Section



[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR352.73]

[Page 299-301]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 352_SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE 
[STAYED INDEFINITELY]--Table of Contents
 
                      Subpart D_Testing Procedures
 
Sec. 352.73  Determination of SPF value.

    (a)(1) The following erythema action spectrum shall be used to 
calculate the erythema effective exposure of a solar simulator:
    Vi ([lambda])=1.0 (250 < [lambda] < 298 nm)
    Vi ([lambda])=1.0^{0.094 (298 -} l) (298 < 
[lambda] < 328 nanometers)
    Vi ([lambda])=1.0^{0.015 (139 -} l) (328 < 
[lambda] < 400 nanometers)
    (2) The data contained in this action spectrum are to be used as 
spectral weighting factors to calculate the erythema effective exposure 
of a solar simulator as follows:

[[Page 300]]

[GRAPHIC] [TIFF OMITTED] TR21MY99.000

    (b) Determination of MED of the unprotected skin. A series of UV 
radiation exposures expressed as Joules per square meter (adjusted to 
the erythema action spectrum calculated according to Sec. 352.73(a)) is 
administered to the subsite areas on each subject with an accurately 
calibrated solar simulator. A series of five exposures shall be 
administered to the untreated, unprotected skin to determine the 
subject's inherent MED. The doses selected shall be a geometric series 
represented by (1.25ⁿ), wherein each exposure time interval 
is 25 percent greater than the previous time to maintain the same 
relative uncertainty (expressed as a constant percentage), independent 
of the subject's sensitivity to UV radiation, regardless of whether the 
subject has a high or low MED. Usually, the MED of a person's 
unprotected skin is determined the day prior to testing a product. This 
MED(US) shall be used in the determination of the series of UV radiation 
exposures to be administered to the protected site in subsequent 
testing. The MED(US) should be determined again on the same day as the 
standard and test sunscreens and this MED(US) should be used in 
calculating the SPF.
    (c) Determination of individual SPF values. A series of UV radiation 
exposures expressed as Joules per square meter (adjusted to the erythema 
action spectrum calculated according to Sec. 352.73(a)) is administered 
to the subsite areas on each subject with an accurately-calibrated solar 
simulator. A series of seven exposures shall be administered to the 
protected test sites to determine the MED of the protected skin 
(MED(PS)). The doses selected shall consist of a geometric series of 
five exposures, where the middle exposure is placed to yield the 
expected SPF plus two other exposures placed symmetrically around the 
middle exposure. The exact series of exposures to be given to the 
protected skin shall be determined by the previously established MED(US) 
and the expected SPF of the test sunscreen. For products with an 
expected SPF less than 8, the exposures shall be the MED(US) times 
0.64X, 0.80X, 0.90X, 1.00X, 1.10X, 1.25X, and 1.56X, where X equals the 
expected SPF of the test product. For products with an expected SPF 
between 8 and 15, the exposures shall be the MED(US) times 0.69X, 0.83X, 
0.91X, 1.00X, 1.09X, 1.20X, and 1.44X, where X equals the expected SPF 
of the test product. For products with an expected SPF greater that 15, 
the exposures shall be the MED(US) times 0.76X, 0.87X, 0.93X, 1.00X, 
1.07X, 1.15X, and 1.32X, where X equals the expected SPF of the test 
product. The MED is the quantity of erythema-effective energy required 
to

[[Page 301]]

produce the first perceptible, unambiguous redness reaction with clearly 
defined borders at 22 to 24 hours postexposure. The SPF value of the 
test sunscreen is then calculated from the dose of UV radiation required 
to produce the MED of the protected skin and from the dose of UV 
radiation required to produce the MED of the unprotected skin (control 
site) as follows:
    SPF value =the ratio of erythema effective exposure (Joules per 
square meter) (MED(PS)) to the erythema effective exposure (Joules per 
square meter) (MED(US)).
    (d) Determination of the test product's SPF value and PCD. Use data 
from at least 20 test subjects with n representing the number of 
subjects used. First, for each subject, compute the SPF value as stated 
in Sec. 352.73(b) and (c). Second, compute the mean SPF value, x, and 
the standard deviation, s, for these subjects. Third, obtain the upper 
5-percent point from the t distribution table with n-1 degrees of 
freedom. Denote this value by t. Fourth, compute ts/ [radic]n. Denote 
this quantity by A (i.e., A =ts/ [radic]n). Fifth, calculate the SPF 
value to be used in labeling as follows: the label SPF equals the 
largest whole number less than x - A. Sixth and last, the drug product 
is classified into a PCD as follows: if 30 + A < x, the PCD is High; if 
12 + A < x < 30 + A, the PCD is Moderate; if 2 + A < x < 12 + A, the PCD 
is Minimal; if x < 2 + A, the product shall not be labeled as a 
sunscreen drug product and shall not display an SPF value.