[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]
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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.
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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