[Federal Register: June 4, 2003 (Volume 68, Number 107)]
[Rules and Regulations]               
[Page 33362-33381]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04jn03-10]                         

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 310, 347, and 352

[Docket Nos. 78N-0021 and 78N-021P]
RIN 0910-AA01

 
Skin Protectant Drug Products for Over-the-Counter Human Use; 
Final Monograph

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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

SUMMARY: 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) skin protectant drug products are generally 
recognized as safe and effective and not misbranded as part of the 
ongoing review of OTC drug products conducted by FDA. The final 
monograph includes OTC skin protectant drug products for minor cuts, 
scrapes, burns, chapped skin and lips, poison ivy, poison oak, poison 
sumac, and insect bites. 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 skin protectant drug products for these specific 
uses that have come to the agency's attention. This final rule amends 
the regulation that lists nonmonograph active ingredients by adding 
those OTC skin protectant ingredients that have been found to be not 
generally recognized as safe and effective. This final rule also lifts 
the stay of 21 CFR part 352 (published at 66 FR 67485, December 31, 
2001) to amend the final monograph for OTC sunscreen drug products to 
include sunscreen-skin protectant combination drug products, and then 
stays Sec.  347.20(d) (21 CFR 347.20(d)) and part 352 until further 
notice in the Federal Register.

DATES: Effective Date: This rule is effective June 4, 2004.
    Compliance Dates: The compliance date for products subject to parts 
310 and 347 (21 CFR parts 310 and 347) with annual sales less than 
$25,000 is June 6, 2005. The compliance date for all other products 
subject to parts 310 and 347 is June 4, 2004. The compliance date for 
combination products containing skin protectant and sunscreen active 
ingredients in Sec.  347.20(d) and for all products subject to part 352 
is stayed until further notice.
    Comment Date: Submit written or electronic comments on specific 
labeling items discussed in section X of the SUPPLEMENTARY INFORMATION 
section of this document by September 2, 2003.

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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments
.

FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, 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 August 4, 1978 (43 FR 34628), FDA 
published an advance notice of proposed rulemaking to establish a 
monograph for OTC skin protectant drug products, together with the 
recommendations of the Advisory Review Panel on OTC Topical Analgesic, 
Antirheumatic, Otic, Burn, and Sunburn Prevention and Treatment Drug 
Products (the Panel), which was the advisory review panel responsible 
for evaluating data on the active ingredients in this drug class (Sec.  
330.10(a)(6) (21 CFR 330.10(a)(6))).
    In the Federal Register of February 15, 1983 (48 FR 6820), FDA 
published the proposed regulation for OTC skin protectant drug products 
in the form of a tentative final monograph (TFM). In the Federal 
Register of October 3, 1989 (54 FR 40808), the agency published a 
document to amend the TFM to include OTC drug products for poison ivy, 
oak, and sumac and for the treatment and/or neutralization of insect 
bites. This final rule completes the TFMs published on February 15, 
1983, and October 3, 1989, amends the final monograph for OTC skin 
protectant drug products used as astringents in part 347 published on 
October 21, 1993 (58 FR 54458), and incorporates the name change 
(``witch hazel'') published in the Federal Register of June 3, 1994 (59 
FR 28767).
    In the Federal Register of May 10, 1993 (58 FR 27636), the agency 
issued a final rule establishing that certain active ingredients, 
including some skin protectant active ingredients, in OTC drug products 
are not generally recognized as safe and effective or are misbranded. 
These skin protectant ingredients are listed in Sec.  310.545(a)(18). 
This final rule adds several ingredients to that section.
    On or after 12 months after date of publication in the Federal 
Register, and 24 months after date of publication in the Federal 
Register, for products with annual sales less than $25,000, except 
combination products containing skin protectant and sunscreen active 
ingredients, and for combination products containing skin protectant 
and sunscreen active ingredients, no OTC drug product that is subject 
to this final rule and that contains a nonmonograph condition may be 
initially introduced or initially delivered for introduction into 
interstate commerce unless it is the subject of an approved new drug 
application or abbreviated new drug application. Further, any OTC drug 
product subject to this final rule that is repackaged or relabeled 
after the effective dates of the final rule must be in compliance with 
the monographs regardless of the date the product was initially 
introduced or initially delivered for introduction into interstate 
commerce. Manufacturers are encouraged to comply voluntarily as soon as 
possible.
    All ``OTC Volumes'' cited throughout this document refer to 
information on public display in the Dockets Management Branch (see 
ADDRESSES).

II. The Agency's Conclusions on the Comments

    (Comment 1) One comment stated its continuing position that OTC 
drug monographs are interpretive, as opposed to substantive, 
regulations.
    The agency addressed this issue and reaffirms its conclusions 
stated in paragraphs 85 through 91 of the preamble to the procedures 
for classification of OTC drug products (37 FR 9464 at 9471 to 9472, 
May 11, 1972); in paragraph 3 of the preamble to the TFM for OTC 
antacid drug products (38

[[Page 33363]]

FR 31260, November 12, 1973); and in paragraph 1 of section I of the 
preamble to the TFM in the present proceeding (48 FR 6820 at 6821).
    (Comment 2) One comment requested that the definition of ``skin 
protectant'' be reworded to add a primary effect of skin protectants, 
i.e., temporary relief of the effects of harmful or annoying stimuli 
and to include the word ``product''. The agency agrees and is revising 
the definition of ``skin protectant'' in Sec.  347.3(d).
    (Comment 3) Four comments opposed the agency's ``exclusivity 
policy,'' which limits the indications used in OTC drug product 
labeling to the ``specific words and phrases'' approved by FDA in a 
final OTC drug monograph.
    After these comments were submitted, the agency published a final 
rule in the Federal Register of May 1, 1986 (51 FR 16258) changing its 
labeling policy (Sec.  330.1(c)(2) (21 CFR 330.1(c)(2))) for stating 
the indications for use of OTC drug products. That policy was revised 
and discussed in the Federal Register of March 17, 1999 (64 FR 13254 at 
13270 to 13271, and 13294). The final rule in this document is subject 
to that new labeling policy.
    (Comment 4) Three comments disagreed with the agency's position of 
prohibiting cosmetic claims from appearing in any portion of the 
labeling that is required by an OTC drug monograph and the agency's 
view that this type of labeling could be misleading (see 48 FR 6820 at 
6823). One comment noted its support for the distinction made by the 
agency between ``drug'' and ``cosmetic'' claims for the same 
ingredient. Two comments cited current agency regulations in Sec.  
701.3(d) (21 CFR 701.3(d)) regarding the combined label declarations of 
active drug ingredients and cosmetic ingredients and requested that 
cosmetic indications be allowed to be stated in a manner that is not 
false or misleading, without regard to their position on the label.
    The agency has revised its labeling requirements for OTC drug 
products by adding Sec.  201.66 (21 CFR 201.66) and amending Sec.  
701.3(d) since stating its position on drug-cosmetic labeling in the 
TFM. Section 701.3(d) now requires separate listing of the active drug 
ingredients and the cosmetic ingredients where a cosmetic product is 
also an OTC drug product. FDA does not review and approve cosmetic 
terminology in OTC drug monographs. Under the new OTC drug product 
labeling format in Sec.  201.66, the ``Drug Facts'' area of a product's 
labeling only contains the indication(s) for the drug part of the 
product. Thus, manufacturers are not allowed to commingle drug and 
cosmetic claims within this specific area of the labeling. However, 
there are no specific restrictions on commingled information outside of 
the ``Drug Facts'' area of a product's labeling. The agency's position 
is that if commingled drug and cosmetic labeling information is 
confusing or misleading, the product's labeling may be misleading 
within the meaning of the Federal Food, Drug, and Cosmetic Act (the 
act) and the product misbranded under sections 502(a) or 602(a) of the 
act (21 U.S.C. 352(a) or 362(a)). The agency will review the labeling 
of affected products on a case-by-case basis.
    (Comment 5) Several comments suggested that limiting the statement 
of identity to one term (``skin protectant'') is too restrictive, 
requested other equally descriptive appropriate terms, and asked for 
distinct statements of identity for each indication proposed in the 
monograph, e.g., ``minor cut protectant.''
    The agency does not find it necessary to have distinct statements 
of identity for each use of a skin protectant drug product. The 
statement of identity is intended to provide information on the 
``general pharmacological category(ies) of the drug or the principal 
intended action(s) of the drug'' (see Sec.  201.61(b) (21 CFR 
201.61(b))). This position is consistent with the statement of identity 
proposed by the agency as ``external analgesic'' for all drug products 
that provide relief of pain and itching caused by a number of 
conditions (48 FR 5852 at 5868, February 8, 1983) and as ``analgesic 
(pain reliever)'' for all drug products that relieve pain due to 
various conditions (53 FR 46204 at 46211, November 16, 1988).
    The agency concurs with one comment's suggestion of adding the 
dosage form to the statement of identity, i.e., ``skin protectant 
(dosage form).'' The United States Pharmacopeia (USP) lists a number of 
dosage forms that might be used for OTC topical drug products (Ref. 1). 
From a marketplace survey (Refs. 2, 3, and 4), the agency finds that 
the most widely used dosage forms for OTC skin protectant drug products 
are lotions, creams, ointments, and gels. The examples of dosage forms 
listed in the statement of identity in Sec.  347.50(a) of this final 
monograph are not all inclusive and depend on products' historical 
marketing as skin protectants.
    (Comment 6) One comment questioned the agency's statement that the 
term ``soothes'' is a cosmetic claim in the context of skin protectant 
products (48 FR 6820 at 6828).
    The agency considers claims such as ``temporarily protects'' and 
``helps relieve'' to be more informative than ``soothes'' in conveying 
to consumers that a drug product provides therapeutic action. The term 
``soothes'' may appear elsewhere in the product's labeling.
    (Comment 7) Several comments contended that the indications 
proposed were too restrictive and omitted indications recommended by 
the Panel. The comments suggested additional labeling claims.
    The agency agrees with some of the comments' suggestions for the 
indications in Sec.  347.50(b)(2). While the agency wishes to emphasize 
the ``protectant'' function of these ingredients, they may also help 
provide some relief for chapped or cracked skin and lips. Therefore, 
the agency is allowing manufacturers to add, at their option, the words 
``and helps relieve'' after the word ``protects'' in the indications in 
Sec.  347.50(b)(2). The agency also agrees that the words ``cold'' and 
``wind'' are informative to consumers, and possibly easier to 
understand than the word ``windburned.'' Accordingly, the agency has 
made this revision in an optional labeling statement.
    The agency considers other suggested claims to be better 
represented in the agency's proposed indications.
    The agency is deleting ``sunburn'' from the indication proposed in 
Sec.  347.50(b)(1) because the agency has reexamined the data and 
determined that they do not support a ``protection of sunburn'' claim 
for these ingredients. The ``sunburn'' claim proposed in the TFM 
originated from the Panel when it recommended the use of ``skin 
protectant active ingredients for symptoms of dryness: `For symptoms of 
chapping, peeling or scaling' (optional, any or all of the following) 
`due to minor burns, sunburn, windburn, scrapes, abrasions, or cracked 
lips''' (see 43 FR 34628 at 34648). The Panel also recommended that the 
ingredients allantoin, cocoa butter, dimethicone, glycerin, petrolatum, 
and shark liver oil be included in the monograph as active ingredients 
for symptoms of dryness. Of these ingredients, petrolatum was the only 
one that the Panel discussed effectiveness for sunburn (43 FR 34628 at 
34639). The Panel stated that ``the use of petrolatum as an emollient 
has been well accepted for dry skin conditions, especially with flaking 
skin such as sunburn, and chapping'' (43 FR 34628 at 34639).
    The Panel's claim was revised in the TFM to a shortened ``drug'' 
claim that stated: ``For the temporary protection of minor cuts, 
scrapes, burns, and sunburn'' (see 48 FR 6820 at 6832). The agency did 
not include peeling or scaling claims in the TFM (48 FR 6820

[[Page 33364]]

at 6828). The Panel's reference to symptoms of dryness was not included 
in the TFM because the agency considers the use of skin protectants for 
dryness to be a cosmetic claim. The agency has now determined that it 
should not have included the ``sunburn'' claim in the TFM because the 
only context in which the Panel discussed it was cosmetic in nature.
    The agency is also concerned that skin protectants may 
inappropriately be used for ``sunburn'' because the data indicate that 
it is not desirable to apply a skin protectant to sunburn that has just 
occurred. As the Panel noted, when petrolatum is applied to sunburn, 
evaporation is curtailed (43 FR 34628 at 34639). The agency is 
concerned that application of skin protectants, such as petrolatum and 
the other igredients for which the Panel recommended a dryness claim 
for sunburn, to sunburn that has just occurred would occlude the area 
and prevent evaporation from occurring or significantly reduce 
evaporation. Thus, there are no data in the administrative record for 
this rulemaking to support a ``protection of sunburn'' claim for these 
ingredients. The agency would consider including such a claim for these 
ingredients, however, if adequate supporting data are provided.
    The agency has determined that insufficient data were submitted to 
include the words ``to allow healing to begin'' and to include uses for 
heat rash, burning feet, and foot discomfort in Sec.  347.50(b)(3). The 
agency concludes that the expanded ``uses'' section in this final 
monograph provides manufacturers an adequate number of options for 
labeling OTC skin protectant drug products.
    (Comment 8) One comment mentioned that no wound healing claim or 
Category I labeling was provided for three skin protectant ingredients: 
Allantoin, live yeast cell derivative (LYCD), and zinc acetate.
    The Panel classified these ingredients as Category III skin 
protectants for wound-healing based on the lack of effectiveness data 
(43 FR 34628 at 34644 through 34647). Insufficient data were submitted 
for LYCD (see section II. comment 25 of this document) and no 
additional data were submitted for allantoin or zinc acetate to support 
a ``wound healing'' use.
    (Comment 9) One comment requested that compound benzoin tincture be 
included as a Category I topical skin protectant. The comment mentioned 
the conclusion of the Advisory Review Panel on OTC Cold, Cough, 
Allergy, Bronchodilator, and Antiasthmatic Drug Products (Cough-Cold 
Panel) that compound benzoin tincture was safe for use in boiling water 
as a steam inhalant for expectorant purposes (41 FR 38312 at 38360, 
September 9, 1976). The comment also cited the recommendation of the 
Advisory Review Panel on OTC Dentifrice and Dental Care Drug Products 
(Dental Panel) that compound benzoin tincture was safe and effective 
for use as an oral mucosal protectant (47 FR 22712 at 22746 and 22747, 
May 25, 1982). The comment cited acceptance of compound benzoin 
tincture in several pharmacopeias, experience over decades of use, and 
the low incidence of adverse reactions or significant side effects in 
the published literature. The comment cited several skin protectant 
uses from well-established references or current product labeling: ``* 
* * to small cuts and to intact skin under occlusive plasters and 
bandages'' (Ref. 5), ``* * * ulcers, bedsores, cracked nipples, and 
fissures of the lips and anus'' (Ref. 6), and ``apply to the skin under 
adhesive dressings, to treat skin fissures and bedsores, to reduce skin 
sensitivity to adhesive plasters, and to prevent skin irritation in 
ischemic areas'' (Ref. 7).
    Compound benzoin tincture is included in the USP as a fixed 
formulation containing 10 percent benzoin, 2 percent aloe, 8 percent 
storax, 4 percent tolu balsam, and 74 to 80 percent ethanol (Ref. 8). 
The agency finds that use as a steam inhalant for expectorant purposes 
evaluated by the Cough-Cold Panel (41 FR 38312 at 38360) has little 
relevance to use as a skin protectant. Although the agency acknowledges 
that standard references (Refs. 5 and 6) and literature articles 
describe numerous uses for compound benzoin tincture, no data from 
controlled clinical studies were provided.
    Gosselin et al. (Ref. 9) indicated that the alcohol in benzoin 
tincture would be responsible for major toxic effects if ingested. The 
Dental Panel discussed literature reports of three cases of irritation 
and hypersensitivity resulting from topical use of benzoin tincture (47 
FR 22712 at 22746 and 22747). In addition, the published literature 
contains numerous other reports of allergic contact dermatitis and 
sensitivity attributed to compound benzoin tincture and benzoin 
tincture. Cullen, Tonkin, and May (Ref. 10) stated that the literature 
was replete with reports of cutaneous sensitivity to compound benzoin 
tincture and its components, citing reports following local 
application. Rademaker and Kirby (Ref. 11) reported two cases of 
bullous contact dermatitis to a skin adhesive spray and mentioned that 
Fisher (Ref. 12) recommends that benzoin no longer be used as a skin 
adhesive. Marks and Rainey (Ref. 13) and James, White, and Yanklowitz 
(Ref. 14) reported other cases of allergic contact dermatitis. Sixteen 
cases resulted when benzoin was applied to prevent friction blisters. 
Other authors report contact dermatitis from benzoin used as an 
ingredient in greasepaint makeup (Ref. 15) and as an antioxidant in 
food additives (Ref. 16). In addition, benzoin provokes pemphigus 
erythematosus (Ref. 17), complicates management of venous leg ulcers 
(Ref. 18), and adversely affects wound healing after circumcision in 
children (Ref. 19).
    Based on these reports of adverse events and the availability of 
other monograph skin protectant ingredients, the agency concludes that 
compound benzoin tincture is not safe for use as a general OTC skin 
protectant ingredient and would be inappropriate for many of the uses 
included in this final monograph.
    (Comment 10) One comment requested that camphorated metacresol be 
included as an active ingredient in the final monograph for OTC skin 
protectant drug products, as long as the amount of metacresol did not 
exceed 1.5 percent (by weight) and the amount of camphor did not exceed 
3 percent. Noting that phenol (0.5 to 1.5 percent) and camphor (0.1 to 
3 percent) were proposed Category I ingredients in the TFM for OTC 
external analgesic drug products (48 FR 5852 at 5867, February 8, 1983) 
and citing an agency letter (Ref. 20) agreeing that metacresol was less 
toxic than phenol, the comment contended that there should be no safety 
concern about products containing camphor and metacresol in these 
concentrations.
    Because information has not been provided to demonstrate a skin 
protectant effect, camphorated metacresol is not included in this final 
monograph.
    (Comment 11) One manufacturer submitted data and information (Refs. 
21 and 22) to FDA's Miscellaneous External Panel in response to the 
call-for-data notice published in the Federal Register of November 16, 
1973 (38 FR 31697). The data were for a drug product containing water-
soluble chlorophyllins in an ointment and a solution dosage form with a 
label indication ``to promote healing and to relieve itching and 
discomfort of minor wounds, burns, surface ulcers, cuts, abrasions and 
skin irritations.''
    The Miscellaneous External Panel was disbanded before reviewing 
these submissions. Subsequently, because the product label contained a 
claim for

[[Page 33365]]

wound healing and products with this claim had previously been included 
in the skin protectant rulemaking, the agency placed the submissions in 
the skin protectant rulemaking as a comment to the February 15, 1983, 
TFM, and the manufacturer submitted a more recent study on 
effectiveness for wound healing (Ref. 23).
    The Dental Panel evaluated water-soluble chlorophyllins as oral 
wound healing agents in its report on OTC oral mucosal injury drug 
products (44 FR 63270, November 2, 1979) and concluded that water-
soluble chlorophyllins were safe but that there were insufficient data 
available to permit final classification of effectiveness for OTC use 
as an oral wound healing agent (44 FR 63270 at 63286). The agency 
accepted the Dental Panel's classification in the TFM for OTC oral 
mucosal injury drug products (48 FR 33984 at 33991, July 26, 1983). No 
additional data were submitted and, in the final rule (51 FR 26112, 
July 18, 1986), the agency included water soluble chlorophyllins in the 
list of nonmonograph ingredients in 21 CFR 310.534.
    The agency has reviewed the manufacturer's submissions (Refs. 21, 
22, and 23). One submission (Ref. 21) contained information on various 
kinds of wounds that were treated with water-soluble chlorophyllins by 
health-care professionals. None were self-treatment conditions. Another 
(Ref. 22) contained translations of three foreign articles reporting 
laboratory and animal studies on water-soluble chlorophyllins that 
contain background information but do not support general recognition 
of safety and effectiveness in humans. A research report (Ref. 23) did 
not assess OTC uses, lacked subject and placebo controls, and 
questioned whether the observed effects were due to the products or the 
manner of caring for the wounds.
    The agency concludes that the data submitted do not support 
effectiveness of water-soluble chlorophyllins for promoting wound 
healing for conditions treated with OTC skin protectant drug products.
    (Comment 12) Cod liver oil was not categorized by the Panel for use 
as an OTC skin protectant because it was not included among the labeled 
ingredients in marketed products submitted to the Panel for review. In 
evaluating cod liver oil for use in diaper rash drug products, the 
agency considered the long history of clinical use as a skin protectant 
ingredient (55 FR 25204 at 25213, June 20, 1990).
    In the rulemaking for OTC anorectal drug products, the Advisory 
Review Panel on OTC Hemorrhoidal Drug Products (Hemorrhoidal Panel) 
classified cod liver oil as Category I for use as an anorectal 
protectant and recommended a maximum daily dose of 10,000 I.U. 
(International Units equivalent to USP Units) for vitamin A and 400 
I.U. for vitamin D (cholecalciferol) per 24 hours (45 FR 35576 at 
35630, May 27, 1980). The Hemorrhoidal Panel stated that an extensive 
review of the literature on cod liver oil revealed no adverse effects 
when applied topically as a protectant and concluded that the 
effectiveness of cod liver oil, as a protectant, is due to its bland 
and soothing effect associated with its oily nature. In the TFM (53 FR 
30756 at 30767, August 15, 1988) and final monograph (55 FR 31776 at 
31780, August 3, 1990) for OTC anorectal drug products, the agency 
affirmed the Hemorrhoidal Panel's Category I classification and 
specified that cod liver oil may be used only in combination with one 
to three other protectant active ingredients.
    The agency has surveyed the marketplace and determined that cod 
liver oil is marketed only in combination with other ingredients in 
several products with skin protectant claims (Refs. 3 and 24). One 
product contains 12.5 percent (Ref. 24), but in most cases the cod 
liver oil concentration is not provided.
    Therefore, the agency is including cod liver oil as an active 
ingredient in skin protectant drug products in accord with Sec.  
347.20(a)(1) and (a)(2), only in combination with certain other skin 
protectant active ingredients, within the concentrations (5 to 13.56 
percent) specified in Sec.  347.10(e), provided that the product is 
labeled so that the amount of the product that is used in a 24-hour 
period represents a quantity that does not exceed 400 USP Units of 
vitamin D and 10,000 USP Units of vitamin A.
    (Comment 13) In the notice of proposed rulemaking (54 FR 40808 at 
40810), the agency stated that it was necessary to have publicly 
available chemical information for colloidal oatmeal. One manufacturer 
submitted a proposed standard for colloidal oatmeal, which it stated 
was patterned after standards for starch and psyllium (Ref. 25). The 
agency sent this information to the U.S. Pharmacopeial Convention 
(USPC) (Ref. 26). Compendial standards were proposed in the 
Pharmacopeial Forum of January and February 1992 (Ref. 27) and a final 
USP monograph became effective on November 15, 1992 (Ref. 28).
    (Comment 14) One comment requested that colloidal oatmeal be 
included in the skin protectant monograph as a safe and effective 
ingredient for the claim: ``For prompt temporary relief of itchy, sore, 
sensitive skin due to rashes, eczema/psoriasis, hemorrhoidal and 
genital irritations, diaper rash, chicken pox, prickly heat, hives, 
poison ivy/oak, and sunburn.'' The comment cited references (Refs. 29 
through 33) to support this claim.
    The agency previously discussed poison ivy/oak claims in comment 1 
of the skin protectant poison ivy, oak, and sumac notice of proposed 
rulemaking (54 FR 40808 at 40809 to 40811). The agency has determined 
the additional references cited by the comment show that colloidal 
oatmeal can provide temporary skin protection and relieve minor 
irritation and itching due to a number of conditions. Further, the 
agency has no adverse reaction reports on file for colloidal oatmeal. 
Thus, the agency is expanding the indications for colloidal oatmeal in 
Sec.  347.50(b)(4) in this final monograph. In addition, manufacturers 
can opt to select one or more of the ``due to'' conditions to list in 
the product's labeling. However, since no data were submitted using 
colloidal oatmeal for chicken pox, sunburn, or hives, these indications 
are nonmonograph. The agency will discuss a ``prickly heat'' claim in 
the skin protectant diaper rash drug products final rule.
    (Comment 15) Two comments noted that the agency's proposed 
directions in Sec.  347.50 (54 FR 40808 at 40818) for the use of 
colloidal oatmeal as a soak in a tub do not allow for the range of use 
concentrations or dosage forms that have been reported in the clinical 
literature and requested that FDA specify a use concentration range. 
The comment stated that colloidal oatmeal is unusual in comparison to 
other barrier skin protectants because it is often intended for 
dispersion in water and is formulated in a variety of other dosage 
forms.
    One comment summarized and calculated the colloidal oatmeal 
concentrations used in baths (Refs. 32 and 34 through 41). The comment 
noted that the most common concentration ranges of colloidal oatmeal 
are from 0.007 to 10 percent in use but added that colloidal oatmeal is 
present in commercial products from 1 to 100 percent. Another comment 
recommended changing the proposed directions in Sec.  347.50(d)(2) from 
one ``cupful'' to ``up to a cupful.''
    The agency has reviewed the recommended concentrations of colloidal 
oatmeal reported in the literature and reference texts (Refs. 4, 29 
through 32, 34 through 45, 47, 48, and 49) and has considered the range 
of

[[Page 33366]]

concentrations for colloidal oatmeal used in bath additive products and 
in other dosage forms. Products containing colloidal oatmeal have been 
formulated in the following dosage forms: Lotion (1 and 10 percent 
colloidal oatmeal), cleansing cream (8 percent colloidal oatmeal), 
shampoo (5 percent colloidal oatmeal), and cleansing bars (30, 50, and 
51 percent colloidal oatmeal) (Refs. 4, 46, and 47). The agency has 
calculated the approximate minimum and maximum concentrations of 
colloidal oatmeal that have been used as follows: For regular colloidal 
oatmeal, a range of 0.023 to 0.625 percent when used as a tub bath soak 
(Refs. 29, 34 through 38, and 44), a range of 0.24 to 1.2 percent when 
used as a foot bath soak (Refs. 30, 31, and 34), a range of 0.24 to 15 
percent in aqueous solution when used in a wet pack (Refs. 30, 31, 32, 
34, and 45), and a range of 3.75 to 15 percent in aqueous solution when 
used as a topical lotion (Refs. 30, 32, and 34); for oilated colloidal 
oatmeal, a range of 0.003 to 0.03 percent when used as a tub bath soak 
(Refs. 35 and 39 through 43).
    With regard to dosage forms, the agency agrees with the comment 
that colloidal oatmeal as a skin protectant does not need to be dosage-
form specific and can be used in a variety of ``barrier type'' topical 
dosage forms, except for ``cleanser type'' topical dosage forms, for 
which the agency has no data to support use as a skin protectant. 
Therefore, based on the additional information that has been submitted, 
the agency is revising the directions for use in Sec.  347.50(d)(2) in 
this final monograph.
    (Comment 16) One comment requested that colloidal oatmeal be 
included in the skin protectant monograph for the claim: ``For prompt 
temporary relief of itchy, sore, sensitive skin due to * * * 
hemorrhoidal and genital irritations * * *.'' The comment provided 
reports recommending use of colloidal oatmeal baths and creams for 
rectal itching and other conditions in the genital area (Refs. 50 
through 54).
    Claims for itching in the genital area (e.g., pruritus vulvae) are 
included in the rulemaking for OTC external analgesic drug products. A 
comment to that rulemaking (Ref. 55) specifically requested a claim for 
colloidal oatmeal for ``prompt temporary relief of itchy, sore, 
sensitive skin due to rashes, eczema/psoriasis, hemorrhoidal and 
genital irritations, diaper rash, chicken pox, prickly heat, hives, 
poison ivy/oak, and sunburn.'' Therefore, the agency will address this 
comment in the final rule for OTC external analgesic drug products.
    The agency concludes that the comment's requested claims for relief 
of rectal itching and hemorrhoids are similar to the indication (21 CFR 
346.50(b)(1)) for OTC anorectal drug products that include protectant 
active ingredients under 21 CFR 346.14, and to the definition of a 
protectant drug under 21 CFR 346.3(i) as a drug that provides a 
physical barrier, forming a protective coating over skin or mucous 
membranes. Since colloidal oatmeal was not reviewed during any stage of 
the rulemaking for OTC anorectal drug products, interested parties 
should provide necessary information to demonstrate that colloidal 
oatmeal meets the standards of an OTC anorectal protectant active 
ingredient and petition the agency to include colloidal oatmeal in the 
final monograph for OTC anorectal drug products (Ref. 56).
    (Comment 17) One comment requested that colloidal oatmeal be 
allowed to be combined with other Category I skin protectants for the 
treatment of minor irritation and itching caused by insect bites and 
poisonous plants. The comment cited reports using an oilated colloidal 
oatmeal bath additive to help treat various dermatoses.
    The agency has reviewed the cited studies (Refs. 34, 43, 57, 58, 
and 59), and finds that these reports support the combination of 
colloidal oatmeal with mineral oil to treat the irritation, itching, 
and dryness of various dry skin dermatoses. The agency is including the 
combination of colloidal oatmeal and mineral oil in new Sec.  
347.20(a)(4) for the uses included in new Sec.  347.50(b)(7) of this 
final monograph. Nevertheless, poison ivy, oak, and sumac are not 
exclusively dry skin dermatoses; they are characterized by a phase of 
weeping, oozing exudation. The studies cited by the comment fail to 
demonstrate the value of adding an additional skin protectant (an 
oilating component) for the treatment of these conditions in the 
exudative phase, and also fail to specify how many of the cases of 
contact dermatitis were due to poisonous plants. In addition, only one 
case of insect bite was identified in the studies. The agency concludes 
that the data are insufficient to support the combination of colloidal 
oatmeal with other skin protectants to treat insect bites and poison 
ivy, oak, and sumac.
    (Comment 18) One comment responded to the agency's request in the 
skin protectant poison ivy, oak, and sumac notice of proposed 
rulemaking (54 FR 40808 at 40810) to provide information and directions 
to support the use of colloidal oatmeal on children under 2 years of 
age. The comment stated that most barrier type skin protectant active 
ingredients have not been restricted to any age group and submitted 
reports of use of colloidal oatmeal in infants (Refs. 34, 45, 50, 51, 
and 57). The comment added that the Miscellaneous External Panel had 
evaluated colloidal oatmeal and placed it in Category I for relief of 
itching claims with no age restrictions (Ref. 61).
    The agency has reviewed the reports submitted by the comment, which 
described the effective use of colloidal oatmeal on infants and 
children from 2 months to 18 years of age for various dermatoses 
associated with dry skin. No adverse effects were reported. The 
Miscellaneous External Panel (Ref. 61) at its twenty-third meeting 
concluded that colloidal oatmeal, at all concentrations, is safe and 
effective for ``the symptomatic relief and treatment of itching.'' 
Based on the Miscellaneous External Panel's evaluation and the 
references provided by the comment, the agency is including colloidal 
oatmeal in the final monograph for use on infants and children under 2 
years of age in the same concentrations, dosage forms, and directions 
for use for adults.
    (Comment 19) One comment noted that in the skin protectant poison 
ivy, oak, and sumac notice of proposed rulemaking the agency proposed 
(in Sec.  347.50(c)(9)) a specific warning for colloidal oatmeal: 
``Take special care to avoid slipping when getting into and out of the 
tub'' (54 FR 40808 at 40818). The comment agreed that a warning against 
slipping is proper and appropriate, but contended that the agency's 
warning is unnecessarily longer than the warning on its labels, ``Take 
special care to avoid slipping.'' Furthermore, the comment contended, 
the reference to entering and leaving the tub may lessen the consumer's 
perception of need for care during bathing or when bathing a child.
    The agency notes that a number of authors have expressed concerns 
about slipping in the bath tub with oil baths in general, and with 
colloidal oatmeal baths in particular (Refs. 29, 40, 44, 48, 54, and 
62). Two authors (Refs. 29 and 48) recommended use of a mat to reduce 
the possibility of slipping. Accordingly, the agency has revised the 
warning, which appears in Sec.  347.50(c)(5) of the final monograph, to 
read: ``When using this product [bullet] to avoid slipping, use mat in 
tub or shower.''
    (Comment 20) One comment objected to the highly specific directions 
for colloidal oatmeal the agency proposed in Sec.  347.50(d)(2) of the 
skin protectant poison ivy, oak, and sumac notice of proposed 
rulemaking (54 FR 40808 at 40818). The comment requested that

[[Page 33367]]

FDA modify the directions for use to allow for other concentrations and 
to address the use of other dosage forms, such as ointments, lotions, 
and cleansing bars. The comment objected to a specified frequency of 
use (``once or twice daily'') because absorption of active agent seems 
unlikely to occur.
    The agency has reviewed the literature and agrees with the comment 
that other directions may also provide safe and effective use 
concentrations. Since a bathtub, foot bath, sitz bath, or infant bath 
can be used to soak and a compress or wet dressing can be applied as a 
soak, the agency is including all of these forms of a ``soak'' in the 
final monograph. Colloidal oatmeal can also be formulated in other 
topical products intended for direct application (e.g., ointment, 
lotion), and the monograph provides directions for these products.
    Frequent and prolonged exposure to water may have a drying effect. 
Authors have different views on recommended frequency and duration of 
bathing (Refs. 37, 48, and 63 through 67) depending on the condition. 
The Miscellaneous External Panel noted that bathing can dry the skin 
out and exacerbate some conditions (Ref. 68). Given the variety of 
conditions for which colloidal oatmeal preparations may be used, the 
agency agrees with the comment and is not specifying a frequency of use 
in the directions but is providing for a warning statement in Sec.  
347.50(c)(7) to fully inform consumers.
    (Comment 21) One comment inquired whether two high-molecular weight 
dimethylpolysiloxanes, designated as SF96-350 and SF96-1000, were 
acceptable active ingredients for skin protectant use. The comment 
included general safety and toxicity information on silicone products, 
and stated that dimethicone, a proposed Category I skin protectant 
ingredient, belongs to the same chemical family as the 
dimethylpolysiloxanes.
    In the notice of proposed rulemaking for OTC skin protectant diaper 
rash drug products, the agency stated that silicone is a general term, 
but it is often used to describe dimethicone (55 FR 25204 at 25218). 
The agency did not classify silicone per se because there are various 
silicone compounds and because the agency considered dimethicone, the 
only silicone ingredient for which data were submitted.
    The agency notes that the information provided by the comment 
summarizes the results of chronic and acute toxicity studies and 
irritation studies for specific classes of silicones. However, no 
specific information was provided for the individual 
dimethylpolysiloxanes SF96-350 and SF96-1000. In addition, no 
information was provided to describe the chemical structure of these 
dimethylpolysiloxanes. The agency concludes that the data provided are 
inadequate to support general recognition of the safety and 
effectiveness of these ingredients for OTC skin protectant use in this 
final monograph.
    (Comment 22) In the TFM for OTC skin protectant drug products, the 
agency discussed a submission on 2 percent glycerin and stated that the 
skin protectant final monograph would not be issued until these data 
were reviewed by the agency and interested persons provided an 
opportunity to comment on an agency proposal (48 FR 6820 at 6823). The 
submission (Ref. 69) contained data on the use of glycerin for the 
indications of dry skin, minor skin irritation, skin protectant, and 
chapping and included a double-blind study.
    The agency has reviewed the data and determined that the study was 
inadequately controlled and failed to demonstrate that 2, 10, or 18 
percent glycerin is effective for the indication ``helps prevent and 
temporarily protects chafed, chapped, cracked, or windburned skin and 
lips,'' as proposed by the agency for 20 to 45 percent glycerin in the 
TFM for OTC skin protectant drug products (48 FR 6820 at 6832). The 
agency's detailed comments and evaluation of the data are on file in 
the Dockets Management Branch (Ref. 70). The agency concludes that 
glycerin at concentrations other than 20 to 45 percent is nonmonograph 
for use in OTC skin protectant drug products.
    (Comment 23) One comment requested the agency to reopen the 
administrative record to include the ingredient ``hard fat,'' as 
described in the ``National Formulary'' (NF) (Ref. 71), as a Category I 
skin protectant.
    In the Federal Register of December 19, 1991 (56 FR 65873), the 
agency agreed with the petition that it would be appropriate to reopen 
the administrative record and include data and information on ``hard 
fat'' in the rulemaking for OTC skin protectant drug products. The 
agency stated that, based on its action in the rulemaking for OTC 
anorectal drug products (55 FR 31776), hard fat would be classified as 
a monograph ingredient in the final skin protectant monograph. Since no 
adverse comments on hard fat were received in response to this 
reopening of the administrative record, the agency is including hard 
fat in Sec.  347.10 at concentrations of 50 to 100 percent as a single 
active ingredient. Hard fat is also allowed in permitted combinations 
in Sec.  347.20(a)(1), (a)(2), (b), (c), and (d) of this final 
monograph. Products containing hard fat may be labeled for the 
indications in Sec.  347.50(b)(1), (b)(2)(i), and (b)(2)(ii) and should 
bear the warnings in Sec.  347.50(c)(1) through (c)(4) and the 
directions in Sec.  347.50(d)(1). In a future issue of the Federal 
Register, the agency will address claims for hard fat in OTC skin 
protectant cold sore/fever blister drug products (see proposed Sec.  
347.50(b)(2)(ii), 55 FR 3362 at 3370).
    (Comment 24) One comment requested that lanolin be categorized as 
an active ingredient in the skin protectant monograph for use as a 
single ingredient or in combination, as permitted by the monograph. In 
support of lanolin's safety and effectiveness as a skin emollient, the 
comment cited animal and human test data submitted to the Miscellaneous 
External Panel (Ref. 72), Kligman, Grove, and Studemayer (Ref. 73), and 
the Advisory Review Panel on OTC Ophthalmic Drug Products' (Ophthalmic 
Panel) Category I classification of lanolin as an ocular emollient for 
the treatment of conditions involving ocular membranes (43 FR 30002 at 
30044 and 30045, May 6, 1980).
    The agency has considered lanolin as a protectant or emollient 
active ingredient in several OTC drug rulemakings. In the TFM for OTC 
skin protectant diaper rash drug products (55 FR 25204 at 25218 to 
25219), the agency determined that the data submitted supported the use 
of 15.5 percent lanolin as a skin protectant active ingredient only in 
combination with other skin protectant active ingredients for the 
treatment and prevention of diaper rash.
    In the final rule for OTC ophthalmic drug products (53 FR 7076 at 
7090, March 4, 1988), lanolin and anhydrous lanolin were included as 
monograph conditions at a 1 to 10 percent concentration in combination 
with one or more oleaginous emollients included in the monograph. In 
the final rule for OTC anorectal drug products (55 FR 31776 at 31780), 
lanolin was included as a monograph protectant active ingredient at 
concentrations of 50 percent and above as a single ingredient or 
between 12.5 and 50 percent in combinations.
    The agency has surveyed the marketplace (Refs. 3, 74, 75, and 76), 
and found that lanolin is being marketed as a skin protectant both as a 
single ingredient and in combination with other ingredients. The 
concentration in two single ingredient products is 37 and 50 percent. 
In almost all cases, the concentration of the lanolin in the 
combination products is not provided. Based on the agency's market 
survey and its previous actions

[[Page 33368]]

in the rulemakings for OTC diaper rash, anorectal, and ophthalmic drug 
products, the agency is including lanolin in the final skin protectant 
drug products monograph as a single ingredient and in combination with 
certain other skin protectant active ingredients, depending on the 
labeled use of the product. The use concentration included in the final 
monograph is 12.5 to 50 percent in accord with the concentration of 
marketed single ingredient skin protectant drug products and the 
concentration used in anorectal protectant combination drug products. 
The use concentration of 15.5 percent proposed in Sec.  347.10(o) for 
OTC diaper rash skin protectant drug products (55 FR 25204 at 25232) 
will be addressed in the final rule for those drug products.
    (Comment 25) One comment submitted data (Refs. 77 through 89), 
including two clinical studies by Kaplan (Refs. 77, 78, 80, 81, and 
84), in support of reclassifying LYCD from Category III to Category I 
as a wound healing aid. The first Kaplan study (Ref. 77) has been 
published (Ref. 90). The comment also submitted data included earlier 
in the rulemaking for OTC anorectal drug products and transcripts of 
meetings of the Hemorrhoidal Panel (Ref. 87).
    The ingredient LYCD was reviewed by both the Hemorrhoidal Panel and 
the Topical Analgesic Panel. Neither panel found LYCD to be effective. 
The agency determined that the data were inadequate to support the use 
of LYCD in the final rule for OTC anorectal drug products (58 FR 46746, 
September 2, 1993).
    The agency has reviewed the wound healing studies (Refs. 77, 78, 
80, 81, and 84) submitted to this rulemaking for OTC skin protectant 
drug products and determined that the studies are inadequate to include 
LYCD as a wound healing aid in this final monograph. The agency's 
detailed comments and evaluations of the nonconfidential data are on 
file in the Dockets Management Branch (Refs. 91 and 92).
    The agency also informed the company that additional information is 
needed on the chemical and physical characterization of LYCD before a 
final classification can be made and suggested the company provide 
information to establish a compendial monograph for the ingredient 
(Ref. 93). The company submitted information, both nonconfidential 
(Refs. 88 and 89) and confidential, but it also was not adequate. The 
agency's detailed comments on the information are on file in the 
Dockets Management Branch (Refs. 94 and 95).
    (Comment 26) The agency has included in the rulemaking for OTC skin 
protectant drug products several submissions (Refs. 96, 97, and 98) for 
drug products containing mineral oil that were originally submitted to 
the Miscellaneous External Panel for review. One submission (Ref. 96) 
did not contain any data on mineral oil as an individual ingredient and 
the other submissions (Refs. 97 and 98) were discussed in the TFM for 
OTC skin protectant diaper rash drug products (55 FR 25204 at 25220 to 
25221). The agency concluded that the ingredient's physical properties 
were sufficient, along with the Category I findings of two other panels 
(Hemorrhoidal and Ophthalmic Panels), to support the effectiveness of 
mineral oil in Sec.  347.10(p) of the skin protectant diaper rash TFM 
(55 FR 25204 at 25232) for diaper rash claims proposed in Sec.  
347.50(b)(5). In this final monograph for OTC skin protectant drug 
products, mineral oil in the first concentration listed in Sec.  
347.10(l) (50 to 100 percent) may be labeled for the claims listed in 
Sec.  347.50(b)(1) and (b)(2). In addition, mineral oil in the second 
concentration listed in Sec.  347.10(1) (30 to 35 percent) when 
combined with colloidal oatmeal may be labeled for the claims listed in 
Sec.  347.50(b)(7).
    (Comment 27) One comment urged FDA to consider a single statement 
of identity for the ingredient petrolatum because of its multi-purpose 
uses in OTC drug products. The comment suggested the term 
``protectant.''
    Petrolatum is generally recognized as safe and effective in two 
other OTC drug final monographs: Ophthalmic (part 349 (21 CFR part 
349)) and anorectal (21 CFR part 346). The statement of identity for 
ophthalmic use is ``lubricant'' or ``emollient (lubricant) eye 
ointment'' (see Sec.  349.65(a)).
    The agency previously considered a related issue in the proposed 
rulemaking for OTC anorectal drug products (see comment 39, 53 FR 30756 
at 30771) and determined that a comment's suggested statement of 
identity (topical protectant and lubricant) did not make it clear that 
such a product could be used anorectally and thus did not fully satisfy 
the requirements of Sec.  201.61(b). The agency believes that the same 
is true of the currently suggested statement of identity 
``protectant.'' Thus, the agency is not adopting a single statement of 
identity for the ingredient petrolatum and is using ``skin protectant'' 
as the statement of identity for drug products containing petrolatum 
included in this final monograph (part 347).
    (Comment 28) One comment argued that petrolatum should be exempt 
from the ``directions for use'' proposed in Sec.  347.50(d), citing 
petrolatum's long history of consumer use, efficacy, and safety and 
contending that petrolatum meets the requirements for such exemption 
under Sec.  201.116 (21 CFR 201.116).
    The agency disagrees. Section 201.116 allows for exemption from 
section 502(f)(1) of the act which requires adequate directions for 
use, if adequate directions for common uses are known to the ordinary 
individual. While some individuals may know that petrolatum may be 
applied as needed, the agency believes that not all people who use this 
drug would know that it can be applied on an as needed basis. 
Therefore, the agency is requiring the standard direction in Sec.  
347.50(d)(1) for products that contain petrolatum.
    (Comment 29) One comment contended that petrolatum should be exempt 
from the warnings proposed in the TFM (48 FR 6820 at 6832 to 6833). The 
comment argued that sufficient evidence to exempt these warnings is 
provided by the universal use of petrolatum over many decades for a 
wide variety of topical indications, the clinical and marketing 
experience over this long period of extensive and universal use, the 
Panel conclusion that ``large amounts of petrolatum are essentially 
nontoxic when ingested * * *'' (43 FR 34628 at 34639), the results of a 
long-term chronic feeding study by Oser et al. (Ref. 99) as 
demonstrating safety on ingestion, and the fact that petrolatum is 
regulated as an approved direct food additive (under Sec.  172.880 (21 
CFR 172.880)) and is listed in the Food Chemicals Codex (Ref. 100).
    Although the comment suggested a revision, it agreed in principle 
with the warning ``Not to be applied over deep or puncture wounds, 
infections, or lacerations. Consult a doctor.'' A second comment 
requested, in the interest of brevity, clarity, and conservation of 
scarce label space, that the warning be shortened to read: ``Do not 
apply over deep or puncture wounds or infections.''
    The agency discussed the importance of each of the proposed 
warnings in comments 25 through 31 of the TFM (48 FR 6820 at 6828 to 
6830) and stated that these warnings are necessary for petrolatum used 
as a skin protectant. In comment 31 of the TFM, however, the agency 
proposed not to require the ``For external use only warning'' for all 
products (including those containing petrolatum) formulated as lip 
balms. The agency is finalizing that proposal in this document.

[[Page 33369]]

    In this final monograph, products containing the skin protectant 
ingredients mineral oil or sodium bicarbonate may omit the ``For 
external use only'' warning if they also provide labeling for oral use 
of the product. The agency believes that it could be confusing to 
consumers if products that contain petrolatum do not have the ``For 
external use only'' warning. Therefore, the agency is not exempting 
petrolatum (except in lip protectant products) from the ``For external 
use only'' warning in Sec. Sec.  201.66(c)(5)(i) and 347.50(c)(1).
    The agency considers the warning about not getting the product into 
the eye useful to help prevent possible improper use of skin protectant 
drug products which are often marketed in nonsterile, multiple use 
containers. The agency believes that the first comment misconstrued the 
purpose of the ``if condition worsens'' warning (Sec.  347.50(c)(3) of 
this final monograph). The warning is intended to direct consumers to 
seek medical attention for a condition if it gets worse or has not 
improved after 7 days of treatment and not to set 7 days as a maximum 
safe treatment period. The agency has shortened this warning for 
products containing petrolatum (or white petrolatum) as a single 
ingredient to state: ``See a doctor if condition lasts more than 7 
days.''
    With regard to the suggestion that the warning in Sec.  
347.50(c)(4) be revised, after the submission of this comment, the 
agency published a similar warning for OTC first aid antibiotic drug 
products (52 FR 47312 at 47324, December 11, 1987) and OTC first aid 
antiseptic drug products (56 FR 33644 at 33677, July 22, 1991). The 
agency is revising the warning in Sec.  347.50(c)(4), accordingly, in 
the new format required by Sec.  201.66.
    (Comment 30) One comment considered the two general warnings in 
Sec.  330.1(g) unnecessary for 100 percent petrolatum. The comment 
cited two references (Refs. 99 and 100) to support its contention that 
petrolatum is a uniquely safe OTC drug and presents no risk to the 
health of children from misuse, overuse, or abuse.
    The agency finds the information in the cited references (as well 
as the information in Sec.  172.880 regarding the regulation of 
petrolatum as an approved food additive) insufficient to support an 
exemption for 30 to 100 percent petrolatum from the two general 
warnings in Sec.  330.1(g). References 99 and 100 list petrolatum 
concentrations at 0.02 to 5 percent, significantly lower than the 
concentration range included in the monograph. The agency revised the 
wording of these warnings in Sec.  330.1(g) in the final rule for the 
new OTC drug product labeling format (64 FR 13254 at 13294).
    (Comment 31). One comment stated that the agency's proposed 
directions for sodium bicarbonate for use as a soak in a tub allow for 
a topical use concentration of about 0.3 percent, which is less than 
the dosage range for topical use of 1 to 100 percent (54 FR 40808 at 
40818).
    The agency has reviewed its calculations and agrees with the 
comment that the proposed directions for use as a soak in a tub allow 
for a topical concentration of less than 1 percent, depending on the 
amount of water in the tub and the size of the cup used. However, these 
directions are consistent with those suggested in the literature (Refs. 
101 through 104). When these measurements are made by consumers, they 
may not be precise. Accordingly, in this final monograph, the agency 
recognizes that it is not possible or critical to make a precise 
determination of the use concentration for this ingredient. Thus, the 
agency has revised its recommendations.
    (Comment 32) The agency has considered topical starch (formerly 
known as corn starch) in several rulemakings. In the advance notice of 
proposed rulemaking for OTC skin protectant drug products (43 FR 34628 
at 34636), the TFM for OTC skin protectant drug products (48 FR 6820 at 
6828), the TFM for OTC skin protectant poison ivy, poison oak, poison 
sumac, and insect bites drug products (54 FR 40808 at 40811 to 40812), 
the Miscellaneous External Panel's statement on OTC diaper rash drug 
products (47 FR 39436 at 39439, September 7, 1982), the TFM for OTC 
skin protectant diaper rash drug products (55 FR 25204 at 25232), and 
the TFM (53 FR 30756 at 30782) and final monograph (55 FR 31776 at 
31780) for OTC anorectal drug products.
    Based on the evaluations of the Topical Analgesic, Miscellaneous 
External, and Hemorrhoidal Panels, and the subsequent inclusion of 
topical starch as a protectant in the final monograph for OTC anorectal 
drug products and in the TFM for OTC diaper rash drug products, the 
agency is including topical starch at a concentration of 10 to 98 
percent as an active ingredient under Sec.  347.10(q) of this final 
monograph for OTC skin protectant drug products. The agency is 
including a minor skin irritation indication for the skin protectant 
uses of topical starch in Sec.  347.50(b)(6). Because topical starch 
should not be used on broken skin, other conditions (e.g., cuts, 
scrapes, chapped/cracked skin and lips) are not included in this final 
monograph. Warnings applicable to topical starch drug products in a 
powder dosage form are included in Sec.  347.50(c)(6).
    (Comment 33) Two comments from the same company requested that 
vitamins A and D be added to the list of Category I active ingredients 
in the skin protectant monograph. The comments stated that shark liver 
oil, which contains significant quantities of vitamins A and D, is an 
oleaginous substance that provides lubricity and emolliency. The 
comments mentioned that vitamins A and D, like cod and shark liver 
oils, have an emollient nature that provides a physical barrier to an 
irritant and aids in the temporary relief of minor skin irritations. 
The comments added that these oleaginous substances can lessen dermal 
injury caused by friction and lessen itching and dryness caused by 
water loss from the stratum corneum, thereby providing additional 
protection for exposed skin. The comments cited the Hemorrhoidal 
Panel's recommendations on the safety and topical use of vitamins A and 
D (45 FR 35576 at 35630 and 35634). Another comment stated that a 
number of the claims recommended by the Hemorrhoidal Panel in the 
advance notice of proposed rulemaking for OTC skin protectant drug 
products (43 FR 34628 at 34648) should be listed in the monograph for 
the ingredients vitamin A and vitamin D.
    The Hemorrhoidal Panel did not review vitamin A or vitamin D 
(cholecalciferol) as single ingredients for use as protectants in OTC 
anorectal drug products but did consider these ingredients in its 
review of ingredients used for wound healing (45 FR 35576 at 35655 and 
35656). The Hemorrhoidal Panel concluded that the data submitted were 
insufficient to prove effectiveness of vitamins A and D as wound 
healing agents and classified these ingredients in Category III for 
this use (45 FR 35576 at 35655 and 35656). The agency did not include 
vitamins A or D in the anorectal final monograph because no data were 
submitted to support the effectiveness of these ingredients for 
protectant uses. However, the Hemorrhoidal Panel recommended that cod 
liver and shark liver oils be included in the Category I list of active 
ingredients for use as protectants in OTC anorectal drug products (45 
FR 35576 at 35630 and 35634) and the agency concluded that these oils 
are monograph ingredients (55 FR 31776 at 31780). The agency pointed 
out in its proposed rulemaking for OTC diaper rash drug products (55 FR 
25204 at 25225) that vitamins A and D have not been classified as skin 
protectants in

[[Page 33370]]

any rulemaking in the OTC drug review, concluded that additional data 
are needed, and placed these ingredients in Category III.
    Because no data were submitted to support the effectiveness of 
vitamins A and D for skin protectant uses, the agency concludes that 
these ingredients are nonmonograph when used individually or in 
combination other than as a component of cod liver oil listed in Sec.  
347.10(e) of this final monograph.
    (Comment 34) In the TFM for OTC first aid antiseptic drug products 
(56 FR 33644 at 33650), the agency deferred data on a physical barrier 
cream product with protective claims to the rulemaking for OTC skin 
protectant drug products. The cream product contains a combination of 
ingredients: Cetyl alcohol, glyceryl stearate, isopropyl palmitate, 
stearyl alcohol, and beeswax, labeled as ``skin wound protectant'' 
ingredients. The product labeling states ``helps protect minor cuts, 
burns, and skin irritations against contamination.'' This claim is very 
similar to the claim included in Sec.  347.50(b)(1) of this final 
monograph. The submission included the results of animal and human 
safety studies on the finished product, including LD50 in mice and 
rats, acute dermal toxicity studies in rabbits, 48-hour and 72-hour 
primary irritation studies in humans using occlusive patch tests, and 
21-day cumulative irritation studies. The submission also included 
reports of studies on the cream product's protective barrier effect and 
a clinical study to evaluate safety and effectiveness. The clinical 
study was described as a randomized, controlled, double-blind, 
parallel-group comparison of two products to determine the cream 
product's safety and effectiveness under actual use conditions. The 
control formulation was not provided.
    The agency finds the submitted data insufficient to establish the 
skin protectant effect of any of the ingredients present in the cream 
product because the contribution, if any, of each of the individual 
active ingredients cannot be determined. The Panel recommended that 
there need be no limit to the number of skin protectant ingredients 
that may be combined in a product (43 FR 34628 at 34631). However, each 
ingredient must make a contribution to the claimed effect(s) in order 
to be deemed an active ingredient (Sec.  330.10(a)(4)(iv)). Further, 
the agency notes that the Miscellaneous External Panel classified the 
ingredients cetyl alcohol and stearyl alcohol as inactive in the 
advance notice of proposed rulemaking for OTC alcohol drug products (47 
FR 22324 at 22326, May 21, 1982). In addition, the Dental Panel 
classified beeswax as inactive in the advance notice of proposed 
rulemaking for OTC drug products for the relief of oral discomfort (47 
FR 22712 at 22715). No additional data on these three ingredients have 
been submitted to any rulemaking in the OTC drug review. The other two 
listed active ingredients, glyceryl stearate and isopropyl palmitate, 
have not been considered in any rulemaking in the OTC drug review. 
Consequently, the agency concludes that the safety and effectiveness 
data are insufficient on beeswax, cetyl alcohol, glyceryl stearate, 
isopropyl palmitate, and stearyl alcohol. Therefore, these ingredients 
are being included in Sec.  310.545(a)(18) as nonmonograph.
    (Comment 35) Two comments contended that, as a class, skin 
protectant ingredients may be combined with more different types of 
therapeutic categories than any other class of ingredients. However, in 
the TFM, proposed Sec.  347.20 does not list any ingredients other than 
skin protectant ingredients that may be combined. The comments stated 
that skin protectant ingredients have been found appropriate for use in 
combination with several other ingredient categories in other OTC drug 
product rulemakings. The comments requested that the agency include a 
provision in the final monograph allowing the combination of skin 
protectant ingredients with any therapeutic class of ingredients when 
such a combination has been found appropriate by any other OTC advisory 
review panel.
    Proposed Sec.  347.20 in the skin protectant TFM was published in 
the Federal Register on February 15, 1983, before the TFMs for many 
other categories of OTC drug products. Subsequently, based on panel 
recommendations in other OTC drug rulemakings and the TFMs for OTC 
external analgesic drug products (48 FR 5852 at 5868), OTC first aid 
antiseptic drug products (56 FR 33644 at 33677), and OTC sunscreen drug 
products (58 FR 28194 at 28296, May 12, 1993), this final monograph 
includes skin protectant active ingredients in combination with other 
ingredients from these therapeutic classes.
    Therefore, the agency has further considered and expanded the 
ingredient combinations included in Sec.  347.20 of this final 
monograph, including skin protectant-sunscreen combinations in Sec.  
347.20(d). The agency is also amending the final monograph for OTC 
sunscreen drug products (64 FR 27666, May 21, 1999) to include 
sunscreen-skin protectant drug products. Further, the agency may be 
expanding the permitted combinations in Sec.  347.20(b) and (c) as data 
submitted to the rulemakings for OTC external analgesic and first aid 
antiseptic drug products are evaluated and the final monographs for 
those OTC drug classes are issued.

III. Conclusion

    Based on the available evidence, the agency is issuing a final 
monograph establishing conditions under which OTC skin protectant drug 
products are generally recognized as safe and effective and not 
misbranded. Any drug product labeled, represented, or promoted for use 
as an OTC skin protectant drug that contains any of the ingredients 
listed in Sec.  310.545(a)(18)(i)(A) or (a)(18)(i)(B) or that is not in 
conformance with the monograph (part 347) may be considered a new drug 
within the meaning of section 201(p) of the act (21 U.S.C. 321(p)) and 
misbranded under section 502 of the act. Such a drug product cannot be 
marketed for skin protectant uses unless it is the subject of an 
approved application under section 505 of the act (21 U.S.C. 355) and 
part 314 of the regulations (21 CFR part 314). An appropriate citizen 
petition to amend the monograph may also be submitted in accord with 21 
CFR 10.30 and 330.10(a)(12)(i). Any OTC skin protectant drug product 
initially introduced or initially delivered for introduction into 
interstate commerce after the compliance dates of the final rule for 
Sec.  310.545(a)(18)(i)(A) or this final rule that is not in compliance 
with the regulations is subject to regulatory action.
    Our decision to revise the warnings set forth in this final rule is 
based on comments made in response to the proposed rule. Mandating 
warnings in an OTC drug monograph does not require a finding that any 
or all of the OTC drug products covered by the monograph actually 
caused an adverse event, and FDA does not so find. Nor does FDA's 
requirement of warnings repudiate the prior OTC drug monographs and 
monograph rulemakings under which the affected drug products have been 
lawfully marketed. Rather, as a consumer protection agency, FDA has 
determined that warnings are necessary to ensure that these OTC drug 
products continue to be safe and effective for their labeled 
indications under ordinary conditions of use as those terms are defined 
in the the act. This judgment balances the benefits of these drug 
products against their potential risks (see 21 CFR 330.10(a)).

[[Page 33371]]

    FDA's decision to act in this instance need not meet the standard 
of proof required to prevail in a private tort action (Glastetter v. 
Novartis Pharmaceuticals, Corp., 252 F. 3d 986, 991 (8th Cir. 2001)). 
To mandate warnings, or take similar regulatory action, FDA need not 
show, nor do we allege, actual causation. For an expanded discussion of 
case law supporting FDA's authority to require such warnings, see the 
final rule entitled ``Labeling of Diphenhydramine-Containing Drug 
Products for Over-the-Counter Human Use'' (67 FR 72555, December 6, 
2002).

IV. Labeling Guidance

    In the Federal Register of March 17, 1999 (64 FR 13254), FDA 
established a standardized format and standardized content for the 
labeling of OTC drug products. Table 1 of this document shows how the 
warnings proposed in the TFM have been revised in this final rule based 
on comments received and using the new format in Sec.  201.66. Using 
the format in Sec.  201.66(c)(4), the warnings in Sec. Sec.  347.50(c) 
and 347.52(c) appear as follows:

                                                                 Table 1.--Revision of Proposed Monograph Warnings to New Format
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                 Skin Protectant Tentative Final Monograph                                                                  Skin Protectant Final Monograph
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Do not use on
Not to be applied over deep or puncture wounds, infections, or              [sbull] deep puncture wounds           [sbull] animal bites
 lacerations. Consult a doctor. Do not use on broken skin.                  [sbull] serious burns                  [sbull] broken skin\1\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            When using this product
Avoid contact with the eyes.                                                [sbull] do not get into eyes
Keep powder away from child's face to avoid inhalation, which can cause     [sbull] keep away from face and mouth to avoid breathing it
 breathing problems.                                                        [sbull] in some skin conditions, soaking too long may overdry
Take special care to avoid slipping when getting into and out of the tub.   [sbull] to avoid slipping, use mat in tub or shower
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                            Stop use and ask doctor if
If condition worsens or does not improve within 7 days, consult a doctor.   [sbull] condition worsens
                                                                            [sbull] symptoms last more than 7 days or clear up and occur again within a few days
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
For external use only.                                                      For external use only\2\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Only required for powder products containing kaolin or topical starch. See Sec.   347.50(c)(6).
\2\ In bold type on the line immediately following the line for the Warnings heading. See Sec.   201.66(c)(5)(i) and (d)(6).

    Section 201.66(d)(10) (21 CFR 201.66(d)(10)), which sets forth 
format and content requirements for OTC drug product labeling, 
establishes a modified labeling format for small packages that need 
more than 60 percent of their total surface area available to bear 
labeling to meet the format requirements of Sec.  201.66(d)(1) through 
(d)(9). The agency stated in the final rule that established these 
labeling requirements that it would consider additional approaches for 
accommodating certain products in their respective monographs, taking 
into consideration the risks and benefits of the drug, the intended 
use, and the need to communicate limitations or restrictions about the 
use of the product to the target population (64 FR 13254 at 13270).
    In the final monograph for OTC sunscreen drug products (64 FR 27666 
at 27678), the agency discussed modified warnings for lip balm products 
and stated that it expects to adopt the same modifications when it 
issues the final monograph for OTC skin protectant drug products. 
Accordingly, the agency is establishing additional labeling exemptions 
for lip balm/lip protectant products that meet the criteria established 
in Sec.  201.66(d)(10). The specifications for products formulated and 
labeled as a lip protectant or lip balm that meet the criteria 
established in Sec.  201.66(d)(10) are in Sec.  347.50(e) of the skin 
protectant final monograph. In making this determination for lip 
protectant/lip balm products, the agency considered a number of factors 
that were discussed in the final rule that established the new OTC drug 
product labeling format in Sec.  201.66 (64 FR 13254 at 13270). These 
factors include the risks and benefits of the drug, the intended use, 
and the need to communicate limitations or restrictions about the use 
of the product to the target population. Lip protectant/lip balm 
products are typically packaged in small amounts, applied to limited 
areas of the body, have a high therapeutic index, carry extremely low 
risk in actual consumer use situations, provide a favorable public 
health benefit, require no specified dosage limitation, and require few 
specific warnings and no general warnings (e.g., pregnancy or overdose 
warnings). For these reasons, the agency has concluded that minimal 
information is needed for the safe and effective use of such products.
    The agency is also including in this final rule some modified 
labeling requirements in Sec.  347.50(f) of the final monograph for 
products containing only cocoa butter, petrolatum, or white petrolatum 
singly or in combination with each other when marketed other than as a 
lip protectant or lip balm. In making this decision for cocoa butter, 
the agency considered the factors discussed in the previous paragraphs 
and the Panel's recommendations on cocoa butter. The Panel stated in 
its safety evaluation of cocoa butter (43 FR 34628 at 34635) that ``No 
reports regarding the safety of cocoa butter have been specifically 
identified. However, the Panel recognizes that its safety has been 
established by its wide and continuous use in pharmaceutical products 
and cosmetics. Clinical and marketing experience has confirmed that 
cocoa butter is safe in the dosage range used as a skin protectant.'' 
Thus, these products have an extremely low risk in actual consumer use 
situations. In addition, the agency has considered the OTC uses for 
this ingredient as providing temporary protection of minor cuts, 
scrapes, burns, and chapped or cracked skin and lips. Application to 
these areas for these uses will likely be infrequent and to limited 
areas of the body. In making this decision for petrolatum and white 
petrolatum, the agency considered the factors discussed in the previous 
paragraphs, the Panel's recommendations, and the evidence and data 
described in section II., comment

[[Page 33372]]

29 of this document. The Panel stated in its safety evaluation of 
petrolatum preparations (43 FR 34628 at 34639) that ``Petrolatum is not 
absorbed through intact or injured skin and is neither sensitizing nor 
irritating. Large amounts are essentially nontoxic when ingested in 
liquid laxative preparations. Clinical and marketing experience has 
confirmed that petrolatum is safe in the OTC dosage range used as a 
skin protectant.'' As noted for cocoa butter, the agency has considered 
the OTC uses for these ingredients and believes that application to 
these areas for these uses will likely be infrequent and to limited 
areas of the body. The agency concludes that petrolatum and white 
petrolatum have an extremely low risk in actual consumer use 
situations. Moreover, both products provide a favorable public health 
benefit, require no specified dosage limitation, and require few 
specific warnings nad no general warnings (e.g., pregnancy or overdose 
warnings).

V. Stay of Sec.  347.20(d) and Part 352

    The agency is lifting the stay for the sunscreen monograph in part 
352 for the sole purpose of amending the codified language as set forth 
in the skin protectant final monograph. Once the codified language is 
amended, part 352 will remain stayed indefinitely. The agency is also 
staying Sec.  347.20(d) because it involves combination products that 
contain sunscreen active ingredients. To the extent that 5 U.S.C. 553 
applies to this action, it is exempt from notice and comment because it 
constitutes a rule of procedure under 5 U.S.C. 553(b)(3)(A). 
Alternatively, the agency's implementation of this action without 
opportunity for public comment comes within the good cause exceptions 
in 5 U.S.C. 553(b)(3)(B) in that obtaining public comment is 
impracticable, unnecessary, and contrary to the public interest. The 
agency complied with the notice and comment procedures in 5 U.S.C. 553 
when it issued the skin protectant final monograph set forth in this 
notice. The agency is lifting the stay for part 352 in order to revise 
part 352 to be consistent with that monograph. As the agency stated in 
the Federal Register of December 31, 2001 (66 FR 67485), FDA intends to 
publish a proposal to amend part 352 in order to develop a 
comprehensive sunscreen monograph that addresses formulation, labeling, 
and testing requirements for both ultraviolet B (UVB) and ultraviolet A 
(UVA) radiation protection. That amendment will propose a new effective 
date for part 352 and for Sec.  347.20(d). Thus, there will be an 
opportunity for public comment on the new effective date within the 
proposed amendment to part 352. In accordance with 21 CFR 10.40(e)(1), 
FDA is providing an opportunity for comment on whether this partial 
stay should be modified or revoked.

VI. Analysis of Impacts

    An analysis of the costs and benefits of this regulation, conducted 
under Executive Order 12291, was discussed in the TFM for OTC skin 
protectant drug products (48 FR 6820 at 6831). The agency certified 
that under the Regulatory Flexibility Act the proposed rule would not 
have a significant economic impact on a substantial number of small 
entities. No comments were received on the economic impact of this 
rulemaking.
    FDA has examined the impacts of the final rule under Executive 
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1501 et seq.). 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 Regulatory 
Flexibility Act, if a rule may have 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 of 1995 
requires that agencies prepare a written statement and economic 
analysis before proposing any rule that may result in an expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100 million in any one year (adjusted annually for 
inflation). The proposed rules that have led to the development of this 
final rule were published on February 15, 1983, and October 3, 1989, 
before the Unfunded Mandates Reform Act of 1995 was enacted. The agency 
explains in this final rule that the final rule will not result in an 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100 million in any one year.
    The agency concludes that this final rule is consistent with the 
principles set out in Executive Order 12866 and in these two statutes. 
The final rule is not a significant regulatory action as defined by the 
Executive order and so is not subject to review under the Executive 
order. The Unfunded Mandates Reform Act does not require FDA to prepare 
a statement of costs and benefits for this final rule, because the 
final rule is not expected to result in any 1-year expenditure that 
would exceed $100 million adjusted for inflation. The current inflation 
adjusted statutory threshold is about $110 million.
    The purpose of this final rule is to establish allowable monograph 
ingredients and labeling under which OTC skin protectant drug products 
are generally recognized as safe and effective. Of the 29 active 
ingredients considered in this final rule, 19 are being included in the 
final monograph while 10 are not. Of the 10 not included, 1 is deferred 
to the final rule on OTC skin protectant diaper rash drug products and 
1 may be included pending development of a USP/NF monograph for the 
ingredient.
    Products containing the remaining eight active ingredients will 
need to be reformulated to delete and replace the ingredient(s) with 
another (monograph) skin protectant active ingredient or an inactive 
vehicle. As discussed in section II, comment 34 of this document, at 
least three and maybe five of these eight ingredients also could be 
used as inactive (vehicle) ingredients in topical drug products. 
Therefore, some of these manufacturers may be able to relabel their 
products without reformulations to comply with this rule.
    The agency's Drug Listing System identifies approximately 4,000 
drug products containing these 8 ingredients; however, only a limited 
number of these products list these ingredients as active for a skin 
protectant drug product (table 2) in the next paragraph of this 
document.

Table 2.--Number of Marketers and Products Listing Ingredients as Active
------------------------------------------------------------------------
         Ingredient             No. of Marketers       No. of Products
------------------------------------------------------------------------
Beeswax                       2                     2
Boric acid                    21                    22
Cetyl alcohol                 3                     9
------------------------------------------------------------------------

    The cost to reformulate a product will vary greatly depending on 
the nature of the change in formulation, the product, the process, and 
the size of the firm. Some of the 33 manufacturers of the 50 products 
containing nonmonograph active ingredients may not have to reformulate. 
For those products that need reformulation, the cost can be 
significant. Because of the large number of monograph active 
ingredients available for reformulation, no manufacturer should need to 
change its

[[Page 33373]]

dosage form; however, it will have to redo the validation (product, 
process, new supplier), conduct stability tests, and change master 
production records. The agency estimates the cost of reformulation to 
range from $100,000 to $500,000. Therefore, if all 50 products are 
reformulated, the midpoint of the cost estimate implies total costs of 
$15 million. However, the agency believes the total costs will be much 
smaller because not all manufacturers will have to reformulate and some 
may choose to discontinue a product line if sales are too low to 
justify the added cost and/or they also produce substitute products 
that do not require reformulation.
    Because these products must be manufactured in compliance with the 
pharmaceutical current good manufacturing practices (21 CFR parts 210 
and 211), all firms would have the necessary skills and personnel to 
perform these tasks either in-house or by contractual arrangement. No 
additional professional skills are needed.
    This final rule establishes the monograph for OTC skin protectant 
drug products and will require relabeling of all products covered by 
the monograph. The agency's Drug Listing System identifies 
approximately 1,300 OTC skin protectant drug products containing the 29 
ingredients covered by this final rule. It is likely that there are a 
number of additional products that are not currently included in the 
agency's system. Also, as indicated previously, a number of the skin 
protectant ingredients can be and often are used as inactive 
ingredients in many of the OTC drug products included in the Drug 
Listing System. While it is difficult to determine an exact number, the 
agency estimates that 2,000 to 2,500 OTC stockkeeping units (SKUs) 
(individual products, packages, and sizes) will need to be relabeled 
based on this final rule. Based on information in the Drug Listing 
System, the agency estimates there are at least 200 manufacturers and 
700 marketers of these products. Marketers, however, generally do not 
incur these costs because manufacturers of OTC drug products are 
usually responsible for product labeling, testing, and formulation.
    Estimates of relabeling costs for the type of changes required by 
this rule vary greatly and range from $500 to $15,000 per SKU depending 
on whether the products are nationally branded or private label. The 
agency assumes the same weighted average cost to relabel (i.e., $3,600 
per SKU) that it estimated for the final rule requiring uniform label 
formats of OTC drug products (64 FR 13254 at 13279 to 13281). Assuming 
2,000 to 2,500 affected OTC SKUs in the marketplace, total one-time 
costs of relabeling would be $7.2 to $9.0 million. Because frequent 
labeling redesigns are a recognized cost of doing business in the OTC 
drug industry, these costs may be less. Manufacturers that make 
voluntary market-driven changes to their labeling during the 
implementation period can implement the regulatory requirements for a 
nominal cost. The final rule would not require any new reporting or 
recordkeeping activities.
    This final rule may have an economic impact on some small entities. 
The agency's Drug Listing System indicates that about 700 marketers 
will need to relabel, and that this relabeling will be prepared by 
about 200 manufacturers, most of which are private label or contract 
manufacturers. Based on the Small Business Administration's 
determination that a small firm in this industry has fewer than 750 
employees, roughly 70 percent of the firms are considered small. The 
economic impact on any particular firm is very difficult to measure, 
because it will vary with the type and number of products affected, the 
number of SKUs per product, and the ability to coordinate these label 
changes with those required for other purposes. For example, assuming 
average industry costs, a small company that had 5 products with 3 SKUs 
each, for a total of 15 SKUs, would experience a one-time cost of 
$54,000 (15 x $3,600). A small private label manufacturer with the same 
product line and 10 customers per SKU, for a total of 150 SKU's, would 
experience a one-time cost of $540,000 (150 x $3,600). If one or more 
products needed to be reformulated, the costs would increase by 
$100,000 to $500,000 per reformulation. Some of these relabeling costs 
may be mitigated to the extent that manufacturers can coordinate this 
relabeling with relabeling requirements for the standardized format and 
content labeling requirements of OTC drug products (Sec.  201.66) and 
the sunscreen rule. Products with annual sales less than $25,000 have 1 
additional year. Therefore, many of the labeling revisions may be done 
in the normal course of business. These steps should help to minimize 
the impact on small entities by providing enough time for 
implementation to enable entities to use up existing labeling stock. 
The agency believes that these actions provide substantial flexibility 
and reductions in cost for small entities.
    The agency considered but rejected several labeling alternatives: 
(1) A shorter or longer implementation period, and (2) an exemption 
from coverage for small entities. While the agency believes that 
consumers would benefit from having this new labeling in place as soon 
as possible, a longer time period would unnecessarily delay the benefit 
of new labeling and revised formulations, where applicable, to 
consumers. The agency rejected an exemption for small entities because 
the new labeling and revised formulations, where applicable, are also 
needed by consumers who purchase products marketed by those entities. 
However, a longer (24-month) compliance date is being provided for 
products with annual sales less than $25,000.
    This analysis shows that the agency has undertaken important steps 
to reduce the burden to small entities. Thus, this economic analysis, 
together with other relevant sections of this document, serves as the 
agency's final regulatory flexibility analysis, as required under the 
Regulatory Flexibility Act.

VII. Paperwork Reduction Act of 1995

    FDA concludes that the labeling requirements 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 
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)).

VIII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between National Government and the States, 
or on the distribution of power and responsibilities among the various 
levels of government. Accordingly, the agency has concluded that the 
rule does not contain policies that have federalism implications as 
defined in the Executive order and, consequently, a federalism summary 
impact statement is not required.

IX. 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

[[Page 33374]]

nor an environmental impact statement is required.

X. Request for Comments

    This final rule includes reduced labeling requirements for products 
formulated and labeled as a lip protectant that meet the criteria 
established in Sec.  201.66(d)(10) (see Sec.  347.60(e)); for products 
containing only cocoa butter, petrolatum, or white petrolatum 
identified in Sec.  347.10(d), (m), and (r), used singly or in 
combination with each other, and marketed other than as a lip 
protectant (see Sec.  347.60(f)); for sunscreen drug products labeled 
for use only on specific small areas of the face (e.g., lips, nose, 
ears, and/or around eyes) and that meet the criteria established in 
Sec.  201.66(d)(10) (see Sec.  352.52(f)); and for combinations of skin 
protectant and sunscreen active ingredients (see Sec.  352.60(b)(2), 
(c), and (d)). Some of this reduced labeling results from the modified 
labeling format for OTC drug products in Sec.  201.66(d)(10), which did 
not exist when the TFM and amended TFM were published. Some of this 
reduced labeling is in response to comments specifically addressing 
petrolatum and white petrolatum, which the agency has extended to cocoa 
butter. The agency is providing 90 days for comment on the specific 
labeling requirements discussed in this section. Comments should be 
identified with the docket number found in brackets in the heading of 
this document. Three copies of all mailed comments are to be submitted. 
Individuals submitting written comments or anyone submitting electronic 
comments may submit one copy. Received comments may be seen in the 
Dockets Management Branch (see ADDRESSES) between 9 a.m. and 4 p.m., 
Monday through Friday. If the comments justify a change in labeling, 
the agency will propose to amend the final monographs accordingly at a 
later date. Because the amendment process can take a significant period 
of time, manufacturers of the products covered by this final rule 
should implement the labeling stated therein at this time, unless the 
compliance date has been stayed.

XI. References

    The following references are on display in the Dockets Management 
Branch (see ADDRESSES) and may be seen by interested persons between 9 
a.m. and 4 p.m., Monday through Friday.
    1. The United States Pharmacopeia 24--National Formulary 19, 
United States Pharmacopeial Convention, Inc., Rockville, MD, pp. 
2107-2118, 1999.
    2. Physicians' Desk Reference for Nonprescription Drugs and 
Dietary Supplements, 20th ed., Medical Economics Co., Inc., 
Montvale, NJ, pp. 214-218, 1999.
    3. ``Emollients'' and ``Skin Protectants,'' in Drug Facts and 
Comparisons, Facts and Comparisons, Inc., St. Louis, MO, pp. 608-
612, 1992.
    4. Billow, J. A., ``Dermatologic Products,'' in Handbook of 
Nonprescription Drugs, 10th ed., American Pharmaceutical 
Association, Washington, DC, pp. 521-541, 1993.
    5. ``Balsams and Resins'' in Martindale, The Extra Pharmacopeia 
28th ed., edited by J. E. F. Reynolds, The Pharmaceutical Press, 
London, England, p. 314, 1982.
    6. Remington's Pharmaceutical Sciences, 15th ed., Mack 
Publishing Co., Easton, PA, p. 715, 1975.
    7. Comment No. C00045, Docket No. 78N-0021, Dockets Management 
Branch.
    8. The United States Pharmacopeia 26--National Formulary 21, 
United States Pharmacopeial Convention, Inc., Rockville, MD, p. 225, 
2002.
    9. Gosselin, R. E. et al., Clinical Toxicology of Commercial 
Products, 4th ed., Williams and Wilkins, Baltimore, MD, pp. 156-157, 
1976.
    10. Cullen, S. I., Al. Tonkin, and F. E. May, ``Allergic Contact 
Dermatitis to Compound Tincture of Benzoin Spray,'' The Journal of 
Trauma 14:348-350, 1974.
    11. Rademaker, M. and J. D. T. Kirby, ``Contact Dermatitis to a 
Skin Adhesive,'' Contact Dermatitis 16:297-298, 1987.
    12. Fisher, A. A., Contact Dermatitis, 3d ed., Lea and Febiger, 
Philadelphia, PA, pp. 665-671, 1986.
    13. Marks, J. G. and M. A. Rainey, ``Cutaneous Reactions To 
Surgical Preparations and Dressings,'' Contact Dermatitis 10:1-5, 
1984.
    14. James, W. D., S. W. White, and B. Yanklowitz, ``Allergic 
Contact Dermatitis to Compound Tincture of Benzoin,'' Journal of the 
American Academy of Dermatology 11:847-850, 1984.
    15. Hoffman, T. E. and R. M. Adams, ``Contact Dermatitis to 
Benzoin in Greasepaint Makeup,'' Contact Dermatitis 4:379-380, 1978.
    16. Fisher, A. A., ``Dermatitis of the Hands from Food 
Additives,'' Current Contact News, Cutis 30:304, 308, 312, 318, 414, 
1982.
    17. Lynfield, Y. L., L. P. Pertschuk, and A. Zimmerman, 
``Pemphigus Erythematosus Provoked by Allergic Contact Dermatitis,'' 
Archives of Dermatology 108:690-693, 1973.
    18. Kokelj, F. and A. Contarutti, ``Contact Dermatitis in Leg 
Ulcers,'' Contact Dermatitis 15:47-49, 1986.
    19. Gough, D. C. S. and N. Lawton, ``Circumcision--Which 
Dressing?,'' British Journal of Urology 65:418-419, 1990.
    20. Letter from W. E. Gilbertson, FDA, to L. Gilson, Otis Clapp 
& Son, Inc., coded ANS002, Docket No. 78N-0301, Dockets Management 
Branch.
    21. OTC Vol. 160034.
    22. OTC Vol. 160165.
    23. Comment No. C00062, Docket No. 78N-0021, Dockets Management 
Branch.
    24. Physicians' Desk Reference for Nonprescription Drugs, 11th 
ed., Medical Economics Co., Inc., Oradell, NJ, p. 606, 1990.
    25. Comments No. C0001 and SUP1, Docket No. 78N-021P, Dockets 
Management Branch.
    26. Letters from J. S. Davis, FDA, to J. G. Valentino, U.S.P.C., 
dated April 10, 1990, and August 7, 1990, included in OTC Vol. 
06DFM, Docket No. 78N-0021, Dockets Management Branch.
    27. Pharmacopeial Forum, The United States Pharmacopeial 
Convention, Inc., Rockville, MD, pp. 2798-2799, January through 
February 1992.
    28. Seventh Supplement to The United States Pharmacopeia 22--
National Formulary 17, The United States Pharmacopeial Convention, 
Inc., Rockville, MD, p. 3034, 1992.
    29. Grais, M. L., ``Role of Colloidal Oatmeal in Dermatologic 
Treatment of the Aged,'' A.M.A. Archives of Dermatology and 
Syphilology 68:402-407, 1953.
    30. Friedman, B. E. and M. L. Sabia, ``Chiropodical Aspects of 
Over Treatment Dermatitis,'' in Comment SUP1, Docket No. 78N-021P, 
Dockets Management Branch.
    31. Freeman, D. W., ``Tape Dermatitis and Podiatry,'' in Comment 
SUP1, Docket No. 78N-021P, Dockets Management Branch.
    32. Ignatoff, W. B., ``The Use of Colloidal Oatmeal Therapy in 
Chiropody,'' in Comment SUP1, Docket No. 78N-021P, Dockets 
Management Branch.
    33. K[uuml]rner, H., ``Report on Therapeutic Experience With the 
Aveeno Series,'' Zeitschrift f[uuml]r Hautkrankheiten 50:631-635, 
1975, Translation from German in Comment SUP1, Docket No. 78N-021P, 
Dockets Management Branch.
    34. O'Brasky, L., ``Management of Extensive Dry Skin 
Conditions,'' Connecticut Medicine 23:20-21, 1959.
    35. Whyte, H. J., ``Atopic Dermatitis,'' in OTC Vol. 160070.
    36. Lewis, G. M. and C. E. Wheeler, Jr., ``Practical 
Dermatology,'' in OTC Vol. 160070.
    37. Davis, R. G., ``Pityriasis Rosea,'' in Current Therapy, p. 
634-635, 1973, in OTC Vol. 160070.
    38. Kierland, R. R. and M. Ede, ``New Type of Colloid Bath,'' 
A.M.A. Archives of Dermatology and Syphilology 63:502, 1951.
    39. Epstein, W. L., ``Contact Dermatitis,'' in OTC Vol. 160070.
    40. Glaser, J., ``Treatment of Atopic Dermatitis'' in Allergy in 
Childhood, p. 111, 1965.
    41. Drug Evaluations, 1st ed., American Medical Association, 
Chicago, IL, p. 492, 1971.
    42. Leibsohn, E., ``The Erythemas,'' in Current Therapy, 1982, 
in Comment SUP1, Docket No. 78N-021P, Dockets Management Branch.
    43. Dick, L. A., ``Colloidal Emollient Baths in Geriatric 
Dermatoses,'' Skin 1:89-91, 1962.
    44. Sulzberger, M. D. et. al., ``Principles of Topical 
Medication,'' in Dermatology: Diagnosis and Treatment, 2d ed., The 
Year Book Publishers, Inc., Chicago, IL, pp. 41-43, 1961, in Comment 
SUP1, Docket No. 78N-021P, Dockets Management Branch.
    45. Sompayrac, L. M. and C. Ross, ``Colloidal Oatmeal in Atopic 
Dermatitis of the Young,'' The Journal of the Florida Medical 
Association 45:1411-1412, 1959.

[[Page 33375]]

    46. OTC Vol. 160069.
    47. Smith, G. H., ``Diaper Rash and Prickly Heat Products,'' in 
Handbook of Nonprescription Drugs, 10th ed., American Pharmaceutical 
Association, Washington, DC, p. 546, 1993.
    48. Wormser, H., ``Poison Ivy and Poison Oak Products,'' in 
Handbook of Nonprescription Drugs, 10th ed., American Pharmaceutical 
Association, Washington, DC, p. 589-596, 1993.
    49. Physicians' Desk Reference for Nonprescription Drugs, 15th 
ed., Medical Economics Data Production Co., Montvale, NJ, pp. 673 
and 674, 1994.
    50. Fabrizi, G., P. Morganti, and L. Cataldi, ``Effecto Barriera 
Dell'Avena Colloidale in Dermatologia Pediatrica,'' Chronica 
Dermatologica 12:465-468, 1981.
    51. Raab, W., ``Allergologic and Clinical Trials with Aveeno 
Baby Cream,'' December 31, 1980, in Comment SUP1, Docket No. 78N-
021P, Dockets Management Branch.
    52. Fisher, A. A., ``Pruritus Ani and Vulvae,'' in Current 
Therapy--1982, edited by H. F. Conn, W. B. Saunders Co., 
Philadelphia, PA, pp. 686-688, 1982.
    53. Barkoff, J. R., ``Pruritus Ani and Vulvae,'' in Current 
Therapy--1973, edited by H. F. Conn, W. B Saunders Co., 
Philadelphia, PA, pp. 639-641, 1973.
    54. Lewis, G. M. and C. E. Wheeler, Jr., Practical Dermatology, 
3d ed., W. B. Saunders Co., Philadelphia, PA, p. 630, 1967.
    55. Comment No. C77, Docket No. 78N-0301, Dockets Management 
Branch.
    56. Letter from W. E. Gilbertson, FDA, to G. L. Carlson, S. C. 
Johnson & Son, Inc., coded LET 25, Docket No. 78N-0021, Dockets 
Management Branch.
    57. Dick, L., ``Colloidal Emollient Baths in Pediatric 
Dermatoses,'' Archives of Pediatrics 75:506-508, 1958.
    58. Franks, A. G., ``Dermatologic Uses of Baths,'' American 
Practitioner and Digest of Treatment 9:1998-1999, 1958.
    59. Smith, G. C., ``The Treatment of Various Dermatoses 
Associated With Dry Skin,'' Journal of the South Carolina Medical 
Association 54:282, 1958.
    60. Memorandum of telephone conversation between G. L. Carlson, 
S. C. Johnson & Son, Inc., and T. North, FDA, dated June 20, 1994, 
in OTC Vol. 06DFM, Docket No. 78N-0021, Dockets Management Branch.
    61. Summary Minutes of the Twenty-Third Meeting of the Advisory 
Review Panel on OTC Miscellaneous External Drug Products, January 29 
and 30, 1978, included in OTC Vol. 06DFM, Docket No. 78N-0021, 
Dockets Management Branch.
    62. ``Bath Dermatologicals Emollient Preparations,'' in Drug 
Facts and Comparisons, Facts & Comparisons, Inc., St. Louis, MO, p. 
613, 1992.
    63. Labeling for Aveeno Bath and Aveeno Bath Oilated for Dry 
Skin, in OTC Vol. 06DFM, Docket No. 78N-0021, Dockets Management 
Branch.
    64. Perry, H. O., ``Treatment of Bullous Dermatoses'' in 
Pharmaceutical Therapeutics in Dermatology, edited by M. Waisman, 
Charles C. Thomas, Springfield, IL, pp. 141-142, 1968.
    65. Kligman, A. M., M. W. Greaves, and H. Steinman, ``Water-
induced Itching Without Cutaneous Signs,'' Archives of Dermatology 
122:183-186, 1986.
    66. Bartlett, B. H., ``Atopic Dermatitis: Aetiology and 
Management,'' Current Therapeutics, 18:41-8, 1977.
    67. Verbov, J., ``Atopic Dermatitis,'' The Practitioner 223:820-
825, 1979.
    68. Transcript of the Twenty-Third Meeting of the Advisory 
Review Panel on OTC Miscellaneous External Drug Products, January 
29, 1978, p. 98, in OTC Vol. 06DFM, Docket No. 78N-0021, Dockets 
Management Branch.
    69. OTC Vol. 160167.
    70. Letter from W. E. Gilbertson, FDA, to H. Dickstein, Warner-
Lambert Co., coded LET27, Docket No. 78N-0021, Dockets Management 
Branch.
    71. The United States Pharmacopoeia 22--National Formulary 17, 
United States Pharmacopeial Convention, Inc., Rockville, MD, p. 
1931, 1989.
    72. OTC Vol. 160179.
    73. Kligman, A. M. et al., ``Some Aspects of Dry Skin and Its 
Treatment,'' in Safety and Efficacy of Topical Drugs and Cosmetics, 
edited by A. M. Kligman and J. J. Leyden, Grune & Stratton, Inc., 
New York, NY, pp. 221, 235, 1982.
    74. Physicians' Desk Reference for Nonprescription Drugs and 
Dietary Supplements, 20th ed., Medical Economics Co., Inc., 
Montvale, NJ, p. 738, 1999.
    75. Handbook of Nonprescription Drugs, 10th ed., American 
Pharmaceutical Association, Washington, pp. 840-853, 1993.
    76. Letter from H. Jenkins, Summit Industries, Inc., to G. 
Rachanow, FDA, in OTC Vol. 06DFM, Docket No. 78N-0021, Dockets 
Management Branch.
    77. Kaplan, J. Z., ``Acceleration of Wound Healing by a Live 
Yeast Cell Derivative,'' study WM-185 dated April 5, 1983, submitted 
by Whitehall Laboratories, Comment No. C00034, vol. I, section I-A, 
Docket No. 78N-0021, Dockets Management Branch.
    78. Kaplan, J. Z., ``A Comparison of the Efficacy and Safety of 
Live Yeast Cell Derivative in Ointment Base (no Shark Liver Oil) vs. 
Ointment Base (no Live Yeast Cell Derivative and no Shark Liver Oil) 
As A Wound Healing Accelerator in Skin Graft Donor Sites,'' study 
WM-288, dated January 22, 1985, submitted by Whitehall Laboratories, 
Comment No. LET 12, vol. I, appendix 1 (medical summary) and vol. II 
(case report forms), Docket No. 78N-0021, Dockets Management Branch.
    79. Comment No. SUP, Docket No. 78N-0021, Dockets Management 
Branch.
    80. Kaplan, J. Z., ``Acceleration of Wound Healing by a Live 
Yeast Cell Derivative,'' updated May 5, 1983, to include supporting 
raw data, submitted by Whitehall Laboratories, Comment No. AMD, 
Docket No. 78N-0021, Dockets Management Branch.
    81. Statistical evaluations, reviews, and statements submitted 
by Whitehall Laboratories, Comment No. C00034, vol. I, sections I-B 
through I-F, Docket No. 78N-0021, Dockets Management Branch.
    82. Comment No. C00057, Docket No. 78N-0021, Dockets Management 
Branch.
    83. Comment No. LET 11, Docket No. 78N-0021, Dockets Management 
Branch.
    84. Comment No. LET 12, vol. I, appendix 2 and appendix 3, 
Docket No. 78N-0021, Dockets Management Branch.
    85. Comment No. LET 13, Docket No. 78N-0021, Dockets Management 
Branch.
    86. Comment No. LET 14, Docket No. 78N-0021, Dockets Management 
Branch.
    87. Comment No. C00034, vol. II, Docket No. 78N-0021, Dockets 
Management Branch.
    88. Comment No. C00059, Docket No. 78N-0021, Dockets Management 
Branch.
    89. Comment No. C00061, Docket No. 78N-0021, Dockets Management 
Branch.
    90. Kaplan, J. Z., ``Acceleration of Wound Healing by a Live 
Yeast Cell Derivative,'' Archives of Surgery, 119:1005-1008, 1984.
    91. Letter from W. E. Gilbertson, FDA, to S. F. Barshay, 
Whitehall Laboratories, coded LET 10, Docket No. 78N-0021, Dockets 
Management Branch.
    92. Letter from W. E. Gilbertson, FDA, to E. V. Henry, Whitehall 
Laboratories, coded LET 26, Docket No. 78N-0021, Dockets Management 
Branch.
    93. Letter from W. E. Gilbertson, FDA, to E. V. Henry, Whitehall 
Laboratories, coded LET 15, Docket No. 78N-0021, Dockets Management 
Branch.
    94. Letter from W. E. Gilbertson, FDA, to E. V. Henry, Whitehall 
Laboratories, coded LET 18, Docket No. 78N-0021, Dockets Management 
Branch.
    95. Letter from W. E. Gilbertson, FDA, to J. R. Jacobs, 
Whitehall Laboratories, coded LET 21, Docket No. 78N-0021, Dockets 
Management Branch.
    96. OTC Vol. 160060.
    97. OTC Vol. 160052.
    98. OTC Vol. 160086.
    99. Oser, B. L. et al., ``Toxicologic Studies of Petrolatum in 
Mice and Rats,'' Toxicology and Applied Pharmacology 7:382-401, 
1965.
    100. Foods Chemicals Codex, 3d ed., National Academy Press, 
Washington, DC, p. 221, 1981.
    101. Lyght, E. E., ed., The Merck Manual, 9th ed., Merck & Co., 
Rahway, NJ, p. 1756, 1956.
    102. Sollmann, T., A Manual of Pharmacology, 7th ed., W. B. 
Saunders Co., Philadelphia, PA, p. 122, 1948.
    103. Schalek, A., Fundamentals of Dermatology, 2d ed., Lea & 
Febiger, Philadelphia, PA, p. 34, 1931.
    104. Tobias, N., Essentials of Dermatology, 4th ed., J. B. 
Lippincott Co., Philadelphia, PA, p. 552, 1952.

List of Subjects

21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

21 CFR Parts 347 and 352

    Labeling, Over-the-counter drugs.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
310, 347, and 352 are amended as follows:

[[Page 33376]]

PART 310--NEW DRUGS

0
1. The authority citation for 21 CFR part 310 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262, 
263b-263n.

0
2. Section 310.545 is amended by revising paragraphs (a)(18)(i), 
(a)(18)(v), (a)(18)(vi), and (d)(1), and by adding paragraph (d)(32) to 
read as follows:


Sec.  310.545  Drug products containing certain active ingredients 
offered over-the-counter (OTC) for certain uses.

    (a) * * *
    (18) * * *
    (i)(A) Ingredients--Approved as of May 7, 1991.
Allantoin (wound healing claims only)
Sulfur
Tannic acid
Zinc acetate (wound healing claims only)
    (B) Ingredients--Approved as of June 4, 2004; June 6, 2005, for 
products with annual sales less than $25,000.
Beeswax
Bismuth subnitrate
Boric acid
Cetyl alcohol
Glyceryl stearate
Isopropyl palmitate
Live yeast cell derivative
Shark liver oil
Stearyl alcohol
* * * * *
    (v) Insect bite and sting drug products.
    (A) Ingredients--Approved as of May 7, 1991.
Alcohol
Alcohol, ethoxylated alkyl
Ammonia solution, strong
Ammonium hydroxide
Benzalkonium chloride
Camphor
Ergot fluid extract
Ferric chloride
Menthol
Peppermint oil
Phenol
Pyrilamine maleate
Sodium borate
Trolamine
Turpentine oil
Zirconium oxide
    (B) Ingredients--Approved as of June 4, 2004; June 6, 2005, for 
products with annual sales less than $25,000.
Beeswax
Bismuth subnitrate
 Boric acid
Cetyl alcohol
Glyceryl stearate
Isopropyl palmitate
Live yeast cell derivative
Shark liver oil
 Stearyl alcohol
    (vi) Poison ivy, poison oak, and poison sumac drug products.
    (A) Ingredients--Approved as of May 7, 1991.
Alcohol
Anion and cation exchange resins buffered
Benzethonium chloride
Benzocaine
Benzyl alcohol
Bismuth subnitrate
Bithionol
Boric acid
Camphor
Cetalkonium chloride
Chloral hydrate
Chlorpheniramine maleate
Creosote
Diperodon hydrochloride
Diphenhydramine hydrochloride
Eucalyptus oil
Ferric chloride
Glycerin
Hectorite
Hydrogen peroxide
Impatiens biflora tincture
Iron oxide
Isopropyl alcohol
Lanolin
Lead acetate
Lidocaine
Menthol
Merbromin
Mercuric chloride
Panthenol
Parethoxycaine hydrochloride
Phenol
Phenyltoloxamine dihydrogen citrate
Povidone-vinylacetate copolymers
Salicylic acid
Simethicone
Tannic acid
Topical starch
Trolamine
Turpentine oil
Zirconium oxide
Zyloxin
    (B) Ingredients--Approved as of June 4, 2004; June 6, 2005, for 
products with annual sales less than $25,000.
Beeswax
Bismuth subnitrate
Boric acid
Cetyl alcohol
Glyceryl stearate
Isopropyl palmitate
Live yeast cell derivative
Shark liver oil
Stearyl alcohol
* * * * *
    (d) * * *
    (1) May 7, 1991, for products subject to paragraphs (a)(1) through 
(a)(2)(i), (a)(3)(i), (a)(4), (a)(6)(i)(A), (a)(6)(ii)(A), (a)(7) 
(except as covered by paragraph (d)(3) of this section), (a)(8)(i), 
(a)(10)(i) through (a)(10)(iii), (a)(12)(i) through (a)(12)(iv)(A), 
(a)(14) through (a)(15)(i), (a)(16) through (a)(18)(i)(A), (a)(18)(ii) 
(except as covered by paragraph (d)(22) of this section), (a)(18)(iii), 
(a)(18)(iv), (a)(18)(v)(A), and (a)(18)(vi)(A) of this section.
* * * * *
    (32) June 4, 2004, for products subject to paragraphs 
(a)(18)(i)(B), (a)(18)(v)(B), and (a)(18)(vi)(B) of this section. June 
6, 2005, for products with annual sales less than $25,000.

PART 347--SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN 
USE

0
3. The authority citation for 21 CFR part 347 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.

0
4. Part 347 is amended by revising the heading for subpart A to read as 
follows:

Subpart A--General Provisions

* * * * *

0
5. Section 347.3 is revised to read as follows:


Sec.  347.3  Definitions.

    As used in this part:
    Astringent drug product. A drug product applied to the skin or 
mucous membranes for a local and limited protein coagulant effect.
    Lip protectant drug product. A drug product that temporarily 
prevents dryness and helps relieve chapping of the exposed surfaces of 
the lips; traditionally called ``lip balm.''
    Poison ivy, oak, sumac dermatitis. An allergic contact dermatitis 
due to exposure to plants of the genus Rhus (poison ivy, poison oak, 
poison sumac), which contain urushiol, a potent skin-sensitizer.
    Skin protectant drug product. A drug product that temporarily 
protects injured or exposed skin or mucous membrane surfaces from 
harmful or annoying stimuli, and may help provide relief to such 
surfaces.

[[Page 33377]]


0
6. Section 347.10 is redesignated as Sec.  347.12 and revised, and 
subpart B, consisting of a new Sec.  347.10, newly redesignated Sec.  
347.12, and new Sec.  347.20, is added to read as follows:

Subpart B--Active Ingredients

Sec.
347.10 Skin protectant active ingredients.
347.12 Astringent active ingredients.
347.20 Permitted combinations of active ingredients.

Subpart B--Active Ingredients


Sec.  347.10  Skin protectant active ingredients.

    The active ingredients of the product consist of any of the 
following, within the concentration specified for each ingredient:
    (a) Allantoin, 0.5 to 2 percent.
    (b) Aluminum hydroxide gel, 0.15 to 5 percent.
    (c) Calamine, 1 to 25 percent.
    (d) Cocoa butter, 50 to 100 percent.
    (e) Cod liver oil, 5 to 13.56 percent, in accordance with Sec.  
347.20(a)(1) or (a)(2), provided the product is labeled so that the 
quantity used in a 24-hour period does not exceed 10,000 U.S.P. Units 
vitamin A and 400 U.S.P. Units cholecalciferol.
    (f) Colloidal oatmeal, 0.007 percent minimum; 0.003 percent minimum 
in combination with mineral oil in accordance with Sec.  347.20(a)(4).
    (g) Dimethicone, 1 to 30 percent.
    (h) Glycerin, 20 to 45 percent.
    (i) Hard fat, 50 to 100 percent.
    (j) Kaolin, 4 to 20 percent.
    (k) Lanolin, 12.5 to 50 percent.
    (l) Mineral oil, 50 to 100 percent; 30 to 35 percent in combination 
with colloidal oatmeal in accordance with Sec.  347.20(a)(4).
    (m) Petrolatum, 30 to 100 percent.
    (n) [Reserved]
    (o) Sodium bicarbonate.
    (p) [Reserved]
    (q) Topical starch, 10 to 98 percent.
    (r) White petrolatum, 30 to 100 percent.
    (s) Zinc acetate, 0.1 to 2 percent.
    (t) Zinc carbonate, 0.2 to 2 percent.
    (u) Zinc oxide, 1 to 25 percent.


Sec.  347.12  Astringent active ingredients.

    The active ingredient of the product consists of any one of the 
following within the specified concentration established for each 
ingredient:
    (a) Aluminum acetate, 0.13 to 0.5 percent (depending on the 
formulation and concentration of the marketed product, the manufacturer 
must provide adequate directions so that the resulting solution to be 
used by the consumer contains 0.13 to 0.5 percent aluminum acetate).
    (b) Aluminum sulfate, 46 to 63 percent (the concentration is based 
on the anhydrous equivalent).
    (c) Witch hazel.


Sec.  347.20  Permitted combinations of active ingredients.

    (a) Combinations of skin protectant active ingredients. (1) Any two 
or more of the ingredients identified in Sec.  347.10(a), (d), (e), 
(i), (k), (l), (m), and (r) may be combined provided the combination is 
labeled according to Sec.  347.50(b)(1) and provided each ingredient in 
the combination is within the concentration specified in Sec.  347.10.
    (2) Any two or more of the ingredients identified in Sec.  
347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) may be 
combined provided the combination is labeled according to Sec.  
347.50(b)(2) and provided each ingredient in the combination is within 
the concentration specified in Sec.  347.10.
    (3) Any two or more of the ingredients identified in Sec.  
347.10(b), (c), (j), (s), (t), and (u) may be combined provided the 
combination is labeled according to Sec.  347.50(b)(3) and provided 
each ingredient in the combination is within the concentration 
specified in Sec.  347.10.
    (4) The ingredients identified in Sec.  347.10(f) and (l) may be 
combined provided the combination is labeled according to Sec.  
347.50(b)(7) and provided each ingredient in the combination is within 
the concentration specified in Sec.  347.10.
    (b) Combinations of skin protectant and external analgesic active 
ingredients. Any one (two when required to be in combination) or more 
of the active ingredients identified in Sec.  347.10(a), (d), (e), (i), 
(k), (l), (m), and (r) may be combined with any of the following 
generally recognized as safe and effective external analgesic active 
ingredients: Single amine and ``caine''-type local anesthetics, 
alcohols and ketones, antihistamines, or any permitted combination of 
these ingredients, but not with hydrocortisone, provided the product is 
labeled according to Sec.  347.60(b)(l).
    (c) Combinations of skin protectant and first aid antiseptic active 
ingredients. Any one (two when required to be in combination) or more 
of the active ingredients identified in Sec.  347.10(a), (d), (e), (i), 
(k), (l), (m), and (r) may be combined with any generally recognized as 
safe and effective single first aid antiseptic active ingredient, or 
any permitted combination of these ingredients, provided the product is 
labeled according to Sec.  347.60(b)(2).
    (d) Combinations of skin protectant and sunscreen active 
ingredients. Any one (two when required to be in combination) or more 
of the skin protectant active ingredients identified in Sec.  
347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) may be 
combined with any generally recognized as safe and effective single 
sunscreen active ingredient, or any permitted combination of these 
ingredients, provided the product meets the conditions in Sec.  
352.20(b) of this chapter and is labeled according to Sec. Sec.  
347.60(b)(3) and 352.60(b) of this chapter.

0
7. Section 347.20(d) is stayed until further notice.
0
8. Section 347.50 is redesignated as Sec.  347.52 and revised, and 
subpart C, consisting of a new Sec.  347.50, newly redesignated Sec.  
347.52, and new Sec.  347.60, is added to read as follows:

Subpart C--Labeling

Sec.
347.50 Labeling of skin protectant drug products.
347.52 Labeling of astringent drug products.
347.60 Labeling of permitted combinations of active ingredients.

Subpart C--Labeling


Sec.  347.50  Labeling of skin protectant drug products.

    A skin protectant drug product may have more than one labeled use 
and labeling appropriate to different uses may be combined to eliminate 
duplicative words or phrases as long as the labeling is clear and 
understandable. When the labeling of the product contains more than one 
labeled use, the appropriate statement(s) of identity, indications, 
warnings, and directions must be stated in the labeling.
    (a) Statement of identity. The labeling of the product contains the 
established name of the drug, if any, and identifies the product with 
one or more of the following:
    (1) For any product. ``Skin protectant'' (optional, may add dosage 
form, e.g., ``cream,'' ``gel,'' ``lotion,'' or ``ointment'').
    (2) For products containing any ingredient in Sec.  347.10(b), (c), 
(j), (s), (t), and (u). ``Poison ivy, oak, sumac drying'' (optional, 
may add dosage form, e.g., ``cream,'' ``gel,'' ``lotion,'' or 
``ointment'').
    (3) For products containing any ingredient in Sec.  347.10(b), (c), 
(f), (j), (o), (s), (t), and (u). ``Poison ivy, oak, sumac 
protectant.''
    (b) Indications. The labeling of the product states, under the 
heading ``Uses,'' one or more of the phrases listed in this paragraph 
(b), as appropriate. Other truthful and nonmisleading statements, 
describing

[[Page 33378]]

only the uses that have been established and listed in this paragraph 
(b), may also be used, as provided in Sec.  330.1(c)(2) of this 
chapter, subject to the provisions of section 502 of the Federal Food, 
Drug, and Cosmetic Act (the act) relating to misbranding and the 
prohibition in section 301(d) of the act against the introduction or 
delivery for introduction into interstate commerce of unapproved new 
drugs in violation of section 505(a) of the act.
    (1) For products containing any ingredient in Sec.  347.10(a), (d), 
(e), (i), (k), (l), (m), and (r). The labeling states ``temporarily 
protects minor: [bullet]\1\ cuts [bullet] scrapes [bullet] burns''.
---------------------------------------------------------------------------

    \1\ See Sec.  201.66(b)(4) of this chapter for definition of 
bullet symbol.
---------------------------------------------------------------------------

    (2) For products containing any ingredient in Sec.  347.10(a), (d), 
(e), (g), (h), (i), (k), (l), (m), and (r)--(i). The labeling states 
``temporarily protects'' (which may be followed by: ``and helps 
relieve'') ``chapped or cracked skin'' (which may be followed by: ``and 
lips''). This statement may be followed by the optional statement: 
``helps protect from the drying effects of wind and cold weather''. [If 
both statements are used, each is preceded by a bullet.]
    (ii) For products formulated as a lip protectant. The labeling 
states ``temporarily protects'' (which may be followed by: ``and helps 
relieve'') ``chapped or cracked lips''. This statement may be followed 
by the optional statement: ``helps protect lips from the drying effects 
of wind and cold weather''. [If both statements are used, each is 
preceded by a bullet.]
    (3) For products containing any ingredient in Sec.  347.10(b), (c), 
(j), (s), (t), and (u). The labeling states ``dries the oozing and 
weeping of poison: [bullet] ivy [bullet] oak [bullet] sumac''.
    (4) For products containing colloidal oatmeal identified in Sec.  
347.10(f). The labeling states ``temporarily protects and helps relieve 
minor skin irritation and itching due to: [select one or more of the 
following: `[bullet] rashes' `[bullet] eczema' `[bullet] poison ivy, 
oak, or sumac' `[bullet] insect bites'].''
    (5) For products containing sodium bicarbonate identified in Sec.  
347.10(o). The labeling states ``temporarily protects and helps relieve 
minor skin irritation and itching due to: [bullet] poison ivy, oak, or 
sumac [bullet] insect bites''.
    (6) For products containing topical starch identified in Sec.  
347.10(q). The labeling states ``temporarily protects and helps relieve 
minor skin irritation''.
    (7) For products containing the combination of ingredients in Sec.  
347.20(a)(4). The labeling states ``temporarily protects and helps 
relieve minor skin irritation and itching due to: [select one or more 
of the following: `rashes' or `eczema'].'' [If both conditions are 
used, each is preceded by a bullet.]
    (c) Warnings. The labeling of the product contains the following 
warnings under the heading ``Warnings'':
    (1) ``For external use only'' in accord with Sec.  201.66(c)(5)(i) 
of this chapter. For products containing only mineral oil in Sec.  
347.10(l) or sodium bicarbonate in Sec.  347.10(o), this warning may be 
omitted if labeling for oral use of the product is also provided.
    (2) ``When using this product [bullet] do not get into eyes''.
    (3) ``Stop use and ask a doctor if [bullet] condition worsens 
[bullet] symptoms last more than 7 days or clear up and occur again 
within a few days''.
    (4) For products labeled according to Sec.  347.50(b)(1) or (b)(2): 
``Do not use on [bullet] deep or puncture wounds [bullet] animal bites 
[bullet] serious burns''.
    (5) For products containing colloidal oatmeal identified in Sec.  
347.10(f) when labeled for use as a soak in a tub. ``When using this 
product [bullet] to avoid slipping, use mat in tub or shower''.
    (6) For powder products containing kaolin identified in Sec.  
347.10(j) or topical starch identified in Sec.  347.10(q)--(i) ``Do not 
use on [bullet] broken skin''.
    (ii) ``When using this product [bullet] keep away from face and 
mouth to avoid breathing it''.
    (7) For products containing colloidal oatmeal identified in Sec.  
347.10(f) or sodium bicarbonate identified in Sec.  347.10(o) when 
labeled for use as a soak, compress, or wet dressing. ``When using this 
product [bullet] in some skin conditions, soaking too long may 
overdry''.
    (d) Directions. The labeling of the product contains the following 
statements, as appropriate, under the heading ``Directions'':
    (1) For products labeled according to Sec.  347.50(b)(1), (b)(2), 
(b)(3), (b)(5), or (b)(6). The labeling states ``apply as needed''.
    (2) For products containing colloidal oatmeal identified in Sec.  
347.10(f)--(i) For products requiring dispersal in water. The labeling 
states ``[bullet] turn warm water faucet on to full force [bullet] 
slowly sprinkle'' (manufacturer to insert quantity to be used) ``of 
colloidal oatmeal directly under the faucet into the tub or container 
[bullet] stir any colloidal oatmeal settled on the bottom''.
    (A) For products used as a soak in a bath. The manufacturer must 
provide adequate directions to obtain a solution containing a minimum 
of 0.007 percent colloidal oatmeal or 0.003 percent colloidal oatmeal 
in the oilated form for a tub bath, sitz bath, or infant bath, or a 
minimum of 0.25 percent colloidal oatmeal for a foot bath. ``For use as 
a soak in a bath: [bullet] soak affected area for 15 to 30 minutes as 
needed, or as directed by a doctor [bullet] pat dry (do not rub) to 
keep a thin layer on the skin''.
    (B) For products used as a compress or wet dressing. The 
manufacturer must provide adequate directions to obtain a solution 
containing a minimum of 0.25 percent colloidal oatmeal. ``For use as a 
compress or wet dressing: [bullet] soak a clean, soft cloth in the 
mixture [bullet] apply cloth loosely to affected area for 15 to 30 
minutes [bullet] repeat as needed or as directed by a doctor [bullet] 
discard mixture after each use''.
    (ii) For topical products intended for direct application. The 
labeling states ``apply as needed''.
    (3) For products containing sodium bicarbonate identified in Sec.  
347.10(o). The labeling states ``[bullet] adults and children 2 years 
of age and over:''
    (i) The labeling states ``For use as a paste: [bullet] add enough 
water to the sodium bicarbonate to form a paste [bullet] apply to the 
affected area of the skin as needed, or as directed by a doctor''.
    (ii) The labeling states ``For use as a soak in a bath: [bullet] 
dissolve 1 to 2 cupfuls in a tub of warm water [bullet] soak for 10 to 
30 minutes as needed, or as directed by a doctor [bullet] pat dry (do 
not rub) to keep a thin layer on the skin''.
    (iii) The labeling states ``For use as a compress or wet dressing: 
[bullet] add sodium bicarbonate to water to make a mixture in a 
container [bullet] soak a clean, soft cloth in the mixture [bullet] 
apply cloth loosely to affected area for 15 to 30 minutes [bullet] 
repeat as needed or as directed by a doctor [bullet] discard mixture 
after each use''.
    (iv) Any of the directions in paragraphs (d)(3)(i), (d)(3)(ii), or 
(d)(3)(iii) of this section shall be followed by the statement: 
``[bullet] children under 2 years: ask a doctor''.
    (4) For products containing aluminum hydroxide gel identified in 
Sec.  347.10(b). The labeling states ``[bullet] children under 6 
months: ask a doctor''.
    (5) For products containing glycerin identified in Sec.  347.10(h). 
The labeling states ``[bullet] children under 6 months: ask a doctor''.
    (6) For products containing zinc acetate identified in Sec.  
347.10(s). The labeling states ``[bullet] children under 2 years: ask a 
doctor''.

[[Page 33379]]

    (e) Products formulated and labeled as a lip protectant and that 
meet the criteria established in Sec.  201.66(d)(10) of this chapter. 
The title, headings, subheadings, and information described in Sec.  
201.66(c) of this chapter shall be printed in accordance with the 
following specifications:
    (1) The labeling shall meet the requirements of Sec.  201.66(c) of 
this chapter except that the title, headings, and information described 
in Sec.  201.66(c)(1), (c)(3), (c)(6), and (c)(7) may be omitted, and 
the headings, subheadings, and information described in Sec.  
201.66(c)(2), (c)(4), and (c)(5) may be presented as follows:
    (i) The active ingredients (Sec.  201.66(c)(2) of this chapter) 
shall be listed in alphabetical order.
    (ii) The heading and the indication required by Sec.  201.66(c)(4) 
may be limited to: ``Use [in bold type] helps protect'' (which may be 
followed by ``and relieve'') ``chapped lips''.
    (iii) The ``external use only'' warning in Sec.  347.50(c)(1) and 
in Sec.  201.66(c)(5)(i) of this chapter may be omitted. The warnings 
in Sec.  347.50(c)(2) and (c)(4) are not required and the warning in 
Sec.  347.50(c)(3) may be revised to read ``Stop use and ask a doctor 
if condition lasts more than 7 days.''
    (iv) The subheadings in Sec.  201.66(c)(5)(iii) through (c)(5)(vi) 
of this chapter may be omitted, provided the information after the 
heading ``Warning'' contains the warning in Sec.  347.50(e)(1)(iii).
    (v) The warnings in Sec.  201.66(c)(5)(x) of this chapter may be 
omitted.
    (2) The labeling shall be printed in accordance with the 
requirements of Sec.  201.66(d) of this chapter except that any 
requirements related to Sec.  201.66(c)(1), (c)(3), (c)(6), and (c)(7), 
and the horizontal barlines and hairlines described in Sec.  
201.66(d)(8), may be omitted.
    (f) Products containing only cocoa butter, petrolatum, or white 
petrolatum identified in Sec.  347.10(d), (m), and (r), singly or in 
combination with each other, and marketed other than as a lip 
protectant. (1) The labeling shall meet the requirements of Sec.  
201.66(c) of this chapter except that the headings and information 
described in Sec.  201.66(c)(3) and (c)(7) may be omitted, and the 
headings, subheadings, and information described in Sec.  201.66(c)(2), 
(c)(4), and (c)(5) may be presented as follows:
    (i) The active ingredients (Sec.  201.66(c)(2) of this chapter) 
shall be listed in alphabetical order.
    (ii) The heading and the indication required by Sec.  201.66(c)(4) 
of this chapter may be limited to ``Use [in bold type] helps protect 
minor cuts and burns'' or ``Use [in bold type] helps protect chapped 
skin'' or ``Use [in bold type] helps protect minor cuts and burns and 
chapped skin''.
    (iii) The warning in Sec.  347.50(c)(3) may be revised to read 
``See a doctor if condition lasts more than 7 days.''
    (iv) The subheadings in Sec.  201.66(c)(5)(iv) through (c)(5)(vii) 
of this chapter may be omitted, provided the information after the 
heading ``Warnings'' contains the warnings in Sec.  347.50(c)(2), 
(c)(4), and (f)(1)(iii).
    (2) The labeling shall be printed in accordance with the 
requirements of Sec.  201.66(d) of this chapter except that any 
requirements related to Sec.  201.66(c)(3) and (c)(7) may be omitted.


Sec.  347.52  Labeling of astringent drug products.

    (a) Statement of identity. The labeling of the product contains the 
established name of the drug, if any, and identifies the product as an 
``astringent.''
    (b) Indications. The labeling of the product states, under the 
heading ``Uses'' any of the phrases listed in this paragraph (b), as 
appropriate. Other truthful and nonmisleading statements describing 
only the indications for use that have been established and listed in 
this paragraph (b) may also be used, as provided in Sec.  330.1(c)(2) 
of this chapter, subject to the provisions of section 502 of the 
Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding 
and the prohibition of section 301(d) of the act against the 
introduction or delivery for introduction into interstate commerce of 
unapproved new drugs in violation of section 505(a) of the act.
    (1) For products containing aluminum acetate identified in Sec.  
347.12(a). ``For temporary relief of minor skin irritations due to: 
[select one or more of the following: `poison ivy,' `poison oak,' 
`poison sumac,' `insect bites,' `athlete's foot,' or `rashes caused by 
soaps, detergents, cosmetics, or jewelry'].''
    (2) For products containing aluminum sulfate identified in Sec.  
347.12(b) for use as a styptic pencil. ``Stops bleeding caused by minor 
surface cuts and abrasions as may occur during shaving.''
    (3) For products containing witch hazel identified in Sec.  
347.12(c). ``Relieves minor skin irritations due to: [select one or 
more of the following: 'insect bites,' 'minor cuts,' or 'minor 
scrapes'].'' [If more than one condition is used, each is preceded by a 
bullet.]
    (c) Warnings. The labeling of the product contains the following 
warnings under the heading ``Warnings'':
    (1) ``For external use only. Avoid contact with the eyes.''
    (2) For products containing aluminum acetate identified in Sec.  
347.12(a) or witch hazel identified in Sec.  347.12(c). ``If condition 
worsens or symptoms persist for more than 7 days, discontinue use of 
the product and consult a'' [select one of the following: 'physician' 
or 'doctor'].''
    (3) For products containing aluminum acetate identified in Sec.  
347.12(a) used as a compress or wet dressing. ``Do not cover compress 
or wet dressing with plastic to prevent evaporation.''
    (d) Directions. The labeling of the product contains the following 
information under the heading ``Directions'':
    (1) For products containing aluminum acetate identified in Sec.  
347.12(a)--(i) For products used as a soak. ``For use as a soak: Soak 
affected area in the solution for 15 to 30 minutes. Discard solution 
after each use. Repeat 3 times a day.''
    (ii) For products used as a compress or wet dressing. ``For use as 
a compress or wet dressing: saturate a clean, soft white cloth (such as 
a diaper or torn sheet) in the solution, gently squeeze, and apply 
loosely to the affected area. Saturate the cloth in the solution every 
15 to 30 minutes and apply to the affected area. Discard solution after 
each use. Repeat as often as necessary.''
    (2) For products containing aluminum sulfate identified in Sec.  
347.12(b) for use as a styptic pencil. ``Moisten tip of pencil with 
water and apply to the affected area. Dry pencil after use.''
    (3) For products containing witch hazel identified in Sec.  
347.12(c). ``Apply to the affected area as often as necessary.''


Sec.  347.60  Labeling of permitted combinations of active ingredients.

    The statement of identity, indications, warnings, and directions 
for use, respectively, applicable to each ingredient in the product may 
be combined to eliminate duplicative words or phrases so that the 
resulting information is clear and understandable.
    (a) Statement of identity. For a combination drug product that has 
an established name, the labeling of the product states the established 
name of the combination drug product, followed by the statement of 
identity for each ingredient in the combination, as established in the 
statement of identity sections of the applicable OTC drug monographs. 
For a combination drug product that does not have an established name, 
the labeling of the product states the statement of identity for each 
ingredient in the combination, as established in the statement of 
identity sections of the applicable OTC drug monographs.
    (b) Indications. The labeling of the product states, under the 
heading

[[Page 33380]]

``Uses,'' the indication(s) for each ingredient in the combination as 
established in the indications sections of the applicable OTC drug 
monographs, unless otherwise stated in this paragraph (b). Other 
truthful and nonmisleading statements, describing only the indications 
for use that have been established in the applicable OTC drug 
monographs or listed in this paragraph (b) may also be used, as 
provided in Sec.  330.1(c)(2) of this chapter, subject to the 
provisions of section 502 of the Federal Food, Drug, and Cosmetic Act 
(the act) relating to misbranding and the prohibition in section 301(d) 
of the act against the introduction or delivery for introduction into 
interstate commerce of unapproved new drugs in violation of section 
505(a) of the act. In addition to the required information identified 
in this paragraph (b), the labeling of the product may contain any of 
the ``other allowable statements'' that are identified in the 
applicable monographs, provided such statements are neither placed in 
direct conjunction with information required to appear in the labeling 
nor occupy labeling space with greater prominence or conspicuousness 
than the required information.
    (1) Combinations of skin protectant and external analgesic active 
ingredients in Sec.  347.20(b). In addition to any or all of the 
indications for skin protectant drug products in Sec.  347.50(b)(1), 
any or all of the allowable indications for external analgesic drug 
products may be used if the product is labeled for concurrent symptoms.
    (2) Combinations of skin protectant and first aid antiseptic active 
ingredients in Sec.  347.20(c). In addition to any or all of the 
indications for skin protectant drug products in Sec.  347.50(b)(1), 
the required indications for first aid antiseptic drug products should 
be used.
    (3) Combinations of skin protectant and sunscreen active 
ingredients in Sec.  347.20(d). In addition to any or all of the 
indications for skin protectant drug products in Sec.  347.50(b)(2)(i), 
the required indications for sunscreen drug products should be used and 
any or all of the additional indications for sunscreen drug products 
may be used.
    (c) Warnings. The labeling of the product states, under the heading 
``Warnings,'' the warning(s) for each ingredient in the combination, as 
established in the warnings section of the applicable OTC drug 
monographs unless otherwise stated in this paragraph (c).
    (1) For combinations containing a skin protectant and a sunscreen 
identified in Sec. Sec.  347.20(d) and 352.20(b). The warnings for 
sunscreen drug products in Sec.  352.60(c) of this chapter are used.
    (2) [Reserved]
    (d) Directions. The labeling of the product states, under the 
heading ``Directions,'' directions that conform to the directions 
established for each ingredient in the directions sections of the 
applicable OTC drug monographs, unless otherwise stated in this 
paragraph (d). When the time intervals or age limitations for 
administration of the individual ingredients differ, the directions for 
the combination product may not contain any dosage that exceeds those 
established for any individual ingredient in the applicable OTC drug 
monograph(s), and may not provide for use by any age group lower than 
the highest minimum age limit established for any individual 
ingredient.
    (1) For combinations containing a skin protectant and a sunscreen 
identified in Sec. Sec.  347.20(d) and 352.20(b). The directions for 
sunscreen drug products in Sec.  352.60(d) of this chapter are used.
    (2) [Reserved]

PART 352--SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

0
9. The authority citation for 21 CFR part 352 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.

0
10. The stay of 21 CFR part 352 published at 66 FR 67485, December 31, 
2001, is lifted.
0
11. Section 352.20 is amended by adding paragraph (b) to read as 
follows:


Sec.  352.20  Permitted combinations of active ingredients.

* * * * *
    (b) Combinations of sunscreen and skin protectant active 
ingredients. Any single sunscreen active ingredient or any permitted 
combination of sunscreen active ingredients when used in the 
concentrations established for each ingredient in Sec.  352.10 may be 
combined with one or more skin protectant active ingredients identified 
in Sec.  347.10(a), (d), (e), (g), (h), (i), (k), (l), (m), and (r) of 
this chapter. The concentration of each sunscreen active ingredient 
must be sufficient to contribute a minimum SPF of not less that 2 to 
the finished product. The finished product must have a minimum SPF of 
not less than the number of sunscreen active ingredients used in the 
combination multiplied by 2, and the product must be labeled according 
to Sec.  352.60.

0
12. Section 352.52 is amended by revising the heading in paragraphs 
(c)(2) and (d)(4) and by revising paragraphs (f)(1)(ii) and (f)(1)(vi) 
to read as follows:


Sec.  352.52  Labeling of sunscreen drug products.

* * * * *
    (c) * * *
    (2) For products containing any ingredient identified in Sec.  
352.10 marketed as a lip protectant or lipstick. * * *
    (d) * * *
    (4) For products marketed as a lip protectant or lipstick. * * *
* * * * *
    (f) * * *
    (1) * * *
    (ii) The heading and the indication required by Sec.  201.66(c)(4) 
of this chapter may be limited to: ``Use [in bold type] helps protect 
against sunburn.'' For a lip protectant product, the heading and the 
indication required by Sec.  201.66(c)(4) may be limited to: ``Use [in 
bold type] helps protect against sunburn and chapped lips.''
* * * * *
    (vi) For a lip protectant product or lipstick, the warnings ``Keep 
out of eyes'' in Sec.  352.52(f)(1)(iv) and ``Keep out of reach of 
children'' in Sec.  352.52(f)(1)(v) and the directions in Sec.  
352.52(d) may be omitted.
* * * * *
    13. Section 352.60 is amended by revising paragraphs (b)(2), (c), 
and (d) to read as follows:


Sec.  352.60  Labeling of permitted combinations of active ingredients.

* * * * *
    (b) * * *
    (2) For permitted combinations containing a sunscreen and a skin 
protectant identified in Sec.  352.20(b), any or all of the applicable 
indications for sunscreens in Sec.  352.52(b) and the indication for 
skin protectants in Sec.  347.50(b)(2)(i) of this chapter should be 
used. For products marketed as a lip protectant, the indication in 
Sec.  352.52(f)(1)(ii) should be used.
    (c) Warnings. The labeling of the product states, under the heading 
``Warnings,'' the warning(s) for each ingredient in the combination, as 
established in the warnings section of the applicable OTC drug 
monographs, except that the warning for skin protectants in Sec.  
347.50(c)(3) of this chapter is not required for permitted combinations 
containing a sunscreen and a skin protectant identified in Sec.  
352.20(b). For products marketed as a lip protectant or lipstick, Sec.  
352.52(f)(1)(iii), (f)(1)(iv) (except

[[Page 33381]]

``Keep out of eyes,'' which may be omitted), and (f)(1)(vi) apply.
    (d) Directions. The labeling of the product states, under the 
heading ``directions,'' directions that conform to the directions 
established for each ingredient in the directions sections of the 
applicable OTC drug monographs, unless otherwise stated in this 
paragraph. When the time intervals or age limitations for 
administration of the individual ingredients differ, the directions for 
the combination product may not contain any dosage that exceeds those 
established for any individual ingredient in the applicable OTC drug 
monograph(s), and may not provide for use by any age group lower than 
the highest minimum age limit established for any individual 
ingredient. For permitted combinations containing a sunscreen and a 
skin protectant identified in Sec.  352.20(b), the directions for 
sunscreens in Sec.  352.52(d) should be used. For products marketed as 
a lip protectant or lipstick, Sec.  352.52(d)(4) applies.

0
14. Part 352 is stayed until further notice.

    Dated: May 16, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-13751 Filed 6-3-03; 8:45 am]

BILLING CODE 4160-01-S