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27666 Federal Register/ Vol . 64 , No. 98 / Fr id ay , May 21, 1999 / Rules an d Regu la tion s

* * * EFFECTIVE UPON PUBLICATION

FDC date State City Airport FDC No. SIAP

04/29/99 .... .. . PA STATE COLLEGE .... ... ... . UNIVERSITY PARK ..... ... .. ... .. ... .. ... ... .. . 9/2846 VOR/DME RNAV or GPS RWY 6AMDT 6

04/29/99 .... .. . PA STATE COLLEGE .... ... ... . UNIVERSITY PARK ..... ... .. ... .. ... .. ... ... .. . 9/2847 VOR or GPSB AMDT 904/29/99 ....... WI APPLETON ..................... OUTAGAMIE COUNTY REGIONAL ... 9/2851 ILS RWY 3, AMDT 16C

04/30/99 .... .. . MO BUTLER .... ... .. ... .. ... .. ... ... . BUTLER MEMORIAL ... ... .. ... .. ... ... .. ... .. . 9/2875 GPS RWY 18, ORIG04/30/99 .... .. . TX AUSTIN ..... .. ... .. ... .. ... ... .. .. AUSTIN-BERGSTROM INTL ... ... .. ... ... . 9/2879 ILS RWY 35L, AMDT 104/30/99 .... .. . TX AUSTIN ..... .. ... .. ... .. ... ... .. .. AUSTIN-BERGSTROM INTL ... ... .. ... ... . 9/2880 GPS RWY 35L, AMDT 104/30/99 .... .. . TX AUSTIN ..... .. ... .. ... .. ... ... .. .. AUSTIN-BERGSTROM INTL ... ... .. ... ... . 9/2881 GPS RWY 17R, AMDT 104/30/99 .... .. . TX AUSTIN ..... .. ... .. ... .. ... ... .. .. AUSTIN-BERGSTROM INTL ... ... .. ... ... . 9/2882 ILS RWY 17R, AMDT 105/1/99 ... ... .. . NH MANCHESTER ...... .. ... .. .. MANCHESTER .... ... .. ... .. ... .. ... ... .. ... .. ... . 9/3102 ILS RWY 2, AMDT 205/1/99 ... ... .. . NH MANCHESTER ...... .. ... .. .. MANCHESTER .... ... .. ... .. ... .. ... ... .. ... .. ... . 9/3103 ILS RWY 35, AMDT 1905/04/99 ....... IL CHICAGO/AURORA ....... AURORA MUNI ................................... 9/2970 VOR or GPSA AMDT 1A05/05/99 ....... IL CHICAGO/AURORA ....... AURORA MUNI ................................... 9/2983 ILS RWY 9, AMDT 1A05/06/99 .... .. . OH MIDDLETOWN ..... .. ... .. ... . HOOK FIELD MUNI ..... .. ... .. ... .. ... ... .. ... . 9/3009 LOC RWY 23, AMDT 7B05/06/99 .... .. . OH MIDDLETOWN ..... .. ... .. ... . HOOK FIELD MUNI ..... .. ... .. ... .. ... ... .. ... . 9/3010 NDB or GPS RWY 23, AMDT 8A05/06/99 .... .. . OH MIDDLETOWN ..... .. ... .. ... . HOOK FIELD MUNI ..... .. ... .. ... .. ... ... .. ... . 9/3011 NDB or GPSA, AMDT 2A05/10/99 .... .. . MN WORTHINGTON .... .. ... ... . WORTHINGTON MUNI .... .. ... .. ... .. ... ... . 9/3086 NDB or GPS RWY 29, ORIG05/10/99 ....... MN WORTHINGTON ............. WORTHINGTON MUNI ....................... 9/3088 ILS RWY 29, ORIG05/10/99 .... .. . VA RICHMOND .... ... .. ... ... .. ... . CHESTERFIELD COUNTY ..... ... .. ... ... . 9/3074 NDB or GPS RWY 33, AMDT 7A05/10/99 .... .. . VA RICHMOND .... ... .. ... ... .. ... . CHESTERFIELD COUNTY ..... ... .. ... ... . 9/3075 VOR/DME or GPS RWY 15, ORIG05/10/99 ....... VA RICHMOND ..................... CHESTERFIELD COUNTY ................. 9/3082 ILS RWY 33, ORIG

[FR Doc. 9912949 Filed 52099; 8:45 am]

BILLING CODE 491013M

DEPARTMENT OF HEALTH ANDHUMAN SERVICES

Food and Drug Administration

21 CFR Parts 310, 352, 700, and 740

[Docket No. 78N0038]

RIN 0910AA01

Sunscreen Drug Products For Over-The-Counter Human Use; FinalMonograph

AGENCY: Food and Drug Administration,HHS.

ACTION: Final rule.

SUMMARY: The Food and DrugAdm inistration (FDA) is issuing a finalrule in th e form of a final monographestablishing cond itions u nder whichover-the-counter (OTC) sun screen dru gprod ucts are generally recognized assafe and effective and n ot misbrand ed aspar t of FDAs ongoin g review of OTCdru g produ cts. FDA is issuing this finalrule after considering public commen tson th e agencys proposed regulation,which was issued in the form of atentative final monograph, and new dataand information on su nscreen d rugprod ucts that h ave come to the agencysattention. FDA is also issuing final rulesregarding the labeling of certaincosmetic products to inform consumersthat these products do not p rovideprotection from the su n.

EFFECTIVE DATES: This regulation iseffective May 21, 2001 for parts 310,352, and 700 and is effective May 22,2000 for part 740.

FOR FURTHER INFORMATION CONTACT: JohnD. Lipn icki, Center for Drug Evalu ationand Research (HFD560), Food andDrug Administration, 5600 FishersLane, Rockville, MD 20857, 301 8272222.

SUPPLEMENTARY INFORMATION:

I. Introduc tion

In the Federal Register of August 25,1978 (43 FR 38206), FDA published ,un der 330.10(a)(6) (21 CFR330.10(a)(6)), an advance notice ofprop osed ru lemaking (ANPRM) toestablish a monograph for OTCsunscreen drug products, together withthe recommendations of the AdvisoryReview Pan el on OTC TopicalAnalgesic, Antirheu matic, Otic, Burn ,and Sunburn Prevention Drug Products(the Panel), which w as the advisoryreview panel that evaluated data on theactive ingredients in this dru g class. Theagencys prop osed regulation for OTC

sunscreen drug p roducts, in the form ofa tentative final mon ograph, waspu blished in the Federal Register ofMay 12, 1993 (58 FR 28194).

In the Federal Register of Jun e 8, 1994(59 FR 29706), the agency p roposed toamend the tentative final mon ograph(and reopened the comment period un tilAugust 22, 1994) to remove fivesun screen ingredients because of a lackof interest in establishing United StatesPharmacop eia (USP) mon ographs:Digalloyl trioleate, ethyl 4-[bis(hyd roxyprop yl)] aminoben zoate,

glyceryl aminoben zoate, lawson e withdih ydroxyacetone (interest wassubsequently shown in d eveloping amonograph for lawsone anddihydroxyacetone), and red petrolatum.The agency also reiterated that allsun screen ingredients must have a USPmonograph before being included in thefinal monograph for OTC sunscreendrug products. This final rule includesthose sunscreen ingredients that haveUSP monographs.

In the Federal Register of September

16, 1996 (61 FR 48645), the agencyamended the prop osed rule to includeavobenzone as a single ingredient and incombination with certain othersun screen ingredients (interimmarketing was allowed in th e FederalRegister of April 30, 1997 (62 FR23350)). In th e Federal Register ofOctober 22, 1998 (63 FR 56584), theagency prop osed to amend th e tentativefinal monograph to include zinc oxideas a single ingredient and incombination w ith any p roposedCategory I sunscreen active ingredientexcept avobenzone.

In the Federal Register of April 5,1994 (59 FR 16042), the agencyreopened the administrative record andannoun ced a pu blic meeting to discussultraviolet A (UVA) radiation claimsand testing procedu res. In the FederalRegister of August 15, 1996 (61 FR42398), the agency reopened theadministrative record and announ ced apu blic meeting to discuss thephotochemistry and photobiology ofsunscreens.

This final monograph comp letes thetentative final mon ograph except for


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27667Federal Register/ Vol . 64 , No. 98 / Fr id ay , May 21, 1999 / Rules an d Regu la tion s

certain testing issues and UVA labeling,which the agency will discuss in futureissues of the Federal Register. Untilthen, UVA labeling may contin ue inaccord with the tentative finalmonograph and its amendmen ts. Theagency advises that on or after May 21,2001, no OTC dru g product that issubject to the monograph an d that

contains a n onmonograph cond itionmay be initially introduced or in itiallydelivered for introduction in to interstatecommerce u nless it is the su bject of anapproved new drug application orabbreviated new drug application.Furth er, any OTC drug prod uct subjectto this monograph that is repackaged orrelabeled after the effective date of themonograph must be in comp liance withthe mon ograph regardless of the date theproduct w as initially introduced orinitially delivered for introdu ction intointerstate commerce. Manufacturers areencouraged to comply volun tarily as

soon as possible.In response to the proposed rule onOTC sunscreen dru g products andsubsequent reopenings of theadm inistrative record, the agencyreceived 433 comments. The commentsinclud ed four p etitions (Refs. 1 throu gh4) requesting consideration of sun screeningredients that have been m arketed inEurope but n ot in the United States. Thestatus of these petitions is discussed insection II.C, comment 13 of thisdocument. One manufacturer requestedan oral h earing before the Commissionerof Food and Drugs if the agencymandated a limit on su n p rotection

factor (SPF) values in th is final rule.Copies of the information con sidered bythe Panel, the comments and petitions,and the hearing request are on p ublicdisp lay in the Dockets Managemen tBranch (HFA305), Food and DrugAdm inistration, 5630 Fishers Lane, rm.1061, Rockville, M D 20852. All OTCVolumes cited throu ghout th isdocument refer to information on publicdisplay.

A nu mber of comments were filed inthe Dockets Management Branch afterthe dates the admin istrative record hadofficially closed. The agency has

considered these comments asfeedback commu nications un der theOTC drug review procedu res, asdiscussed in the Federal Register ofSeptember 29, 1981 (46 FR 47740), andclarified in th e Federal Register of April1, 1983 (48 FR 14050). Whenfeedback material sub mitted after anadm inistrative record h as officiallyclosed directly influences or forms oneof the bases for th e agencys d ecision ona matter in an OTC drug rulemakingproceedin g, the agency adds it to theadministrative record without

subm ission of a formal petition by aninterested party.

The agency has inclu ded th ese dataand information in the administrativerecord and addressed them in thisdocument. The agency has consideredthe request for an oral hearing in itsrespon se to the commen t and believes ithas adequately responded to the

man ufacturer and that a hearing is notneed ed. As discussed in section II.G,comment 29 of this document, theagency is allowing the marketing of OTCsunscreen drug products with SPFvalues above 30 und er one collectiveterm (i.e., 30 p lus or 30 +). Theagency will also consider includ inglabeling in the mon ograph with actuallabel SPF values on produ cts with SPFvalues over 30 wh en adequ ate data aresubm itted to substantiate a testingproced ure app licable to SPF values over30 .

II. The Agencys Conclusions on the

Comments

A . Gen eral Com m en ts on OT CSunscreen Drug Products

1. Several commen ts asked that theagency either exemp t currentlymarketed su nscreen produ cts from therequiremen t for redeterminin g the SPFor provide a 2-year imp lementationperiod. One comm ent requested a 3-yearimplementation period. The commentscontended that the p roposed 12-monthimplementation p eriod w ould result inlost business and a serious economichard ship for manu facturers, estimated

to be 35 million dollars forreformulating, retesting, and relabelingsunscreen produ cts.

The agency agrees with the comm entsthat the proposed 12-monthimplementation p eriod may causeun due economic burden on somemanu facturers of these produ cts withouta correspondin g benefit to consum ers(see section VII of this document). Asdiscussed in section VII, a 24-montheffective date would allow most firms torelabel products d uring a n ormalrelabeling cycle withou t incurringadd itional costs. Accordingly, the finalrule w ill be effective 24 mon ths fromthe d ate of this pu blication. Because thisfinal rule provides testing proceduresthat were prop osed in the tentative finalmonograph, currently marketedprod ucts that have already been testedby those procedu res will not need to beretested. However, sunscreen productsthat have not been tested w ill need tobe tested usin g the method s describedin this d ocument. The agency intends topropose modified test procedures in afuture issue of the Federal Register an dany n ecessary retesting time will be

specified when the final rule for testingprocedures pu blishes.

2. Several comments recommendedmod ifications to the definition ofminim al erythema dose (MED) inprop osed 352.3(a). Some commentsobjected to the presumption thateryth ema is a diffusin g reaction thatstarts from with in the exposed site and

moves outward in a dose dependentman ner, i.e., redn ess reaching th eborders of the exposure site. Othercommen ts asserted that the d efinition istoo limiting because it may n ot beapp ropriate for all solar simu latorconfigurations (e.g., no template). Manycomments recommended the d efinitionof MED used by the Europ ean TradeAssociation COLIPA (Ref. 5): Thequan tity of radiant en ergy required toprod uce the first perceptible,unambiguous redn ess reaction withclearly defined borders. Anothercomment recommended erythema-

effective ultraviolet radiation in placeof radia nt ener gy.

The agency agrees that the prop oseddefinition of MED shou ld be m odifiedfor the reasons discu ssed by thecommen ts and is revising 352.3(a) inthis fin al rule, as follows : Min im alerythema dose (MED). The quantity oferythema-effective energy (expressed inJoules p er square meter) required toprod uce the first perceptible rednessreaction with clearly defined bord ers.The agency considers this d efinitionbroad enou gh to encom pass testsconducted with solar simulator

configurations with n o template andconsistent with COLIPAs d efinition.3. One comment noted that the

wavele ngth r anges for UVA, UVB, andUVC radiation in the ten tative finalmon ograph d iffered from th e officialranges of the Comm ission Internationalde LEclairage (CIE), which are: (1)UVCradiation of less than 280nanometers (nm), (2) UVB280 to 315nm , and (3) UVA315 to 400 nm. Thecomment mentioned the agreementreached at the 11th InternationalCongress on Photobiology (Ref. 6) on theshort w avelength end of UVB radiation(280 or 290 nm) and su ggested that thescientific evidence supp orts 320 nm asthe long-wavelength bound ary of UVBradiation.

The agency agrees with the comm entthat the scientific evidence sup ports 320nm as the long-wavelength boun dary ofUVB radiation. However, the short-wavelength bou nd ary for UVB radiationhas been accepted as either 280 or 290nm. Given that the comment did n otprovid e a compelling reason to chan gethe prop osed definition of UVBradiation, the agency will contin ue to


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define the bou nd aries of UVB radiationas 290 to 320 nm .

4. Comm ents requested th e agency toamend the definition of a sunscreenactive ingredient in prop osed 352.3(c)to include mechanisms other thanabsorption, to expand the UV range toinclud e UVA radiation, and to providea minimu m SPF value requirement. The

comments added that some proposedCategory I active ingredien ts (e.g.,menthyl anthranilate and titaniumdioxide) do not meet the p roposeddefinition, and that the definition is notinterpretable with out sp ecifications formeasurin g 85 percent absorbance.

The agency discussed the need tomod ify the definition in a 1996proposed amend ment of the tentativefinal monograph (61 FR 48645 at48646). The agency agrees thatmod ifications shou ld be to: (1) Inclu demechanisms other than absorption, (2)redefine wavelengths, and (3) removethe percent absorbance requirement.The agency does n ot agree that aminimum SPF value should be includedin the definition because thisinformation is more approp riately acharacteristic of the final formulation.Therefore, the agency has revisedproposed 352.3(c) in this document, toread: Sun screen active ingredient. Aningredient listed in 352.10 thatabsorbs, reflects, or scatters radiation inthe u ltraviolet range at wavelengths of290 to 400 n anom eters.

5. One comment recommended thatthe agency reevaluate statements in thetentative final monograph on the

harm ful nature of tann ing. The agencydiscussed the h armful effects of UVradiation-indu ced tanning in thetentative final m onograph (58 FR 28194at 28238 to 28239). The commen tsuggested that a natural tan redu cescumulative sun exposure and maypotentiate sun screen effectiveness. Thecomment did not, however, providedata or references to sup port this claimor to otherwise cause the agency tochange its position.

6. One comment requested that thefinal monograph requ ire expirationdating and storage information in the

labeling of OTC sun screen dru gproducts. The comment noted thatun der 21 CFR 211.137, OTC drugproducts with d ata demonstratingstability for 3 years and w ithout labeleddosage limitations are not requ ired toinclude an expiration date in theirlabeling. The comm ent stated that it wasaware of num erous cases that suggestthese prod ucts may n ot be stable for 3years.

The agency requested the comment toprovide data and information about thespecific produ cts it was aw are of (Ref.

7), but non e were subsequentlyprovid ed. The agency is not currentlyaware of stability problems that wou ldrequire expiration d ating for OTCsunscreen drug products but willadd ress such a requirement if databecome available. All sunscreen activeingredients included in the finalmon ograph also have a USP monograph

that contains p ackaging and storagerequirements and standards for produ ctscontainin g these ingredients.

7. Comments recommended that theagency establish p rocedures forensu ring batch-to-batch SPF test results,and that it approve testing laboratoriesand regulate their performance.

Regulations already exist to assurethat each batch of dru g prod uct meetsestablished sp ecifications for theiden tity and strength of each activeingredient. Specifically, 21 CFR 211.160requires that produ ct specifications andlaboratory controls be established andperformed. Although the agency wouldnot require SPF testing on hum ansubjects for every batch produ ced,manufacturers need to assureconformance to their finished produ ctspecifications. Further, an y chan ges tothe batch formula would, at a minimu m,require review and documentation bythe man ufacturers quality control unitto determin e if SPF retesting isnecessary. Finally, 21 CFR 211.180provid es for the inspection of recordspertainin g to produ ction, control, anddistribution of batches of dru g produ cts.Thu s, testing laboratories are subject tothese regulations.

B. Com m en ts on th e Dru g/Cosm eticStatus of Su nscreen Products

8. One comment questioned w hethersunscreen produ cts should be regulatedas drugs. The commen t asserted thatsuch p roducts are not active in themitigation or elimination of a diseasecondition, and that sunscreen produ ctshave no m ore affect on the structu re andfunction of the bod y than being inph ysical shade.

The basis for th e agencysdetermination that p roducts intendedfor use as sun screens are subject toregulation as drugs und er section201(g)(1) of the Fed eral Food , Dru g, andCosmetic Act (the act) (21 U.S.C.321(g)(1)) is set forth at len gth in th etentative final m onograph (58 FR 28194at 28203 to 28206). Essentially,sun screen active ingredients affect thestructure and function of the body byabsorbing, reflecting, or scattering theharm ful, burn ing rays of the sun ,thereby altering the norm alph ysiological response to solarradiation. Proper use of sunscreeningredients (see section II.L, comm ent

51 of this docu men t) may help toprevent skin damage and may helpredu ce the risk of skin lesions, skincancer, and other disease conditions.Produ cts that are marketed to achievethese importan t health benefits meet thedefinition of a dru g und er section201(g)(1)(B) and (g)(1)(C) of the act.

9. One comment disagreed with the

agencys tentative conclusion th atproducts containing a sunscreeningredient, but labeled for the pu rposeof obtain ing an even tan, are su bjectto regulation as dru gs. According to thecommen t, such a produ ct is subject toregulation as a dru g only if it bears aclaim to treat or prevent sun burn . Thecommen t asserts that this has been theagencys consistent app roach since1940.

Another comment stated that sun lesstanning products, used to impart colorwithout exposure to the sun, could beimproved by addin g a sunscreen toprovide users protection during theirnorm al outside activities. The commen trequested that such produ cts should beregarded as cosmetics, because theywou ld be used p rimarily for a cosmeticeffect, with the su nscreen p rotectionserving only a secondary pu rpose.

The agency thoroughly discussed theregulatory status of tanning products,includ ing the basis for withd rawing its1940 advisory opinion on sunbu rn andsuntan preparations, in the tentativefinal monograph (58 FR 28194 at 28203to 28207, 28293 to 28294). As discussedin the tentative final mon ograph, thepresence of a sunscreen active

ingredient, in conjunction with labelingclaims that the produ ct may be used,e.g., to permit tann ing or to acquire aneven tan, generally establishes that th eprod ucts intend ed u se is that of a dru g.Such p rodu cts suggest, amon g otherthings, that the ingredients in theproduct w ill allow the consum er to stayin the sun longer without su ffering skindam age (58 FR 28194 at 28204).Likewise, produ cts that claim toaccelerate or stimulate the tann ingprocess are claiming, either expressly orimpliedly, to stimulate the productionof melanin in the bod y. Such a claim to

affect the structure or function of thebody rend ers the produ ct subject toregulation as a dru g und er section201(g)(1) of the act (see 58 FR 281 94 at28293). Finally, a sunless tannin gproduct th at contains a sunscreeningredient, to provide protection to theconsum er, is subject to regulation as adrug. The idea that the sunburnprotection offered by the prod uct mayonly be a secon dary feature for th econsum er is not relevant. If an inten deduse of the prod uct is to provide u serswith sun protection when they go


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outside (as the com ment suggests), thenthe p rodu ct is subject to regulation as adrug.

On the other hand , products that donot make express or implied sunprotection claims, and d o not containsun screen ingredients, may be regardedas cosmetics und er section 201(i) of theact. If the produ ct is intended solely to

provid e cosmetic effects on th e skin(e.g., to moisturize th e skin w hilesun bathing), or solely to impart color tothe skin without exposure to the sun orother sou rces of light (i.e., sunlesstanning), then the product m ay bemarketed as a cosmetic. Such p rodu cts,however, must include a w arningstatement (discussed in th is section,commen t 10 of this docu men t) to informthe consumer that the product does notprovide any protection against sunbu rn.Products marketed to enh ance or permittanning that do n ot contain a sunscreeningredient mu st be reviewed on a case-

by-case basis to determine w hether th eproduct is intend ed solely to provide acosmetic benefit (such as moisturizing)or whether the produ ct is intended toenhance or permit tanning by someother mechan ism of action.

The commen ts offered no oth erreasoning and n o data to the contrary,other th an to suggest that th e agencysapproach wou ld encourageman ufacturers to remove sunscreeningredients from su ntan p roducts and,thereby, expose consum ers to evenhigher levels of harmful ultraviolet rays.The agency is not persuad ed that asignificant nu mber of manufacturers

will choose to reformulate theirprod ucts, to make them less safe forconsu mers, as a result of this final rule.Moreover, consum ers will continue tohave an array of sun screen-containingprod ucts from which to choose. Finally,as discussed below, certain tann ingproducts (including sunless tanningproducts) that do not contain su nscreeningredients must bear a p rominentwarning to the consumer. This willensu re that the consumer is fullyinformed as to which p rodu cts offer sunprotection and wh ich do not.

10. One comment requested that the

signal w ord Caution replac e thesignal word Warning preceding thefollowin g statement for sun tannin gprep arations: WarningThis prod uctdoes not contain a sun screen and doesnot p rotect against sun burn . Thecomment stated that the wordWarn ing suggests safety h azardsassociated with th ese produ cts that areunrelated to sunburn. Another commentpetitioned to ad d a second sentence tothe w arning: Tannin g in sun light orund er tanning lamps can cause skincancer and p remature skin aging-even if

you d ont burn. The comm entconclud ed that the availability oftanning produ cts without a protectivesun screen ingredient is a serious h ealthissue and detrimental to pu blic health.A third comm ent objected to any suchwarnings on tanning produ cts.

The agency consid ers it an imp ortantpu blic health issue that users of

suntannin g products be alerted whenthese products do n ot contain asunscreen and do n ot protect againstsun burn or other harmful effects to theskin. Because suntanning products areintended for repeated use und er the sunor suntann ing lamps wh ile acquiring atan, the agency consid ers failure toprovide information on hazardsassociated with repeated, unprotectedexposu re to UV radiation to be a failureto reveal material facts (see sections201(n), 502(a), and 6 02(a) of the act (21U.S.C. 352(a) and 362(a))), especially inlight of the representations that are

mad e for the p rodu ct (e.g., sun tann ing).Therefore, the agency is requiring thelabeling of sun tann ing preparations thatdo n ot contain a sunscreen ingredient( 740.19 (21 CFR 740.19)) to bear thefollowing: WarningThis productdoes not contain a sun screen and doesnot p rotect against sunbu rn. Repeatedexposure of unprotected skin wh iletann ing may increase the risk of skinaging, skin cancer, and oth er harmfuleffects to the skin even if you do n otburn . The agency con siders th isinformation to be sufficiently imp ortant,for safety reasons, to require a 12-mon theffective date (as opposed to 24 mon ths

for the balance of the rule) and torequire the stron gest possible signalwo rd, i.e., Warn ing.

11. One comment disagreed with theprop osal that hair care and nailprodu cts that contain a su nscreeningredient for a non therapeu tic use (e.g.,to protect the color of the p rodu ct), andthat u se the term sun screen in th elabeling, mu st describe in the labelingthe functional role of the sun screen.According to the comm ent, it is highlyun likely that consumers would thinkthat these products are intended toprotect the skin. If this requiremen t

were finalized, the comment requestedthat the agency perm it the termsun screen to ap pear on ce anyw herein the labeling, with the pu rpose of thesunscreen explained elsewhere in thelabeling.

The agency disagrees with th eprem ise of this commen t. The use of theterm sun screen in lab eling su ggeststhat the product in some way willprotect the consumer from the harmfuleffects of the su n. The h ealth risksassociated w ith relying on a produ ct forprotection from the sun, wh en in fact

the product does not provide suchprotection, are su fficiently serious torequire the type of disclosure outlinedin the prop osed rule. Information aboutthe pu rpose of a sunscreen ingredient ina hair care or nail prod uct will be usefulto consumers to inform them that theingredient protects only the hair or onlythe color of the prod uct.

This information need ap pear onlyonce and can appear anywhere in thelabeling, provided the qualifyingpurp ose appears prominently andconspicuously and in conjunction withthe word sunscreen. The informationmay, e.g., be combined in a singlestatement, e.g., Contains a sunscreento protect p rodu ct color. This w illensu re that consumers will see andreadily associate the two pieces ofinformation.

12. Two commen ts objected to the useof an OTC drug rulem aking process tochange cosmetic labeling requirements,i.e., the add ition of a warnin g on certaintanning products and the labelingrequiremen ts for hair care or nailprod ucts that contain a sunscreen for anontherapeutic use.

The agency addressed this proceduralconcern, wh ich was also raised inresponse to th e ANPRM, at length in th etentative final m onograph (58 FR 28194at 28201 to 28202). The ind ustry andconsumers have had ample notice of thefact that this proceedin g includ edseveral cosmetic labeling issues thatarise out of the same facts and find ingsat issue in developin g the OTC drugmonograph. It is not u ncommon for the

agency to add ress in an OTC rulemakingdocu men t the status of, or the regulationof, prod ucts that fall outside of themon ograph. In this instance, thecosmetic labeling issues were so closelyrelated to the OTC drug issues that aseparate proceeding would h ave beenoverly dup licative and inefficient.

C. Com m ents on Sp ecific Sun screenA ctive In gred ien ts

13. Several commen ts noted th at FDAhad d eferred a decision on th e citizenpetitions requesting that sunscreenactive ingredien ts marketed solely in

foreign countries be included in th eOTC sunscreen monograph. Thecommen ts urged FDA answer thesepetitions and establish a policyconcernin g the inclu sion of OTCsun screens based solely on foreign d ataand marketing experience.

In the Federal Register of October 3,1996 (61 FR 51625), the agencypublished an ANPRM that addressedestablishing eligibility criteria forconsidering additional OTC conditions(i.e., OTC drug active ingredients,ind ications, dosage forms, dosage


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strengths, routes of adm inistration, andactive ingredient combin ations) in theOTC dru g monograph system. Theseproposed criteria would address howforeign or d omestic OTC marketingexperience could be used to support theinclusion of an ingredient in an OTCdru g monograph. Specifically, thecriteria would add ress how OTC

marketing experience in the UnitedStates or abroad could be u sed to meetthe statutory requirement under section201(p) of th e act of m arketin g to amateria l exten t and for a materialtime. Material extent and materialtime are needed to qualify a specificOTC drug condition for consid erationund er the OTC drug monograph system.

The decision on w hether to proceedwith a final rulemaking on this su bjectwill be based, in part, on theinformation and comments submitted inresponse to the n otice of prop osedrulemakin g that the agency is preparin g

for publication in a future issu e of theFederal Register. Resolution of thepend ing sunscreen petitions mu st awaitthe outcom e of any final rulemakin g onthis su bject.

14. One comment requested that theagency adopt simp ler, more user-friend ly, names for several sunscreeningredients: (1) Roxadimate for ethyl-[bis(hyd roxyprop yl)] amin obenzoate, (2)lisadimate for glyceryl aminobenzoate,and (3) diolamine methoxycinnamatefor diethanolamine methoxycinnamate.The comment claimed that these nameshad been ad opted or designated by theUnited States Adop ted Names (USAN)

Council. The commen t also requestedthat if USAN adop ts a name forphenylbenzimidazole sulfonic acid,FDA adop t this name as well. Thecommen t also suggested the u se of theacronyms TEA and DEA fortriethanolamine and diethanolamine,respectively.

The agency is inclu din g in th is finalmonograph only those activeingredients that are th e subject of anofficial USP comp end ial monographthat sets forth its standard s of identity,strength, quality, and p urity (see sectionI of this docu ment). In th e FederalRegister

of Jun e 8, 1994, FDA deletedethyl-[bis(hydroxypropyl)]aminoben zoate and glycerylaminoben zoate from the ten tative finalmon ograph du e to the lack of interest inestablishin g USP monographs for theseingredients. Moreover, two sun screeningredients (including diethanolaminemethoxycin nam ate) have been deferredfrom the final monograph d ue to thelack of a current or p roposedcompendial monograph. Therefore, theissue of whether a user-friendly namefor these ingredients shou ld be

developed or adopted need not beresolved in this proceed ing at this time.Similarly, TEA and DEA need not beadd ressed in this proceeding, astriethanolamin e is not a sunscreenactive ingredient, and d iethanolamin e isonly used in the ingredientdiethanolamine m ethoxycinnamatewh ich, as discussed , is not a monograph

ingredient at this time.With respect to the comment on th e

monograph ingredientphenylbenzimidazole sulfonic acid, theagency agrees that if USAN or the USPwere to ad opt a d ifferent or alternativenam e for this ingredien t, such a nam ecould be u sed in the labeling of aprod uct that contains this ingredient. Asdiscussed in comment 30 of thetentative final m onograph (58 FR 28194at 28207 to 28209), the agency is usin gthe comp end ial name as the establishednam e for each active ingredient.

15. Two comm ents requested that theterm PABA con tinu e to be allowed inlabeling. The comm ents stated that thenam e aminobenzoic acid is meaninglessto consumers and p hysicians, who overthe years have learned to recognize thisingredient on the label as PABA. Onecomment recommended the u se ofaminoben zoic acid in the ingredient listand the use of PABA in othercommun ications about the produ ct. Thecommen t add ed that th e term PABA-free shou ld be allowed on prod uctsthat do n ot contain amin obenzoic acid.The other comment p roposed either toperm it the listing of the ingredient asPABA or, if that is u nacceptable, as

PABA (aminobenzoic acid).In commen t 30 of the tentative final

mon ograph (58 FR 28194 at 28207 to28209), the agency discussed th e issueof the approp riate established nam e forthis and other sunscreen ingredients. Asthe agency stated in th at discussion, therecognized compendial name foraminobenzoic acid no longer includesthe term PABA.

The agency acknowledges, however,that the term PABA formerly was partof the established n ame for thisingredient and that the use of the termin consu mer labeling has continueddespite the change in th e compendialnam e. In ad dition, the agency agreeswith the comment that many consum ershave learned to recognize thisingredient as, and only as, PABA. Theagency also recognizes that con sum ersseeking to avoid th e use of thisingredient for health-related reasons(e.g., allergy) may, in this case, bemisled if the term PABA were no longerperm itted. Some consu mers may believethat a produ ct that lists aminobenzoicacid as an ingredient, but does not listPABA, is PABA-free. If such a con sum er

has an allergy to aminobenzoic acid, theind ividual may su ffer adverse healthconsequences.

For these reasons, and esp ecially inlight of th e poten tial safety concerns forcertain consum ers, the agencyconcludes that wherever the ingredientaminobenzoic acid appears in th elabeling of an OTC sunscreen d rug

prod uct, includin g labeling that notesthe absence of this ingredient, thedescriptive term PABA mu stimmed iately follow the establishedname, i.e., Aminobenzoic acid(PABA). Thu s, e.g., a prod uct th at iscurr ently mark eted as PABA-freewould now be required to state that theprod uct is Aminoben zoic acid (PABA)-free. This convention will allowconsum ers to begin to recognize that theingredient they may w ish to avoid isamin oben zoic acid . After a su fficientperiod of time, the agency w ill revisitthe need for consu mer labeling to

continu e to bear the descriptive termPABA.16. One commen t stated that claims of

protection by artificial melanin ,melanin-containing products, andantioxidants should be enumerated,well regulated, and d efined .

The agency agrees with the comm ent,but these claims are not covered by th isfinal monograph. Melanin and artificialmelanin s are not recognized sunscreenactive ingredients. Any produ ctcontainin g melanin or artificialmelanin s as active ingredients andmaking sun protection claims wouldhave to seek marketing approval un der

a new d rug app lication (NDA).The agency is aware that claims of

protection from antioxidants are used inthe labeling of some cosmetic prod uctswith or with out a sunscreen. The agencywill ascertain the n ature of any suchclaims (drug or cosmetic) on a case-by-case basis.

17. Several comm ents objected to theagencys proposal th at OTC sunscreendrug produ cts must contain less than500 parts p er billion (ppb) of N-methyl-N-nitrosoaminobenzoate octyl ester(NMPABAO) for several reason s: (1)Toxicological studies in dicate thatNMPABAO does not h ave mutagenic orsusp ected carcinogenic p otential (Ref.8), (2) NMPABAO may be p resen t insunscreens containing pad imate O onlyin small amoun ts (ppb range) and therisks associated w ith NMPABAO arevery low, (3) NMPABAO d ecomposesquickly when exposed to UV radiation,and (4) indu stry is aware not toformulate with know n n itrosating agentsin the p resence of amines in ord er toavoid nitrosamine contam ination of itsproducts. Some comments stated thatFDAs own conclusion s in the ten tative


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final monograph con cerning the safetyof both NMPABAO and pad imate O donot supp ort the imposition ofconcentration limits for NMPABAO insun screens nor do th ey justify the highcost of analyzing each batch ofsun screen prod uct for NMPABAO. Onecomment contended that any proposedlimit should apply to all nitrosamines

and n ot just NMPABAO. The comm entstated that nitrosamin es can be formedfrom any second ary or tertiary amine.Several sunscreen active ingredientscontain this moiety in their chemicalstructure and many inactive ingredientsare secondary or tertiary amines. Thecomment conclud ed that targetingNMPABAO falsely conveys th atpadimate O is a unique concern,resulting in manu facturers using otheringredients to avoid costly testing andnegative implications.

In the tentative final mon ograph, theagency did not prop ose a concentration

limit on NMPABAO. Rather, based onconcerns that had been raised, theagency asked for commen t on wh etherit should con sider prop osing a fixedlimit. As discussed in th e tentative finalmon ograph (58 FR 28194 at 28288 to28293), toxicological studies sup port th eagencys belief that the risk associatedwith NMPABAO contamin ation ofsunscreen drug produ cts is very low du eto NMPABAOs low mu tagenicity andcarcinogenicity potential and rapiddecomp osition in the presence of UVradiation. The agency has not becomeaware of any new data or informationsince the p ublication of the tentative

final mon ograph su ggesting a safetyconcern w ith NMPABAO in sunscreendru g produ cts. Therefore, the agencyhas decided n ot to propose or otherwiseinclude in th is final monograph arequirement that OTC sunscreen drugproducts mu st contain less than 500 pp bof NMPABAO.

In the tentative final monograph (58FR 28194 at 28292), the agencydiscussed its analysis for NMPABAO in25 comm ercially available sunscreenprod ucts. Of the 11 samples found to becontamin ated with NMPABAO, the fourhighest con tained 2-bromo-2-nitro-1,3-

propanediol, an indirect nitrosatingagent. The agency concluded that therewould be no n itrosamine contaminationif these prod ucts were formulatedwithou t the nitrosating agent. As notedby several of the comm ents, the indu stryis aware not to formulate with know nnitrosating agents in th e presence ofamines in order to avoid nitrosaminecontamination of its products.

18. One comment submitted areference to a subchron ic oral toxicitystudy in rats conducted with pad imateO wh ich a chemical manufacturer had

subm itted to the Toxic SubstanceControl Act 8(e) coordinator of theUnited States Environm ental ProtectionAgency for consideration. The stud ywas a 4-week repeated dose study atdoses of 0, 100, 300, and 1,000milligrams (mg)/kilogram (kg)/day ofpad imate O admin istered by gavage ina corn oil veh icle (10 to 15 rats/group/

sex). The stud y includ ed a 4-weekrecovery period to assess the persistenceor reversib ility of any toxic effects. Atthe end of the 4-week treatment period,toxic effects were seen in four targetorgans: Testes, epid idym is, spleen, andliver. The no-observed-effect-level inthis stud y was 100 mg/kg/day for bothmales and females. Toxic effectsapp eared reversible in the animalsnecrop sied after the 4-week recoveryperiod w ith the exception of markedepididymal h ypospermia at the 1,000mg/kg/day d ose (5/5 anim als).

The clinical relevance of this animal

toxicity study is difficult to assess.Padimate O was admin isteredchron ically and at very high oral doses.Under n ormal use conditions, sunscreendrug produ cts containing padimate Oare applied topically and usedintermittently. In addition,pharmacokinetic parameters were notcalculated and th e different routes ofadm inistration (oral in this study versustopical for sunscreen products) precludecalcu lation of a safety margin on th ebasis of dose per u nit of body weight orsurface area. Similarly, kinetic data arenot available for a comparison of serumlevels of drug or metabolites. Literature

searches indicate no publishedinformation on th e kinetics of pad imateO with top ical application in man . Ifpercutaneous absorption of padimate Odoes occur in m an, it seems likely thatthe p eak and/or cumulative levelsachieved w ith sunscreen usage wouldbe quite low compared to the systemicexposure achieved in this animaltoxicity stud y. Further, it is not know nwhether the irreversible epididymalhypospermia found in the 1,000 mg/kg/day group w ould also be reversible withmore time.

The agency has determin ed that this

stud y does not presen t sufficient data toexclude p adimate O from the finalmonograph and that an adequate safetymargin exists for its use as an OTCsunscreen ingredient.

19. Two comments su bmitted safetyand /or efficacy data to sup port CategoryI status for micronized titanium d ioxide(Refs. 9 and 10). One commen t statedthat micronized titanium dioxide is nota new material but is a selecteddistribution of existing material thatprovid es higher SPF values while beingtransparen t and esthetically pleasing on

the skin. The comments added thatmicronized titanium dioxide meets allsafety and efficacy criteria and alsomeets the USP sp ecifications for purityexcept pure water content.

Anoth er comment asserted for thefollowin g reasons th at micronizedtitanium dioxide is a new ingredientwith several un resolved safety and

efficacy issu es: (1) It does n ot meet th edefinition of a sunscreen op aquesun block, (2) there is no con trol ofparticles to agglomerate, which iscritical to effectiveness, (3) no standardsexist to ensure integrity of coatings, (4)there are no performance-basedstandard s of identity; micronizedtitanium d ioxide is not included in theUSP, (5) its ph otocatalyst p otential, and(6) the p otential for the smaller p articlesize to accumulate und er the skin.

The agency find s the data with thecomments sup portive of monographstatus for micronized titanium d ioxide.

Acute anim al toxicity, irritation,sensitization, photoirritation,photosensitization, and hum an repeatinsult patch and skin penetrationstudies revealed no deleterious effects.SPF values for four produ ctformulations contain ing from 4.4 to 10percent micronized titanium dioxidewere from 9 to 24 and supp orteffectiveness as a sunscreen ingredient.

The agency is aware that sun screenmanu facturers are using micronizedtitanium d ioxide to create high SPFproducts that are transparent andesthetically pleasing on th e skin. The

agency d oes not consider micron izedtitanium d ioxide to be a new ingredientbut con siders it a specific grade of thetitanium d ioxide originally reviewed bythe Panel. Fairhu rst and Mitchnick (Ref.11) note th at fines have been part o fcommercially u sed titanium dioxidepow ders for decades, and th at amicronized p rodu ct simply refers to arefinem ent of particle size distribution.Based on d ata and informationpresented at the September 19 and 20,1996, public meeting on thephotobiology and photochemistry ofsun screens (Ref. 12), the agency is n otaware of any evidence at this time thatdemon strates a safety concern from theuse of micronized titaniu m dioxid e insunscreen products. While micronizedtitanium dioxide does not meet theprop osed definition of a sunscreenopaqu e sunblock, the agency has notinclud ed the use of this term in the finalmon ograph (see section II.L, commen t52 of this docum ent). The potential fortitanium d ioxide particles toagglomerate in formu lation, whichcould resu lt in lower SPF values, isadd ressed by the final produ ct SPF test.


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The SPF data that th e agency reviewed(Ref. 9) did n ot indicate such a problem.

Micronized titanium dioxide meetscurrent USP monograph specificationsfor titanium d ioxide with the exceptionthat the material contains moreassociated w ater. In both the Julythrou gh August 1996 and 1998 issues ofth e Pharmacopeial Forum (Refs. 13 an d

14), the Un ited States PharmacopeialConvention published in-processrevision prop osals to make themonograph for titanium d ioxide m oreapp licable to ingredients used insunscreen dru g products. The agencywill work with the USP in the future toupd ate this monograph as necessary.

20. One commen t stated that it isunn ecessary to set the maximum limitof titanium dioxide at 25 percent.

The Panel discu ssed the safety andeffectiveness of 2 to 25 p ercent titaniumdioxide in the ANPRM (43 FR 38206 at38250) and th e agency concurred withthe Panels find ings in the tentative finalmon ograph (58 FR 28194 at 28295). Thecomment submitted no data and theagency has no d ata to supp ort the useof titanium dioxide in sun screen dru gproducts at concentrations higher than25 percent.

D. Com m en ts on Dosages for SunscreenDrug Prod ucts

21. Several comments objected to theminimum concentration requirementsfor sun screen active ingredients wh enused in combination because they: (1)Are a less effective measuremen t ofeffectiveness than a performance based

SPF test, (2) impact on creativity andinnovation of new formulations(techn ological advances sin cepu blication of the 1978 ANPRM haveresulted in higher SPF values usinglower concen trations of activeingredients), (3) increase potential forirritation an d allergic reactions du e toun necessarily high concen tration levelsof active ingredients, (4) contradictFDAs position that the lowest effectivedose of an active ingredient be used toprod uce the desired treatmen t effect, (5)result in higher manufacturing andconsumer costs due to u nnecessary

levels of active ingredients, and (6)affect international h armonizationbecause Canada, Australia, and theEuropean Union have no concentrationminimums for active ingredients whenused in combination.

One commen t petitioned the agencyto amend proposed 352.20 of thetentative final mon ograph to includ e aprovision for formulating combinationsunscreen products at lower minimu mconcentrations. Two commentssubm itted efficacy data to supp ort lowerconcentrations of sunscreen active

ingredients when used in combination.One com men t (Ref. 15) submitted invitro SPF testing data for severaldifferent combin ations. Althou gh thesedata sh owed a statistically significantincreased efficacy for lower thanminimu m concentrations, they were notpred ictive of the SPF values that wouldbe obtained with hum an testing and,

therefore, were not used to sup portlower concentrations of sunscreenactive ingredients when used incombination . The other comm ent (Ref.16) submitted in vivo SPF testing dataconducted according to the procedureprop osed in the tentative finalmon ograph (58 FR 28194 at 28298 to28301) in wh ich a selected cross sectionof active ingredients w ere tested in p airsby substituting water or the solventsystem for the active ingredients. Thedata were evaluated usin g a matchedpairs comparison statistical hyp othesistest procedure an d d emonstrated that

concentrations of sunscreen activeingredients lower than the minimu mconcentrations proposed in 352.20(a)(2) for combination p rodu ctscan provid e a significant contribution toprod uct effectiveness.

The agency recognizes thattechnological advan ces in sunscreenformulation techn ology since 1978 haveresulted in the ability to formu lateprodu cts with lower concentrations ofactive ingredients and higher SPFvalues. The agency also recognizes thatfinal produ ct testing, and n ot theconcentration of the active ingredientsin the combination, ensures product

effectiveness.Due to the recent advances in

sunscreen formulation and the datareferenced previously, the agency isconcerned that setting minimu mconcentration requ irements for activeingredients in sunscreen combinationdrug produ cts could subject consumersto un necessary levels of activeingredients. Therefore, the agency isonly requiring the m aximumconcentration limits in 352.10 forsunscreen active ingredients wh en u sedin combination with another sunscreenor when the combination is used with

any other perm itted active ingredient.However, any such ingredient used incombination w ith one or moresun screen active ingredients mu st beconsistent with th e regulations in 330.10(a)(4)(iv), i.e., each of thecombined active ingredients must makea contribution to the claimed effect, thecombinin g of active ingredients m ustnot decrease the safety or effectivenessof any individu al active ingredient, andthe combination mu st provide rationalconcu rrent therap y for a significantprop ortion of the target popu lation.

Although the agency needs assurancethat each ingredient is con tributing tothe effectiveness of the produ ct, it doesnot want to impose unnecessary testingrequirements on su nscreen p roductmanu facturers. Therefore, the agency isremoving the minimu m concentrationrequiremen t for sun screen activeingredients proposed in 352.20 and is

add ing the requiremen t that: (1) Theconcentration of each active sunscreeningredient used in a combinationprod uct mu st be sufficient to contributea minim um SPF of not less than 2 to thefinished prod uct, and (2) the finishedproduct mu st have a minimum SPF ofnot less than the nu mber of thesun screen active ingredients used incombination m ultiplied by 2.

E. Com m en ts on Labeling an d Testin gProcedures for UVA Sun screen DrugProducts

22. In th e sun screen tentative finalmon ograph (58 FR 28194 at 28232 and28233), the agency prop osed to allowclaims relating to broad spectrumpro tection or UVA rad iationprotection for su nscreen prod ucts: (1)Containing sunscreen active ingredientswith absorption sp ectra extendin g to360 nm or above, and (2) thatdemon strate meaningful UVA radiationprotection using appropriate testingprocedu res to be developed . The agencyreceived nu merous commentsconcerning such claims and currentscientific eviden ce imp licates UVAradiation as a m ajor cause of, amongother thin gs, ph otoaging of the skin

(Refs. 17 throu gh 20).In the Federal Register of September

16, 1996, and October 22, 1998, theagency p roposed a sp ecific skin dam ageand prem ature skin aging claim forsunscreen products containing specificconcentrations of avobenzone or zincoxide based up on the subm ission ofdata to sup port claims of UVA radiationprotection in such products. The agencywill address comments pertaining tomeasurem ent of UVA radiationprotection in sun screen prod ucts andrelated UVA radiation protection claimsin a future issue of the Federal Register.

Until then , UVA labeling may continuein accord with the tentative finalmonograph an d its amendments.

F. General Com m ents on the Labeling ofSunscreen Drug Products

23. Several comments requested th atproducts containing su nscreeningredients as an adjunct to their mainpu rpose (e.g., a daily moisturizer or alipstick with a sun screen) be consideredsecondary sun screens (intend ed onlyfor inciden tal or casual sun exp osure),and sh ould be su bject to different


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labeling requirements from primarysunscreen products. A num ber ofcomments likewise contended that someof the labelin g requirem ents for beach or primary sun screen prod ucts are n otapp rop riate for non -beach orsecondary sun screen prod ucts.

For example, the commen ts statedthat neither the proposed

Recommended Sunscreen ProductGuide nor any other references tosunburn or sunburn p rotection shouldbe required for secondary sun screens.Some suggested that the w arnings beredu ced for secondary sun screens to astatement su ch as For external u seonly, keep out of eyes. Discontinu e useif signs of irritation app ear. Onecomment recommend ed that thestatement of identity for a secondarysunscreen should be its cosmeticfun ction , e.g., mois turizer . Anotherrecommend ed stating the primary(cosmetic) fun ction first, then th e

secondary (drug) fun ction, e.g.,moisturizing face cream withsun screen (or with SPFsunscreen).

The comm ents also suggested thatsecondary prod ucts be permitted to bearcertain labeling claims relating to aging,such as Helps redu ce the chance ofskin aging caused by inciden tal (orcasua l) exposu re to the su n, or Helpsredu ce premature aging from incidental(or casual) exposure to th e sun . Somealso requested the option of beingallowed to relate skin aging claimsdirectly to sun exp osure, to informconsu mers more clearly that sun

protection is not the prim ary attribute ofthe prod uct, e.g., Provides m oisture tofacial skin throu ghout the day wh ileprotecting facial skin from skin agingdu e to exposure to sun . Othercomments recommend ed that theproposed Sun alert statement or otherreferences to skin cancer or othercancers should n ot be required forsecondary products.

On the oth er hand , the agency alsoreceived comments opp osing the idea ofrecognizin g prim ary and secon dar yor beach and non-beach categoriesof sunscreen p roducts. One comment

stated that any produ ct containing asun screen for the pu rpose of protectionfrom the sun s harmful effects should beheld to the same standard s as othersunscreen products. Another commentdisagreed with the id ea of allowingdifferent sets of claims for prim aryand secondary prod ucts. Accordin g tothis comm ent, claims such as Helpsreduce the chance of skin aging aredru g claims and shou ld be regulated assuch . Finally, one comment stated thatany sun screen p roduct (primary orsecondary) mu st have an SPF of 15 to

30 or higher to provide adequ ateprotection, wh ether for continuousbeach exposu re or everyday (inciden tal)sun exposure.

The agency agrees that all sun screenprodu cts (whether dru g only or drug-cosmetic) shou ld be held to the samestandards (e.g., active ingredient(s),testing requirements, and labeling).

Regardless of what type of prod uct aconsumer chooses for sun protection,the essential information relevant to sunprotection is the same. Thus, to ensurethat consu mers are adequately protectedfrom overexposure to the sun , allprodu cts intended for use as sunscreensshould have similar labelingrequiremen ts, irrespective of theirmethod of use and irrespective ofwhether the sunscreen use is consideredprimary or secondary to the produ ct.Consistent with this approach, theagency has developed uniform,streamlined labeling for all sun screen

products (see sections II.I through II.L ofthis docum ent).The agency also notes, how ever, that

a nu mber of the labeling issues raised inthese commen ts, includ ing the issue ofthe Recommended Sunscreen ProductGuide, are add ressed elsewhere in thisdocument. In addressing these issues,the agency gave careful con sideration tothe wid e variety of products marketedfor sun screen uses.

Finally, the agency notes that un derthe recently issued standardized OTCdru g product labeling format ( 201.66(21 CFR 201.66)), manufacturers willnot be allowed to commingle drug and

cosmetic claims within the Drug Factsportion of the labeling.

24. One comment requestedclarification of the agencys discussionof the term anti-aging as a claim or aspart of a trade n ame (58 FR 28194 at28287). The commen t was concernedthat produ cts containing no sunscreenactive ingredients and n o sunscreenclaims, but wh ich are sold u nd er anti-aging trade n ames, wou ld be subject toregulation und er the OTC drugsunscreen monograph.

The use of anti-aging langu age in aprodu ct that made no sun screen claimsand contained n o sunscreen activeingredients would not, as the commentasked, cause the produ ct to fall withinthe scope of the OTC sun screen dru gmonograph. Such a product may,how ever, be subject to regulation as adrug and as a new d rug, under section201(g)(1) and (p ) of the act, or as acosmetic un der section 201(i), or as botha drug and a cosmetic, depending uponall of the circumstan ces surroun din g itsdistribution. A prod uct that is marketedun der the final OTC sunscreen d rugmonograph, but which uses anti-aging

language in the labeling to suggest orimply an un approved therapeutic orph ysiologic effect, would likely besubject to regulatory action as anun app roved new d rug (58 FR 28194 at28286 to 28287; see commen ts 37 and38 in section II.I of this d ocumen t).

25. Three comments contended thatthe terms natu ral, non -chem ical,

and chem ical free are false an dmisleading in the labeling of OTCsunscreen drug produ cts. The commentsrequested the agency to restrict the useof these terms, especially for sunscreenproducts containing titanium dioxideand zinc oxide.

Generally, the app ropriateness ofthese terms requires case-specificanalysis to determine whether their usewould render the produ ct false ormisleading in an y particular (seesection s 502(a) and 60 2(a) of the act).The agency notes, however, that the useof the term s no n-ch emical andchem ical-free in the labelin g of anOTC sun screen drug prod uct, todescribe the ingredients contained inthe prod uct, is likely to be consideredunacceptable. Sunscreen d rug produ ctscontain active (and often in active)ingredients that have been obtainedthrou gh a chemical process, or that havebeen formulated into the finishedproduct th rough a chemical process.The ter m natu ral is mo re likely torequire con text-specific analysis,particularly when used in labeling todescribe certain cosmetic aspects oruses of a sun screen prod uct. The termnatural, however, would not be

permitted to ap pear within the requiredOTC drug labeling of a sunscreenproduct and is not considered to beinterchan geable with an y of the finalsunscreen monograph language.

26. Four comments opp osed anylabeling that a sunscreen prod uct doesnot p rovide UVA protection,contend ing that FDAs policy does n otrequire disclaimers of broader pu rposesfor wh ich prod ucts are not useful. Onecomment added that an SPF 15 productmu st block UVA radiation to beeffective in preven ting sunbu rn.

Two comments argued that a

negative warning would be useful andnecessary to warn an d p rotectconsum ers and suggested Does notprovide broad spectrum UVAprotection, or Caution: This productdoes not provid e protection from therecognized dan gers of UVA rays whichmay contribute to skin cancer and otherchron ic skin disease.

Labeling should p rimarily directconsumers towards the p urposes forwhich a product is considered useful.However, in establishing the cond itionsfor the safe and effective use of an OTC


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dru g produ ct, the agency also mu st takeinto account, amon g other things, thecontext in wh ich a product iscustomarily marketed and the potentialthat consumers may use the produ ct fora use for which it may not be beneficial(see sections 201(n) and 502(a) of theact; 330.10(a)(3)).

With these factors in m ind , the agency

will furth er evaluate w hether negativewarn ings or disclosure statements areneeded w hen it completes the UVAportion of the sunscreen monograph ina future issue of the Federal Register.

27. Four comments contended thatthe signal words Indications andDirections are n ot n eeded , take upvaluable label space, and shou ld eithernot be required or be optional,especially for sunscreen -containing drugprod ucts th at have some traditionalcosmetic uses (e.g., lipsticks).

The agency allows the signal wordUse or Uses in place ofIndication or Indications. Thisshort signal word is u seful forconsumers, appropriate for dual useprod ucts, and does not clutter labelspace. Likewise, the agency conclud esthat th e signal w ord Directions isuseful for consumers and does notclutter label space (64 FR 13254 at13264 to 13268, March 17, 1999). Theagency is includin g 352.52(f) in thisfinal monograph to provide labelingmodifications for sunscreen productsthat meet the sm all packagespecifications in 201.66(d)(10) and arelabeled for use on specific small areasof the face (e.g., lips, n ose, ears, and /or

around eyes). These produ cts includeman y tradition al cosmetics (e.g., lipstickor eye makeup) that may containsunscreens. These products will beallowed to present a cond ensed Usessection and m ay omit directions for useif they are marketed in a lipstick form.

28. One comment requested that themonograph include professionallabeling for both UVB and UVAradiation p rotection to assist healthprofessionals to select app ropriateproducts. The comment recommendedinclusion of the absorption spectrum ofeach sunscreen in th e product and

suggested that th e labeling includ einformation that the p rodu ct: (1)Protects against dru g-ind ucedphotosensitization reactions induced byUV radiation in the ranges nm to

nm , and (2) other truthful andnonmisleading statements describingboth UVB and UVA radiation p rotectionagainst p hotosensitization reactions.

The agency did not proposeprofessional labeling in the tentativefinal monograph, but d id ask for data tobe subm itted (58 FR 28194 at 28210 and28245). No data w ere received. The

agency will consider inclu din g this typeof professional labeling in themonograph in the future when specificsupp ortive data are provided.

G. Com m ents on Su nscreen DrugProducts With High SPF Values

29. Numerous comm ents objected tothe proposed m aximum SPF value of 30

for OTC sun screen drug prod ucts. Thecomments requested either that theagency adopt n o limit or a limit of SPF50, for the followin g reasons: (1) UVradiation exposu re is increasing due toboth lifestyle changes and dep letion ofthe atm osph eric ozone layer, (2) skincancer rates are increasing and there isno safe threshold to p revent cancer, (3)people using an SPF 30 sunscreen willhave slight sunbu rn after receiving their30 MED and th erefore should haveavailable sun screens with h igher SPFvalues, (4) high SPF su nscreens areneed ed for extremely sun -sensitive

people du ring periods of unavoidableintense or lengthy sun exposure, andbecause of less than id eal usage byconsu mers du e to misjud ging of theirskin type and /or inadequate/infrequentapp lication, (5) there is a significantvariation of skin typ es, sensitivities, andUV radiation exposu res among people,(6) formulation techn iques can in creaseSPF values withou t necessarilyincreasing ingredient con centrations, (7)current information does not su pport anassociation between h igh SPF prod uctsand safety concerns, and (8) high SPFprod ucts p rovide for greater relative

exposure times and decreased UVradiation transmission. Three comments(Refs. 21, 22, and 23) submittedsupp orting d ata.

Some com men ts stated th at HighSPF (i.e., above SPF 30) p rod ucts areon the market and used by consum ers,and th at limiting SPF values wouldstifle sunscreen p roduct d evelopmentand preventative health benefits. Othercomments argued that sun screens w ithhigh SPF values provide in creasedprotection from u ltraviolet radiationeffects such asph otoimmu nosupp ression and areneed ed by th ose with dermatologicalproblems.

In contrast, some comm entssup ported th e agencys prop osal to limitSPF values to 30 to stop the prom otionalbid din g war or ho rsep ower race.Another comment contended that realconsu mer benefit is achieved throughapp ropriate balance of SPF,substantivity, UVA radiation p rotection,irritation potential, and cost, wh ereasSPF values above 30 provide on lyincr emen tal ben efit and anunnecessary increase in drug exposure.

The data provided by the commentsin sup port of allowing num erical valuesabove 30 were of only limited use. Datafrom a field survey of 62 sunbath ers onMiamis South Beach d urin g July 1993(Ref. 21) did not p rovide an y reliableconclusion s on the frequen cy or extentof solar overexposure by light-skinnedind ividuals or a benefit provided by

sunscreen products with an SPF valueabove 30 as: (1) The samp le size wassmall and the survey population did notrepresent a rand om samp le, (2) the MEDwas not determined u nder controlledconditions or standardized procedure,and (3) full-day UVB radiation exposu rewas based on crud e extrapolation ofweather data.

Data from MED determination s on1,332 people w ith skin types I, II, andIII, and UV radiation data for the mon thof Jun e 1974 in 5 cities in the Un itedStates (Ref. 22), sup port th e conten tionthat a sizeable popu lation may exist that

is at risk to m ore th an 3 0 MEDs of UVradiation p er day. However, the data areinsufficient for extrapolation to thegeneral pop ulation. The small samplesize in this stud y limits the sensitivityof the study and the study popu lationdid n ot represent a random sample.

Finally, data from an imal stud ies (Ref.23) showed that: (1) Limiting sun screenprotection to SPF 30 may not be pruden tif UV radiation d amage is not related toSPF; (2) a greater amou nt of su nscreenis needed to completely inhibit some ofthe nonerythemogenic damage causedby UV radiation, and (3)nonerythemogenic effects (e.g.,

photoimmun osuppression) occur withsuberythem al doses of UV radiation (ascan be obtained with the use of low orhigh SPF sun screens). While the agencyagrees that higher SPF valu es mayprovid e for greater relative exposu retimes, the SPF test is not the ap prop riatemeasurem ent of protection fromnon erythemogenic damage because SPFis only a measure of erythema. Theagency finds th at the data from thesestudies w ere not sufficient to eithersupport or dismiss limiting themaximu m SPF value in this final rule.

The agency continu es to agree with

the comm ents about overall increases inboth UV radiation exposu re (58 FR28194 at 28223), skin can cer rates (58FR 28194 at 28227), and the variation ofskin types, sensitivities, and UVradiation exposu res among people (58FR 28194 at 28222). The agency alsoagrees with the comm ent that a personusing an SPF 30 sunscreen could havea slight su nbu rn after being exposed totheir 30 MED (i.e., after th eir skinreceives a MED). However , the agencycontinu es to believe that an SPF 30sunscreen produ ct provides adequate


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protection for the m ajority of consumerseven under extreme conditions, lessthan ideal usage, or in varying weathercond itions (58 FR 28194 at 28225).

On the oth er hand , the agency is alsoaware that many OTC sunscreenprod ucts with SPF values above 30 arecurrently marketed and are increasinglyused by consum ers. Numerous

commen ts from health p rofessionals,consumers, and ind ustry provide actualuse information in sup port of SPFvalues above 30 for wh at may be asubstantial nu mber of sun -sensitivepeop le in this country. Further, asnu merous comm ents noted: (1) There isa lack of data to correlate higher th anSPF 30 sunscreen produ cts withcorrespond ing safety problems, and (2)modern formulation techniques haveresulted in higher SPF values usinglower active ingredient concen trations.

Because of the nu merous concern sfrom health p rofessionals, new d ata tosup port the need for SPF values above30, and the lack of data concernin gsafety problems with su ch SPF values,the agency concludes that OTCsunscreen drug produ cts with SPFvalues above 30 shou ld be available forthose sun-sensitive consumers wh orequire such p roducts based up onpersonal kn owledge of their skinssusceptibility to sunburn, experiencewith specific produ cts, planned sunexposu re, or the recommend ation of ahealth professional. The agency agreeswith the comments that higher SPFvalues generally can p rovide for greaterrelative exposure times and decreased

UV radiation transmission. However,the agency continu es to believe that theadditional sunburn protection providedby an SPF 30 su nscreen an d, e.g., anSPF 50 su nscreen (i.e., about a 1.3percent increase in absorption oferythemal UV radiation) is extremelysmall for most peop le. The agency isalso concerned abou t the ability ofcurrent testing method s to accuratelyand reproducibly determine SPF valuesfor high SPF p rodu cts (see section II.M,commen t 53 of this docu men t). Inadd ition, nonlin earity of the SPF ratingsystem is a concep t difficult to explain

in the limited space on a produ ct label.Therefore, the agency conclud es that thelabel SPF declaration for sun screenswith SPF values above 30 should belimited to one collective term, whichapp ears in 352.50(a) of this docum entas follow s: For produ cts with S PFvalues over 30. SPF 3 0 (select o ne ofth e followi ng: plu s or +). An ystatement accompanyin g the marketedprod uct that states a specific SPF valueabove 30 or similar language indicatinga person can stay in the sun more than30 times longer than with out sun screen

will cause the produ ct to be misbrandedun der section 502 of the Federal Food,Drug, and Cosmetic Act (th e act).

Numerous comm ents fromderm atologists asked that a specific SPF50 produ ct be allowed to remain on th emarket because it is needed for theultrasensitive patient and for patientswith dermatological problems. The

agency has previously discussed the useof high SPF sunscreen d rug produ cts toprotect consumers with photosensitivitydiseases (58 FR 28194 28225) and th eneed to p rovide data for such uses (seesection II.F, comment 28 of thisdocument) as the absorption spectrumof a specific prod uct, not n ecessarily theSPF, may be the m ore clinicallysignificant factor for such peop le.

As discussed previously in thiscomment 29 of section II.G of thisdocument, the agency has concludedthat the u se of SPF label values above30 in OTC dru g products is notsup ported at this time. The agency,how ever, invites interested persons tocontinue developing the test methodsneed ed to measure high SPF values, andto submit the data in sup port of suchmethod s to FDA. If test method s aredeveloped , the agency also invitesinterested persons to consider proposedmethods for communicating in labelingthe level of protection associated withhigh SPF values (given the n onlinearnatu re of the SPF rating system). Theseand other well-supp orted improvementsto the meth odology for accurately andreprod ucibly measurin g SPF values willbe addressed, as approp riate, in future

issues of the Federal Register. Untilthen, OTC sunscreen drug products areperm itted to be labeled with SPF valuesno high er th an 30+ or 30 p lus.

Finally, the agency does n ot agreewith th e argum ent that limiting SPFvalues would stifle sunscreen produ ctdevelopment and preventative healthbenefits. Undue emphasis for sunburnprotection should not be placed up onSPF valu e alon e (i.e., single focu sprod ucts). As noted by anoth ercommen t, consumer benefit is achievedthrou gh approp riate balance of severalfactors, includ ing substan tivity, UVA

radiation protection, and irritationpotential.

H. Com m en ts on Water Resist an tLabeling an d Testin g for SunscreenDrug Prod ucts

30. One comment agreed and severaldisagreed with proposed 352.52(e)(2)(iii) and (e)(3)(iii)concernin g sweat resistant claims basedup on water resistance testing instead ofa specific sweat resistance test. Onecomment submitted d ata from twosweat resistance stud ies and two water

resistance studies (Ref. 24) utilizingmethods proposed by the Panel in theANPRM (43 FR 38206) and in volving atotal of 117 subjects. The com men tconclud ed that the w ater resistance testis less stressful than the sw eat resistancetest.

The agency does not find the d atasubm itted in the stud ies sufficient to

supp ort the comments contention. Thestudies each comp rised distinct subjectpopu lations and addressed a singlevariable, i.e., the effect of waterexposure or induced sw eating on aprod ucts SPF. Therefore, a comparisonof mean SPF values across studies is notthe app ropriate measure of relativestress associated with thes e variables.The agency believes that a rand omized,two-period crossover study d esign in asingle patient population would betterhave addressed the commentscontention . Further, the Panels sweatand w ater resistance protocols provide

qualitative information and w ere notdesigned to provide comparativeassertions requiring valid statisticalinferences. Thus, the agency is allowin gwater and sweat resistant claims basedup on the water resistance testprocedures in 352.76 of thisdocument.

31. One comment contended that thewater res istant labelin g prop osed in 352.50(b)(1) and (c)(1) shou ld n ot berequired for produ cts labeled orpurchased for uses other thanswimming or bathing.

The agency notes that the w ater

resistance statemen ts referenced by thecomment were not required un less themanufacturer wished to make waterresistant claims in the labeling of itssun screen produ cts. This final rule alsowill not require a manu facturer to makea water resistance claim for itssunscreen produ ct, even if the produ ctis determined to be water resistant.However, a manufacturer wishin g tomake water resistance claims mu stcomply w ith 352.50(b) or (c) and352.52(b)(1)(ii) or (b)(1)(iii) of thisdocu men t, as app licable for waterresistan t or very water resistan tproducts.

32. Several comments u rged theagency to return to the waterproofand water resistan t label claimsproposed by the Panel and to limit thelabeled SPF value to only th e SPF afterwater resistance testing. Anothercomment requested only generalguidelines for claims such as waterresistan t or sweat resistan t on th ebasis that such claims reflect theinh erent ch aracteristics of specificformulations and not sun screeningredients.


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The agency thoroughly discussed useof the terms waterp roof and waterresistant in the tentative finalmon ograph (58 FR 28194 at 28228). Thecomments did n ot present anyarguments or data that the agency didnot previou sly consider. In add ition, theagency points out that performanceclaims such as these for OTC sun screen

dru g prod ucts are based on finalproduct formulation.

The agency agrees with the comm entsthat the m ore relevant SPF value forproducts labeled water resistant orvery w ater resistan t is th e SPF valu eof the final prod uct formulationfollowin g water resistance testing.Therefore, in this docu ment th e agencyis limiting the SPF label declaration tothe SPF after water resistance testingand is mod ifying the testing procedu resin 352.76 to reflect deletion of theproposed dual SPF testing requirementfor sun screen p roducts with w ater

resistant claims.33. Two commen ts suggested thatwater resistan t labelin g be perm ittedfor drug prod ucts retaining at least 80percent of their SPF value after statictesting in pools and that any productmeeting this criterion could also belabeled sweat p roof. The com men tsfurther su ggested th at the term verywater resistant shou ld be permitted forprod ucts retaining 90 to 98 percent oftheir SPF after testing.

The agency disagrees with thecomments. Simple immersion p rovidesneither an aqueou s shear stress northermal challenge, and thu s is an

inadequ ate assessment of waterresistance. In add ition, no justificationwas offered for the resp ective thresholdvalues of 80 percent and 90 to 98percent.

34. Several comments contended thatthe water resistance testing proceduresin 352.76 should be amended to allowfor continu ation of the water exposu reregimen beyon d the 80 minu te total andsuggested that the very water resistantclaim be expanded beyond 80 minutesfor prod ucts meeting such testingrequirements. One comm ent p rovideddata (Ref. 24) to supp ort extended water

resistance claims. Another commen talso prop osed a testing p rotocol (Ref.25) for an ad ditional claim ofrubproof or abrasion proof.

The agency does not concur with anexpansion of the very water resistantclaim. Althou gh data submitted by thecommen t (Ref. 24) show th at und ertesting cond itions produ cts may retaintheir SPF values for up to 270 min utesof water exposure, no u sage data werepresented to refute the Panelsdetermination of an 80 minu te upp erexposu re limit (58 FR 28194 at 28277).

In add ition, the agency believes that forconsumers to compare produ cts withmu ltiple performance ch aracteristics, alabelin g claim of very w ater resistan tis best sup ported by a un iform testingstandard . Should the agency receivedata in the future ind icating customaryusage patterns in excess of 80 minutesof water exposure, it will reconsider this

limit.35. One comment disagreed with the

agencys prop osal in th e tentative finalmon ograph (58 FR 28194 at 28278) thatmanufacturers determine the waitingperiods for the most effective use oftheir sun screen prod ucts (i.e., the timebetween application and exposure to thesun or water, if applicable). Thisinformation would then be included inthe directions for the prod uct. Thecommen t asserted there is no reason torequ ire a time versu s efficacy studyfor every sun screen formula becausestudies show th at products maintain

their efficacy for up to 8 hou rs.In the tentative final mon ograph, theagency did not p ropose a specificmethod or testing procedu re for thedetermination of a proper waitingperiod because of the variation insunscreen produ ct dosage forms andformulations. Instead, the agencyallowed man ufacturers to make thisdetermin ation. However, the agency didprop ose in 352.52(d)(2) that a waitingperiod before sun or water exposu re, ifapp licable, be includ ed in the labelingof sun screen produ cts for their mosteffective use. In th is final rule, th eagency has included th e requirement for

a waiting period in the sun screenproduct application statement inprop osed 352.52(d)(1) for the reasonsstated in the ten tative final mon ograph(58 FR 28278). The agency contin ues toallow the manufacturer to determineboth th e necessity for this statement(based on th e produ cts formulation anddosage form) and how the waitingperiod, if applicable, is determined .

I. Com m en ts on Indica tio ns forSunscreen Drug Products

36. One comment u rged the agency tomore stron gly state the effectiveness ofsun screens (a specific claim was notsuggested). The commen t cited acontrolled stud y of a broad spectrum,SPF 17 sun screen on 431 Caucasiansubjects over one sum mer in Au stralia(Ref. 26). The stud y show ed th at thegroup using the sunscreen hadsignificantly fewer solar keratoses andmore remissions than the control group.Another comment expressed concernthat u se of the term help prevent skindam age may m islead consu mers tothink that these produ cts prevent skincancer and p remature skin aging.

The agency agrees that solar keratosesare a clinical sign of skin d amage.However, althou gh sunscreens areassociated with a statistically significantdecrease in solar keratoses after 1 or 2years, the solar keratoses reduction inthis study was small and n either theclinical nor biological significance ofthis reduction has been established.

Most solar keratoses never become skincancers and typically resolvespon taneously (Refs. 27 and 28).

Because of the wid e variabilitypossible in the formulation of sunscreenproducts, not all sunscreen produ cts areidentical in their UV radiationabsorption ch aracteristics. Sunscreenprod ucts may contain active ingredientsthat absorb in different regions of theUVB radiation spectru m (the prim arycause of sun burn ) or absorb in both theUVB and different regions of the UVAradiation spectrum . Therefore, even thedegree/type of UV radiation p rotection

reported in on e study usin g a specificsunscreen formulation m ay not berelevant to all possible sun screenprod ucts within th e scope of this finalmon ograph. Further, the agency doesnot believe that it is prud ent toextrapolate claims for skin cancer orskin aging based up on a test designed toonly m easure erythema (i.e., the SPFtest).

The agency has reviewed in formationconcernin g the mechan isms of skincancers and ph otoaging. UV radiationapp ears to have a du al role in theind uction of skin cancers as it can cause

several varieties of direct DNA damage(Refs. 23 and 29 throu gh 32) plussupp ress the immu ne response todevelopin g skin can cers (Refs. 33through 37). This immun e supp ressionmay be a critical variable as skincancers, unlike other cancer types,evoke a strong immun e response(especially by Langerhans cells and T-lymphocytes) (Ref. 38). In photoaging,there are multiple sites in the skin thatcan be d amaged by UV radiation (Ref.17). For example, recent studies sup portthe concep t that specific UV radiation-ind uced en zymes (i.e., matrixmetalloproteinases) can m ediateconn ective tissue damage and resu lt inthe p remature aging effects seen in skinexposed to UV radiation (Refs. 19 and20). These data also suggest that thesemechan isms of carcinogenesis andph otoaging can occur from doses of UVradiation below that required to producesun burn (i.e., suberythem al doses).Thus, even if no sunburn has occurredwith th e use of a sunscreen, theconsumer cannot assume that sun-indu ced skin damage that mightcontribute to the eventual development


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1 See 201.66(b)(4)

of skin cancer or signs of photoaging hasnot occurred.

The agency agrees with the comm entthat terms su ch as help prevent skindam age may m islead consu mers tothink that sun screen u se alone willprevent skin cancer and p remature skinaging. However, the agency believes thatan app ropriate statement can be used to

inform consumers that sun screens mayredu ce the risks of skin aging, skincancer, and other h armful effects fromthe sun when used in a regular programthat includes limiting sun exposure andwearing p rotective clothing (see sectionII.L, commen t 51 of this d ocumen t).

37. Several commen ts expressedconcern that th e statements Allowsyou to stay in the sun up to (insert SPFof product u p to 30) times longer thanwithou t sunscreen p rotection andProvides u p to (insert SPF of produ ctup to 30) times your natu ral protectionfrom sunbu rn in p roposed 352.52(b)(1)(iii) and (b)(1)(iv) maymislead consum ers as to the amoun tand d egree of protection sun screenproducts p rovide. The comments w ereconcerned that this message will conveya more expansive meanin g thanintended and that consumers might bemisled about h ow long they can stay inthe sun w ithout risking any sun-indu ced skin injury. One commentexpressed additional concern becausethe SPF value is on ly a laboratory testof a few min utes du ration.

One comm ent also objected to theun qualified use of terms such asshields from, protects from,

filters or scre en s ou t the su nsrays , sun s harsh rays , or su nsharmful rays to help prevent skindam age proposed in 352.52(b)(1)(v)and (b)(1)(vi). The com men t expressedconcern that these unqualified termscould imp ly complete protection fromthe sun s harmful rays and m ay misleadconsu mers by indu cing a false sense ofsecurity wh en u sing sunscreenproducts.

As discussed in section II.I, comm ent36 of this docum ent, the agency believesthat sunscreen use alone will notprevent all of the possible harm fuleffects du e to the sun . Variationbetween ind ividuals, UV radiationabsorption and substantivity ofsunscreen produ cts, exposureconditions, and conditions of usecannot p romise a precise result for eachind ividual. Thu s, the agency agrees thatthese statements could provide thewron g message and a false sense ofsecurity to some consu mers. The agencytherefore is not includin g prop osed 352.52(b)(1)(iii) throu gh (b)(1)(vi) inthis final rule and con siders these andsimilar statements to be nonmonograph.

For the same reasons, the agency alsoconsiders extended wear claimsconcernin g a specific nu mber of hou rsof pr otection (or sim ilar term ino logy)or an absolute claim su ch as all-dayprotection to be nonm onograph.Instead, the agency is inclu din g anaccurate, simp ler, and less confusingind ication statement in this final rule

using two bulleted statements un der theUses heading, as follows: [bullet]help s preven t sun burn and [bullet]higher SPF gives more sunbu rnprotection.1

38. Several comments contended thatterms such as skin aging,wrinkling, premature skin aging, orphotoaging should be permitted asind ications for sun screens, especially ifprotection is provided in the UVA II(320 to 340 nm) radiation region. Onecommen t suggested th at a label claimsuch as Helps redu ce the chan ce ofskin aging caused by inciden tal (or

casual) exposure to the sun may h elpto furth er position the produ ct as acosmetic for consum ers. The commen talso suggested an in dication statement:Excessive, chronic sun exposure canlead to prematu re photoaging of theskin, characterized by d rying, wrinklingand thinn ing of the skin. Regular use ofa sunscreen can help p rotect against thiscondition.

The agency discussed the u se of termssuch as skin aging, wrinkling,pr ematu re skin aging, orph otoaging on sun screen p rodu cts inthe tentative final monograph (58 FR28194 at 28236 and 28287). As

discussed in the response to comments36 and 37, the agency has determin edthat the labeling shou ld describe theprodu cts use in preventing sunburn. Amore expan sive set of ind ications iscurrently unsup ported. The agencynotes, h owever, that th e final Sunalert statement (discussed in sectionII.L, commen t 51 of this docu men t) doesprovide the consu mer with informationabout the role of sun screens in reducin gskin aging, in a context that en sures thatthe information w ill not be misleading.The agency, however, is continu ing toconsider wh ether certain sun screens

may provid e protection againstph otoaging (58 FR at 28287) and h asdiscussed this in tentative finalmonograph amendments for certainsunscreens containing avobenzone orzinc oxide based up on specific datasubmitted to the agency (see section II.E,commen t 22 of this docu ment). Theagency will evaluate this issue furtherwh en it completes the UVA portion ofthe sun screen m onograph, in a futureissue of the Federal Register.

39. Several comments contended thatthe extensive labeling proposed in th etentative final mon ograph wasexcessive. For environ men tal concerns,the comm ents objected to the use ofextra packaging materials as a method ofincluding added labeling. One commen tdisagreed with th e need for a specificstatement of prod uct ind ications on

individual un its of non-beach p roductsprop erly labeled with an SPF value, andcited limitations on labeling space. Thecommen t suggested that manu facturersbe given th e option to p rovide off-package information at the p oint-of-salerather than be required to p lace thestatement(s) on each ind ividual un it ofthe product.

To balance the environm ental andregulatory concerns, the agency hasstreamlined labeling in this finalmon ograph by significantly reducing theamount of required labeling and makingoptional other labeling that was

prop osed as required in the tentativefinal monograph . The agency is alsoinclud ing 352.52(f) in this finalmonograph to provide for additionallabeling accommod ations for sunscreenprod ucts that meet the small packagespecifications in 201.66(d)(10) and arelabeled for use on s

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