Perspective TheNEWENGLANDJOURNALofMEDICINEjuly 9, 2015n engl j
med 373;2nejm.orgjuly 9, 2015101FDAhasdeclinedtopermituse
ofeightnewsunscreeningredi-entswithoutadditionaldata,al-thoughthoseingredientshave
beenusedinEuropeformore than 5 years and despite the recent passage
of a U.S. law intended to expedite the marketing-approval
processfornewproducts.The controversysaysasmuchabout the challenges
facing the agency as it does about sunscreen regulation.Melanoma is
a significant pub-lichealthproblem.Eachyear, 75,000 people in the
United States arediagnosedwithand10,000 die from the disease (see
graph).1 The primary cause of melanoma
isknown:DNAdamageresult-ingfromexposuretoultraviolet
radiation.Nevertheless,melano-marateshavebeenincreasing
fordecades.Reducingexposure toultraviolentradiation,from
boththesunandartificial sourcessuch as tanning beds, is essential
to prevention.In2012,theFDAdetermined that sunscreens blocking a
broad spectrumofultravioletradiation with a sun protection factor
(SPF) of15orgreatercouldbemar-keted as reducing the risk of skin
cancer.However,itdidnotre-move from the market other
sun-screens,suchasthosewitha lower SPF that may only help pre-vent
sunburns. As a result, some Americansmaybepurchasing
sunscreenswithoutknowing that theres no evidence that they
protectagainstcancer.Inaddi-tion, many Americans fail to use
sunscreen as recommended
alto-gether.Mostbroad-spectrumsun-screensmarketedintheUnited States
contain oxybenzone or avo-benzonetoblockthetypeof
ultravioletradiation,knownas UVA,thatismostcloselylinked
tocancer.Since1999,theFDA has approved one new ingredient,
ecamsule, for use in limited for-mulationsforthispurpose.In
2002,theagencyestablisheda mechanismforconsideringdata from
experience elsewhere, includ-ing in European countries, where
sunscreensareregulatedascos-metics and other ingredients are
widelyused.Buttheagencydid nottakeactiononapplications
submittedthroughthispathway for more than a decade.In 2013,
advocates for patients A Spotlight on Sunscreen RegulationJoshua M.
Sharfstein, M.D.There may be nothing new under the sun, but the
U.S. Food and Drug Administration (FDA) is facing calls for
something new under the agencys authority over sunscreens. In
recent months, the The New England Journal of Medicine Downloaded
from nejm.org on August 3, 2015. For personal use only. No other
uses without permission. Copyright 2015 Massachusetts Medical
Society. All rights reserved. PERSPECTI VEn engl j med
373;2nejm.orgjuly 9, 2015102withmelanoma,dermatologists, and
manufacturers of new ingre-dients came together in a coalition
calledPublicAccesstoSun-Screens (PASS). This group argued
thatthenewingredientswould resultinproductsthataremore
attractivetoconsumers,suchas longer-lasting products that dont
requirefrequentreapplication. Expressingitsdismayoverthe
lackofactiononthepending sunscreen applications, the coali-tion
pressed Congress to impose tighter deadlines for FDA decision
making. This approach, however, didnotfullyconsidertheagen-cys
framework for review of sun-screens, resource needs, and pub-lic
health role.With respect to new prescrip-tiondrugs,theFDAgenerally
moves faster than European regu-latoryagencies,anditapproved 41
products in 2014 the most in18years.Keytothispaceis
thefactthatunderU.S.regula-torylaw,theagencytailorsits approval
decisions to the data at hand,receivesextraresources (from user
fees) for drug reviews, and if problems emerge after
ap-proval,hastheabilitytomove quickly with a range of actions to
protect the public. Although this process is well suited to
individual newtherapeutics,itiscumber-someformanyproductsintend-ed
to be sold over the counter in a wide variety of formulations and
concentrations.Over-the-counter products such as sunscreens are
usually regulat-edthroughanentirelydifferent
processdesignedforproducts posing little to no risk, under the
standard of generally recognized as safe and effective. There is no
product-specific approval decision; rather, the agency must issue
pro-posed and final rules, with multi-ple opportunities for public
com-ment,beforeauthorizingeach classofproducts.Aswithother agency
regulations, rules for over-the-counterproductsgenerally require
economic analyses, with clearanceoftenrequiredfrom
boththeDepartmentofHealth andHumanServicesandthe
WhiteHouseOfficeofManage-ment and Budget.Unlike review of new
prescrip-tion drugs, the pathway for over-the-counter products is
supported bynoadditionalresources.Be-tweenproceduralrequirements
andinadequateresources,over-the-counterproductregulation proceeds
in slow motion as com-pared with the rest of the agency.
Rulemakingtypicallyconsumes many years, or even decades. Exist-ing
sunscreen ingredients, for ex-ample, are not, even now, the
sub-jectofafinalregulationbythe agency.Once issued, rules for
over-the-counter products allow companies
tomanufactureabroadarrayof formulationsanddosagesand
tomarketthemextensively.The agency has little ability to require
the collection of data on long-term safetyorefficacy.Evenifnew
troublingsafetyinformationon over-the-counterproductscomes to
light, the FDA cannot alter its approach quickly. Instead, it must
beginthelaboriousrulemaking processalloveragain.These limitations
understandably lead to a cautious approach to approving
products,suchassunscreens, thataredesignedforlong-term
usebymillionsofchildrenand adults in the absence of disease.Indeed,
in early 2014, the FDA releasedlettersfindinginsuffi-cient evidence
to consider several of the new sunscreen ingredients generally
recognized as safe and effective. Then, in September, an
FDAadvisorycommitteerecom-mended that the agency collect a
broadsetofdataforevaluating all new sunscreen ingredients,
in-cludingdataonskinirritation, carcinogenicity, and developmen-tal
toxicology.2Attheendoftheyear,with the support of the PASS
coalition, CongresspassedandPresident BarackObamasignedbipartisan
legislation called the Sunscreen In-novationAct.Thenewlawset
deadlinesforFDAreviewandre-movedseveralproceduralrequire-ments for
agency action. However, A Spotlight on Sunscreen RegulationNo. per
100,000 Persons2550101520New
casesDeaths199219931994199519961997199819992000200120022003200420052006200720082010200920112012New
Cases of Melanoma of the Skin and Deaths per 100,000 Persons, 1992
through 2012.Data are from the Surveillance, Epidemiology, and End
Results Program, National Cancer Institute.The New England Journal
of Medicine Downloaded from nejm.org on August 3, 2015. For
personal use only. No other uses without permission. Copyright 2015
Massachusetts Medical Society. All rights reserved. n engl j med
373;2nejm.orgjuly 9, 2015PERSPECTI VE103thelegislationprovidednonew
resources,nonewauthorityfor postmarketingsafety,andlittle
newflexibilityfortheagencyin the review
process.Soonafterthelawspassage, the FDA released a proposed
de-cision to reject all eight pending
ingredients,citingmultiplegaps in data, including key safety
stud-ies and reports of adverse events in countries where relevant
prod-ucts are marketed.The agencys proposal provoked a swift and
angry response. In a pressrelease,thePASScoalition
statedthattheagencydemon-stratescleardisregardforin-creasedratesofmelanomaand
thepublicsdemandforlatest sunscreen technology.3 The Wall
StreetJournaleditori-al board stated that
theagencyswill-fulcultureofcon-trolanddelayistherealpublic-healthmenace....Theonly
solution is to strip the sunscreen policeofallpowersoverthe stuff.
4Theseattacksmissedtheir mark.Itsnosurprisethatthe
FDAwouldactcautiouslygiven thescientificadviceitsreceived
andalegalstructurethatessen-tially provides it with just one tool:
authorizingextensivemarketing
ofmultipleproductsandformu-lations.UnderstandingtheFDA means
recognizing that the
frame-workforover-the-counterprod-uctsisnotdesignedtopromote
innovation, even innovation with potential public health
benefits.Inmyview,Congressshould try again and pass legislation
es-tablishing an alternative approval pathway that combines the
flexi-bilityofthenewdrugpathway with the ability to simultaneously
approve multiple formulations and concentrations.TheFDAshould
beabletonegotiatewithspon-sors to get the right data without
yearsofrulemaking,establish postmarketing data requirements,
consultwithothercountries regulators to establish consistent
standardswherepossible,and movequicklyintheeventthat
safetyconcernsemerge.Con-gressshouldprovideadditional
resourcestofacilitatetimely analysisandreview.Thatthis path is
viable is evidenced by the factthattheoneapprovalofa product with a
new sunscreen in-gredient in the past decade came through the new
drug pathway.More timely and flexible review can expand sunscreen
options for consumers and complement other measurestoreducemelanoma
prevalence.Promisingstepsin-cludeFDAeffortstodiscourage
useoftanningbedsandinitia-tivesbytheCentersforDisease
ControlandPreventiontopro-motepreventionmeasures.The
federalgovernmentshouldalso reconsider whether it makes sense to
continue allowing some prod-ucts to be marketed as sunscreen
withoutevidenceofprotection against cancer. After all, the
ulti-mategoalistomakemeaning-fulprogressagainstthispublic health
problem.Disclosure forms provided by the author are available with
the full text of this article at NEJM.org.From the Johns Hopkins
Bloomberg School of Public Health,
Baltimore.1.NationalCancerInstitute.Asnapshot
ofmelanoma(http://www.cancer.gov/
researchandfunding/snapshots/melanoma).2.Tucker ME. FDA advisory
panel calls for
sunscreensafetytesting.MedscapeMedi-calNews.September8,2014(http://www
.medscape.com/viewarticle/831359).3.PublicAccesstoSunScreensCoalition
(PASS).FDAsannouncementonecamsule and enzacamene applications
demonstrates cleardisregardforincreasedratesofmela-noma, publics
demand for latest sunscreen technology.February24,2015(http://www
.passcoalition.com/index.php/media-info/
173-fda-s-announcement-on-ecamsule-and
-enzacamene-applications-demonstrates
-clear-disregard-for-increased-rates-of
-melanoma-public-s-demand-for-latest
-sunscreen-technology).4.Washingtons skin cancer hostages: the
FDAisdefyingCongressandObamaon bettersunscreens.WallStreetJournal.
March 13, 2015 (http://www.wsj.com/articles/
washingtons-skin-cancer-hostages -1426287044).DOI:
10.1056/NEJMp1504912Copyright 2015 Massachusetts Medical Society.A
Spotlight on Sunscreen RegulationSynthetic CannabinoidRelated
Illnesses and DeathsJordan Trecki, Ph.D., Roy R. Gerona, Ph.D., and
Michael D. Schwartz, M.D., M.P.H.Syntheticcannabinoids(SCs) were
first created in the 1980s as laboratory research tools (lig-ands)
for studying human endo-cannabinoidreceptorsystems. SC-containing
products supplied by illicit manufacturers were then
marketedthroughoutEuropeas herbalincense,beforearriving
intheUnitedStatesinNovem-ber2008.Theprevalenceand variety of SCs on
the illicit mar-kethavesteadilyincreasedover the past 6 years, as
manufactur-ersanddistributorsofSCsand
dealersofSC-containingprod-ucts have attempted to circumvent
federal,state,andlocallaws. An audio interview with Dr. Sharfstein
is available at NEJM.org The New England Journal of Medicine
Downloaded from nejm.org on August 3, 2015. For personal use only.
No other uses without permission. Copyright 2015 Massachusetts
Medical Society. All rights reserved.
