63554 Federal Register I Vol. 56,. No. 233 I Wednesda,y, December 4, 1991 I R~les and Regulation~
`
`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES.
`
`Food and Drug' Administration
`21 CFR Parts s1o and 358
`.
`[Docket No. 82N-02'!4]
`
`.
`
`RIN 0905-AAOS
`
`Dandruff, Seborrheic Dermatitis, and
`Psoriasis Dmg Products for Over-the(cid:173)
`Counter Human Use; final Monograph
`AGENCY: Food and Drug Administration,
`HHS.
`ACTION: Final rule.
`
`SUi\UtliARY:.The Food andDrug
`Administration (FDA) is issuing a final
`rule in the form of a final monograph·
`establishing conditions under which
`over-the-counter (OTC) dandruff, .
`seborrheiC dermatitis, arid psoriasis' 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 all new data· and
`information on dandruff, seborrheic
`dermatitis, and psoriasis 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.
`EFFECTIVE DATE: December 4, 1992.
`FOR FURTHER INFORMATION CONTACT:
`William E. Gilbertson, Center fm: Drug
`Evaluation and Research (HFD-210),
`Food and Drug Administration, 5600
`Fishers Lane, Rockville, MD 20857, 301~
`295-8000.
`SUPPLEMENTARY INFORMATION: In the
`Federal Register of December 3, 1982 ( 47
`FR 54646), 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
`dandruff, seborrheic dermatitis, and
`psoriasis drug products, together with
`the recommendations of the Advisory
`Review Panei on OTC Miscellaneous
`External Drug Products (Miscellaneous
`External Panel), which was the advisory
`review panel responsible for evaluating
`data on the active ingredients in these
`drug classes. Interested persons were
`invited to submit comments by March 3,
`1983. Reply comments in response to
`comments filed in the initial comment
`period could be submitted by April4,
`1983.
`In the Fed!;}ral Register of February 8,
`1983. (48 FR 5761), the agency advised
`that it had extended the comment period
`until April4, 1983, and the reply
`·
`comment period to May 4, 1983, on the
`
`advance not\!:;e of proposed. rulerp.aking .
`for OTC dandruff, seborrheic dermatitis,
`and psoriasis drug products to allow for
`consideration o£ additional.data and
`information ..
`In accordance with § 330.10(a)(10), the
`data and information considered by the
`Panel, after deletion of a small amount
`of trade secret information, were placed
`on display in the Dockets Management
`Branch (HFA-305], Food and Drug
`Administration, currently located in rm.
`1-23, 12420 Parklawn Drive, Rockville,
`MD 20857.
`The agency's proposed regulation, in
`the form of a tentative final monograph,
`for OTC dandruff, seborrheic dermatitis,
`and psoriasis drug products was
`.
`published in the Federal Register of July
`30, 1986 (51 FR 27346). Interested
`persons were invited to file by
`September 29, 1985, written comments,
`objections, or requests for oral hearing
`before the Commissioner of Food and
`Drugs regarding the proposal. Interested
`persons wer,e invited to file comments
`on the agency's economic impact
`determination by November 28, 1986.
`New data could have been submitted
`until July 30, 1'987, and comments on the
`new data until September 30, 1987.
`In the Federal Register of October 1,
`1986 (51 FR 35003), the agency advised
`that it had extended the comment period
`until October 29, 1986, on the proposed
`rulemaking, to allow for greater
`participation by interested persons.
`Final agency action occurs with the
`publication of this final monograph,
`which is a final rule establishing a
`monograph for OTC dandruff,
`seborrheic dermatitis, and psoriasis drug
`products.
`The OTC drug procedural regulations
`(21 CFR 330.10) provide that any testing
`necessary to resolve the safety or
`effectiveness issues that formerly
`resulted in a Category III classification,
`and submission to FDA of the results of
`that testing or any other data, must be
`done during the OTC drug rulemaking
`process before the establishment of a
`final monograph. Accordingly, FDA is
`no longer using the terms "Category I"
`(generally recognized as safe and
`effective and not misbranded),
`"Category II" (not generally recognized
`as safe and effective or misbranded),
`and "Category HI" {available data are
`insufficient to classify as safe and
`effective, and further testing is required)
`at the final monograph stage, hut is
`using instead the terms "monograph
`conditions" (old Category I) and
`"nonmonograph conditions" (old
`Categories 1I and III).
`In the proposed regulation for OTC
`dandruff, seborrheic dermatitis, and
`psoriasis drug products (51 FR 27346),
`
`the agency advised that the conditions
`under which the drug products that are
`subject to this monograph will be
`generally recognized as safe and
`effective and not misbranded
`(monograph conditions) will be effective
`12 months after the date of publication
`in the Federal Register, Therefore; on or
`after December 4, 1992, no OTC drug
`product that is subject to the monograph
`and that contains a nonmonograph
`condition, i.e., a conditionthqt would
`cause the drug to be not generally
`recognized as safe and effective or to be
`misbranded, may be initially introduced
`or initially delivered for introduction
`into interstate commerce unless .it is the
`subject of an approved application.
`Further, any OTC drug product subj.ect
`to this monograph that is repackaged or.
`relabeled after the effective date of the
`monograph must be in compliance with
`the monograph regardless of the date
`the product was initially introduced or
`initially delivered for introduction into
`interstate commerce. Manufacturer$ are
`encouraged to comply voluntarily with
`the monograph at the earliest possible
`date.
`In response to the proposed rule on
`OTC dandruff, seborrheic dermatitis,
`and psoriasis drug products, six
`manufacturers, two trade associations,
`one medical association, and one health
`care professional submitted comments.
`Copies of the comments received are on
`public display in the Dockets
`Management Branch (address above).
`Any additional information that has
`come to the agency's attention since
`publication of the proposed rule is also
`on public display in the Dockets
`Management Branch.
`All "OTC Volumes" cited throughout
`this document refer to the submissions
`made by interested persons pursuant to
`the call-for-data notices published in the
`Federal Register of November 16, 1973
`(38 FR 31697) and August 27, 1975 (40 FR
`38179) 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
`1. One comment contended that OTC
`drug monographs are interpretive, as
`opposed to substant~ve, regulations, The
`comment referred to statements on this
`issue submitted. earlier to other OTC
`drug rulemaking proceedings.
`The agency address,ed this issue in
`paragraphs 85 through 91 of the
`
`

`
`Federal Rt;!gister / Vol. 56, No. 233 / Wednesday, Dece,mber 4, 1991 I Rules and Regulations 63555
`
`preamble to the procedures for
`classification of OTC drug products, ...
`published in the Federal Register of May
`11, 1972 .(37 FR 9464 at 9471 to9472); in
`paragraph 3 of the preamble to the
`tentative final monograph for OTC
`antacid drug products, published in the
`Federal RegisteJ." of November 12, 1973
`(38 FR 31260); and in paragraph 1 of the
`preamble to the tentative final
`monograph in the present proceeding (51
`FR 27346 at27347). FDA reaffirms the
`conclusions stated in those documents.
`Court decisions have confirmed the
`agency's authority to issue substantive
`regulations by informal rulemaking.
`(See, e:g., National Nutritional Foods
`Association v. Weinberger, 512 F.2d 688,
`696-698 (2d Cir. 1975) and National
`Association of Pharmaceutical
`Manufacturers v. FDA, 487 F. Supp. 412
`(S.D.N.Y. 1980), aff'd, 637 F.2d 887 (2d
`Cir. 1981).)
`2. One comment recommended that
`any use of the word "dandruff" in
`labeling be limited only to drug products
`and not be allowed for cosmetic
`products. The comment contended that
`the description "remove(s) loose flakes
`of dandruff' will create an impression in
`the mind of t.IJe consumer that the
`product being used is designed to
`mitigate or treat a.disease; and thus is a
`drug. Two other comments contended
`that references to dandruff, if allowed,
`on cosmetic shampoos can lead to
`consumer confusion. The comments
`disagreed with the following statement
`in the proposed rule:
`• • • The product's intended use,
`therefore, determines whether it is a "drug," a
`"cosmetic," or both. This intended use may
`be inferred from the product's labeling,
`promotional material, advertising, and any
`other relevant factor. * • • When the use of
`the term "dandrufr' deals only with
`appearance and not with the treatment or
`prevention of the underlying disease
`condition, as in the context that a product
`removes loose flakes of dandruff or cleans
`the hair of dandruff flskes or scales, the
`product is cosmetic in nature. (See 51 FR
`27346 at 27347.)
`The comments requested the agency
`to reconsider its position "that the mere
`use of the word 'dandruff does not
`automatically render a shampoo a
`drug." In support of their requests, the
`comments provided the results of a
`survey (Ref. 1) that assessed 100
`consumers' interpretations of the
`statement "Shampoo X removes loose
`flakes of dandruff and dears the hair of
`dandruff flakes or scales." The target
`audience was an equal number of men
`and women, aged 18 to. 54 years, who
`used a dandruff shampoo for the control
`of dandruff in the past year. Based on
`the question asked, 71 percent of the
`
`responders stated that the product "is
`an antidandruff shampoo," ,72 percent
`considered it to be ;,a dandruff . . ..
`treatment," and 76 percent stated it
`"controls dandruff." On the negative
`side, 52 percent felt that the product
`would not "prevent dandruff." The •
`comments contended that the results of·
`the survey showed that consumers
`overwhelmingly interpreted the removal
`of dandruff flakes as synonymowi with
`"antidandruff," "dandruff control
`shampoo," and "dandruff treatment."
`The comments concluded that the
`survey shows that the type of claims
`being allowed for "cosmetic shamp.oos"
`actually describe antidandruff OTC drug
`products.
`A fourth comment ai:gued that the
`results .of the consumer survey do not
`support the argument that. claims
`referring solely to a product's
`effectiveness in cleaning the hair, a
`traditional co.smetic claim, are also
`claims that the product is.effective for
`drug purposes. The comment argued that
`a consumer survey may provide· some
`evidence of how consumers interpret a
`particular advertising or labeling claim,
`but it is not determinative of the
`regulatory status of the product making
`that claim.
`The comment contended that the
`consumer survey had a number of
`defects and, thus, its results are
`unreliable. The comment described in·
`detail the purported defects in the study.
`The comment also stated that the claim
`presented to the consumers was that the
`shampoo "cleared the hair," not
`"cleaned the hair," of dandruff flakes.
`The comment argued that the word
`"dear" suggests a more permanent and
`more drug-like effect and that the
`researcher's choice of terminology may
`have skewed the results. The comment
`concluded that the survey did not show
`that consumers perceive the shampoo to
`have clear-cut therapeutic effects that
`treat a pathologic condition, because the
`survey never asked that precise
`question.
`i\nother comment raised issues about
`the validity of the methodology of the
`survev. These issues included whether
`"cont~ol'' questions should have been
`used to screen out certain respondents,
`whether screening questions were
`neutral, whether terms should have been
`defined for the respondents, whether
`any effort should have been made to
`ascertain the consumers' understanding
`of certain terms, and whether the
`researcher's choice of terminology niay
`have influenced the results.
`In the tentative final monograph, the
`agency stated that when the use Qfthe
`term "dandruff' deals only with
`appearance and not with the treatment
`
`or prevention of the underlying disease
`condition:, sud1 as a statement that a
`. product removes loose flakes of
`dandruff or deans the hair. of dandruff.
`flakes or scales, the product is a
`cosmetic (51 FR 27346 at 27348). In the
`survev mentioned above, consumers
`were asked to. interpret the statement .
`"Shampoo X removes loose flakes. of
`dandruff and clears the hair of dandruff
`flakes or·scal.es." The agency considers
`each Clause of this statement to be a
`· cosmetic claim, because removal of
`loose flakes and dearing the hair are
`actions of .cleansing, beautifying, or .
`promoting attractiveness within the
`definition.of cosmetic in section 201(i) .of •
`the Federal Food, Drug, and Cosmetic
`Act(the actj (21 u.s.c. 321(i)). As stated
`in the tentative final monograph, any
`use of the term dandruff thatwould
`make or imply a claim for the · ·
`/
`prevention, control, or treatment of
`dandruff b~yond the simple mechanical
`removal of flakes and scales would
`· render the product a drug (51 FR 27346
`at 2734:8). As discussed in comment 3
`·. below, dandruff removal products can
`be drugs, cosmetics, or both ..
`
`References
`(1} Shampoo Product Statement Study,
`Kornhauser and Calene, Inc., October 1986, in·
`Comment C00031, Docket No. 82N-n214,
`Dockets Management Branch.
`3. One comment disagreed with the
`agency's position .of prohibiting cosmetic
`claims from appearing in any portion of
`the labeling that is required by the
`monograph. The comment stated that so
`long as the labeling is truthful and not
`misleading, the joint placement of
`information about both the cosmetic and
`drug claims of a product should be
`permitted anywhere on the labeling. The
`cominent contended that although
`dandruff, seborrheic dermatitis, and
`psoriasis are medical conditions treated
`with drug products, these products may
`also have important cosmetic functions.
`For example, a dandruff shampoo may
`have a cleansing or shampoo [cosmetic)
`function, and a relief of itching, flaking
`and scaling (drug} function. The
`comment argued that consumers need
`both kinds of information and urged the
`agency to expressly allow the joint
`placement of drug and cosmetic claims
`in a dandruff, seborrheic dermatitis. and
`psoriasis product used both as a drug
`and as a cosmetic. The comment
`contended that if this information iNere
`to appear on entirely different portions
`ofthe label, consumers could be
`confused and misled as to what the
`product will do. Ihe comment requested
`that the following language be added to
`all relevant final regulations: "The
`
`

`
`'63556 Federal Register l Vol. 56, No. 233 I Wednesday,· Oecember 4, 1991 I Rules and R~gulations
`
`agency emphasizes that OTC drug
`monographs do not pertain to cosmetic
`terminology contained on such products
`and do not preclude in anyway the use
`of truthful andnonmisleading cosmetic
`terminology in the. labeling of cosmetic/
`drug products:·
`A final OTC drug monograph cover-s
`only the drug use ef the active
`ingredients listed therein. The
`concentration range limitations,
`statements of identity, indications,
`warnings, and directions established for
`these ingredients in the monograph do
`not apply to the use of the same
`ingredients in products intended solely
`as cosmetics. However, if a product is
`intended for both drug and cosmetic use,
`it must conform to the requirements of_
`the final OTC drug monograph as well
`.as applicable cosmetic labeling
`requirements.
`In addition to the indications allowed
`for OTC dandruff, seborrheic dermantis,
`and psoriasis drug products, such
`products may also bear appropriate
`labeling for cosmetic uses, in conformity
`with section 602 of the act (21 U.S.C.
`362) and the provisions of 21 CFR part
`701. In accordance with the revised
`labeling requirements for OTC drug
`products (21 CFR 330.1(c)[2)), it is the
`agency's position that cosmetic claims
`may not appear within the boxed area
`designated "APPROVED USES." As
`discussed at 51 FR 16264 (paragraph 14),
`cosmetic terminology is not reviewed.
`and approved by FDA in the OTC drug
`monographs and therefore could not be
`placed in the box. Cosmetic claims may
`appear elsewhere in the labeling, but not
`in the box, should manufacturers choose
`the labeling alternative provided in
`§ 330.1(c)(2)(i) or 2(iii) for labeling
`cosmetic/ drug products.
`The agency does not disagree with the
`comment's statement that consumers
`need both drug and cosmetic
`information about these products.
`However, the agency does not agree that
`if the drug and cosmetic information
`appears in different places in the
`labeling consumers would necessarily
`be confused or misled. The agency
`believes the manner in which the
`information is presented, as well as its
`location, is important to consumer
`understanding.
`Although the agency does not
`specifically prohibit commingled drug
`and cosmetic labeling (other than in the
`Indications section), the agency believes
`that information about the product's
`claims should be appropriately
`described so that consumers will be
`readily able. to differentiate th!'l drug and
`cosmetic aspects of the labeling. If
`commingled drug and cosmetic labeling
`claims ar1_3 confusing or misleading, ths
`
`product's labeling may be misleading
`within the meaning of the act and the
`product misbranded under sections
`502(a) or 602(a) of.the act. This position
`is consistent with that stated in the final
`rule for OTC topical acne drug products
`published in the Federal Register of
`August 16, 1991 {56 FR 41008 at 41017).
`Accordingly, the agency is not adding
`the comment's suggested language to
`this final monograph.
`4. One comment stated that the
`Miscellaneous External Panel limited its
`review of OTC dandruff, seborrheic
`dermatitis, and psoriasis drug products
`to determining which ingredients are
`safe and effective for "controlling" these
`conditions and ignored the symptomatic
`relief that may or may not be related to
`treatment of the condition. The comment
`interpreted the definitions for OTC drug
`products that "control" dandruff,
`seborrheic dermatitis, and psoriasis to
`include those having only symptomatic.
`relief and/or those having curative
`action.
`The Panel stated (47 FR 54646 at
`54653}, and the agency agrees, that OTC
`drugs for dandruff, seborrheic
`dermatitis, and psoriasis do not cure,
`but with regular use at best can only
`control or relieve the symptoms of these
`conditions; The indications for the use
`of these products in § 358.750(b} of this
`final monograph dearly establish that
`they are used to "control" or "relieve the
`symptoms or· dandruff, seborrheic
`dermatitis, and psoriasis. The terms
`"relief" or "control" are used
`synonymously to describe the action of
`the products. The indications state that
`the product's action is on the symptoms
`of the condition or describe the
`symptoms as itching, irritation, redness,
`flaking, and scaling associated with
`dandruff, seborrheic dermatitis, and
`psoriasis.
`5. One comment suggested that the
`monograph provide for the use of
`emollients and/ or lubricants in the
`treatment of psoriasis. In support of its
`position, the comment cited statements
`from a reference discussing treatment of
`psoriasis: "The simplest forms of
`treatment-lubricants • • • should be
`tried first * * *" and "Lubricatin<>
`creams, hydrogenated vegetable"
`(oooking) oils, or white petrolatum are
`applied • • • while the skin is still
`damp after bathing" (Ref. 1). The
`comment added that these materials are
`classified as emollients in another
`textbook and are described as fats or
`oils used for their local action.on the
`skin (Ref. 2). Stating that the use of such
`ingredients is widely regarded as a safe,
`effective, economical means of treating
`psoriasis, the comment complained that
`none of those types of ingredients have
`
`been included in the tentative final
`monograph. The comment further
`contended that because of demonstrated
`, problems and expense of one or more· ·
`"active" ingredients listed in the
`tentative final monograph, the public is
`poorly served by the omission of
`emollients from the monograph.
`The agency has no basis on which to
`grant the comment's request. No data
`were submitted with the textbook
`statements in support of the use of an
`emollient and/ or lubricant in the·
`treatment of psoriasis. If adequate
`supporting data are submitted to the
`agency in the form of a petition to
`amend the final monograph, the
`monograph could be amended to include
`emollients and/or lubricants.
`References
`(1) Berkow, R., editor, "The Merck Manual
`of Diagnosis and Therapy," 14th ed., Merck
`Sharp and Dohme Research Laboratories,
`Jll.ahway, NJ, p. 2054, 1982.
`.
`(2) Swinyard, E. A., "Surface-Acting
`Drugs," in "The Pharmacologic Basis of
`Therapeutics," 5th ed., edited by L. S.
`Goodman and A. Gilman, MacMillan
`Publishing Co., New York, p. 947,1975.
`B. Comments on Active Ingredients
`16. One comment suggested that any
`product containing boric acid or its salt
`approved for OTC use be labeled "not
`for use in children," "not for use on
`broken or severely irritated skin," and/
`or "for topical use only." The comment
`stated that boric acid poisoning has
`been reported after accidental ingestion
`or from absorption through the skin (Ref.
`1).
`The Panel concluded that borate
`preparations are not safe, and data were
`lacking to permit their final
`classification as effective for OTC
`topical use for controlling dandruff or
`seborrheic dermatitis (47 FR 54646 at
`54667}. In response to the Panel's report,
`one comment requested a reevaluation
`of the Panel's conclusions, and called
`attention to a 2-year feeding study on
`rats and dogs that was not considered
`by the Panel. The agency reviewed all
`available data on borates, including the
`reports of other panels. Based upon that
`reevaluation, the agency concluded in
`the tentative final monograph that there
`was ample evidence to support the
`safety of up to 1 percent borates for
`OTC topical use in dandruff and
`seborrheic dermatitis preparations, but
`that the effectiveness of borates for the
`treatment of those conditions has not
`been demonstrated (51 FR 27346 at
`27351). No additional effectiveness
`studies were submitted. Accordingly,
`boric acid and sodium borate were
`included in a final rule published in the
`
`

`
`Federal Register I Vol. 56, No. 233 I Wednesday, December 4, 1991 I Rules and Regulations 6355'1
`
`Federal Register of N:ovember.7, 1990 (55
`FR 46914 at 46917) that listed certain
`OTC active ingredients that lue· not
`ge_neraHy recognized as safe and
`effe.ctive. (See 21 CFR 310.545(a)(7}.}
`Thus, there is no need at the present
`time to further consider inclusion of the
`comment'srequested labeling in t.,is
`monograph. •
`
`Reference
`(l)Rubenstein, A. D., and D. M. Musher,
`"Epidemic Boric Acid Poisoning Simulating
`Staphylococcal Toxic Epidermal Necrolysis .
`of the Newborn Infant: Ritters Oisease,'' The
`Journal of Pediatrics, 77:834-887, 1970.
`
`7. One comment inquired whether
`, there is any evidence that chloroxylenol
`is effective as a topical antifungal agent
`Referring to a discussionin the tentative
`final monograph (51 l\R27346 at 27351)
`that the Advisory Review Panel on
`Antimicrobial II Drug Products had
`concluded that chloroxylenol is safe for
`OTC use as a topical antifungal, the
`comment noted thatthere was no
`discussion of effectiveness.
`The issue raised in the tentative final
`monograph for OTC dandruff,
`seborrheic dermatitis, and psoriasis drug
`products only concerned the safety of
`chloroxylenoL In another OTC drug
`rule making, the Advisory Review Panel
`on Antimicrobial II Drug Products
`concluded that there were insufficient
`data available to permit final
`classification of the effectiveness of
`chloroxylenol for OTC topical antifungal
`use (47 FR 12480 at 12533). A study
`. submitted in response to the Panel's
`· report on topical antifungal drug
`products was inadequate to show
`effectiveness, and in the tentative final
`monograph for OTC antifungal drug
`products, chloroxylenol remained in
`Category HI for effectiveness (54 FR
`51135 at 51139].
`The Miscellaneous External Panel
`evaluated chloroxylenolfor controHing
`dandruff and seborrheic dermatitis (47
`FR 54645 at 54672 to 54673]. The Panel
`recognized one theory that dandruff is
`caused by Pityrosporum ovale (a yeast(cid:173)
`like fungus resident to the scalp] (47 FR
`54651 and 54653]. However, based on the
`submitted studies, the Panel stated that
`chloroxyleno! was shown to have an
`antimicrobial effect on selected bacteria,
`but it had little or no effect on fungi and
`yeast (47 FR 54673). The Panel
`concluded~ therefore, that addition!ll
`data are needed to demonstrate the
`, ·effectiveness of chloroxylenol for
`controlling dandruff and seborrheic
`dermatitis. The agencY did not receive
`any submissions of effeCtiveness data on
`chloroxylenol in response to the Panel's
`report or the 'tentative final monograph.
`
`Therefore, chloroxylenol was ·also
`included with those OTC drug active
`ingredients not generally recognized as
`safe and effective in 21 CFR
`310.545(a)(7). (See comment 6 above).
`8. One comment agreed with the
`definition and concentration limits
`proposed for coal tar in.§ 358.703(a) of
`the tentative final monograph, i.e., the
`concentration of the coal tar portion of
`the final product should be in a relative
`concentration range of 0.5 to 5 percent
`coal tar. Noting that a variety of coal tar
`solutions an:d fractions are used in OTG
`dandruff, seborrheic de'rmatitis~ and
`psoriasis drug products,,the-comment
`contended there should be a labeling
`requirement'to state the actual coal tar
`equivalent concentration contained in
`any coal tar solution, derivative, or
`fraction. As an example; the comment
`. stated that a preparation containing a 10-
`percent solution of coal tar U.S.P. would
`be listed as "10 percent LCD (2 percent
`Coal Tar U.S.P. equivalent}." The
`comment concluded that this approach
`,would allow consumers to compare
`'"apples with apples" when comparing
`two coal tar-containing preparations.
`The agency agrees with the comment
`that information concerning the coal tar
`equivalent concentration is useful and
`would allow consumers to be able to
`evaluate the comparative strengths of
`coal tar-containing drug products.
`Although section 502( e) of the act
`requires statement of the active
`ingredient in the labeling of OTC drug
`products, it only requires labeling of
`quantitative information for a number of
`named ingredients and their derivatives,
`alcohol, and prescription drugs. Agency
`regulations in 21 CFR 1.21(a)(1) provide
`that labeling of a drug shaH be deemed
`misleading if it fails to reveal facts that
`are "material in light of other
`representations made or suggested by
`statement, word, design, device or amy
`combination thereof." Other agency
`regulations in 21 CFR 201.10(c) state that
`"the labeling of a drug may be
`misleading by reason [among other
`reasons) of: * • • [2] Failure to reveal
`the proportion of, or other fact with
`respect to, an ingredient present in such
`drug, when such proportion or other fact
`is material in the light of the
`representation that such ingredient is
`present in such drug."
`In the case of coal tar, the agency
`believes that, without the equivalent
`concentration of coal tar appearing in
`the product's labeling, the labeling could
`be misleading. Accordingly, the agency
`is requiring in this final monograph that
`the labeling of OTC drug products for
`the control of dandruff, seborrheic
`dermatitis, and psoriasis state ~he
`equivalent concentration of coal tar
`
`contained in any coal tar solution,
`derivative, or fraction used as. the source
`of the coal tar in the product. The
`concentration for coal tar in this final
`monograph will now read as follows in
`§ 358.710(a)(1), (b)(1) and (c)(1): "Coal
`tar, 0.5 to 5 percent When .a coal tar
`.
`solution, derivative. or fraction is used
`as the source of the coal tar, the labeling
`shall specify the identity and
`·
`concentration of the coal tar .source used
`and the concentration ofthe coal tar
`present in the final product."
`The comment described a product
`named LCD. LCD is an abbreviation for
`Liquor Carbonis Detergens, which is
`(;oal Tar Topical Solution, U.S.P. (Ref.
`1). This solution is a 20-percent solution
`of coal tar i.n alcohoL The product
`described by the comment would. be
`labeled as follows: "Contains 10 percent
`of coal tar topical solution, equivalent to
`2 percent coal tar." The determination of
`the coal tar concentration in the final
`product is made as follows: When 10
`percent of a final product constitutes
`Coal Tar Topical Solution, U.S.P., that
`means that the final product contains.ll)
`percent of the U.S.P. solution (20% coali
`tar), or 2 percent coal tar. The coal tar
`topical solution appears in the labeling
`as the actual active ingredient used in
`the product, while the equivalent coal
`tar percentage tells the user of the
`product the actual amO'ant of coal tar
`that is present.
`
`Reference
`(1] "The United! States Pharmacopeia
`XXXI-The National Formulary XVII," The
`United States Pharmacopeia! Convention
`Inc., Rockville, MD, p. 341, 1989.
`9. One comment strongly
`recommended that hydrocortisone in
`OTC drug products not be increased
`above 0.5 percent The comment stated
`that as a manufacturer of
`hydrocortisone creams it was aware
`that dermatologists are reporting seeing
`many patients who could have "run into
`trouble" from use of 0.5 percent
`hydrocortisone. The comment
`contended that increasing the strength
`of OTC hydrocortisone above 0.5
`percent would create an even greater
`· safety probl.em. Another comment also
`recommended that 1 percent
`hydrocortisone not be included in OTC
`drug products in any form.
`In the Federal Register of July 30, 1986
`(51 FR 27360), the agency deferred
`hydrocortisone from the rulemaking for
`OTC dandruff, seborrheic dermatitis,
`and psoriasis drug products to the
`rulemaking for OTC external analgesic
`drug products. Atthat time, the agency
`amended the tentative final monograph
`for OTC external analgesic drug
`
`

`
`63558 Federal Register I Vol. 56, No. 233 I Wednesday, December 4, 1991 I Rilles and Regulations
`
`produc'ts to add seborrheic dermatitis
`and psoriasis to the list of condHions for
`which hydrocortisone is safe and
`effective in providing symptomatic relief
`rather than to include hydrocortisone as
`an ingredient in the tentative final
`monograph for OTC dandruff,
`seborrheic dermatitis, and psoriasis drug
`products (51 FR 27363). Since the
`comments were submitted, the agency
`published another amendment of the
`tentative final monograph on OTC
`external analgesic drug products on
`February 27, 1990 (55 FR 6932), in which
`it proposed to increase the
`concentrations for OTC hydrocortisone
`and hydrocortisone acetate from the
`current levels of 0.25 to 0,5 percent to
`from 0.25 to 1 percent. The agency's
`proposal to switch above 0.5 to 1
`·percent hydrocortisone to OTC
`marketing status was based on an
`extensiv.e review of safety data. The
`comments did not present any evidence
`that 0.25 to 1 percent concentrations
`were potentiaHy unsafe. The one
`comment did not provide any specific
`information about the types of problems
`with hydrocortisone that are being
`reported by dermatologh;;ts. However.
`the agency has received numerous
`comments to the proposal that was
`published in the Federal Register of
`February 27, 1990. After these comments
`have been evaluated, the agency's final
`determination on OTC use of
`hydrocortisone above 0.5 up to 1 percent
`will be stated in a future issue of the
`Federal Register, as part of the
`rulemaking for OTC external analgesic
`drug products.
`10. One comment noted that the Panel
`classified povidone-iodine in Category I
`for safety but ln Category m for
`effectiveness (47 FR 54646 at 54679), and
`the agency proposed the same
`classification in the tentative final
`monograph for OTC dandruff,
`seborrheic dermatiti