Introduction
The acute and chronic dermatologic complications from
the ultraviolet (UV) component of sunlight are well characterized. Among other complications, exposure
to UV radiation from sunlight is associated with approximately 90 percent of non-melanoma skin cancer cases,1 approximately
65 percent of melanoma cases1 and approximately 90 percent of the cosmetic changes attributed to aging.2,3 The UV radiation
causing these dermatologic complications falls in the UVB (290–320 nm) and UVA (320–400 nm) wavelengths. Various organic
and inorganic UV filters have been identified to protect against the spectrum of UV radiation through mechanisms of
absorption, reflection or diffusion, or a combination thereof.
Although sunscreens are generally considered effective for protecting against photocarcinogenesis,4 photoimmunosuppression5
and photoaging,6 concern has been expressed that certain UV filters may lose part of their protective capability following
exposure to UV radiation.7–16 Certain filters are known to degrade with exposure to UV; however, relatively little has
been reported on the effectiveness of UV-irradiated sunscreen formulations in protecting skin against damage from UVB
and UVA.
The U.S. Food and Drug Administration's (FDA's) proposed amendment to the final monograph on "Sunscreen Drug Products
for Over-the-Counter Human Use" includes new provisions to help ensure that sunscreen products remain effective over
typical periods of exposure.17 These provisions call for pre-irradiation of sunscreen prior to assessing the UVB sun protection
factor (UVB-SPF) and UVA-protection factor (UVA-PF).17 The purpose of the two studies described herein was to evaluate the
UVB-SPF and UVA-PF of a commercially available sunscreen formulation, Cetaphil® UVA/UVB Defense SPF 50 (Galderma Laboratories,
L.P., Fort Worth, TX), that has been exposed to UV radiation in the form of natural sunlight.
Methods
Study Population
Men and women 18 years or older in general good health, as determined by a health questionnaire, were eligible for participating in these studies if they had Fitzpatrick skin type I, II or III (UVBSPF study) or type II or III (UVA-PF study). Individuals who were instructed by a healthcare professional to avoid sunlight due to a medical condition or medication contraindication were excluded from participation. Other major exclusion criteria included known abnormal response to sunlight; known hypersensitivity to sunscreens; observable suntan, scars or active cutaneous lesions on areas of the back to be tested; or any disease or condition that the study investigator deemed inappropriate for participation.
Men and women 18 years or older in general good health, as determined by a health questionnaire, were eligible for participating in these studies if they had Fitzpatrick skin type I, II or III (UVBSPF study) or type II or III (UVA-PF study). Individuals who were instructed by a healthcare professional to avoid sunlight due to a medical condition or medication contraindication were excluded from participation. Other major exclusion criteria included known abnormal response to sunlight; known hypersensitivity to sunscreens; observable suntan, scars or active cutaneous lesions on areas of the back to be tested; or any disease or condition that the study investigator deemed inappropriate for participation.
Study Design and Conduct
These were randomized, controlled, evaluator-blinded, single- center trials. The study protocols were approved by an Institutional Review Board, and the studies were conducted in accordance with Good Clinical Practice Guidelines. Written informed consent was provided by the enrolled participants.
These were randomized, controlled, evaluator-blinded, single- center trials. The study protocols were approved by an Institutional Review Board, and the studies were conducted in accordance with Good Clinical Practice Guidelines. Written informed consent was provided by the enrolled participants.
The test product for these two studies was Cetaphil UVA/UVB Defense SPF 50, which has the following active ingredients: octinoxate
(7.5%), octisalate (5%), octocrylene (7%), oxybenzone (6%) and titanium dioxide (5.7%). The UVB-SPF and UVA-PF values
on the label for this product are 50 and 9, respectively (Data on File, Galderma Laboratories, L.P.).
Both studies were conducted according to the procedures as described in the 2007 Proposed Amendment (21 CFR Parts 247
and 252) to the Federal Register 64 (98), entitled "Sunscreen Drug Products for Over-the-Counter Human Use."17 Prior to the
start of each study, a thin film of sunscreen (2 mg/cm2) was appliedto a glass plate and exposed to UV radiation in the form of natural sunlight to approximately the following levels of
minimal erythemal dose (MED)–2 MED (42 mJ/cm2), 4 MED (84 mJ/cm2), 8 MED (164 mJ/cm2) or 16 MED (336 mJ/cm2) of
UVB and the associated UVA. Exposures occurred on 02/04/09, 02/05/09, 02/11/09, 02/18/09 and 02/19/09 between 11:00am
and 4:00pm in Dallas, TX; noontime MED levels during this time of year range from 1.5–2.0 MED/hour. UVB radiation was
monitored using a Solar Light PMA 2100 detector (Solar Light Company, Inc., Glenside, PA) with a PMA 2101 SUV detector
calibrated for 21 mJ/cm2 (erythremically effective dose). UVA radiation was measured using a Solar Light PMA 2100 detector
with a PMA 2110 SUV detector. Following exposure, sunscreen was removed from the glass plates and stored in photo-protected
vials under refrigeration.
Eligible subjects were assessed for their inherent (unprotected) MED associated with UVB exposure and minimal pigment
darkening (MPD) dose associated with UVA exposure. For determining the unprotected MED and MPD, each subject
received at least five irradiation exposures on adjacent unprotected skin sites on the lower back. Each exposure represented
a 25 percent increase in energy over the previous exposure. UV radiation was provided using a single-port solar simulator
with a 150-watt xenon arc lamp (Model 16S Solar UV Simulator, Solar Light Company, Inc.), with UG-11 and WG-320 filters
(Schott Glass, Inc., Elmsford, NY) providing UVA and UVB radiation, respectively. The light source was placed 6.5 cm from
the test sites, and the UVA and UVB radiation exposure was measured using the 3D-600 meter (Solar Light Company, Inc.).
The sites were examined by a clinical grader for immediate erythema (MED) and immediate pigment darkening (MPD) after
the completion of each exposure.
Erythema was assessed approximately 16–24 hours after UV exposure using a 4-point scale (no erythema, questionable
response/unclear, erythema extending to the borders and erythema with or without edema present). The site receiving
the lowest dose of UV radiation that produced erythema extending to the borders was selected as the unprotected MED
for that subject. Pigment darkening was assessed approximately three to 24 hours after UV exposure using a similar
4-point scale (no pigment darkening, questionable response/ unclear, darkening over essentially the entire test site and
definite darkening over the entire test site). The site receiving the lowest dose of UV radiation that produced darkening over
essentially the entire test site was selected as the unprotected MPD for that subject.
