[Federal Register: February 19, 2003 (Volume 68, Number 33)]
[Proposed Rules]
[Page 7951-7956]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19fe03-29]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 349
[Docket No. 80N-145B]
RIN 0910-AA01
Over-the-Counter Ophthalmic Drug Products for Emergency First Aid
Use; Proposed Amendment of Final Monograph for Over-the-Counter
Ophthalmic Drug Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the final monograph for over-the-counter (OTC) ophthalmic drug products
to include OTC emergency first aid eyewash drug products. These
products are used to flush or irrigate the eye to remove acid and
alkali chemicals or particulate contamination. This proposal is part of
FDA's ongoing review of OTC drug products.
DATES: Submit written or electronic comments by May 20, 2003. Submit
written or electronic comments on the agency's economic impact
determination by May 20, 2003. Please see section IX of this document
for the effective date of any final rule that may publish based on this
proposal.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments
.
FOR FURTHER INFORMATION CONTACT: Marina Y. Chang, Center for Drug
Evaluation and Research (HFD-560), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-2222.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of March 4, 1988 (53 FR 7076), FDA
published a final monograph for OTC ophthalmic drug products in part
349 (21 CFR part 349). The monograph provides for eyewash drug products
in Sec. 349.20, but does not include emergency first aid eyewash drug
products because there were no submissions or comments on these
products during the rulemaking process.
After the final monograph was published, the agency received a
request for an advisory opinion (Ref. 1) concerning the status of a
product used for emergency first aid treatment of chemical burns of the
eyes and skin. This product was described as a sterile phosphate
buffered solution containing sodium phosphate, USP and monobasic
potassium phosphate, NF, preserved with edetate disodium, USP 1:2,000
and benzalkonium chloride, USP 1:5,000, for use immediately following a
chemical burn to thoroughly flush the eyes and skin for the express
purpose of removing the chemical irritant, and to relieve the
discomfort and burning caused by the irritating chemical prior to
seeking medical treatment.
As a result, the agency published a request for data and
information on this category of drugs in the Federal Register of
December 5, 1989 (54 FR 50240). The agency stated that it was unaware
of sufficient data to make a determination as to the safety,
effectiveness, and proper labeling of these ophthalmic drug products.
Specifically, the agency noted that the majority of these products: (1)
Are not intended to be marketed directly to individual consumers; (2)
are often packaged in large volume containers not normally found at the
retail level of distribution, especially for OTC ophthalmic drug
products; (3) may be stored for long periods of time under different
environmental conditions; (4) may be marketed in different types of
containers and closure systems; and (5) may be used with plumbed,
nonplumbed, self-contained emergency eyewash, or shower equipment/
stations. The agency noted it was not aware of all of the various
labeling formats, labeling statements, and formulations of all the
various emergency first aid eyewash products.
In response to the request for data and information, three
manufacturers and one manufacturer's association provided submissions
(Refs. 2 through 7) that included several journal articles in support
of the safety and effectiveness of products that provide immediate
emergency care by neutralization and dilution to the most serious burns
due to strong acids and alkalis. The submitted literature explained
that acid burns cause instantaneous coagulation of protein and result
in limited damage, whereas strong alkalis penetrate the ocular tissues
rapidly and produce damage that is widespread, uncontrolled, and
progressive (Ref. 8). The literature (Ref. 2) included a quote from the
National Institute of Occupational Safety and Health occupational
health guidelines which states: ``If (chemical) gets into the eyes,
wash eyes immediately with large amounts of water, lifting the lower
and upper lids occasionally. Get medical attention immediately.'' The
comment included an excerpt from the regulations of the Occupational
Safety and Health Administration (OSHA) entitled ``Requirements for
Medical and First Aid'' (42 CFR 1910.151). This portion of the OSHA
regulations assures that workers exposed to injurious corrosive
materials be provided with ``suitable facilities for quick drenching or
flushing of the eye.'' One manufacturer also provided sample labeling
of several marketed products (Ref. 5).
II. Comments Received and the Agency's Responses
A. Neutralization
Three comments addressed the term ``neutralization.'' One comment
stated that it removed this term from the principal display panel of
its product's labeling and replaced it with ``Wash/Flush'' because the
latter term better expressed the action of the product. Another comment
considered the term ``neutralization'' to be relative and not absolute.
The third comment believed that neutralizing was part of the action of
the product and provided a chart demonstrating the buffering capacity
of a neutralizer solution towards strong acids and bases versus
purified water (Ref. 7).
The agency reviewed available medical literature (Refs. 8 through
15) and found the treatment of choice for acid and alkali burns listed
in this literature to be copious and continuous irrigation of the area
with water or a pH balanced solution for at least 20 to 30 minutes.
According to the American Academy of Ophthalmology (Ref. 8), ``Specific
neutralizing agents are not useful; simple dilution (with water or
saline solution) is the most effective and practical way of
neutralizing strong chemicals.'' Casarett and Doull's Toxicology: The
Basic Science of Poisons (Ref. 9) states: ``Attempts to obtain some
special buffered solution or
[[Page 7952]]
mildly alkaline wash will only delay the start of treatment. Washing
should begin as close in time and place to the site of the accident as
possible.'' Conn's Current Therapy 1990 (Ref. 10) states:
The severity of the chemical burn is related directly to length
of time that a given agent is exposed to the skin * * *. Exact
identification of the burning chemical may suggest appropriate
specific measures; but an acid should not be neutralized with a base
or vice versa.
The agency is concerned that attempts to adjust the pH of the
affected area, such as by testing with litmus paper and then adding
drops of neutralizing solution, would delay or, at a minimum, reduce
the vigorous flushing needed to prevent further eye damage. Therefore,
the agency tentatively concludes that initial treatment is best
accomplished by copious and continuous amounts of water or saline
solution. Any attempt to provide a corrective solution, if necessary,
should be left to health care professionals following transport of the
accident victim to the facility's first aid station or a hospital.
Accordingly, the agency considers the term neutralization as
inappropriate to describe the pharmacological action of these products.
B. Water Lavage
Four comments emphasized the importance of immediate and continuous
water lavage for emergency care of the eye following chemical burns.
The Tulane University Research Report (Ref. 7) compared administration
of 50 milliliters (mL) of distilled water and a test product, called
``Neutralize'' (exact formulation not provided), to each eye 10 seconds
after acid was dropped on the eye. The studies showed no significant
difference in the rate of healing or in the final condition of both
eyes.
The agency agrees that the medical literature and the American
Academy of Ophthalmology support the use of copious amounts of fluid as
the best approach for emergency eyewash care. The agency also
recognizes the value of providing a sterile and stable product in large
quantities in an industrial setting where flowing water may not be
available.
C. Container Size and Ease of Opening
One comment referred to a 32-ounce (oz) container, intended for
only one use, as having a closure that requires 1\1/4\ turns. The
comment explained that a 38-millimeter unrestricted opening is
approximately the diameter needed to cover an average adult eye. The
comment added that this product is easily opened by a small stature
adult under stress. The comment noted that a tamper evident plastic
heat shrink seal that breaks away easily is used.
All eyewash products must comply with the monograph standards in
part 349. The products must also meet current good manufacturing
practices (CGMPs) as stated in 21 CFR parts 210 and 211.
The agency believes that emergency eyewash products must contain
enough fluid to permit adequate flushing of the eye. While a maximum
volume may depend on the configuration of the container or the plumbing
system, the minimum volume should be no less than 16 oz (473 mL (500 mL
or 1/2 liter is acceptable)). Because of concerns about sterility, the
product should be for a single individual's use unless it is part of a
plumbing system with a one-way valve.
D. pH Adjustment
Several comments supported the pH range of 6.6 to 7.4 as
appropriate for these products. One comment mentioned a lack of adverse
event reports in the many years of use of these products as an
indicator that the present pH is appropriate. Another comment stated it
was unlikely that the pH of a product would have a clinically
significant impact on the outcome of a chemical burn. One comment,
however, felt that the agency should not require a specific range but
define the requirement as ``needing to be at or near neutral pH, 6.6 to
7.4.''
The agency agrees that 6.6 to 7.4 is an appropriate pH range for
emergency eyewash solutions. The agency believes this pH range provides
sufficient flexibility for manufacturers to adjust agents to maintain
stability, yet provides a solution that does not cause further harm or
additional irritation to the accident victim. The agency, however,
agrees that the pH within this range is not likely to impact on the
outcome of a chemical burn. The agency believes that the inclusion of
an antimicrobial preservative would aid the stability of the product.
Accordingly, the agency is proposing the following in new Sec.
349.22 Emergency first aid eyewashes: ``These products contain water,
agents to achieve the pH within a range of 6.6 to 7.4, and a suitable
antimicrobial preservative agent.''
E. Buffering
One comment noted that buffering is an added feature to help
neutralize the chemical burn but that both buffered and unbuffered
solutions can be extremely beneficial to achieve dilution and
neutralization because the main treatment is by dilution. Another
comment added that buffers help ensure product integrity during storage
in an industrial setting, while another comment was unaware of any
superiority of either buffering or not buffering.
The product that led to the request for data was described as a
sterile phosphate buffered solution (Ref. 1) for use immediately
following a chemical burn to thoroughly flush the eyes and skin for the
express purpose of removing the chemical irritant, and to relieve the
discomfort and burning caused by the irritating chemical prior to
seeking medical treatment. The comment provided excerpts from studies
presented in a Tulane University Research Report (Ref. 7) to
demonstrate the superiority of its product when compared to water as an
emergency first aid eyewash to treat a caustic acid splash.
The agency notes that a medical dictionary (Ref. 16) defines
``buffering'' as ``a chemical system that prevents change in
concentration of another chemical substance, e.g., proton donor and
acceptor systems serve as buffers preventing marked changes in hydrogen
ion concentration (pH).'' The agency acknowledges the buffer system
contributes to the tonicity of the ophthalmic product but adds that the
tonicity of the entire formulation should approximate lacrimal fluids.
The agency agrees with the comment that stated it was unaware of
any superiority of either buffering or not buffering these products.
Accordingly, the agency is proposing in Sec. 349.22 that emergency
first aid eyewash products may contain agents for buffering the pH.
F. Phosphate Treatment of Chemical Burns
One comment provided references to support ``phosphate therapy'' to
treat burns caused by acidic or basic substances (Ref. 1). The
references reported a phosphate buffer is prepared by dissolving 70
grams (g) of monobasic potassium phosphate
(KH2PO4) and 180g of dibasic sodium phosphate
(Na2HPO4.12 H2O) in 850 mL of water.
The concentration of the solution is molar with respect to phosphate,
but as the phosphates are physiologically occurring substances they can
be safely employed in such high concentrations and provide prompt
neutralization. The comment contended that some antidotes are too
acidic or alkaline; that burns caused by acids or bases require
different treatment; and that the phosphate buffer is neutral in its
reaction, and thus is well suited for the treatment of injuries caused
by acidic or basic chemicals.
[[Page 7953]]
At this time, the agency considers a phosphate buffered solution
acceptable for emergency first aid eyewash products. The increased
concentration of phosphates would not alter the pH range but could be
more effective against an acid or alkali burn.
G. Industrial Glare
One comment briefly referred to emergency first aid eyewash
solutions to treat industrial glare (i.e., from welder's arc) but did
not provide any data to support this use. At this time, the agency is
not including this use as an indication for these products without
adequate supporting documentation. The agency requests interested
parties to provide supporting data.
H. Five to 15-gallon Container Plus Preservative Concentrate
One comment explained that a 15-minute emergency eyewash requires
14 gallons (gal) of potable water and a 5-minute eyewash requires 9 1/2
gal of potable water. The comment stated that the unit would be filled
with potable water and the preservative concentrate added. The comment
offered that a concentrate will preserve 5 to 20 gal of potable water
for up to 180 days. The comment further stated that potable eyewash
units should be flushed and cleaned and the water and concentrate
replaced every 60 days.
All emergency eyewash products must be able to meet monograph
requirements, which include safety and effectiveness, a pH range of 6.6
to 7.4, and compliance with CGMPs. The agency is aware that there are
preservative concentrates in the marketplace for use in potable eyewash
units, as the comment noted. Under Sec. 349.82(d)(3), the agency is
proposing that the labeling contain the word ``concentrate'' in bold
type. The labeling must provide adequate directions for adding the
concentrate to potable water to obtain a solution that meets the
requirements of Sec. 349.22. The directions should also state that the
concentrate should be added to potable water to have a fully
constituted solution available in advance of an emergency. The agency
is unaware of data to support the length of time that any particular
preservative concentrate is safe and effective. Manufacturers of these
products are advised to follow CGMPs.
I. Labeling
One comment proposed several labeling revisions under Sec. 349.78.
Under Sec. 349.78(a), the comment added to the statement of identity
the terms ``neutralizer'' and ``neutralizing solution.''
As stated in section II.A of this document, the agency does not
believe that the term ``neutralize'' properly describes the action of
these products and, therefore, is not proposing this term or any
variation of this term in the monograph.
Under Sec. 349.78(b)(1) and (b)(2), the comment added the terms
``acid'' and ``alkali.'' Under Sec. 349.78(b)(5), the comment provided
for indications for eyes that have been subjected to industrial glare
such as welder's arc and ``other workplace irritants.'' The comment
argued that demulcents have a long history of use for soothing the
burning sensation associated with welder's arc and other workplace
irritants that dry the eye. The comment explained that this indication
is an extension of Sec. 349.60(b)(2), which provides for temporary
relief due to exposure to the sun.
The agency agrees that if an emergency first aid eyewash will
assist in the prevention of permanent damage to the eye(s) due to
industrial glare, this indication should be included in the uses
section of the labeling. However, as stated in section II.G of this
document, the agency needs supporting documentation for this use.
The agency believes the term ``particulate contamination'' is a
general term that could include the comment's request for an indication
for ``other workplace irritants.'' The agency agrees that there are
potential instances in the industrial setting where particulate matter
could cause eye damage and that an eyewash solution could alleviate the
seriousness of the condition. Accordingly, the agency is proposing the
terms ``acid,'' ``alkali,'' and ``particulate contamination'' in new
Sec. 349.82(b) as examples of causes of injury.
Under Sec. 349.78(d)(3), the comment suggested the following
directions for emergency first aid eyewash products:
For eyewash products packaged in a container that also serves as
an eyecup. Remove safety seal and cap. Avoid contamination of rim of
bottle. Place rim over affected eye, pressing tightly to prevent the
escape of the liquid, and tilt the head backward. Open eyelid wide
and rotate eyeball to ensure thorough bathing with the solution. Use
only unopened bottle on the eyes.
The comment explained that many large volume (up to 32 oz) first aid
eyewash solutions are packaged in containers with wide flanged rims
that fit over the eye.
The agency agrees that containers that also serve as eyecups should
be addressed in the monograph and is including this information, with a
few modifications, in Sec. 349.82(d)(1). The agency notes that eyecups
generally promote retention of material that may be injurious to the
eye instead of allowing the injurious material to be washed away and
down the face. The use of eyecups in the setting of workplace irritants
should be discouraged. The agency also obtained and reviewed
representative current labeling for a number of these products (Ref.
17) to develop the labeling in this proposal.
III. The Agency's Proposal
The agency tentatively concludes that the references support the
safety and effectiveness of emergency first aid eyewash drug products
to remove acid or alkali chemicals and that, in particular, immediate
flushing of the eye with fluid is urgently needed to lessen the impact
of the alkalis. The agency also acknowledges that burns from alkalis
penetrate the ocular tissues rapidly and produce damages that are
widespread, uncontrolled, and progressive. However, the agency does not
believe that a chemical irritant should be counteracted with another
chemical. The agency believes that immediate and copious irrigation
with fluid is the most important step and that the amount of time prior
to irrigation is a critical factor in determining the amount of
residual damage.
The effectiveness of an emergency eyewash appears dependent upon
the steady flow of copious amounts of fluid to the injured eye(s).
Emergency first aid eyewashes serve as an interim step in first aid
care by providing immediate flushing of the eye and allowing the
accident victim to be transported to the facility's first aid station
or a hospital while the flushing treatment is in progress. Accordingly,
the agency is proposing to amend the final monograph for OTC ophthalmic
drug products to include a section on emergency first aid eyewashes.
IV. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (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). Under the
[[Page 7954]]
Regulatory Flexibility Act, if a rule has a significant economic
impact on a substantial number of small entities, an agency must
analyze regulatory options that would minimize any significant impact
of the rule on small entities. Section 202(a) of the Unfunded Mandates
Reform Act requires that agencies prepare a written statement of
anticipated costs and benefits before proposing any rule that may
result in an expenditure in any one year by State, local, and tribal
governments, in the aggregate, or by the private sector, of $100
million (adjusted annually for inflation).
The agency believes that this proposed rule is consistent with the
principles set out in Executive Order 12866 and in these two statutes.
In addition, the proposed rule is not a significant regulatory action
as defined by the Executive order. The Unfunded Mandates Reform Act
does not require FDA to prepare a statement of costs and benefits for
this proposed rule because the proposed rule is not expected to result
in any 1-year expenditure that would exceed $100 million adjusted
annually for inflation. The current inflation adjusted statutory
threshold is approximately $110 million.
With respect to the Regulatory Flexibility Act, FDA does not
believe that the proposed rule would have a significant economic impact
on a substantial number of small entities. However, the agency
recognizes the uncertainty of its estimates with respect to the number
of affected small entities as well as the economic impact of the rule
on those small entities. The agency therefore requests detailed public
comment regarding any substantial or significant economic impact that
this rulemaking would have on manufacturers of OTC emergency first aid
eyewash drug products.
The purpose of this proposed rule is to amend the final monograph
for OTC ophthalmic drug products to include OTC emergency first aid
eyewash drug products. This proposed rule may increase OTC availability
of these products and may, as a result, lower the costs to industrial
facilities and individuals that use such products.
Manufacturers of the affected products should incur only minor
costs to relabel their products to meet the monograph requirements.
These manufacturers can make the required changes whenever they are
ready to order new product labeling within the 12 months after the
final rule is issued. Manufacturers of products with annual sales of
less than $25,000 will have 24 months to complete the required
relabeling. The agency has been informed that this type of relabeling
generally costs approximately $3,000 to $4,000 per stockkeeping unit
(SKU) (i.e., individual products, packages, and sizes). The agency
estimates that there are approximately 25 manufacturers or marketers of
40 to 45 products and 50 to 60 SKUs that would be affected by this
proposed rule.
Based on this information, the total one-time costs of relabeling
would be between $150,000 ($3,000 per SKU x 50 SKUs) and $240,000
($4,000 per SKU x 60 SKUs). Assuming an equal distribution of these
costs across the 25 affected entities results in an average cost burden
of $6,000 to $9,600 per firm. The agency believes that actual costs
would be lower for several reasons. First, most of the required changes
will be made by private label manufacturers that tend to use relatively
simple and less expensive labeling. Second, the agency is proposing a
12-month implementation period that would allow manufacturers to
coordinate the required changes with routinely scheduled label printing
and/or revisions. Labeling changes for these products would not be
required until 12 months after the monograph amendment is issued as a
final rule and becomes effective. Furthermore, products with less than
$25,000 per year in sales would not need to be relabeled until 24
months after the rule becomes final. Thus, manufacturers would have
time to use up existing labeling stocks and plan for new labeling,
thereby mitigating some of the costs of this proposed rule. Third,
manufacturers may be able to implement the new labeling required by
this proposal at the same time that they implement the new standardized
format and content labeling required by 21 CFR 201.66. Thus, the total
relabeling costs associated with two different but related final rules
may be reduced by implementing the required changes at the same time.
According to standards established by the Small Business
Administration, a small pharmaceutical preparations manufacturer (NAICS
code 325412) employs fewer than 750 people. FDA has determined that
approximately 88 percent (22 out of 25) of OTC ophthalmic drug product
manufacturers meet these criteria and can therefore be categorized as
small entities. The average annual revenue of small entities affected
by this rule was found to be approximately $10.7 million. Thus, the
cost of the rule per affected small entity would be between 0.056
percent ($6,000 / $10.7 million) and 0.09 percent ($9,600 / $10.7
million) of average annual revenues. FDA is aware of one small entity
that has average annual revenues of approximately $1 million and
produces 3 SKUs. The total cost of the final rule for this small entity
would be between 0.9 percent (3 SKUs x $3,000 per SKU / $1 million) and
1.2 percent (3 SKUs x $4,000 per SKU / $1 million) of annual revenues.
Thus the economic impact of the proposed rule on the majority of small
entities is expected to be much less than 1 percent of annual revenues.
While these estimates are uncertain, it appears that this proposed rule
would not have a significant economic impact on a substantial number of
small entities.
The agency considered but rejected several alternatives: (1) A
shorter or longer implementation period, and (2) an exemption from the
requirements for small entities. While the agency believes that
industries and accident victims who use these products would benefit
from having the new labeling in place as soon as possible, the agency
also acknowledges that coordination of the labeling changes with
implementation of the new OTC ``Drug Facts'' labeling may significantly
reduce the costs associated with this proposed rule. Thus, an
alternative specifying a shorter implementation period was rejected due
to its inflexibility and potentially greater cost. A longer
implementation period was also rejected because it would unnecessarily
delay the benefits of new labeling and revised formulations, where
applicable, to parties who use these OTC drug products. The agency also
rejected an exemption for small entities because the new labeling and
revised formulations, where applicable, would also generate benefits
for parties who purchase products marketed by those entities.
Furthermore, the vast majority of firms affected by this proposed rule
can be classified as small entities. However, an additional year is
being allowed for products with annual sales of less than $25,000 to
implement the required changes in order to reduce the potential impact
of the rule on small entities.
This proposed rule allows for continued marketing of affected
products without the risk of regulatory action provided the following
conditions are met: (1) The product or similarly formulated and labeled
products were marketed as OTC drugs at the inception of the OTC drug
review on May 11, 1972, a date that was later extended to on or before
December 4, 1975 (see 21 CFR 330.13); (2) such product does not
constitute a hazard to health; (3) the product formulation is not
regarded to be a prescription drug within the meaning of section 503(b)
of the Federal Food, Drug, and Cosmetic
[[Page 7955]]
Act (21 U.S.C. 353(b)); (4) the product is an OTC drug and does not
bear claims for serious disease conditions that require the attention
and supervision of a licensed practitioner.
Emergency first aid eyewash products and eye irrigating solutions
that do not meet the previous criteria may not be marketed OTC pending
evaluation of these products for the treatment of chemical burns and
for irrigation of the eye(s) unless the product is the subject of an
approved new drug application (NDA).
This analysis of impacts shows that the proposed rule is not
economically significant under Executive Order 12866 and that the
agency has undertaken important steps to reduce the burden to small
entities. This analysis of impacts, together with other relevant
sections of this document, serves as the agency's initial regulatory
flexibility analysis, as required by the Regulatory Flexibility Act.
The agency will reassess the economic impact of this rulemaking in the
preamble to the final rule.
V. Paperwork Reduction Act of 1995
FDA tentatively concludes that the labeling requirements proposed
in this document are not subject to review by the Office of Management
and Budget because they do not constitute a ``collection of
information'' under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501
et seq.). Rather, the proposed labeling statements are a ``public
disclosure of information originally supplied by the Federal government
to the recipient for the purpose of disclosure to the public'' (5 CFR
1320.3(c)(2)).
VI. Environmental Impact
The agency has determined under 21 CFR 25.31(a) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
the agency tentatively concludes that the proposed rule does not
contain policies that have federalism implications as defined in the
Executive order and, consequently, a federalism summary impact
statement has not been prepared.
VIII. Request for Comments
Interested persons may submit to the Dockets Management Branch (see
ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments to http://www.fda. gov/
dockets/ecomments or three hard copies of any written comments, except
that individuals may submit one hard copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document and may be accompanied by a supporting memorandum or
brief. Received comments may be seen in the Dockets Management Branch
between 9 a.m. and 4 p.m., Monday through Friday.
IX. Proposed Effective Date
FDA is proposing that any final rule that may issue based on this
proposal become effective 12 months after its date of publication in
the Federal Register.
X. References
The following references are on display in the Dockets Management
Branch (see ADDRESSES) under Docket No. 80N-145B and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Comment No. AP.
2. Comment 1.
3. Comment 2.
4. Comment 3.
5. Comment 4.
6. Comment 5.
7. Comment 6.
8. ``External Disease and Cornea,'' 1989-1990, Basic and
Clinical Science Course, American Academy of Ophthalmology, San
Francisco, CA, pp. 130-133, 1989.
9. Potts, A. M., ``Toxic Responses of the Eye,'' Casarett and
Doull's Toxicology: The Basic Science of Poisons, 3d ed., Macmillan
Publishing Co., New York, NY, pp. 478-485, 1986.
10. Raker, R. E., Conn's Current Therapy 1990, W. B. Saunders
Co., Philadelphia, PA, p. 1035, 1990.
11. Dreisbach, R. H., and W. O. Robertson, ``Emergency
Management of Poisoning,'' Handbook of Poisoning: Prevention,
Diagnosis & Treatment, 12th ed., Appleton & Lange, Norwalk, CT, pp.
28-29, 1987.
12. Siverston, K. T., ``Ocular Toxicity,'' Manual of Toxicologic
Emergencies, Year Book Medical Publishers, Inc., Chicago, IL, pp.
115-118, 1989.
13. Tapley, D. F. et al., ``The Eyes,'' The Columbia University
College of Physicians and Surgeons Complete Home Medical Guide,
Crown Publishers, Inc., New York, NY, pp. 696-697, 1989.
14. Behrman, R. E., and V. C. Vaughan, ``Injuries to the Eye,''
Nelson Textbook of Pediatrics, 13th ed., W. B. Saunders Co.,
Philadelphia, PA, pp. 1472-1473, 1987.
15. ``Occupational Health Guidelines for Ethyl Chloride,''
National Institute for Occupational Safety and Health, pp. 1-4,
September 1978.
16. Dorland's Illustrated Medical Dictionary, 27th ed., W. B.
Saunders Co., Philadelphia, PA, p.252, 1988, s.v. ``buffer.''
17. Comment 7.
List of Subjects in 21 CFR Part 349
Labeling, Over-the-counter drugs.
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 part 349 be amended as follows:
PART 349--OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
1. The authority citation for 21 CFR part 349 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
2. Section 349.22 is added to subpart B to read as follows:
Sec. 349.22 Emergency first aid eyewashes.
These products contain water, agents to achieve the pH within a
range of 6.6 and 7.4, and a suitable antimicrobial preservative agent.
Additionally, they may contain tonicity agents to establish isotonicity
with tears and agents for buffering the pH.
3. Section 349.82 is added to subpart C to read as follows:
Sec. 349.82 Labeling of emergency first aid eyewash drug products.
(a) Statement of identity. The labeling of the product identifies
the product with one of the following: ``Emergency first aid eyewash,''
``First aid eye rinse,'' or ``Emergency eyewash.''
(b) Indications. The labeling of the product states, under the
heading ``Uses'', ``for'' [select one of the following: ``flushing,''
or ``irrigating''] ``the eye to reduce chances of severe injury caused
by acid, alkali, or particulate contamination''.
(c) Warnings. In addition to the warnings in Sec. 349.50 (the
``Replace cap after using,'' warning in Sec. 349.50(c)(1) should only
be used if applicable), the labeling of the product contains the
following warnings under the heading ``Warnings'' for all emergency
eyewash products:
(1) ``Do not use [in bold type] [bullet]\1\ for injection [bullet]
in intraocular surgery [bullet] internally [bullet] if
[[Page 7956]]
solution changes color or becomes cloudy''.
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\1\ See Sec. 201.66(b)(4) of this chapter for definition of
bullet symbol.
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(2) ``Ask a doctor if you have [in bold type] [bullet] eye pain
[bullet] changes in vision [bullet] redness or irritation of the eye
after use [bullet] an injury caused by an alkali''.
(d) Directions. The labeling of the product states, as appropriate,
under the heading ``Directions'', ``[bullet] do not dilute solution or
reuse bottle [in bold type] [bullet] hold container a few inches above
the eye [bullet] control rate of flow by pressure on bottle [bullet]
flush affected area for a minimum of 20 minutes [bullet] continue
flushing with water if necessary [bullet] obtain medical treatment''.
(1) For products packaged in a container that also serves as an
eyecup. The labeling states ``[bullet] use only unopened bottle
[bullet] remove safety seal and cap [bullet] avoid contamination of rim
of bottle [bullet] place rim over affected eye [bullet] tilt head
backward [bullet] open eyelids wide [bullet] throughly bathe eye with
solution [bullet] allow solution to flow away from eye''. The
directions in this paragraph shall be placed in sequence with the
directions provided in paragraph (d) of this section, as appropriate.
(2) For products intended for use with a nozzle applicator. The
labeling states ``[bullet] flush affected eye as needed [bullet]
control flow of solution by pressure on bottle''.
(3) For products that use a concentrate with potable water. The
word ``concentrate'' shall be in bold type. Labeling must provide
adequate directions for adding the concentrate to potable water to
obtain a solution that meets the requirements of Sec. 349.22. The
directions shall also state that the concentrate should be added to
potable water to have a fully constituted solution available in advance
of an emergency.
Dated: January 31, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-3927 Filed 2-18-03; 8:45 am]
BILLING CODE 4160-01-S