[Docket No. 80N-0145]
`Ophthalmic Drug Products for Over-
`the-Counter Human Use; Final
`Monograph
`
`FOR FURTHER INFORMATION CONTACT:
`
`7076
`
`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`Food and Drug Administration
`21 CFR Parts 349 and 369
`
`Federal Register / Vol. 53, No. 43 / Friday, March 4, 1988 / Rules and Regulations
`period could be submitted by September
`no longer using the terms “Category I”
`3,1980.
`(generally recognized as safe and
`In accordance^with § 330.10(ia)(10), the
`effective and not misbranded),
`data and information considered by the
`“Category II” (not generally recognized
`Panel were put on display in the
`as safe and effective or misbranded),
`Dockets Management Branch (HFA-
`and “Category III” (available data are
`305), Food and Drug Administration, Rm.
`ihsufficient to classify as safe and
`4-62, 5600 Fishers Lane, Rockville, MD
`effective, and further testing is required)
`20857, after deletion of a small amount
`afc the final monograph stage, but is
`of trade secret information.
`using instead the terms “monograph
`The agency’s proposed regulation, in
`conditions” (old Category I) and
`the form of a tentative final monograph,
`“nonmonograph conditions” (old
`for OTC ophthalmic drug products was
`Categories II and III).
`published in the Federal Register of June
`As discussed in the proposed
`28,1983 (48 FR 29788). Interested
`regulation for OTC ophthalmic drug
`persons were invited to file by August
`products (48 FR 29788), the agency
`29,1983, written comments, objections',
`advises that the conditions under which
`or requests for oral hearing before the
`the drug products that are subject to this
`Commissioner of Food and Drugs
`monograph will be. generally recognized
`regarding the proposal. Interested,
`as safe and effective and not
`persons were invited to file comments
`misbranded (monograph conditions) will
`on the agency’s economic impact
`be effective 12 months after the date of
`determination by October 27,1983. Ntew
`publication in the Federal Register.
`data could have been submitted until
`Therefore, on or after March 6,1989, no
`June 28,1984 and comments on the. new
`OTC drug product that is subject to the
`data until August 28,1984.
`monograph and that contains a
`In considering the antiinfective
`nonmonograph condition, i.e., a
`portion of the ophthalmic monograph,
`condition that would cause the drug to
`the agency has determined that there
`be not generally recognized as safe and
`are complex scientific issues that need
`effective or to be misbranded, may be
`to be resolved before a final
`initially introduced or initially delivered
`determination can be made with respect
`for introduction into interstate
`to ingredients ini this class. These issues
`commerce unless it is the subject of an
`do not directly relate to the other
`approved application. Further, any OTC
`segments of the ophthalmic monograph.
`drug product subject to this monograph
`Accordingly, in order to complete the
`that is repackaged or relabeled after the
`publication o£ other segments of the
`effective date of the monograph must be
`ophthalmic final! monograph without
`in compliance with the monograph
`undue delay, the agency is not including
`regardless of the date the product was
`an antiinfective segment in this
`initially introduced or initially delivered
`document.. Elsewhere in this issue of the
`for introduction into interstate
`Federal Register, FDA is reopening the
`commerce. Manufacturers are
`administrative record for OTC
`encouraged to comply voluntarily with
`ophthalmic drug products to include
`the monograph at the earliest possible
`only those data on antiinfective-
`date.In response to the proposed rule on
`ingredients, that were submitted after the-
`closing of the administrative record. The
`OTC ophthalmic drug products, one drug
`administrative record will remain open
`manufacturers’ association, eight drug
`until July 5,1988* for submission of
`manufacturers, two consumer groups,
`public comments on that data. The
`one professional medical organization,
`agency intends to publish its final
`and one consumer submitted comments.
`decision on ophthalmic antiinfectives in
`A request for an oral hearing before the
`a future iissue of the Federal Register.
`Commissioner was also received on one
`Final agency action for the other
`issue. Copies of the comments and the
`segments of the ophthalmic drug product
`hearing request received are on public
`rulemaking occurs with the publication
`display in the Dockets Management
`of this final monograph, which is a final
`Branch. Additional information that has
`rule establishing a monograph for OTC
`come to the agency’s attention since
`ophthalmic drug products.
`publication of the proposed rule is also
`The OTC drug procedural regulations
`on public display in the Dockets
`(21 CFR 330.10) now provide that any
`Management Branch.
`testing necessary to resolve the safety or
`In proceeding with this final
`effectiveness issues that formerly
`monograph, the agency has considered
`resulted in a Category III classification*
`the objections, a request for oral
`and submission to FDA of the results of
`hearing, and changes in the procedural
`that testing or any other data, must be
`regulations.
`done during the OTC drug rulemaking,
`All “QTC Volumes” cited throughout
`process before the establishment of a
`this document refer to the submissions
`final monograph. Accordingly, FDA is
`
`a g e n c y : Food and Drug Administration.
`ACTION: Final rule.
`s u m m a r y: The Food and Drug
`Administration (FDA) is issuing a final
`rule in the form of a final monograph
`establishing conditions under which
`over-the-counter (OTC) ophthalmic drug
`products (drug products applied to the
`eyelid or instilled in the eye), other than
`antiinfective OTC ophthalmic drug
`products, are generally recognized as
`safe and effective and not misbranded.
`FDA is issuing this final rule after
`considering public comments on the
`agency’s proposed regulation, which
`was issued in the form of a tentative
`final monograph, and new data and
`information on OTC ophthalmic drug
`products that have come to the agency’s
`attention. This final monograph is part
`of the ongoing review of OTC drug
`products conducted by FDA. Elsewhere
`in this issue of the Federal Register, FDA
`is reopening tho administrative record
`for OTC ophthalmic drug products to
`include only those data, on antiinfective
`ingredients that were submitted after the
`closing of the administrative record. The
`administrative record will remain open
`until July 5,1988, for submission of
`public comments on that data.
`EFFECTIVE DATE: March 6,, 1988.
`William E. Gilbertson, Center for Drug
`Evaluation and Research (jHFN^ZlO);
`Food and Drug Administration, 5600
`Fishers Lane, Rockville* MD 20857, 301-
`295-8000.
`SUPPLEMENTARY INFORMATION: In the
`Federal Register of May 6,1980 (45 FR
`30002), FDA published, under
`§ 330.10(a)(6) (21 CFR 330.10(a)(6)), an
`advance notice of proposed rulemaking
`to establish a monograph for OTC
`ophthalmic drug products, together with
`the recommendations of the Advisory
`Review Panel on OTC Ophthalmic Drug
`Products, which was the advisory
`review panel responsible for evaluating
`data on the active ingredients in this
`drug class. Interested persons were
`invited to submit comments by August 4,
`1980. Reply comments in response to
`comments filed in the initial comment
`
`Page 1 of 18
`
`SLAYBACK EXHIBIT 1009
`
`

`

`Ophthalmic Drug Products
`
`made by interested persons pursuant to
`the call-for-data notice published in the
`Federal Register of April 26,1973 (38 FR
`10306} or to additional information that
`has come to the agency’s attention since
`publication of the notice of proposed
`rulemaking. The volumes are on public
`display in the Dockets Management
`Branch. ,
`I. The Agency’s Conclusions on the
`Comments
`A. General Comments on O T C
`1. One comment contended that OTC
`drug monographs are interpretive, as
`opposed to substantive, regulations. The
`comment referred to statements on this
`issue submitted earlier to other OTC
`drug rulemaking proceedings.
`The agency addressed this issue in
`paragraphs 85 through 91 of the
`preamble to the procedures for
`classification of OTC drug products,
`published in the Federal Register of May
`II, 1972 (37 FR 9464) and in paragraph 3
`of the preamble to the tentative final
`monograph for antacid drug products,
`published in the Federal Register of
`November 12,1973 (38 FR 31260). FDA
`reaffirms the conclusions stated there.
`Subsequent court decisions have
`confirmed the agency’s authority to
`issue substantive regulations by
`rulemaking. See, e.g., National
`Nutritional Foods Association v.
`Weinberger, 512 F.2d 688, 696-98 (2d Cir.
`1975) and National Association o f
`Pharmaceutical Manufacturers v. FDA,
`487 F. Supp. 412 (S.D.N.Y. 1980), a ff’d637
`F.2d 887 (2d Cir. 1981).
`2. Two comments disagreed with the
`definition of eyewash products proposed
`in § 349.3(f) and the description of
`eyewashes proposed in § 349.20 of the
`tentative final monograph (48 FR 29798).
`Both comments felt that a statement that
`these products contain no
`pharmacologically active ingredients is
`unnecessary and should be deleted from
`both the definition and the description
`of eyewashes. One comment listed the
`mgredients suggested by the Panel as
`suitable for buffering or adjusting the pH
`of ophthalmic solutions (45 FR 30016)
`snd stated that many of these
`ingredients are pharmacologically active
`ot concentrations higher than the
`amounts usually present when these
`ingredients are used as buffers or pH
`adjusters in eyewash products. The
`comment contended that manufacturers
`should not have to be concerned if an
`ingredient happens to reach a level that
`Is Pharmacologically active if no claim
`or any pharmacologic action is being
`made for these ingredients. The
`comment recommended that the
`
`description of eyewashes in § 349.20 be
`amended to read: "These products may
`only contain water, tonicity agents to
`establish isotonficity with tears, agents
`for establishing pH and buffering to
`achieve the same pH as tears, and a
`suitable preservative agent.” The
`comment added that the definition of
`eyewashes should be consistent with
`§ 349.20 and proposed the following
`definition: “Eyewash, eye lotion,
`irrigating solution. A sterile aqueous
`solution for bathing or mechanically
`flushing the eye containing tonicity
`agents to establish isotonicity with tears
`and agents to establish pH and buffering
`to achieve the same pH as tears.” The
`second comment asserted that a
`definition without the phrase
`“containing no pharmacologically active
`ingredients” is more appropriate
`because classes of products should be
`defined positively, in terms of what
`those products are or what they contain,
`rather than what they are not or do not
`contain. The comment suggested
`substituting the word “washing” for the
`term “flushing” for additional clarity.
`The agency agrees with the comments
`that the statement that eyewashes
`“contain no pharmacologically active
`ingredients” is unnecessary. As one of
`the comments noted, this statement may
`be unclear because many of the
`ingredients present in low
`concentrations in eyewashes as buffers
`or pH adjusters are pharmacologically
`active at higher concentrations. The
`agency also agrees that, wherever
`possible, classes of products should be
`defined positively by stating what those
`products contain, rather than what they
`do not contain. Therefore, in this final
`monograph, the agency is deleting the
`words “contain no pharmacologically
`active ingredients” from the product
`description for eyewashes in § 349.20
`and is revising the statement to read:
`“These products contain water, tonicity
`agents to establish isotonicity with
`tears, agents for establishing pH and
`buffering to achieve the same pH as
`tears, and a suitable preservative
`agent.”
`In addition, the agency is deleting the
`words “containing no pharmacologically
`active ingredients” from the definition
`for eyewash, eye lotion, and irrigating
`solution in § 349.3(f). The agency also
`believes that the word “mechanically” is
`unnecessary in this definition and thus
`is revising the definition to read: “A
`sterile aqueous solution intended for
`washing, bathing, or flushing the eye.”
`B. Comments on O T C Ophthalmic Drug
`3.
`One comment contended that boric
`acid meets the definition of an
`
`Ingredients
`
`Federal Register / Yol. 53, No. 43 / Friday, March 4, 1988 / Rules and Regulations
`
`7077
`
`astringent and an eyewash as stated in
`the notice of proposed rulemaking (48
`FR 29791): For astringents—“helps to
`clear mucus from the outer surface of
`the eye.” and For eyewashes—“bathes
`or mechanically flushes the eye.” The
`comment stated that “some cognizance
`must be taken of the long history of
`mishap-free use of mild borte acid
`solution in eyewashes, etc.” The
`comment maintained that, although
`boric acid is not bactericidal, it has
`demonstrated some bacteriostatic
`properties, is a pharmaceutical necessity
`as a pH buffer and a preservative, and
`its “efficacy in ophthalmic preparations
`is more of an astringency action than a
`therapeutic action.” The comment
`further noted that ophthalmologists
`often prescribe mild boric acid solution
`and that the product is a standard first
`aid item, which is noncorrosive,
`nonirritating, and nonmutagenic.
`The “definitions” cited by the
`comment appeared at 48 FR 29791 as
`"claims based on the Panel’s
`definitions” and are partial excerpts
`from the definition of each of these
`ophthalmic drug classes proposed in
`§ 349.3 of the tentative final monograph
`(48 FR 29797 and 29798). The complete
`definitions read as follows: “Astringent.
`A locally acting pharmacologic agent
`which, by precipitating protein, helps to
`clear mucus from the outer surface of
`the eye”; and “Eyewash, eye lotion,
`irrigating solution. A sterile aqueous
`solution containing no
`pharmacologically active ingredients,
`intended for bathing or mechanically
`flushing the eye.”
`Boric acid was reviewed by the
`Ophthalmic Panel as an antiinfective
`ingredient and was found to be safe
`when used in the amounts contained in
`OTC ophthalmic drug products;
`however, the Panel found that there
`were insufficient data to prove its
`effectiveness as an ophthalmic
`antiinfective (45 FR 30029). Although the
`Ophthalmic Panel did not evaluate boric
`acid as an ophthalmic astringent, the
`Advisory Review Panel on OTC
`Miscellaneous External Drug Products
`included boric acid in its review of
`astringent drug products. That Panel did
`not find any data demonstrating the
`safety and effectiveness of boric acid
`when used as an OTC astringent active
`ingredient and, therefore, classified it as
`Category II for that purpose. (See the
`Federal Register of September 7,1982; 47
`FR 39426 and 39444.) The comment did
`not submit any data or cite any
`references to show that boric acid in an
`ophthalmic formulation acts as an
`astringent by precipitating protein.
`Therefore, because the agency has no
`
`Page 2 of 18
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`SLAYBACK EXHIBIT 1009
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`

`Federal Register / Vol. 53, No. 43 / Friday, March 4, 1988 / Rules and Regulations
`
`7078
`
`data to establish boric acid as a safe
`and effective astringent in ophthalmic
`drug products, it is not including this
`ingredient as an ophthalmic astringent
`in this final monograph.
`The Ophthalmic Panel found boric
`acid solutions to be “at best
`bacteriostatic when in contact with
`pathogenic bacteria for less than one
`hour” (45 FR 30029). The Panel stated
`that studies were needed to establish
`the usefulness of boric acid in the
`treatment of eye infections, e.g„ the
`bacteriostatic effects of boric acid must
`be demonstrated to be sufficiently rapid
`to be useful in infections of the eye. The
`Panel acknowledged that boric acid and
`its sodium salt are used as a buffer
`system in ophthalmic preparations and
`that this buffer system is effective and
`well tolerated in eye drops. The Panel
`listed boric acid among the buffering
`agents, but not among the preservative
`agents, suitable for the formulation of
`eyewashes and other ophthalmic
`solutions (45 FR 30016). In the tentative
`final monograph for OTC ophthalmic
`drug products, the agency proposed in
`§ 349.20 that eyewash products contain
`no pharmacologically active ingredients,
`but contain water, tonicity agents to
`establish isotonicity with tears, agents
`for establishing pH and buffering to
`achieve the same pH as tears, and a
`suitable preservative agent.
`Boric acid is not being included as an
`active ingredient in this final
`monograph. It is considered an inactive
`ingredient when used as part of a
`buffering system in ophthalmic drug
`products. Inactive ingredients, although
`not included in OTC drug monographs,.
`must meet the requirements of § 330.1(e)
`(21 CFR 330.1(e)) that they be suitable
`ingredients that are safe in the amounts
`administered and do not interfere with
`the effectiveness of the product or with
`tests to be performed on the product.
`Boric acid may be included as a
`buffering agent in the formulation of
`OTC ophthalmic drug products provided
`that it meets the above criteria. (For
`further discussion of inactive
`ingredients, see comment 4 below.)
`4.
`Acknowledging that preservative
`systems were not addressed in the
`tentative final monograph, one comment
`submitted, for the record, data to
`support a sorbic acid/edetate disodium
`(EDTA) preservative system for
`ophthalmic solutions. The data
`consisted of: (1) Summaries of clinical
`investigations in support of sorbic acid/
`EDTA as a suitable preservative system
`for saline and cleaning solutions for
`contact lenses, (2) a bibliography of
`articles on sorbic acid from the scientific
`literature, (3) summaries of animal
`
`testing data, and (4) summaries of
`laboratory testing data. The comment
`stated that the Panel concluded in its
`report that sorbic acid in combination
`with suitable preservatives might be an
`effective preservative system (45 FR
`30020). The comment pointed out that
`the sorbic acid/EDTA combination
`preservative system has been approved
`as safe and effective in ophthalmic
`solutions by FDA’s Office of Medical
`Devices and described a variety of
`currently marketed ophthalmic solutions
`preserved with sorbic acid/EDTA, such
`as various wetting, cleaning, and storage
`solutions for soft (hydrophilic) contact
`lenses. The comment claimed that a
`sorbic acid preservative system is less
`toxic than preservatives such as
`thimerosal, chlorhexidine, and
`quaternary ammonium compounds.
`Although the data submitted were
`compiled from ophthalmic solutions
`used with soft (hydrophilic) contact
`lenses, the comment believed that the
`sorbic acid/EDTA preservative system
`has been extensively studied for use in
`the eye area and that the data support
`this preservative system in general for
`OTC ophthalmic drug products.
`Sorbic acid and EDTA, used as
`preservatives, are inactive ingredients.
`The OTC drug review is an active, not
`an inactive, ingredient review. The OTC
`panels occasionally made
`recommendations with respect to
`inactive ingredients; however, these
`recommendations were made for public
`awareness and were not intended to be
`included in the OTC drug monographs.
`Accordingly, the agency is not reviewing
`the data submitted by the comment in
`this rulemaking proceeding.
`Inactive ingredients, although not
`included in OTC drug monographs, must
`meet the requirements of § 330.1(e) (21
`CFR 330.1(e)) that they be suitable
`ingredients that are safe and do not
`interfere with the effectiveness of the
`product or with tests to be performed on
`the product. In addition, § 330.1(a)
`requires that all products covered by an
`applicable OTC drug monograph be
`manufactured in compliance with
`current good manufacturing practices, as
`established in 21 CFR Parts 210 and 211.
`Section 200.50 (21 CFR 200.50) requires
`all ophthalmic drug products to be
`sterile. Paragraph (b)(1) states that
`liquid ophthalmic drug products
`packaged in multiple-dose containers
`should: “contain one or more suitable
`and harmless substances that will
`inhibit the growth of microorganisms.”
`In conclusion, based on these
`regulations, the agency evaluates
`inactive ingredients used as
`preservatives on an individual basis for
`
`Ophthalmic Drug Products
`
`each ophthalmic drug product and does
`not include such conditions in the
`applicable OTC drug monograph.
`C. Comments on Labeling o f O T C
`5. Several comments contended that
`FDA should not prescribe exclusive lists
`of terms from which indications for use
`for OTC drugs must be drawn, thereby
`prohibiting alternative OTC drug
`labeling terminology to describe such
`indications which is truthful, not
`misleading, and intelligible to the
`consumer. Two comments stated that
`their views on this subject were
`presented to FDA in oral and written
`testimony in connection with the
`September 29,1982 agency hearing on
`the exclusivity policy.
`In the Federal Register of May 1,1986
`(51 FR 16258), the agency published a
`final rule changing its labeling policy for
`stating the indications for use of OTC
`drug products. Under the final rule, the
`label and labeling of OTC drug products
`are required to contain in a prominent
`and conspicuous location, either (1) the
`specific wording on indications for use
`established under an OTC drug
`monograph, which may appear within a
`boxed area designated “APPROVED
`USES”; (2) other wording describing
`such indications for use that meets the
`statutory prohibitions against false or
`misleading labeling, which shall neither
`appear within a boxed area nor be
`designated “APPROVED USES”; or (3)
`the approved monograph language on
`indications, which may appear within a
`boxed area designated “APPROVED
`USES,” plus alternative language
`describing indications for use that is not
`false or misleading, which shall appear
`elsewhere in the labeling. All required
`OTC drug labeling other than
`indications for use (e.g., statement of
`identity, warnings, and directions) must
`appear in the specific wording
`established under an OTC drug
`monograph where exact language has
`been established and identified by
`quotation marks in an applicable
`monograph or other regulation, e.g., 21
`CFR 201.63 or 330.1(g). The final rule in
`this document is subject to the final rule
`revising the labeling policy.
`6. One comment objected to the
`agency’s proposed substitution of the
`word “doctor” for “physician” in OTC
`drug labeling. The comment indicated an
`essential difference between these
`terms. The term “physician” means
`"doctor of medicine,” whereas the term
`“doctor” can refer to any of a broad
`spectrum of academic disciplines. The
`comment recommended that the agency
`specify use of the term "physician,” as
`
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`7079
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`Federal Register / Vol, 53r No. 43 / Friday, March 4, 1988 / Rules and Regulations
`opposed to the term “doctor,” oh OTC
`The agency recognizes the need for
`the warning by stating that it applies
`drug labels to enhance consumers’
`concise wording in the labeling of
`only to solutions, whereas it equally
`awareness of the proper individual they
`ophthalmic drug products that are likely
`applies to ointments. The agency is
`should consult if further medical care is
`to be marketed in small packages. In the
`revising the warning and including it in
`tentative final monograph, the agency
`needed. The comment also stated that it
`§ 349.50(c)(1) of the final monograph to
`revised the Panel’s recommended
`seemed contradictory to label OTC
`read in part as follows: “To avoid
`labeling statements to include only
`drugs with their scientific names (e.g.,
`contamination, do not touch tip of
`essential information. (See comment 18
`container to any surface * *
`This
`ophthalmic hypertonicity agent) and, at
`at 48 FR 29795.) The agency emphasizes
`wording is also included in a warning in
`the same time, be concerned that the
`that its proposed warnings provide
`§ 349.50(c)(2) to accommodate single-use
`common term “physician” would
`information that is essential for the safe
`packages. (See comment 8 below.)
`confuse consumers.
`and effective use of OTC ophthalmic
`The agency concludes that all of the
`In an effort to simplify OTC drug
`drug products by the consumer. The
`warnings included in this final
`labeling, the agency proposed in a
`comment’s suggested combining and
`monograph are essential to ensure the
`number of tentative final monographs,
`“streamlining” of the warnings for OTC
`proper and safe use of OTC ophthalmic
`including the one for OTC ophthalmic
`ophthalmic demulcent and
`drug products by the public. Therefore,
`drug products, to substitute the word
`vasoconstrictor drug products deletes
`all the warnings need to appear on OTC
`“doctor” for “physician” in OTC drug
`some of the warnings proposed by the
`ophthalmic drug products regardless of
`monographs on the basis that the word
`agency. The comment neglected to
`the size of the container. In those
`“doctor” is more commonly used and
`include the statements about “eye pain,”
`instances where an OTC ophthalmic
`better understood by consumers. Based
`“changes in vision,” and "continued
`drug product is packaged in a container
`on comments received to these
`redness” in its suggested warning
`that is too small to include all the
`proposals, the agency has determined
`statements. The Panel felt that this type
`required labeling, the product can be
`that final monographs and any
`of information was necessary in the
`enclosed in a carton or be accompanied
`applicable OTC drug regulation will give
`labeling for these products (45 FR
`by a package insert that contains the
`manufacturers the option of using either
`30024), and the agency concurs. In the
`information complying with the
`the word “physician” or the word
`proposed rulemaking for OTC
`monograph. The labeling provisions in
`“doctor." This final monograph provides
`ophthalmic drug products, the agency
`Part 201 (e.g., §§ 201.10(i), 201.15, 201.60,
`that option. (See § 349.50(a).)
`modified the wording of this information
`201.61, and 201.62) address various
`7.
`Expressing concern about the
`without changing the Panel’s intent in
`requirements for labeling drugs
`labeling “verbiage” proposed in the
`order to make the warning more
`including drugs packaged in containers
`tentative final monograph for OTC
`understandable to consumers. (See
`too small to accommodate a label with
`ophthalmic drug products, one comment
`comment 16 at 48 FR 29794.)
`sufficient space to bear all the
`maintained that the use of this verbiage
`information required for compliance
`The general term "irritation,”
`on small bottles and cartons will deter
`suggested by the comment, does not
`with various regulations. When an OTC
`consumers from reading the labeling,
`ophthalmic drug product is packaged in
`inform the consumer of specific
`thus decreasing the chances that
`a container that is too small or
`symptoms which may indicate a serious
`consumers will be made aware of
`condition requiring medical attention.
`otherwise unable to accommodate a
`important information and warnings.
`label with sufficient space to bear all of
`The comment also suggested deleting
`The comment recommended
`the information required by this final
`the warning “If solution changes color or
`“streamlining” and combining the
`monograph, the required information
`becomes cloudy, do not use.” The
`proposed warning for all ophthalmic
`agency feels that this statement is
`shall appear elsewhere in the label in
`drug products in § 349.50(b)(1) with the
`accord with the labeling requirements in
`necessary because it alerts the
`proposed warnings for ophthalmic
`consumer against using a possibly
`Part 201. Manufacturers are also
`demulcent drug products in § 349.60(c)
`encouraged to print a statement on the
`defective product. The comment’s
`(1) and (2) to read: “Do not touch bottle
`product container label, carton, or
`suggested revision of the warning for
`tip to any surface since this may
`package insert suggesting that the
`ophthalmic demulcent drug products
`contaminate solution. Replace cap after
`consumer retain the carton or package
`deletes the phrase limiting the OTC use
`using. If irritation persists or increases,
`insert for complete information about
`of the product to 72 hours. The agency
`discontinue use and consult a
`the use of the product when all the
`believes that such a limitation is
`physician.” The comment also
`required labeling does not appear on the
`necessary. (See comment 9 below.) The
`recommended that the proposed
`product container label.
`comment’s proposed alternatives do not
`warning in § 349.50(b)(1) and the
`provide the consumer with all of the
`8.
`One comment pointed out that the
`warnings proposed for ophthalmic
`essential warning information; therefore,
`part of the warning proposed in
`vasoconstrictor drug products in
`the warnings for ophthalmic demulcents
`§ 349.50(b)(1) that reads “replace cap
`§ 349.75(c) (l) through (4) be combined
`and vasoconstrictors proposed in
`after using” is inappropriate for
`end revised as follows: “Do not touch
`§§ 349.60(c) and 349.75(c), respectively,
`ophthalmic drug products which are
`bottle tip to any surface since this may
`are being included in this final
`packaged in single-use containers. The
`contaminate solution. Replace cap after
`monograph without the requested
`comment suggested that wording such
`using. If irritation persists for more than
`changes.
`as “Do not reuse—Once opened,
`72 hours, discontinue use and consult a
`discard” be permitted for single-use
`The agency believes that the warning
`Physician. If you have glaucoma, do not
`packages.
`proposed in § 349.50(b)(1) of the
`Ufe e.x9ePt under the supervision of a
`tentative final monograph may be
`The agency agrees that an alternative
`physician. Overuse of this product may
`shortened without changing its intent.
`warning statement is appropriate for
`produce increased redness of the eye.”
`Although the comment’s suggested
`single-use ophthalmic drug products.
`. comment contended that these
`rewording shortened the warning, it also
`Therefore, in this final monograph, the
`revisions would convey the intended
`changed the emphasis of the warning by
`agency is specifying that the warning in
`message in a concise manner.
`rearranging it and changed the intent of
`§ 349.50(c)(1) applies to multi-use
`
`Page 4 of 18
`
`SLAYBACK EXHIBIT 1009
`
`

`

`Federal Register / Vol. 53, No. 43 / Friday, March 4, 1988 / Rules and Regulations
`
`7080
`
`Once opened, discard.”
`
`methylcellulose).
`
`containers and is including an
`alternative warning for single-oise
`packages in § 349.50(c)(2) as follows:
`For ophthalmic drug products
`packaged in single-use containers. “ To
`avoid contamination, do hot touch tip of
`container to any surface. Do not reuse.
`9.
`One comment recommended
`deletion of the phrase limiting use to 72
`hours from the warning for OTC
`ophthalmic demulcent drug products
`proposed in § 349.60(c)(1), which reads:
`“If you experience eye pain, changes in
`vision, continued redness or irritation of
`the eye, or if the condition worsens or
`persists for more than 72 hours,
`discontinue use and consult a doctor.”
`The comment argued that there are no
`medical reasons for restricting the use of
`an ophthalmic demulcent product and
`noted that, currently, ophthalmic
`demulcent products, particularly those
`used to relieve dry eye syndrome, are
`recommended for use as often as
`necessary. The comment also pointed
`out that contact lens lubricating
`solutions, which are used as often as
`necessary, may contain the same active
`ingredient as ophthalmic demulcent
`products (i.e., hydroxypropyl
`In the tentative final monograph, the
`agency combined and modified two long
`warning statements recommended by
`the Panel and proposed the above
`warning for all OTC ophthalmic drug
`products except hypertonicity agents
`and eyewashes. (See comment 16 at 48
`FR 29794.) In doing so, the agency
`retained the Panel’s recommendation
`that consumers should not self-medicate
`for more than 72 hours without
`consulting a doctor. This warning was
`combined with information about
`discontinuing use and consulting a
`doctor if the condition worsens or
`persists during this time, and with
`information on certain conditions under
`which use should be discontinued.
`The agency also discussed a 72-hour
`limitation in the tentative final
`monograph. (See comment 17 at 48 FR
`29794.) The agency disagrees with the
`comment’s contention that OTC
`ophthalmic demulcent drug products
`may be use