4.43               1.15               5.4                4.43               0.53               1.2               (4.3)
7                              4.60               1.20               5.9                4.60               0.55               1.3               (4.7)
8                              4.78               1.24               6.4                4.78               0.57               1.4               (5.1)
9                              4.97               1.29               7.0                4.97               0.60               1.5               (5.5)
10                             5.16               1.34               7.6                5.16               0.62               1.6               (6.0)
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Powder level of 0.260 g per glove
\2\ Powder level of 0.120 g per glove


[[Page 41734]]

    There is no methodology that permits a precise assignment of 
monetary values to regulatory health benefits. However, one approach 
recently described in the health economics literature (Refs. 47 and 48) 
combines relative states of well-being with observed willingness to pay 
for risk avoidance. FDA adopted this methodology and used the Kaplan-
Bush Indices of Well-Being (Refs. 49 and 50) to estimate the value of 
reducing the number of allergic reactions.
    The first step was to assign to each category of reaction a 
functional index based on mobility/physical/sociability scales. The 
index of relative well-being (as described in Refs. 49 and 50) utilize 
functionality levels as a basis for estimating well-being. The 
functionality scales are described in Table 8. Baseline levels of well-
being were defined for 43 distinct combinations of mobility, physical 
activity, and sociability. For example, if a hypothetical patient could 
drive a car and use transportation without help (mobility equals 5), 
could walk without a physical problem (physical activity equals 4), and 
had no morbidity symptoms or problem, then this patient would have an 
assigned well-being of 1.0000. However, if this hypothetical patient 
could perform all of these activities, but suffered from any morbidity 
(including requiring eyeglasses), the assigned baseline level of well-
being was found to equal 0.7433. The baseline levels of well-being are 
then adjusted, either up or down, based on the predominant symptom or 
problem that is on-going. This methodology is described in detail in 
Refs. 49 and 50. For example, a local topical reaction is unlikely to 
interfere with normal activities, such as driving a car or performing 
housework. A patient suffering from a local topical reaction is 
expected to continue to be able to interact with others in a normal 
manner. This functional state is assigned a relative well-being rate of 
0.7433, or roughly 74 percent of optimum well-being. This baseline 
functional index is based on the prevailing medical problem. In this 
case, the problem/symptom is identified as ``burning and/or itching of 
skin'' and the 0.0171 value for this problem/symptom (from Refs. 49 and 
50) is added to the basic functional state. Thus, by combining these 
indices, a person suffering a local, topical allergic reaction is 
expected to have a relative well-being of 0.7604. Each of the 
categories of reactions have been assigned values, as included in Table 
7. Mortalities are valued as 0.0000.
    Next, optimum values of well-being were derived for both short-term 
durations (1 day) and long-term durations (2 months). The economic 
literature includes many attempts to quantify society's willingness-to-
pay (WTP) to avoid risks. Various methodologies have resulted in an 
average value of approximately $5.0 million as a measure of the WTP to 
avoid a statistical death (Refs. 51, 52, and 53). By amortizing this 
value to account for life expectancy and expected disability-days 
(Refs. 54 and 55), FDA estimates that a quality-adjusted life-year 
(QALY) has an approximate value of $373,000. Using this estimate, the 
expected value of a quality-adjusted life-day is approximately $1,022 
and the expected value of two quality-adjusted life-months is $62,166.
    The relative wellness values for each category shown in Table 7 
represent the proportion of wellness relative to an optimum level. The 
willingness of society to pay for avoiding each incident were reflected 
as the difference between the wellness state and an optimum level 
multiplied by the duration of the event. For example, a local topical 
allergic reaction has an expected wellness value of 0.7604, or 0.2396 
below optimum. This difference is used to calculate the amount that 
society is willing to pay to avoid a reaction of this type.

[[Page 41735]]



                                        Table 7.--Characteristics of Reductions in Second Year Allergic Reactions
--------------------------------------------------------------------------------------------------------------------------------------------------------
                        Number of    Number of                                                                   Value per     Value per
Category   Number of     Avoided      Avoided                  Problem/                Value per    Value per    Short-Term    Long-Term
   of       Avoided     Short-Term   Long-Term   Functional    Symptom     Relative    Short-Term   Long-Term     Reaction     Reaction     Total Value
Reaction   Reactions    Reactions    Reactions    State\1\    Weight\2\    Wellness     Reaction   Reaction ($   Avoided ($   Avoided ($      ($ 000)
             (000)        (000)        (000)                                                           000)         000)         000)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Local          0.89         0.84         0.05        0.7433       0.0171      0.7604     245       14,900          205           794            999
 Topical
Systemic       0.94         0.69         0.24        0.6065       0.0171      0.6236     385       23,400          267         5,709          5,976
 Topical
Systemic      13.24         9.66         3.57        0.525       -0.0075      0.5175     493       30,000        4,764       107,194        111,958
 Respira
 tory
Respirat       0.05         0.03         0.03        0.5284      -0.1507      0.3777     636       38,700           17           972            989
 ory
 Requiri
 ng
 Aggress
 ive
 Treatme
 nt
Mortalit       0.00        NA           NA           0            0           0           NA           NA           NA            NA         514\3\
 y
Totals        15.11        11.22         3.90                                                                                               120,436
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Functional states:  Mobility - 5; Physical activity - 4; Social - 5 = 0.7433
                  Mobility - 4; Physical activity - 4; Social - .4 = 0.6065
                  Mobility - 4; Physical activity - 3; Social - 3 = 0.525
                  Mobility - 4; Physical activity - 1; Social - 2 = 0.5284
                  Mortality                                 = 0.0000
\2\ Problem/Symptom Adjustments:
                  Burning or itching rash on body = +0.0171
                  Wheezing or shortness of breath = -0.0075
                  Loss of consciousness, fainting = -0.1507
\3\ Value per mortality is $5 million. May not add due to rounding.


[[Page 41736]]

For 1 day, this value is $245 ($1,022 x .2396) and for 2 months, the 
estimated value per reaction is $14,895. The derived values for each of 
the reaction categories and terms are shown in Table 7.
    The values for each category, when multiplied by the number of 
decreased reactions expected due to this regulation, result in the 
expected annual benefit. Table 7 includes this estimate for only the 
second evaluation year. It indicates that society would be willing to 
pay a value of approximately $120.4 million to avoid 15,100 allergic 
reactions to NL protein.
    Taking these steps for each year in the evaluation period yields 
estimates of the willingness to pay to avoid these reactions as shown 
in Table 9. The undiscounted benefits equal $120.4 million in year 2, 
then decrease to $30.4 million in year 4. Between years 4 and 10, the 
estimated annual benefit increases to a value of $47.5 million. The 
estimated annualized benefit of avoiding these reactions is $46.9 
million.
    FDA notes that other potential benefits, such as the avoidance of 
third-party payments as a result of treating fewer allergic reactions, 
the value of reduced anxiety due to lowering NL sensitization, the 
reduction in defects in glove barrier integrity, and the reduction in 
other foreign body reactions caused by glove powder have not been 
quantified at this time. FDA recognizes the considerable uncertainty of 
all of these estimates, however, and requests comment on all of the 
data and assumptions.

                             Table 8.--Description of Inputs to Functionality Levels
----------------------------------------------------------------------------------------------------------------
              Mobility                          Physical Activity                      Social Activity
----------------------------------------------------------------------------------------------------------------
5-Drove car and used transportation                                         5-Did work, school, or housework and
 without help                                                                other activities
4-Did not drive, needed help with     4-Walked without physical problem     4-Did work, school, or housework,
 transportation                                                              but other activities limited
3-In house                            3-Walked with physical problem        3-Limited in work, school or
                                                                             housework
2-In hospital                         2-Moved own wheelchair without help   2-Performed self-care
1-In special unit                     1-In bed or chair                     1-Had help in self-care
----------------------------------------------------------------------------------------------------------------
Source: Kaplan, Bush, et. al. (Refs. 49 and 50)


                Table 9.--Expected Benefit of Decreased NRL Allergic Reactions Due to Regulation
----------------------------------------------------------------------------------------------------------------
                                                                                        Net Present Value of
        Year           Decreased Reactions (000)     Value of Decreased Reactions      Decreased Reactions ($
                                                             ($ million)                     millions)
----------------------------------------------------------------------------------------------------------------
Current                                   NA                             NA                             NA
1                                          0.0                           NA                             NA
2                                        (15.1)                         120.4                          105.2
3                                         (9.5)                          76.0                           62.0
4                                         (3.8)                          30.4                           23.2
5                                         (3.9)                          31.1                           22.2
6                                         (4.3)                          34.0                           22.7
7                                         (4.7)                          37.1                           23.1
8                                         (5.1)                          40.3                           23.4
9                                         (5.5)                          43.7                           23.8
10                                        (6.0)                          47.5                           24.2
Average Annual                                                                                          46.9
 Benefit ($
 million)
----------------------------------------------------------------------------------------------------------------

G. Sensitivity Analyses

    FDA examined the impact of various assumptions that affect future 
conditions. These analyses are as follows:
1. Growth Rate of the Demand for Surgical and Patient Examination 
Gloves
    FDA used 1992 to 1994 rates of employment growth within the health 
services industry (SIC 80) to project a 3.9 percent annual growth in 
the future demand for surgical gloves (Ref. 41). However, more recent 
data obtained for the period up to 1998 suggest the more modest growth 
rate of 2.7 percent for this industry (Ref. 55a). Examining the 
expected costs and benefits after lowering the expected growth for 
surgical and patient examination gloves to 2.7 percent indicates that 
average annual costs decrease from $33.4 to $31.5 million and average 
annual benefits decrease from $46.9 to $42.1 million. If the forecast 
relied instead on the growth of total employment hours in the health 
service industry (Ref. 55b), the rate in recent years has been 
approximately 2.0 percent. Using this rate as the expected growth rate 
for surgical and patient examination gloves results in average annual 
costs of $30.4 million and average annual benefits of $39.6 million.
    FDA notes that under the alternative assumptions, both costs and 
benefits are lower than under the scenario presented earlier, but the 
regulation would still be justified.
2. Market Shares of Powder-Free and Synthetic Gloves
    FDA has estimated that in the absence of regulation, within 4 
years, 80 percent of the glove market would consist of powder-free 
gloves; and within 5 years, 20 percent of all gloves would be 
manufactured of synthetic material. The proposed regulation is expected 
to accelerate these trends to within 2 years of implementation.
    To examine the sensitivity of these assumptions, FDA calculated the 
costs and benefits of the rule assuming that, in the absence of 
regulation, it would take 10 years rather than 4 years for powder-free 
gloves to account for 80 percent of the market and 10 years rather than 
5 years for synthetic gloves to account for 20 percent of the market. 
The expected average annual costs in this scenario equal $72.7 million, 
and the average annual benefits equal $112.1 million. FDA also examined 
the impact of assuming no expected change in baseline market share from 
the first implementation year, in the absence of regulation. In this 
case, the average

[[Page 41737]]

annual costs equal $135.7 million, and the average annual benefits 
equal $283.2 million.
3. Linear Relationship between Environmental Protein/Powder and 
Allergic Reactions
    FDA expects that an exponential relationship exists between 
protein/powder levels and allergic reactions, but the agency also 
examined the effect of a linear relationship. The linear model 
increased the expected average annual benefit of reducing exposure from 
$46.9 million to $75.7 million, by increasing the number of avoided 
incidents as protein/powder levels were decreased. Table 9 indicates 
the magnitude of the expected decrease in NL reactions using the 
expected exponential relationship. A total of 57,900 avoided reactions 
were forecast. If the actual relationship were linear, the rule would 
be expected to result in the avoidance of 88,100 incidents over the 
same period.
4. Conclusion
    FDA has tested several key assumptions used in the analysis of 
impacts. Each simulation resulted in estimated benefits exceeding 
costs. Nonetheless, FDA recognizes the significant uncertainty in this 
analysis and requests any additional information that would improve the 
projections.

H. Small Business Impact

1. Initial Regulatory Flexibility Analysis
    FDA believes that the proposed regulation will not have a 
significant impact on a substantial number of small entities, but 
conducted an initial regulatory flexibility analysis (IRFA) to ensure 
that impacts on small entities were assessed and to alert any 
potentially impacted entities to the opportunity to submit comments to 
the agency.
2. Description of Impact
    The objectives of the proposed regulation are to reduce the adverse 
health effects attributable to allergic and foreign body reactions from 
NL allergens and glove powder and to defects in barrier protection and 
quality of surgeon's and patient examination gloves. The proposed 
regulation will accomplish these objectives by reclassifying surgeon's 
and patient examination gloves into class II products, and requiring 
product labeling. In addition, the proposed regulation recommends 
protein and powder levels for surgeon's and patient examination gloves. 
FDA's statutory authority for the proposed rulemaking under the act is 
discussed in section II of this document.
    Two separate industries will be affected by the proposed 
regulation: Manufacturers of surgeon's and patient examination gloves 
(found in Standard Industrial Classification 3842, Medical Equipment 
and Supplies) and Health Facilities (found in SIC 80).

   Table 10.--Non-Health Care Industries That Use Gloves as Protection
------------------------------------------------------------------------
                                          Number of         Number of
  Industry Sector       SIC Code       Establishments       Employees
------------------------------------------------------------------------
Government              9,461            10,893            56,345
Residential Care          836             2,423                NA
Personal Services       7,362             1,348           163,477
Funeral Services          726            19,890            57,013
Health Units in            NA           202,540           178,732
 Industry
Non-Health              8,221             1,453            89,159
 Research
 Laboratories
Linen Services          7,218             1,250            50,000
Medical Equipment         384             1,076             6,185
 Repair
Law Enforcement         9,221             4,946           341,546
Fire and Rescue         9,224             3,174           252,048
Lifesaving              9,229               100             5,000
Schools                 9,411             6,321             4,132
Waste Removal           4,953               940            13,300
------------------------------------------------------------------------
Source: OSHA (Ref. 40)

    FDA considered the potential impact of the proposed regulation on a 
number of nonhealth industries, but found that any impact would be 
insignificant. When OSHA issued its final regulations on blood-borne 
pathogens (Ref. 40), it considered a wide-range of establishments 
including: Law enforcement agencies, schools, linen services, and 
funeral parlors (see Table 10). While a substantial number of these 
establishments are small under the Small Business Administration 
definition, this proposed regulation does not require the use of FDA-
regulated medical gloves at these sites. OSHA assumed that many of 
these industries would use utility gloves or consumer-grade gloves to 
provide barrier protection. For example, janitorial services and waste 
removal establishments were assumed to use utility work gloves, while 
law enforcement agencies were expected to use consumer-grade vinyl 
gloves. Few industries or establishments were expected to use FDA-
regulated medical gloves in nonmedical settings. However, even in 
settings where medical gloves may be used, the frequency of glove usage 
was much less in these sectors. OSHA estimated that an average school 
would use approximately eight pairs of gloves per day. In contrast, a 
small physician/dental office would be expected to use 30 pairs of 
gloves per day. Both the relative frequency of glove use and the 
concentration of FDA-regulated medical gloves convinced FDA to focus on 
the Health Services Industry (Table 11) as the area of largest 
potential impact.

                         Table 11.--Establishment and Employment in the Health Services1
----------------------------------------------------------------------------------------------------------------
                                                             Number of          Number of      Average Number of
 Establishments and (Standard Industrial Classification    Establishments       Employees        Employees per
                         Codes)                              (thousand)         (thousand)       Establishment
----------------------------------------------------------------------------------------------------------------
Total Health Services (80)                                     1,030.0           11,000.0               10.7

[[Page 41738]]

 
Clinics and Offices of MD's (801)                                328.9            1,908.4                5.8
Clinics and Offices of Dentists (802)                            138.5              709.4                5.1
Clinics and Offices of Osteopathy (803)                           18.4               60.6                3.3
Other Health Practitioners (804)                                 243.0              483.6                2.0
Nursing Facilities (805)                                          57.7            2,011.8               34.9
Hospitals (806)                                                    7.1            4,496.5              633.3
Medical/Dental Laboratories (807)                                 29.4              229.3                7.8
Home Health Services (808)                                        99.9              743.9                7.4
Other Allied Services (809)                                      107.7              356.5                3.3
----------------------------------------------------------------------------------------------------------------
\1\ 1992 Census of Service Industries and Bureau of Labor Statistics projections of employment trends in the
  health services industries.

    Glove manufacturers will be affected by labeling that requires 
additional warnings and statements concerning recommended protein and 
powder limits, testing and validation measures that are necessary to 
ensure the accuracy of this information, and limitations on the use of 
powder for mold release. Health facilities will face increased 
expenditures for surgeon's and patient examination gloves by either 
shifting from powdered gloves to more expensive powder-free products or 
continuing to use powdered gloves that cost more due to production cost 
increases.
    Manufacturers classified within the four-digit SIC code 3842 are 
typically small. Only 38 percent of all establishments had 20 or more 
employees in 1992 (Ref. 56), and companies had an average of 1.12 
separate establishments. The manufacturers are highly specialized, with 
over 92 percent of their products considered within the medical 
equipment and supplies industry, and 94 percent of all medical 
equipment and supplies manufactured by these firms. The Small Business 
Administration classifies as small any entity within this industry with 
500 or fewer employees (Ref. 57), capturing the majority of 
establishments. However, the affected manufacturers of surgeon's and 
patient examination gloves have some product-specific characteristics 
that distinguish them from the average establishment in this industry.
    FDA's registration system for medical devices shows 198 
manufacturers of surgeon's and patient examination gloves, the vast 
majority of which are located outside the United States and operate in 
a world-wide market, although the U.S. constitutes the most significant 
regional market. FDA examined the records of current manufacturers and 
identified 10 domestic manufacturers of surgeon's and patient 
examination gloves out of the total 198 marketers. Only 1 of these 10 
domestic manufacturers reported employment of fewer than 1,200 
employees. However, FDA acknowledges that additional small domestic 
manufacturers could enter the market in the future.
    The main impacts of the proposed regulations on small manufacturers 
would occur if the manufacturer had to conduct additional validation 
tests to ensure the accuracy of protein and powder levels displayed on 
the product labeling and if increased inventory loss or slower 
production times occurred due to limited uses of powder as a mold 
release. Although FDA does not stipulate the acceptable validation test 
method in the regulation, and is soliciting comments on this issue in 
order to minimize its impact, it is possible that a chemist would be 
required on a contract basis to ensure that the actual levels of 
protein and powder matched the levels on the label. FDA is working with 
industry groups to ensure that an acceptable and reliable test method 
is chosen. Despite this outreach, the selected test method could impose 
additional and disparate costs to a small manufacturer. Similarly, 
increased inventory loss because of tearing in the production process 
due to limited powder would affect small production runs to a greater 
degree than large production runs. Discussions with manufacturers have 
indicated that any additional validation testing or negative impacts on 
production capability could increase the production costs of medical 
gloves by 5 percent or more.
    As discussed earlier in the analysis of impacts section (section 
IX.D of this document), the demand for medical gloves is highly price 
inelastic due to the regulatory requirement for health facilities (SIC 
80) to provide barrier protection (Ref. 40) and the lack of substitute 
products (Ref. 42). The characteristics of the medical glove market 
therefore indicate that production cost increases resulting from the 
proposed rule are likely to be passed through in the form of higher 
contract prices. In addition, many facilities are currently accepting 
increased glove prices by establishing powder-free environments in the 
absence of any rule-making. Thus, production cost increases by glove 
manufacturers are likely to be offset by revenue gains for these same 
manufacturers, with the result of shifting the cost impact to the 
health facilities.
    Small health facilities therefore will also bear some regulatory 
impact. The Small Business Administration has defined as small any 
``for-profit'' health facility with annual revenues of $5 million or 
less (Ref. 57). Most hospitals and nursing facilities would be 
considered large under this definition. However, nonprofit facilities 
not dominant in their field are also considered small entities. 
Industry characteristics of the health facility industry are shown in 
Table 11. Approximately 95 percent of the hospitals and nursing 
facilities are considered as small entities (6,700 hospitals and 54,800 
nursing facilities).
    FDA examined the potential impact of the proposed regulations on 
two types of health care user facilities: Small physician/dental 
facilities and small hospitals. A small physician or dental facility 
may use as many as 25,000 (based on 120 patient visits per week) gloves 
each year. If the facility substitutes powder-free for powdered gloves 
as a result of this regulation, costs would increase by $475 per year 
((25,000/100) x $1.90).
    Similarly, a small hospital is also likely to experience increased 
annual costs of acquiring gloves. An extremely small hospital with only 
6 beds and a staff of 11 might use about 22,000 gloves annually. If the 
facility faced increased glove costs, the total increase in costs could 
amount to about $950.
    FDA wishes to collect additional information on the nature of the 
impacts on small entities in order to ensure that all such impacts are 
noted. In addition,

[[Page 41739]]

other public facilities such as prisons, and police or fire departments 
may face higher glove prices due to this regulation. FDA does not 
expect these costs to be significant, but solicits comments on this 
potential burden.
3. Analysis of Alternatives
    FDA has examined and rejected the following alternatives to the 
proposed rule:(1) Banning powdered gloves; (2) mandating protein and 
powder levels on medical gloves; (3) requiring all users of powdered 
gloves to comply with restrictions on distribution and use; (4) 
retaining the class I classification for all (or some) of the medical 
gloves; and (5) excluding powdered synthetic gloves from this 
rulemaking; and (6) providing for a shorter or longer compliance 
period. FDA has rejected the alternatives at this time for the 
following reasons:
    Alternative 1: A ban of all powdered medical gloves has been 
requested in a citizen petition submitted to FDA. FDA considered 
banning powdered gloves because that action would meet the stated 
objective of eliminating airborne powder and greatly reducing exposure 
to airborne allergens associated with the use of medical gloves. 
However, FDA did not select this alternative because a ban would not 
address exposure to NL allergens from medical gloves with high levels 
of NL proteins. Moreover, such a ban of powdered gloves might 
compromise the availability of high quality medical gloves and greatly 
increase the annual costs by almost as much as $64 million over the 
selected alternative.
    Alternative 2: FDA also considered mandating powder and protein 
levels for medical gloves because this alternative would accomplish the 
stated objectives more completely than banning. FDA rejected mandating 
powder and protein levels for medical gloves because the agency 
believes that the increased regulatory flexibility of the proposed rule 
may reduce the costs of compliance by allowing for more efficient 
methods of reaching the goal. Inventories could be lowered and industry 
capacity could be assured. Mandating specific protein and powder 
levels, as well as the acceptable test method, may preclude all parties 
from developing a more efficient system. In addition, FDA inspectional 
and compliance costs are minimized by relying on recommended levels of 
powder and protein. By ensuring user access to relevant information, 
the agency believes that users will move the market to a more efficient 
level.
    Alternative 3: FDA considered restricting the distribution and use 
of powdered NRL or synthetic material medical gloves by requiring that 
establishments using powdered gloves establish and maintain written 
procedures for selecting, purchasing and distributing gloves. FDA 
further considered restricting the distribution and use of powdered NRL 
or synthetic material medical gloves by requiring establishments using 
powdered gloves with more than the recommended powder levels to 
establish and maintain written procedures to evaluate, monitor and 
control airborne particulate matter at the point of use, through the 
use of an externally exhausted air handling system, HEPA filtration, or 
other system. FDA believes that these restrictions would reduce the 
risk of adverse foreign body and allergic reactions associated with 
powdered glove use. However, the extent of the expected reduction is 
uncertain. The expected costs of complying with these restrictions was 
estimated to be over $21 million. Furthermore, any such workplace 
restrictions may impede or preempt the authority of OSHA to regulate 
gloves and glove powder in the workplace.
    Before rejecting this alternative, the agency had examined the 
feasibility of exempting small facilities from the requirements of 
developing written procedures and air quality measures. Based on the 
expectation that small establishments with 10 or fewer employees would 
be able to communicate and control risks associated with powdered 
medical easier than larger institutions. Exempting small medical 
facilities from these controls lowers the added costs to $6.6 million. 
However, FDA rejected this alternative because the expected benefits of 
restricting glove use remained uncertain, and the potential overlap of 
authority with OSHA would still exist.
    Alternative 4: FDA considered retaining the class I classification 
for all or some of the medical gloves. This alternative was rejected 
because it did not meet the stated objectives. In light of new 
information concerning barrier integrity, degradation of quality during 
storage, contamination concerns and concerns about exposure to foreign 
bodies and allergens, FDA found that general controls are no longer 
sufficient to provide reasonable assurances of the safety and 
effectiveness of medical gloves. Moreover, such concerns were not 
limited to only powdered gloves. To require a device to meet special 
controls as well as general controls, a device must be classified (or 
reclassified) into class II. Consequently, although compliance costs 
would have been reduced by this alternative, retaining some or all 
gloves as class I devices was rejected.
    Alternative 5: Alternative 5 (excluding powdered synthetic gloves 
for this rulemaking) was considered in order to reduce cost by as much 
as $2.4 million per year. FDA rejected this alternative because it 
would not meet the stated objective of the applicable statutes. While 
synthetic gloves do not contain NL proteins, FDA is concerned about 
foreign body reactions caused by glove powder. These reactions occur 
whether the powder is present on a NRL or synthetic glove. 
Consequently, FDA is rejecting exempting powdered synthetic gloves from 
this regulation.
    Alternative 6: FDA considered providing a shorter compliance period 
for implementation of the regulation. A compliance period of 90 days or 
1 year would significantly increase the expected benefits of the rule 
by decreasing the number of annual allergic reactions. FDA estimates 
that a 90-day or 1-year implementation period would result in between 
3,300 and 3,600 fewer annual allergic reactions to NL proteins than the 
number expected with the selected 2-year compliance period. However, 
FDA is concerned that the lead times necessary to manufacture limited 
powder gloves would make compliance difficult. As stated earlier, 
manufacturing equipment used to control glove powder levels is 
currently backordered as much as 18 months, and short compliance 
periods may result in inadequate supplies of medical gloves. Not 
including the potential of shortages, FDA has estimated that average 
annualized costs of shorter compliance periods could equal $10 million 
to $16 million more than the selected alternative. The 2-year 
compliance period allows firms to combine recommended changes with any 
other market driven changes, and will allow firms to deplete their 
supply of existing labels. As set forth above, however, FDA is 
soliciting comment on the timeframe for implementation to determine 
whether a 2-year compliance period is really needed. FDA also rejected 
providing a longer compliance period. FDA has tentatively determined 
that the decrease in costs is outweighed by the decrease in benefits if 
the compliance period is lengthened to as many as 3 years. While annual 
costs would decrease by almost $9 million, allowing such a long 
compliance period would result in about 1,800 additional average annual 
allergic reactions as compared to the selected alternative and benefits 
would be reduced to $32.0 million. Since glove manufacturers would have 
ample opportunity to comply within the

[[Page 41740]]

selected 2-year period, FDA does not believe that additional time is 
justified.
    FDA solicits comments on other alternatives that meet the stated 
objectives.
4. Assuring Small Entity Participation in Rulemaking
    At this time, FDA does not believe that the proposed regulation 
will have a significant economic impact on a substantial number of 
small entities. However, the agency recognizes that many facilities 
will be affected. The impact may range from increased glove 
manufacturing costs due to validation testing and control of mold 
powder to increased contract prices of powdered gloves used by health 
facilities. FDA solicits comments from affected entities to ensure that 
this impact is analyzed.
    FDA plans to provide for access to the Federal Register analysis 
through FDA's website on the Internet. Notice of the availability of 
this proposed rule and request for comment will be communicated to all 
glove-related associations and include a request for comments.
    FDA is currently preparing an article for publication in latex-
related trade publications that will highlight the proposed 
requirements. In addition, notice of the proposed rulemaking and 
request for comments will be available in health-related publications 
and sent to trade organizations. FDA actively seeks input into this 
proposal and requests comments on all aspects of the analysis of 
impacts and the regulatory flexibility analysis.

X. Conclusion

    FDA has examined the impacts of the proposed regulation of protein 
and powder levels of NL gloves. Based on these estimates, the average 
annual quantifiable benefits ($46.9 million) exceed the average annual 
quantifiable costs ($32.5 million). Given the high level of uncertainty 
and the existence of unquantified benefits, FDA solicits comment on 
this analysis and all of its assumptions and projections.

XI. Environmental Impact

    FDA has determined under 21 CFR 25.30(k) and 25.34(b) that this 
action is of the 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.

XII. Paperwork Reduction Act of 1995

    This proposed rule contains information collections provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A 
description of these provisions is given below with an estimate of the 
annual reporting burden. Included in the estimate is the time for 
reviewing instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing each 
collection of information.
    FDA invites comments on: (1) Whether the proposed collection of 
information is necessary for the proper performance of FDA's functions, 
including whether the information will have practical utility; (2) the 
accuracy of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques, when appropriate, and other forms of 
information technology.
    Title: Labeling and Written Procedures Requirements for Powdered 
and Powder-Free Patient Examination Gloves, and Powdered and Powder-
Free Surgeon's Gloves.
    Description: The proposed rule intends to provide users with 
material information to safely use patient examination and surgeon's 
gloves. The proposed rule expands the labeling for medical gloves to 
include: (1) Caution statements including the actual levels of protein 
and powder on the gloves, and (2) expiration dating.
    The proposed labeling requirements would require manufacturers to 
conduct tests to support the protein and glove powder levels and 
expiration date. The proposed special control, a guidance document 
entitled ``Medical Glove Guidance Manual,'' recommends that protein 
levels be measured by the ASTM D 5712 modified Lorry method and that 
glove powder levels be measured by the ASTM D6124-97 method. The 
labeling requirements also require stability testing to support the 
expiration date. The special control recommends that stability testing 
include tensile strength, elongation and water leak tests.
    The labeling is intended to communicate useful information to users 
about FDA's guidance recommending the use of gloves with no more than 
1,200 g of protein and 120 mg of glove powder (or 2 mg of 
powder, for powder-free gloves) and to ensure that the labeling 
contains adequate directions for use. The labeling would require 
manufacturers to indicate the actual levels of protein and powder on 
the gloves so that the user can ascertain if the gloves meet the 
recommended limits on protein and powder, which are intended to reduce 
exposure to particulates and airborne allergens. The expiration date 
labeling is intended to ensure that medical glove users have 
appropriate information regarding shelf life to enable them to use 
medical gloves safely by avoiding products that may have degraded.
    Description of Respondents: Businesses or other for profit 
organizations.

                                  Table 12.--Estimated Annual Reporting Burden1
----------------------------------------------------------------------------------------------------------------
                                    Annual
21 CFR Section      No. of       Frequency per   Total Annual      Hours per      Total Hours     Total Capital
                  Respondents      Response        Responses       Response                           Costs
----------------------------------------------------------------------------------------------------------------
801.440(a)          180               1             180              22           3,960          $985,248
801.440(b)           18               1              18              14             252
801.440(c)          178               1             178              16           2,848
801.440(d)          376              42           1,504              72         108,288
Total                                                                           115,348          $985,248
----------------------------------------------------------------------------------------------------------------
\1\ There are no operating and maintenance costs associated with this collection of information.
\2\ The annual burden reported here represents the first year in which a manufacturer would have conducted
  testing at 0 days, 3 months, 6 months, and 1 year. FDA expects in any succeeding years, testing would only be
  done at 6-month intervals.


[[Page 41741]]

    For the proposed labeling requirements, the hours per response 
included the hours estimated, based upon communications with industry, 
to run the tests to support the powder and protein levels and the 
expiration date, as well as the hours estimated to change the 
respondent's labeling. The total capital costs were derived from 
multiplying the total annual responses for protein testing and 
multiplying it by the estimated costs of buying a spectrometer and a 
plate reader, instruments that are necessary to conduct the protein 
testing. That cost was then annualized over a 5-year period.
    Based on communication with industry, FDA estimates that a 
respondent would take approximately 8 hours to run the protein tests 
necessary to obtain a protein level to add to the labeling. FDA bases 
its estimate on the ASTM D 6124-97 protein test.
    Based on communication with industry, FDA estimates that a 
respondent would take approximately 6 hours to run the powder tests 
necessary to obtain a powder level to add to the labeling. FDA bases 
its estimate on the ASTM D 5712 modified Lowry method powder test.
    Based on communication with industry, FDA estimates that a 
respondent would take approximately 16 hours to run the elongation, 
tensile strength, and waterleak tests recommended to support the 
expiration date. In the first year, FDA estimates that the tests would 
be run 4 times, at 0 days, 3 months, 6 months, and 1 year (16 X 4 = 
64). In the second, or succeeding years, FDA expects the tests to be 
run twice a year.
    FDA estimates that a respondent would take approximately 8 hours to 
change the labeling and approximately 8 hours to change the promotional 
materials to include the appropriate caution statement and the 
expiration date. This 16 hours is divided between the labeling changes 
proposed in Sec. 801.440(a) and (d) resulting in 8 hours being assessed 
for the caution statement and 8 hours being assessed for the expiration 
date.
    FDA estimates the number of burden hours per response for 
Sec. 801.440(a) is 22. That burden comes from the sum of the hours for 
running the powder and protein tests (8 hours plus 6 hours) and the 
hours for changing the labeling (8 hours).
    FDA estimates the number of burden hours per response for 
Sec. 801.440(b) is 14. That burden comes from the sum of the hours for 
running the powder tests (6 hours) and the hours for changing the 
labeling (8 hours).
    FDA estimates the number of burden hours per response for 
Sec. 801.440(c) is 16. That burden comes from the sum of the hours for 
running the protein tests (8 hours) and the hours for changing the 
labeling (8 hours).
    FDA estimates the number of burden hours per response for 
Sec. 801.440(d) is 72. That burden comes from the sum of the hours for 
running the elongation, tensile strength, and waterleak tests four 
times in the first year (64 hours) and the hours for changing the 
labeling (8 hours).
    FDA believes that manufacturers already have the equipment 
necessary to do the tests to support the powder levels and expiration 
dating because such equipment is currently being used to test the 
gloves. In order to do the protein tests recommended by FDA, FDA 
believes a manufacturer would need to obtain a spectrometer and a plate 
reader. FDA estimates that buying this equipment would cost 
approximately $22,000 (approximately $10,000 for the spectrometer and 
$12,000 for the plate reader). In addition, FDA assumed a 7 percent 
discount on the price of the equipment and that the equipment would be 
annualized over a 5-year period. In order to obtain a per annualized 
year estimate, FDA multiplied the cost by the discount ($22,000 x 
.244). FDA added the discounted amount ($5,368) to the cost of the 
equipment ($22,000) for a total equipment cost of $27,368. That cost 
annualized over a 5-year period is $5,473.60. FDA multiplied that cost 
by the number of respondents testing for protein levels (180) for a 
total capital cost of $985,248.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3507(d)), FDA has submitted the information collection provisions of 
this proposed rule to OMB for review. Interested persons are requested 
to send comments regarding information collection by August 30, 1999, 
to the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn.: 
Wendy Taylor, Desk Officer for FDA.

XIII. 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. Kaczmarek, R., R. Moore, J. McCrohan, et al., ``Glove Use by 
Health Care Workers: Results of a Tri-state Investigation,'' 
American Journal of Infection Control, 19:228-232, 1991.
    2. Kibby, T., and M. Akl, ``Prevalence of Latex Sensitization in 
a Hospital Employee Population,'' Annals of Allergy, Asthma & 
Immunology, 78:41-44, 1997.
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[[Page 41742]]

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List of Subjects

21 CFR Part 801

    Labeling, Medical devices, Reporting and recordkeeping 
requirements.

21 CFR Parts 878 and 880

    Medical devices.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR parts 801, 878, and 880 be amended as follows:

PART 801--LABELING

    1. The authority citation for 21 CFR part 801 is revised to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 360c, 360i, 360j, 371, 
374.

    2. Section 801.437 is amended by revising paragraph (d) to read as 
follows:


Sec. 801.437  User labeling for devices that contain natural rubber.

* * * * *
    (d)(1) As described in paragraph (b) of this section, devices 
containing natural rubber latex that contacts humans, except natural 
rubber latex surgeon's and patient examination gloves 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.
    (2) Natural rubber latex surgeon's and patient examination gloves 
shall bear the appropriate caution statement delineated in 
Sec. 801.440(a) or (c). 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.
* * * * *
    3. Section 801.440 is added to subpart H to read as follows:

[[Page 41743]]

Sec. 801.440  User labeling for powdered and powder-free surgeon's and 
patient examination gloves.

    The caution statements required in this section 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.
    (a) Natural rubber latex powdered surgeon's gloves and powdered 
patient examination gloves shall bear the following statement: 
``Caution: This product contains natural rubber latex which may cause 
allergic reactions. FDA recommends that this product contain no more 
than 120 mg powder and 1,200 g extractable protein per glove. 
This product contains no more than [insert level] mg powder and no more 
than [insert level] g extractable protein per glove.''
    (b) Synthetic material powdered surgeon's or powdered patient 
examination gloves shall bear the following statement: ``Caution: Glove 
powder is associated with adverse reactions. FDA recommends that this 
product contain no more than 120 milligrams powder per glove. This 
product contains no more than [insert level] mg powder per glove.''
    (c) Natural rubber latex powder-free surgeon's gloves and powder-
free patient examination gloves shall bear the following statement: 
``Caution: This product contains natural rubber latex which may cause 
allergic reactions. FDA recommends that this product contain no more 
than 1,200 g extractable protein per glove. This product 
contains no more than [insert level] g extractable protein per 
glove.''
    (d) All surgeon's and patient examination gloves shall bear an 
expiration date as follows:
    (1) The expiration date shall state the month and year of the 
shelf-life as supported by data from the studies described in paragraph 
(d)(3) of this section;
    (2) The expiration date must be prominently displayed on the 
exterior of the primary and retail package, and on the shipping carton;
    (3) The expiration date must be supported by stability studies 
demonstrating acceptable physical and mechanical integrity of the 
product over the shelf-life of the product from its date of 
manufacture;
    (4) For each glove design, the testing data and stability study 
protocol supporting an expiration date must be maintained by the 
manufacturer for a period equivalent to the design and expected life of 
that glove type, and shall be made available for inspection and copying 
by FDA; and
    (5) Sterile surgeon's and patient examination gloves that have a 
date of expiration based on sterility that is different from the 
expiration date based upon physical and mechanical integrity testing 
shall bear only the earlier expiration date.

PART 878--GENERAL AND PLASTIC SURGERY DEVICES

    4. The authority citation for 21 CFR part 878 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.

    5. Section 878.4460 is revised to read as follows:


Sec. 878.4460  Surgeon's gloves, powdered.

    (a) Identification. A powdered surgeon's glove is a disposable 
device made of natural rubber latex or synthetic material that bears 
powder to facilitate donning, and it is intended to be worn on the 
hands, usually in surgical settings, to provide a barrier against 
potentially infectious materials and other contaminants. The 
lubricating or dusting powder used on these gloves is classified 
separately in Sec. 878.4480.
    (b) Classification. Class II special controls are as follows:
    (1) Guidance document. The Center for Devices and Radiological 
Health, FDA, ``Medical Glove Guidance Manual,'' as revised. The 
guidance document is available from the Division of Small Manufacturers 
Assistance (HFZ-220), Center for Devices and Radiological Health, Food 
and Drug Administration, 1350 Piccard Dr., Rockville, MD 20850.
    (2) Labeling. User labeling requirements in Sec. 801.440 of this 
chapter.
    6. Section 878.4461 is added to subpart E to read as follows:


Sec. 878.4461  Surgeon's gloves, powder-free.

    (a) Identification. A powder-free surgeon's glove is a disposable 
device made of natural rubber latex or synthetic material that may bear 
a trace amount of glove powder and is intended to be worn on the hands, 
usually in surgical settings, to provide a barrier against potentially 
infectious materials and other contaminants.
    (b) Classification. Class II special controls are as follows:
    (1) Guidance document. The Center for Devices and Radiological 
Health, FDA, ``Medical Glove Guidance Manual,'' as revised (See 
Sec. 878.4460(b)(1)).
    (2) Labeling. User labeling requirements in Sec. 801.440 of this 
chapter.

PART 880--GENERAL HOSPITAL AND PERSONAL USE DEVICES

    7. The authority citation for 21 CFR part 880 continues to read as 
follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

    8. Section 880.6250 is revised to read as follows:


Sec. 880.6250  Patient examination gloves, powdered.

    (a) Identification. A powdered patient examination glove is a 
disposable device made of natural rubber latex or synthetic material 
that bears powder to facilitate donning and is intended to be worn on 
the hand or finger(s) for medical purposes to provide a barrier against 
potentially infectious materials and other contaminants.
    (b) Classification. Class II special controls are as follows:
    (1) Guidance document. The Center for Devices and Radiological 
Health, FDA, ``Medical Glove Guidance Manual,'' as revised. The 
guidance document is available from the Division of Small Manufacturers 
Assistance (HFZ-220), Center for Devices and Radiological Health, Food 
and Drug Administration, 1350 Piccard Dr., Rockville, MD 20850.
    (2) Labeling. User labeling requirements in Sec. 801.440 of this 
chapter.
    9. Section 880.6251 is added to subpart G to read as follows:


Sec. 880.6251  Patient examination gloves, powder-free.

    (a) Identification. A powder-free patient examination glove is a 
disposable device made of natural rubber latex or synthetic material 
that may bear a trace amount of glove powder and is intended to be worn 
on the hand or finger(s) for medical purposes to provide a barrier 
against potentially infectious materials and other contaminants.
    (b) Classification. Class II special controls are as follows:
     (1) Guidance document. The Center for Devices and Radiological 
Health, FDA, ``Medical Glove Guidance Manual,'' as revised (See 
Sec. 880.6250(b)(1)).
     (2) Labeling. User labeling requirements in Sec. 801.440 of this 
chapter.

    Dated: March 2, 1999.
Jane E. Henney,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 99-19191 Filed 7-29-99; 8:45 am]
BILLING CODE 4160-01-F