49070 Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 347 and 352 

[Docket No. 1978N–0038] (formerly Docket 

No. 78N–0038) 

RIN 0910–AF43 

Sunscreen Drug Products for Over-theCounter Human Use; Proposed 

Amendment of Final Monograph 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Proposed rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is issuing a 

proposed rule that would amend the 

final monograph (FM) for over-thecounter (OTC) sunscreen drug products 

as part of FDA’s ongoing review of OTC 

drug products. This amendment 

addresses formulation, labeling, and 

testing requirements for both ultraviolet 

B (UVB) and ultraviolet A (UVA) 

radiation protection. FDA is issuing this 

proposed rule after considering public 

comments and new data and 

information that have come to FDA’s 

attention. This rule proposes to lift the 

stays of 21 CFR 347.20(d) and 21 CFR 

Part 352 when FDA publishes a final 

rule based on this proposed rule. 

DATES: Submit written or electronic 

comments by November 26, 2007. 

Submit written or electronic comments 

on FDA’s economic impact 

determination by November 26, 2007. 

Please see section X of this document 

for the effective and compliance dates of 

any final rule that may publish based on 

this proposal. 

ADDRESSES: You may submit comments, 

identified by Docket No. 1978N–0038 

and RIN number 0910–AF43, by any of 

the following methods: 

Electronic Submissions 

Submit electronic comments in the 

following ways: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Agency Web site: http:// 

www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting 

comments on the agency Web site. 

Written Submissions 

Submit written submissions in the 

following ways: 

• FAX: 301–827–6870. 

• Mail/Hand delivery/Courier (for 

paper, disk, or CD–ROM submissions): 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

To ensure more timely processing of 

comments, FDA is no longer accepting 

comments submitted to the agency by email. FDA encourages you to continue 

to submit electronic comments by using 

the Federal eRulemaking Portal or the 

agency Web site, as described in the 

Electronic Submissions portion of this 

paragraph. 

Instructions: All submissions received 

must include the agency name, docket 

number and regulatory information 

number (RIN) for this rulemaking. All 

comments received may be posted 

without change to http://www.fda.gov/ 

ohrms/dockets/default.htm, including 

any personal information provided. For 

additional information on submitting 

comments, see the ‘‘Request for 

Comments’’ heading of the 

SUPPLEMENTARY INFORMATION section of 

this document. 

Docket: For access to the docket to 

read background documents or 

comments received, go to http:// 

www.fda.gov/ohrms/dockets/ 

default.htm and insert the docket 

number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Division of Dockets 

Management, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Matthew R. Holman, Office of 

Nonprescription Products, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 22, rm. 5414, 

Silver Spring, MD 20993, 301–796– 

2090. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. Background 

II. Summary of Major Changes to the FM 

A. Ingredients 

B. UVB (SPF) Labeling 

C. UVA Labeling 

D. Indications 

E. Warnings 

F. Directions 

G. UVB Testing 

H. UVA Testing 

III. FDA’s Tentative Conclusions on the 

Comments 

A. General Comments on OTC 

Sunscreen Drug Products 

B. Comments on Tanning and 

Tanning Preparations 

C. Comments on Specific Sunscreen 

Active Ingredients 

D. General Comments on the Labeling 

of Sunscreen Drug Products 

E. Comments on the Labeling of 

Sunscreen Drug Products With 

UVA Protection 

F. Comments on the Labeling of 

Sunscreen Drug Products With High 

SPF Values 

G. Comments on Indications for 

Sunscreen Drug Products 

H. Comments on Directions for 

Sunscreen Drug Products 

I. General Comments on SPF Testing 

Procedure 

J. Comments on the Sunscreen 

Standard for SPF Testing Procedure 

K. Comments on Artificial Light 

Sources for SPF Testing Procedure 

L. Comments on the Design/Analysis 

of SPF Testing Procedure 

M. General Comments on UVA 

Testing Procedure 

N. Comments on UVA Testing 

Procedure Design and Testing 

Criteria 

O. Comments on the Photostability of 

Sunscreen Drug Products 

IV. FDA’s Tentative Conclusions and 

Proposals 

V. Analysis of Impacts 

A. Background 

B. Number of Products Affected 

C. Cost to Relabel 

D. Cost to Test or Retest Products for 

UVA Protection 

E. Total Incremental Costs 

F. Small Business Impact 

G. Analysis of Alternatives 

VI. Paperwork Reduction Act of 1995 

VII. Environmental Impact 

VIII. Federalism 

IX. Request for Comments 

X. Proposed Effective and Compliance 

Dates 

XI. References 

I. Background 

In the Federal Register of May 12, 

1993 (58 FR 28194), FDA published a 

notice of proposed rulemaking in the 

form of a tentative final monograph 

(TFM) for OTC sunscreen drug 

products. In the TFM, FDA proposed 

the conditions under which OTC 

sunscreen drug products would be 

considered generally recognized as safe 

and effective (GRASE), under section 

201(p) of the Federal Food, Drug, and 

Cosmetic Act (the act) (21 U.S.C. 

321(p)), and not misbranded, under 

section 502 of the act (21 U.S.C. 352). 

In the Federal Register of April 5, 

1994 (59 FR 16042), FDA reopened the 

administrative record until July 31, 

1994, to allow additional submissions 

on UVA-related issues and announced a 

public meeting for May 12, 1994, to 

discuss UVA testing procedures. As 

explained in that Federal Register 

notice, the TFM included proposed 

UVB (i.e., 290–320 nm) testing and 

labeling. The sun protection factor (SPF) 


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test and corresponding labeling reflects 

the level of protection against sunburn, 

which is caused primarily by UVB 

radiation. The TFM also explained the 

importance of protection against UVA 

radiation (i.e., 320–400 nm), the other 

UV component of sunlight (58 FR 28194 

at 28232 and 28233). The TFM 

referenced published UVA test methods 

but did not propose a method (58 FR 

28194 at 28248 to 28250). Rather, the 

TFM stated that a product could be 

labeled as ‘‘broad spectrum’’ or a similar 

claim if it protected against UVA 

radiation. Thus, FDA held the 1994 

public meeting to gather further 

information about an appropriate UVA 

test method and labeling. 

In the Federal Register of June 8, 1994 

(59 FR 29706), FDA proposed to amend 

the TFM (and reopened the comment 

period until August 22, 1994) to remove 

five proposed sunscreen ingredients 

from the TFM because of lack of interest 

in establishing United States 

Pharmacopeia—National Formulary 

(USP–NF) monographs. FDA also 

reiterated that all sunscreen ingredients 

must have a USP–NF monograph before 

being included in the FM for OTC 

sunscreen drug products. 

In the Federal Register of August 15, 

1996 (61 FR 42398), FDA reopened the 

administrative record until December 6, 

1996, to allow additional submissions 

on zinc oxide and titanium dioxide as 

well as sunscreen photostability. FDA 

also announced a public meeting for 

September 19 and 20, 1996, to discuss 

the safety and efficacy of these two 

ingredients and photostability of 

sunscreens in general. 

In the Federal Registers of September 

16, 1996 (61 FR 48645) and October 22, 

1998 (63 FR 56584), FDA amended the 

TFM to add the UVA-absorbing 

sunscreen ingredients avobenzone and 

zinc oxide to the proposed list of 

monograph ingredients. FDA also 

proposed indications for these 

ingredients. As a result of this 

amendment to the TFM, in the Federal 

Register of April 30, 1997 (62 FR 

23350), FDA announced an enforcement 

policy allowing interim marketing of 

OTC sunscreen drug products 

containing avobenzone. 

On November 21, 1997, Congress 

enacted the Food and Drug 

Administration Modernization Act of 

1997 (FDAMA). Section 129 of FDAMA 

stated that ‘‘Not later than 18 months 

after the date of enactment of this Act, 

the Secretary of Health and Human 

Services shall issue regulations for overthe-counter sunscreen products for the 

prevention or treatment of sunburn.’’

FDA identified the UVB portions of the 

monograph (and related provisions on 

water resistant test methods and 

cosmetic labeling) as items that could be 

finalized within the timeframe set by 

FDAMA. Because of outstanding issues 

related to the development of testing 

standards and labeling for UVA 

radiation protection, FDA deferred final 

action on these items. 

Therefore, in the Federal Register of 

May 21, 1999 (64 FR 27666), FDA 

published the FM for OTC sunscreen 

drug products in part 352 (21 CFR part 

352) with an effective date of May 21, 

2001, but deferred UVA testing and 

labeling for future regulatory action. 

FDA stated that more time was required 

to review comments from interested 

parties on active ingredients, labeling, 

and test methods for products intended 

to provide UVA protection. This 

proposed amendment to the FM for OTC 

sunscreen drug products will complete 

the FM by addressing both UVB and 

UVA testing and labeling. 

In the Federal Register of June 8, 2000 

(65 FR 36319), FDA reopened the 

administrative record of the rulemaking 

for OTC sunscreen drug products to 

allow for specific comment on high SPF 

and UVA radiation testing and labeling. 

FDA also extended the effective date for 

the FM to December 31, 2002. 

In the Federal Register of December 

31, 2001 (66 FR 67485), FDA stayed the 

December 31, 2002, effective date of the 

FM for OTC sunscreen drug products in 

part 352 until we provided further 

notice in a future issue of the Federal 

Register. FDA took this action because 

we planned to amend part 352 to 

address formulation, labeling, and 

testing requirements for both UVB and 

UVA radiation protection. This 

document proposes such changes. This 

document also proposes an effective 

date related to publication of an 

amended FM (see section X of this 

document). The existing stay of the 

effective date for part 352 remains in 

effect at this time. 

In the Federal Register of June 20, 

2002 (67 FR 41821), FDA published a 

technical amendment to change the 

names of four sunscreen active 

ingredients in § 352.10 of the 

monograph to be consistent with name 

changes that appeared in USP 24. The 

new names, which are simpler and more 

convenient, are meradimate for menthyl 

anthranilate, octinoxate for octyl 

methoxycinnamate, octisalate for octyl 

salicylate, and ensulizole for 

phenylbenzimidazole sulfonic acid. 

Because the names became official on 

March 1, 2001, manufacturers could 

begin using them at any time after that 

date. 

In the Federal Register of June 4, 2003 

(68 FR 33362), FDA issued a final rule 

establishing conditions under which 

OTC skin protectant products are 

generally recognized as safe and 

effective and not misbranded. This final 

rule lifted the stay of 21 CFR part 352 

to amend the final monograph for OTC 

sunscreen drug products to include 

sunscreen-skin protectant combination 

drug products. This final rule concluded 

by placing a stay on both part 352 and 

on § 347.20(d). The proposed rule that is 

the subject of this document provides 

UVA testing and labeling that is 

necessary on sunscreen and sunscreenskin protectant combination drug 

products. This proposed rule, therefore, 

proposes that the stays of both part 352 

and § 347.20(d) be lifted when this rule 

is finalized. These stays will be 

maintained until a final rule based on 

this proposed rule becomes effective. 

In the Federal Register of September 

3, 2004 (69 FR 53801), FDA delayed the 

implementation date for OTC sunscreen 

drug products subject to the final rule 

that established standardized format 

and content requirements for the 

labeling of OTC drug products (i.e., 

Drug Facts rule). FDA explained that we 

postponed the Drug Facts 

implementation date because we did not 

expect to complete the final amendment 

of the sunscreen monograph to include 

UVA testing and labeling by the Drug 

Facts implementation date of May 16, 

2005 (64 FR 13254 at 13273 and 13274, 

March 17, 1999). Thus, FDA delayed the 

implementation date of the Drug Facts 

rule with respect to OTC sunscreen drug 

products until further notice to avoid 

issuing successive relabeling 

requirements for sunscreen drug 

products at two closely related time 

intervals, as required by the Drug Facts 

rule and the final amendment to the 

sunscreen monograph. 

II. Summary of Major Changes to the 

FM 

In response to the TFM and FM, FDA 

received substantial data and 

information regarding UVA and UVB 

active ingredients, claims, and testing 

procedures, as well as on other issues 

addressed in this document. FDA 

summarizes these issues and proposed 

changes to the FM in this section. 

A. Ingredients 

FDA proposes to add combinations of 

avobenzone with zinc oxide and 

avobenzone with ensulizole as 

permitted combinations of active 

sunscreen ingredients in the FM (see 

section III.C, comment 7 of this 

document). 


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B. UVB (SPF) Labeling 

The FM allowed specific labeled SPF 

values up to, but not exceeding, 30. OTC 

sunscreen drug products with SPF 

values greater than 30 could be labeled 

with the collective term ‘‘30+.’’ In this 

amendment, FDA proposes to increase 

the specific labeled SPF value to 50 and 

revise the collective term to ‘‘50+.’’ FDA 

will consider higher specific labeled 

SPF values upon receipt of adequate, 

validated data (see section III.F, 

comment 15 of this document). 

In addition, FDA proposes to revise 

the following FM labeling: 

• The phrase ‘‘sun protection’’ to 

‘‘sunburn protection’’ where used in 

§§ 352.3(b)(1), (b)(2), (b)(3), and (d) and 

352.52(e)(1)(i), (e)(1)(ii), and (e)(1)(iii) 

(see section III.D, comment 10 of this 

document); and 

• Section 352.50(a) to include the 

term ‘‘UVB’’ before the term ‘‘SPF’’ on 

the principal display panel (PDP), along 

with the product category designation 

(PCD) (see section III.E, comment 14 of 

this document). 

FDA also proposes to revise the PCD 

SPF ranges in § 352.3(b)(1), (b)(2), and 

(b)(3) (proposed § 352.3(c)(1) through 

(c)(4)) to reflect the following: 

• The current standard public health 

message concerning use of sunscreens, 

• The proposed increase of the 

labeled SPF value to ‘‘50+,’’ and 

• The proposed addition of the term 

‘‘UVB’’ before the word ‘‘sunburn.’’

Proposed § 352.3(c)(4) contains a new 

PCD of ‘‘highest UVB sunburn 

protection product’’ for products that 

provide an SPF value over 50. FDA 

further proposes to revise current 

§ 352.3(b)(1) and (b)(2) to replace the 

current category descriptors of 

‘‘minimal’’ and ‘‘moderate’’ with the 

terms ‘‘low’’ and ‘‘medium,’’

respectively. FDA considers the new 

terms to be simpler and uniform with 

the proposed UVB and UVA ‘‘Uses’’

statements. Proposed changes to PCDs 

and category descriptors also occur in 

proposed § 352.52(e)(1) (see section 

III.D, comment 13 and section III.G, 

comment 16 of this document). In 

addition, FDA proposes optional UVB 

radiation protection statements (see 

proposed § 352.52(e)(2) and (e)(3)). 

C. UVA Labeling 

FDA proposes new labeling to 

designate the level of UVA protection 

on the PDP of OTC sunscreen drug 

products. FDA proposes the use of 

symbols (‘‘stars’’) in conjunction with a 

descriptor (i.e., ‘‘low,’’ ‘‘medium,’’

‘‘high,’’ or ‘‘highest’’). FDA also 

proposes to add new § 352.50(b) 

specifying the required PDP labeling for 

OTC sunscreen products tested in 

accordance with the proposed UVA 

testing procedures in §§ 352.71 and 

352.72 (see section III.E, comment 14 

and section III.N, comment 45 of this 

document). 

D. Indications 

The FM allowed the following two 

UVB indications in § 352.52(b)(1): 

• ‘‘helps prevent sunburn’’

• ‘‘higher SPF gives more sunburn 

protection’’

In this amendment, FDA proposes to 

revise the first statement to read ‘‘low,’’

‘‘medium,’’ ‘‘high,’’ or ‘‘highest’’ ‘‘UVB 

sunburn protection’’ in proposed 

§ 352.52(b)(1)(i) through (b)(1)(iv). FDA 

is proposing to revise the additional 

indications in § 352.52(b)(2) to reflect 

the new PCD ranges in proposed 

§ 352.3(c) (e.g., SPF of 2 to under 12 

becomes SPF of 2 to under 15) and 

create the new PCD range over SPF 50. 

These proposed revisions are based 

upon the revised PCD categories in 

proposed § 352.3(c) (see section III.G, 

comment 16 of this document). FDA 

proposes that the second statement in 

current § 352.52(b)(1) (‘‘higher SPF gives 

more sunburn protection’’) no longer be 

required and proposes an additional 

indication regarding UVA protection 

(see proposed § 352.52(b)(2)(v)). 

In proposed § 352.52(b)(2)(v), FDA 

includes a new indication for UVA 

protection that involves selection of the 

appropriate descriptor (‘‘low,’’

‘‘medium,’’ ‘‘high,’’ or ‘‘highest’’) to 

describe the level of protection. In 

proposed § 352.52(b)(2)(vi), FDA 

includes a modified version of the 

sunburn ‘‘Uses’’ statement required by 

proposed § 352.52(b)(1)(i) through 

(b)(1)(iv) when the additional statement 

in proposed § 352.52(b)(2)(v) is used 

and bears the same category descriptor 

as the SPF value (e.g., medium UVA/ 

UVB protection from sunburn) (see 

section III.G, comment 17 of this 

document). 

E. Warnings 

FDA is proposing to shorten the 

warning in § 352.52(c)(1)(ii) (proposed 

§ 352.52(c)(3)) under the subheading 

‘‘Stop use and ask a doctor if’’ from 

‘‘[bullet] rash or irritation develops and 

lasts’’ to ‘‘[bullet] skin rash occurs.’’

FDA proposes removing the optional 

‘‘sun alert’’ product performance 

statement (current § 352.52(e)(2)) and 

requiring a revised ‘‘sun alert’’

statement in the ‘‘Warnings’’ section 

(proposed § 352.52(c)(1)). FDA proposes 

that this revised statement be required 

on all OTC sunscreen drug products 

except lip cosmetic-drug and lip 

protectant-sunscreen products subject to 

§ 352.52(f), which are not required to 

include this statement under proposed 

§ 352.52(f)(1)(v) and (f)(1)(vi) (see 

section III.G, comment 19 of this 

document). The statement in proposed 

§ 352.52(c)(1) reads as follows: ‘‘UV 

exposure from the sun increases the risk 

of skin cancer, premature skin aging, 

and other skin damage. It is important 

to decrease UV exposure by limiting 

time in the sun, wearing protective 

clothing, and using a sunscreen.’’ FDA 

proposes that the statement appear in 

bold type as the first statement in the 

‘‘Warnings’’ section. 

F. Directions 

FDA proposes changes to the 

directions to reduce the likelihood that 

OTC sunscreen drug products are 

underapplied. Section 352.52(d)(1)(i) 

currently provides manufacturers the 

option to select one or more of the 

following terms: ‘‘liberally,’’

‘‘generously,’’ ‘‘smoothly,’’ or ‘‘evenly.’’

FDA is proposing to allow the choice of 

one of two required terms (i.e., 

‘‘liberally’’ or ‘‘generously’’) and to 

include ‘‘evenly’’ as an additional 

optional term. FDA is proposing to 

eliminate the term ‘‘smoothly’’ because 

it is vague. 

FDA also proposes to add a new 

direction ‘‘apply and reapply as directed 

to avoid lowering protection’’ (proposed 

§ 352.52(d)(1)(ii)). Because new 

information demonstrates the 

importance of sunscreen reapplication, 

FDA also proposes to make the optional 

directions in paragraph (d)(2) a 

requirement. As a result of this change, 

FDA is proposing to remove the current 

language in paragraph (d)(3) because it 

is no longer necessary. Instead, FDA is 

proposing, in paragraph (d)(3), required 

information for products that do not 

satisfy the water resistant testing 

procedures in § 352.76. FDA is also 

proposing a required reapplication 

statement in § 352.52(d)(1)(ii). The 

reapplication information in current 

§ 352.52(d)(2) appears in proposed 

§ 352.52(d)(2) and (d)(3) of this 

document (see section III.H, comment 

22 of this document). 

G. UVB Testing 

FDA is proposing to revise the SPF 

(UVB) testing procedure (see section III, 

paragraphs I through L of this 

document) and to move the SPF testing 

procedure currently in §§ 352.70 

through 352.73 to proposed § 352.70. 

FDA proposes a padimate O/ 

oxybenzone sunscreen standard in 

§ 352.70 that will be required for testing 

sunscreen products with SPF values 

over 15. Manufacturers may use either 

this padimate O/oxybenzone standard 


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or the homosalate standard to test 

products with SPF values of 2 to 15. 

FDA proposes a high pressure liquid 

chromatography (HPLC) method to 

replace the spectrophotometric method 

used to assay the homosalate and 

padimate O/oxybenzone standards. 

FDA proposes the following 

modifications to the SPF testing 

procedure: 

• Specifications for the solar 

simulator in § 352.71 (proposed 

§ 352.70(b)), 

• Instructions for the application of 

test materials and response criteria in 

§ 352.72 (proposed § 352.70(c)), and 

• Doses and determination of 

minimal erythema dose (MED) in 

§ 352.73 (proposed § 352.70(d)). 

FDA proposes to continue requiring a 

finger cot to be used in the application 

of sunscreen standard and test product 

as specified in § 352.72(e) (proposed 

§ 352.70(c)(5)). However, FDA now 

proposes that the finger cot be 

pretreated. These two proposed UVB 

testing changes also apply to UVA in 

vivo testing. 

H. UVA Testing 

FDA proposes a combination of 

spectrophotometric (in vitro) and 

clinical (in vivo) UVA test procedures in 

proposed §§ 352.71 and 352.72, 

respectively. To assure UVA protection 

for ‘‘water resistant’’ and ‘‘very water 

resistant’’ sunscreen products, FDA 

proposes that the in vivo UVA test be 

conducted after the appropriate water 

immersion period for OTC sunscreen 

drug products making a UVA claim. 

Therefore, FDA proposes modification 

of § 352.76 to state that the water 

resistance claim applies to the SPF and, 

if appropriate, UVA values determined 

after the appropriate water immersion 

period as described in proposed 

§ 352.70 and, if appropriate, proposed 

§ 352.72. 

III. FDA’s Tentative Conclusions on the 

Comments 

A. General Comments on OTC 

Sunscreen Drug Products 

(Comment 1) Several comments asked 

that FDA provide more time to comply 

with requirements of the FM in order to 

avoid an adverse economic impact on 

the suncare industry and consumers. 

The comments described the seasonal 

dynamics of the suncare industry (i.e., 

products are sold in two marketing 

cycles over a period of 18 months) and 

stated that the industry would need 

more time to develop products that meet 

the FM requirements and allow for 

shipment of the previous year’s returns. 

The comments mentioned times from 2 

to 3 years after publication of the FM as 

appropriate or necessary for 

implementation. Several of these 

comments added that the date should be 

in the June/July time period because the 

shipping season is practically over at 

that time and manufacturing for the next 

season is just beginning. 

FDA understands the seasonal nature 

of the sunscreen industry and the time 

required for product testing and 

relabeling. FDA is also aware that more 

than 1 year may be needed for 

implementation. FDA is proposing an 

18- to 24-month implementation date 

and will try to have it coincide with the 

June/July time period (see section XI of 

this document). 

(Comment 2) One comment requested 

that FDA and the Federal Trade 

Commission (FTC) take steps to make 

sure that sunscreen manufacturers 

provide information to the American 

public to help them understand and use 

the Ultraviolet Index (UVI) to determine 

their risk of sunburn. 

The National Weather Service, the 

Environmental Protection Agency 

(EPA), and the Centers for Disease 

Control and Prevention (CDC) 

developed the UVI, which has been in 

use since 1995. This index is an 

indication of the amount of UV 

radiation reaching the surface of the 

earth as a function of ozone data, 

atmospheric pressure, temperature, and 

cloudiness and is generated for 58 cities 

around the United States. 

Usage information required by the 

OTC sunscreen drug product 

monograph applies regardless of the 

UVI value. Therefore, FDA believes that 

UVI information need not be required in 

the monograph for the safe and effective 

use of these products and should not be 

included in the ‘‘Drug Facts’’ labeling. 

However, manufacturers who wish to do 

so may voluntarily include such 

information in their labeling outside the 

‘‘Drug Facts’’ box. 

(Comment 3) One comment requested 

that FDA make clear, through either the 

FM for skin protectant or sunscreen 

drug products, or both, that combination 

products containing sunscreen and skin 

protectant ingredients may be lawfully 

marketed. 

Section 347.20(d) of the skin 

protectant FM (21 CFR 347.20(d)), 

which published in the Federal Register 

of June 4, 2003 (68 FR 33362), provides 

for combinations of sunscreen 

ingredients and specific skin protectant 

ingredients. The final rule for OTC skin 

protectant drug products also included 

an amendment to the sunscreen FM, 

adding new § 352.20(b), which allows 

combinations of sunscreen and skin 

protectant active ingredients. Thus, both 

monographs now state the same 

conditions for lawfully marketing these 

combination products. The existing 

language in §§ 347.20(d) and 352.20(b) 

would include the two new 

combinations that FDA is proposing to 

add to the sunscreen monograph (see 

section II.A, comment 7 of this 

document). 

B. Comments on Tanning and Tanning 

Preparations 

(Comment 4) One comment requested 

that the effective date of § 740.19 (21 

CFR 740.19) be extended to December 

31, 2002, consistent with the delay of 

the effective date for § 310.545(a)(29) 

and (d)(31), part 352, and § 700.35 (65 

FR 36319). The comment stated that 

singling out § 740.19 to become effective 

earlier might constitute an arbitrary and 

capricious decision by FDA. 

The May 21, 1999, final rule set a 2- 

year effective date (May 21, 2001) for 

§ 310.545(a)(29) and (d)(31), part 352, 

and § 700.35. In the Federal Register of 

June 8, 2000 (65 FR 36319), FDA 

extended the effective date for 

compliance with § 310.545(a)(29) and 

(d)(31), part 352, and § 700.35 until 

December 31, 2002, to provide time for 

completion of a more comprehensive 

UVA/UVB FM for OTC sunscreen drug 

products. On December 31, 2001, FDA 

then stayed the effective date of part 352 

(but not § 310.545(a)(29) and (d)(31), 

and § 700.35) until further notice (66 FR 

67485). FDA took this action because we 

are amending part 352 to address 

formulation, labeling, and testing 

requirements for both UVA and UVB 

radiation protection. The May 21, 1999, 

final rule also set a 1-year effective date 

(May 22, 2000) for new § 740.19, which 

addresses a warning statement for 

cosmetic suntanning preparations that 

do not contain a sunscreen active 

ingredient. These products are not 

subject to the monograph for OTC 

sunscreen drug products in part 352. 

FDA considered this warning to be 

sufficiently important for safety reasons 

when we issued the final rule (64 FR 

27666 at 27669) to require a 12-month 

effective date as opposed to the 24- 

month effective date for the other 

sections of the rule. Further, FDA’s 

primary reason for extending the 

effective date of those other sections to 

December 31, 2002, and then staying 

part 352 to address formulation, 

labeling, and testing requirements for 

both UVA and UVB protection, was to 

allow FDA to develop a comprehensive 

UVB/UVA final monograph. This reason 

does not apply to § 740.19. Accordingly, 

FDA did not extend the effective date 

for § 740.19, and § 740.19 is in effect at 

this time. FDA concludes that this 


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decision is not arbitrary and capricious, 

but is based on valid health concerns 

related to the products subject to the 

warning requirement in § 740.19. 

(Comment 5) One comment requested 

that FDA and FTC take steps to ensure 

sunscreen manufacturers inform 

consumers that their natural skin 

pigmentation provides protection from 

sunlight. The comment stated that these 

adaptive individuals might not require a 

daily application of a sunscreen. 

Another comment submitted a copy of 

a patent for an electronic sensor device 

to measure solar radiation. The 

comment stated that the personal device 

could alert consumers to their level of 

UV exposure so they could either come 

out of the sun or apply a sunscreen to 

avoid sunburn and skin cancer. 

FDA has no objection to sunscreen 

manufacturers informing consumers 

that their natural skin pigmentation 

provides protection from sunlight. 

However, FDA has no basis to require 

such information as part of the required 

labeling for OTC sunscreen drug 

products. Thus, manufacturers may 

include this information in labeling 

outside of the ‘‘Drug Facts’’ box, but are 

not required to include this information. 

FDA considers the comment regarding 

the UV measuring device to be outside 

the scope of this rulemaking, which 

evaluates the safety, effectiveness, and 

labeling of OTC drug products. 

C. Comments on Specific Sunscreen 

Active Ingredients 

(Comment 6) Several comments 

requested that dihydroxyacetone (DHA) 

be added to the monograph as a single 

active ingredient for UVA protection. 

The comments claimed that DHA alone 

provides an SPF of 2 to 4. One comment 

claimed that a 15 percent topical 

solution of DHA provided a 

photoprotective factor of 10 in the UVA 

region. Other comments contended that 

the brown color produced by DHA, 

resembling melanin, should potentiate 

the action of sunscreens. Another 

comment stated that DHA alone is not 

a sunscreen, but forms a sunscreen 

when combined with lawsone. The 

comment cited unpublished 

observations by two independent 

investigators that the melanoidins of 

DHA-induced skin pigment resemble 

melanin in that they absorb UVB 

strongly, with decreasing absorbance 

through the UVA region and into visible 

light. The comment added that, because 

DHA alters the structure of the skin 

surface, it is, by definition, a drug. 

One comment provided information 

on the safety and UVA effectiveness of 

DHA alone (Ref. 1). Safety studies 

included the following: 

• Oral and dermal toxicity studies, 

• A chronic skin painting 

carcinogenicity study in mice, 

• Comedogenecity tests in rabbits, 

• Repeated insult patch test in 

humans, and 

• Photoallergy tests. 

Effectiveness studies consisted of 

published articles using either humans 

or photosensitized rats. Another 

comment discussed investigations with 

DHA on psoriasis patients sensitized 

with 8-methoxypsoralen (8–MOP). 

FDA is not proposing to include DHA 

in the monograph as a single active 

ingredient in OTC sunscreen products. 

Although there were no product 

submissions to the Advisory Review 

Panel on Topical Analgesic, 

Antirheumatic, Otic, Burn, and Sunburn 

Prevention and Treatment Drug 

Products (the Panel) using DHA as a 

sunscreen ingredient, the Panel 

discussed available scientific evidence 

for DHA as a single sunscreen 

ingredient. The Panel concluded that 

DHA is not a sunscreen but a cosmetic; 

it is a sunscreen only when used with 

lawsone (43 FR 38206 at 38215 to 

38216, August 25, 1978). Although one 

comment stated that DHA alters the 

structure of the skin, it did not provide 

data to support this claim. Thus, at this 

time, FDA agrees with the Panel that 

DHA is a cosmetic. 

FDA acknowledges that DHA is the 

subject of an approved color additive 

petition and its safety as a color additive 

has been established. However, the 

submitted chronic (life-span) skin 

painting study in mice does not support 

the safe use of DHA as a sunscreen 

because no group of mice was included 

in the study to determine the possible 

photocarcinogenic effect of DHA. This 

effect needs to be studied because DHA 

is associated with carbonyl compounds 

known to react with pyrimidine bases in 

the presence of UV radiation, and it 

appears to be a potent inducer of 

thymine dimers, premutagenic 

deoxyribonucleic acid (DNA) lesions. 

Therefore, its safety, in terms of the 

type, extent, and location of photoinduced DNA damage, is of concern and 

should be determined. Whether DHA 

contributes or promotes UV 

carcinogenesis is not known. 

The submitted studies on the 

effectiveness of DHA as a single UVA 

sunscreen ingredient add only 

qualitative information. Many of the 

studies utilized animal models; few 

included human subjects. One study 

involved only five subjects, three with 

erythropoietic protoporphyria and two 

with polymorphic light eruptions. 

Another study involved six subjects 

sensitized with 8–MOP. In both studies, 

too few subjects were enrolled, and the 

study subjects were not representative 

of the average sunscreen user. 

Well-controlled clinical trials with 

DHA alone are lacking. Although some 

investigations described by the 

comments suggest that DHA may help 

protect the normal skin of psoriasis 

patients, concerns remain about the 

usefulness of DHA products in the OTC 

market. For example, one comment 

stated that photoprotection provided by 

DHA depends upon the way the product 

polymerizes in the stratum corneum and 

that polymerization depends on the skin 

of each individual. Therefore, the 

photoprotection provided by DHA 

varies from person to person and has to 

be determined for each person by 

diffuse reflectance spectroscopy. Given 

these statements, it is not clear how 

appropriate OTC drug product labeling 

could be written to aid consumers in 

proper selection and use of a DHA 

sunscreen. 

FDA concludes that current 

information is inadequate to include 

DHA in the monograph as a single 

sunscreen ingredient. None of the 

comments provided information to 

establish the appropriate number of 

consecutive product applications and 

the timing of these applications (how far 

apart or how soon before sun exposure) 

that are necessary to achieve the desired 

protection using products containing 

various concentrations of DHA. In two 

submitted studies, a preparation 

containing 3 percent DHA was applied 

six times prior to sun exposure and a 

preparation containing 15 percent DHA 

preparation was applied one time 24 

hours prior to sun exposure, 

respectively (Ref. 1). The comments did 

not include any information on 

appropriate regimens for various skin 

types, which is necessary because the 

level of photoprotection provided by 

DHA is dependent on skin type. 

Therefore, based upon this lack of 

information, it is not clear how to state 

appropriate label directions for 

consumer use. FDA needs additional 

information from clinical studies to 

determine the effective concentration of 

DHA in sunscreen product formulations 

and the frequency and timing of product 

application. 

(Comment 7) One comment submitted 

data to support the combination of 

avobenzone with ensulizole and 

avobenzone with zinc oxide (Ref. 2). 

The safety data included the following: 

• A repeat insult patch test, 

• A phototoxicity study, and 

• A photoallergy study. 

The effectiveness data involved a 

clinical study using the in vitro ‘‘critical 

wavelength’’ (CW) method and the in 


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vivo ‘‘protection factor A’’ (PFA) 

method to support the UVA radiation 

protection potential of the combination 

products. The PFA test data were from 

a double blind clinical study using five 

sunscreen formulations. 

The safety studies demonstrated that 

the following combinations of active 

ingredients have a low potential for 

irritation, allergenic sensitization, and 

phototoxicity: 

• 3 percent or less avobenzone with 

2 percent ensulizole 

• 3 percent or less avobenzone with 

5 percent zinc oxide 

The data further suggested that the 

photoallergenic potential of avobenzone 

is not augmented by its combination 

with either ensulizole or zinc oxide. 

The clinical study using the PFA in 

vivo method demonstrated that the 

following combinations of active 

ingredients are significantly more 

effective than 1.5 percent ensulizole or 

3 percent zinc oxide alone in protecting 

against UVA radiation: 

• 3 percent avobenzone with 1.5 

percent ensulizole 

• 3 percent avobenzone with 4 

percent zinc oxide 

FDA’s detailed comments on the safety 

and effectiveness studies are on file in 

the Division of Dockets Management 

(Ref. 3). 

FDA considers the data submitted by 

the comment sufficient to support the 

safety and effectiveness of avobenzone 

with ensulizole and avobenzone with 

zinc oxide when used in the 

concentrations established for each 

ingredient in § 352.10 of the sunscreen 

monograph. Accordingly, FDA is 

proposing to amend § 352.20(a)(2) by 

adding ensulizole and zinc oxide. 

Marketing of products containing 

avobenzone with ensulizole and 

avobenzone with zinc oxide will not be 

permitted unless and until the following 

three actions occur: 

1. The comment period specific to 

this proposal closes. 

2. FDA has evaluated all comments on 

these combination products submitted 

in response to the proposal. 

3. FDA publishes a Federal Register 

notice announcing our determination to 

permit the marketing of OTC sunscreen 

drug products containing these 

combinations. 

D. General Comments on the Labeling of 

Sunscreen Drug Products 

(Comment 8) One comment agreed 

that the labeling modifications allowed 

by the FM in § 352.52 for OTC 

sunscreen products marketed as a 

lipstick or labeled for use only on 

specific small areas of the face (e.g., lips, 

nose, ears, and/or around eyes) are 

appropriate for these products. Based on 

the labeling in § 352.52, the comment 

proposed eight additional modifications 

for all other OTC sunscreen products 

regardless of package size: 

1. Delete ‘‘Drug Facts’’ title because it 

is inappropriate and unnecessary for 

sunscreens. 

2. Omit ‘‘Purpose’’ because it is 

repetitive of the statement of identity on 

the PDP and ‘‘Uses’’ information. 

3. Revise ‘‘higher SPF gives more 

sunburn protection’’ in ‘‘Uses’’ to read 

‘‘higher SPF products give more sun 

protection, but are not intended to 

extend the time spent in the sun,’’ and 

require this statement only on products 

with an SPF value over 30. 

4. Omit ‘‘For external use only’’

warning because it is self-evident for 

sunscreen products. 

5. Revise ‘‘When using this product 

[bullet] keep out of eyes. Rinse with 

water to remove’’ to read ‘‘Keep out of 

eyes.’’

6. Revise ‘‘Stop use and ask a doctor 

if [bullet] rash or irritation develops and 

lasts’’ to read ‘‘Stop use if skin rash 

occurs.’’

7. Omit barlines, hairlines, and box 

enclosure. 

8. Allow the option to list inactive 

ingredients in a different location on the 

label or in labeling accompanying the 

product. 

The comment stated that these 

modifications would allow reduced 

Drug Facts labeling for all OTC 

sunscreen drug products. 

The comment contended that 

sunscreen products meet all of FDA’s 

criteria for reduced labeling (64 FR 

13254 at 13270): 

• Packaged in small amounts, 

• High therapeutic index, 

• Extremely low risk in actual 

consumer use situations, 

• A favorable public health benefit, 

• No specified dosage limitation, and 

• Few specific warnings and no 

general warnings (e.g., pregnancy or 

overdose warnings). 

The comment added that OTC 

sunscreen products are a unique 

category substantially different from 

most other types of OTC drug products 

because they are recommended for use 

on a daily basis to prevent serious 

disease. The comment concluded that 

FDA’s rationale for standardized 

labeling format and content 

requirements does not necessarily 

transfer to OTC sunscreen products and 

specifically not to drug-cosmetic 

products with a sunscreen. 

When FDA created the standardized 

labeling format and content 

requirements (i.e., ‘‘Drug Facts’’

labeling) for OTC drug products, we 

recognized that some product packages 

were too small to accommodate all of 

the required labeling. Therefore, under 

§ 201.66(d)(10) (21 CFR 201.66(d)(10)), 

FDA allows labeling format 

modifications for all OTC drug products 

sold in small packages. In the final rule 

establishing ‘‘Drug Facts’’ labeling, FDA 

also stated that we may allow reduced 

labeling requirements beyond those 

specified under § 201.66(d)(10) for OTC 

drug products that meet the criteria 

listed in the preceding paragraph (see 

section III.D, comment 9 of this 

document). 

In the final rule for OTC sunscreen 

drug products (64 FR 27666 at 27681 to 

27682), FDA recognized that some OTC 

sunscreen drug products meet these 

criteria for reduced labeling. 

Specifically, FDA identified OTC 

sunscreen drug products that qualify for 

the small package specifications in 

§ 201.66(d)(10) and are labeled for use 

only on specific small areas of the face 

as meeting the criteria for reduced 

labeling. Therefore, FDA allows content 

and format modifications for these 

products under § 352.52(f). FDA allows 

further modifications for lip products 

containing sunscreen because these 

products for small areas of the face are 

sold in even smaller packages than the 

other sunscreen products marketed 

under § 352.52(f) (68 FR 33362 at 33371; 

64 FR 13254 at 13270). FDA believes 

that sunscreen products labeled for use 

only on small areas of the face, 

including lip products containing 

sunscreen, serve an important public 

health need and FDA does not want to 

discourage manufacturers from 

marketing these products (64 FR 13254 

at 13270). 

FDA does not find it appropriate to 

extend the labeling modifications for 

OTC sunscreen drug products marketed 

under § 352.52(f) to all OTC sunscreen 

drug products. FDA disagrees with the 

comment’s argument that all sunscreen 

products meet the criteria for reduced 

Drug Facts labeling (64 FR 13254 at 

13270), because most sunscreen 

products are not sold in small packages. 

Therefore, because sunscreen products 

do not generally meet all of the criteria 

for reduced Drug Facts labeling, FDA is 

not proposing reduced labeling for all 

OTC sunscreen products. 

FDA does not consider sunscreens as 

a unique category substantially different 

from other types of OTC drug products 

because they are recommended for use 

on a daily basis to prevent serious 

disease, as argued by the comment. 

Other OTC drug products are used on a 

daily basis, some to prevent serious 

disease and some for other reasons. For 

example, anticaries drug products are 


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used daily to prevent dental caries. 

Antiperspirant drug products can be 

used daily to reduce underarm wetness. 

FDA has concluded that these various 

products should generally be labeled 

using the standardized content and 

format in § 201.66. The standardized 

labeling allows consumers to more 

easily recognize that these products are, 

in fact, drug products and to more easily 

read and understand the labeling 

information. 

The same principle applies when the 

product is a drug cosmetic product (e.g., 

sunscreen moisturizer or antiperspirant 

deodorant). Consumers need to be 

informed that the product has a drug 

effect, and the uniform Drug Facts 

labeling for all OTC drug and drug 

cosmetic products helps convey this 

message. FDA applied this rationale 

when it finalized the requirements in 

the final rule that established § 201.66. 

FDA agrees that some OTC sunscreen 

drug products meet the criteria for 

reduced information for safe and 

effective use (64 FR 13254 at 13270, 64 

FR 27666 at 27681 to 27682). However, 

FDA disagrees with most of the 

modifications proposed by the comment 

for all package sizes of OTC sunscreen 

products. FDA disagrees with deletion 

of the ‘‘Drug Facts’’ title and the 

‘‘Purpose’’ information because many 

sunscreen products do not meet the 

parameters for reduced Drug Facts 

labeling. 

FDA disagrees that the ‘‘Purpose’’

information is repetitive and, therefore, 

disagrees that it may be omitted where 

there is sufficient labeling space. The 

‘‘Purpose’’ section is a standard part of 

Drug Facts labeling and is intended to 

inform consumers which ingredients are 

sunscreens in a product. This 

information is even more important 

when a sunscreen is marketed in a 

combination product. For example, in a 

sunscreen skin protectant drug product, 

the ‘‘Purpose’’ section informs 

consumers which ingredients are 

sunscreens and which are skin 

protectants. 

FDA has revised the ‘‘Uses’’ section 

and deleted the statement ‘‘higher SPF 

gives more sunburn protection’’ (see 

section III.G, comment 16 of this 

document). FDA disagrees with omitting 

the ‘‘For external use only’’ warning for 

all OTC sunscreen drug products. FDA 

finds no basis to exclude all OTC 

sunscreen products from this 

requirement. Likewise, FDA finds no 

reason to omit the two standard 

subheadings that accompany the 

warning statements, as proposed by the 

comment. Further, FDA disagrees with 

the comment’s suggestion to omit the 

statement ‘‘Rinse with water to 

remove.’’ This is useful information if a 

sunscreen product gets into the eyes. 

FDA agrees with part of the proposed 

shortened warning for OTC sunscreen 

drug products to ‘‘Stop use if skin rash 

occurs’’ in place of ‘‘Stop use and ask 

a doctor [bullet] if rash or irritation 

develops and lasts.’’ Therefore, FDA is 

proposing to amend § 352.52(c)(1)(ii) 

(proposed § 352.52(c)(3)) to state: ‘‘Stop 

use and ask a doctor if [bullet] skin rash 

occurs.’’

FDA finds no reason to omit barlines, 

hairlines, or the box enclosure for all 

OTC sunscreen drug products regardless 

of package size. These labeling formats 

help consumers identify a product as a 

drug and help make labeling 

information easier to read and 

understand. Thus, they should be 

included when package size allows. The 

FM already allows horizontal barlines 

and hairlines and the box enclosure to 

be omitted if a small package meets the 

criteria in §§ 352.52(f) and 

201.66(d)(10). 

Finally, FDA has no basis to provide 

an option for sunscreen products to list 

inactive ingredients in labeling that 

accompanies the products. FDA 

interprets section 502(e)(1)(A)(iii) of the 

act (21 U.S.C. 352(e)(1)(A)(iii)) as 

requiring the inactive ingredients to be 

listed on the outside container of a retail 

package or on the immediate container 

if there is no outside container or 

wrapper (§ 201.66(c)). Because this 

information, by law, must appear either 

on the outside container or immediate 

container of the product, FDA does not 

find a basis for allowing an option to list 

the inactive ingredients in a different 

location, such as other labeling 

accompanying the product. In 

accordance with § 201.66(c)(8), the 

inactive ingredients must be listed on 

the product label in the ‘‘Drug Facts’’

box. 

(Comment 9) Two comments 

supported extending the labeling in 

§ 352.52(f) for products intended for use 

only on specific small areas of the face 

and sold in small packages to all OTC 

sunscreen products. The comments 

contended that all OTC sunscreen drug 

products meet most of FDA’s criteria for 

products that require minimal 

information for safe and effective use 

(64 FR 13254 at 13270) (see section 

III.G, comment 8 of this document). 

The first comment added that FDA 

should permit the labeling 

modifications in § 352.52(f) for the 

following products: 

• Makeup products (as defined in 21 

CFR 720.4(c)(7)) with sunscreen, and 

• Lotions and moisturizers for the 

hands or face with sunscreen in 

containers of 2 ounces (oz) or less (by 

weight or liquid measure). 

The comment added that most facial 

makeup products are typically packaged 

in small containers. The comment stated 

that to meet any of FDA’s concerns that 

lotions and moisturizers sold in larger 

packages may be used over the entire 

body despite labeling that restricts use 

to the face or hands, FDA could limit 

the flexible labeling to containers of 2 oz 

or less. Furthermore, the comment 

added that containers of 2 oz or less 

could not feasibly include the full OTC 

drug labeling. 

The second comment contended that 

the modified labeling in § 352.52(f) is 

particularly compelling for color 

cosmetic products for the face that 

contain sunscreens (i.e., ‘‘facial 

makeups with sunscreen’’). The 

comment added that these products and 

OTC sunscreen drug products for use 

only on specific small areas of the face 

have the same overall safety profile, 

and, therefore, FDA should allow these 

products to be labeled similarly. 

A third comment strongly disagreed 

with a specific labeling exemption for 

makeup with sunscreen and moisturizer 

products for use on the face and hands. 

The comment contended that an 

exemption would not be in the best 

interest of consumers. The comment 

also argued that consumer confusion 

and subsequent misuse of sunscreen 

products, particularly failure to apply 

adequate amounts of sunscreen or to 

reapply a product after certain activities, 

will occur if FDA permits reduced 

labeling for these products. The 

comment added that many consumers 

use face and hand cosmetic products 

with sunscreen as their primary and 

only source of UV radiation protection 

for those areas of the body. Moreover, 

consumers are more likely to use these 

products properly if they contain full 

sunscreen drug labeling. The comment 

concluded that makeup foundations, 

tints, blushes, rouges, and moisturizers 

that are intended to be used on a daily 

or frequent basis to protect against the 

adverse health and skin aging effects of 

acute and chronic sun exposure must be 

labeled as drugs similar to other OTC 

sunscreen products. 

FDA is not proposing to extend the 

labeling modifications in § 352.52(f), 

which is specific for products used only 

on small areas of the face and sold in 

small packages, to all OTC sunscreen 

products. FDA has determined that most 

OTC sunscreen products should have 

full drug labeling information using the 

standardized content and format in 

§ 201.66 to ensure the safe and effective 

use of these products. In establishing 

the labeling modifications in § 352.52(f), 


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FDA determined how the labeling 

information for sunscreen drug 

products, including drug cosmetic 

products, could best be presented on 

products with limited labeling space 

and still provide consumers with 

adequate information to use these 

products safely and effectively. 

Although any sunscreen products sold 

in small packages that meet the criteria 

in § 201.66(d)(10) are allowed the format 

exemptions under that section, FDA is 

also proposing content exemptions for 

sunscreen products marketed under 

§ 352.52(f). FDA is proposing these 

exemptions under § 352.52(f) because 

sunscreen products labeled for use only 

on small areas of the face and sold in 

small packages are generally sold in 

packages substantially smaller than 

other sunscreen products, even those 

sunscreen products labeled for other 

uses that meet the criteria in 

§ 201.66(d)(10). 

FDA continues to believe that 

requiring full Drug Facts labeling on 

sunscreen products used only on 

specific small areas of the face and sold 

in small packages (i.e., § 352.52(f)) 

would discourage manufacturers from 

marketing some of these products for 

drug use. Many of these products, such 

as sunscreen-lip protectant products, are 

sold in extremely small packages that 

cannot accommodate the required 

labeling even with the format 

exemptions allowed under 

§ 201.66(d)(10). As explained in a 

number of rulemakings (64 FR 27666 at 

27681 to 27682; 68 FR 33362 at 33371; 

64 FR 13254 at 13270), these products 

meet the criteria for additional reduced 

labeling. Removal of these products 

from the OTC market would have a 

negative impact on public health. FDA 

believes that the benefit of UV radiation 

protection provided by these products 

outweighs the need for manufacturers to 

include all sunscreen labeling 

information. In contrast, FDA believes 

manufacturers of sunscreen products 

that are not within the scope of 

§ 352.52(f) will continue to market their 

products even though full Drug Facts 

labeling is required. Unlike sunscreen 

products that meet § 352.52(f), the 

package size of products that do not 

meet § 352.52(f) will accommodate full 

Drug Facts labeling. 

Although FDA is not extending the 

labeling modifications in § 352.52(f) to 

all OTC sunscreen products, as 

requested by the first and second 

comments, we are allowing these 

labeling modifications for certain 

makeup with sunscreen products. 

Specifically, these labeling 

modifications would apply to makeup 

with sunscreen products that are labeled 

for use only on specific small areas of 

the face and that meet the criteria in 

§ 201.66(d)(10). However, FDA does not 

agree that these labeling modifications 

should apply to all makeup products 

identified in § 720.4(c) (21 CFR 720.4(c)) 

that contain sunscreen, because most 

are not sold in small packages and, 

therefore, do not meet all of the criteria 

for reduced labeling (64 FR 13254 at 

13270). Thus, most of these products 

can accommodate full Drug Facts 

labeling, and FDA finds no reason to 

extend the labeling modifications in 

§ 352.52(f) to all makeup with 

sunscreens products. 

As explained in the previous 

paragraph, the labeling modifications in 

§ 352.52(f) apply to makeup with 

sunscreen products labeled for use only 

on specific small areas of the face and 

sold in small packages. FDA also 

believes that any sunscreen products 

that are used only on specific small 

areas of the face and sold in small 

packages meet FDA’s reduced labeling 

criteria regardless of whether they are 

drug or drug-cosmetic products. 

Therefore, FDA is proposing to amend 

the heading of § 352.52(f) to read as 

follows: ‘‘Products, including cosmeticdrug products, containing any 

ingredient identified in § 352.10 labeled 

for use only on specific small areas of 

the face (e.g., lips, nose, ears, and/or 

around the eyes) and that meet the 

criteria established in § 201.66(d)(10) of 

this chapter.’’

In addition, FDA is proposing to 

extend the labeling exemptions, with 

some modifications, currently allowed 

for lipsticks in § 352.52(f)(1)(vi) to the 

following lip products with sunscreen, 

as defined in § 720.4(c): 

• Lipsticks, 

• Lip products to prolong wear of 

lipstick, 

• Lip gloss, and 

• Lip balm. 

FDA has identified lip products to 

prolong wear of lipstick as ‘‘makeup 

fixatives’’ under § 720.4(c)(7)(viii). Lip 

gloss and lip balm fall under ‘‘other 

makeup preparations’’ in 

§ 720.4(c)(7)(ix). As long as these lip 

products with sunscreen are used only 

on specific small areas of the face and 

are sold in small packages (i.e., meet the 

criteria in § 201.66(d)(10)), they would 

meet FDA’s reduced labeling criteria. As 

discussed earlier in this comment, FDA 

believes not allowing Drug Facts 

labeling exemptions for these products 

would discourage manufacturers from 

marketing some of these products for 

drug use. In proposed § 352.52(f)(1)(vi), 

FDA is proposing to extend the labeling 

modifications for lipsticks to other lip 

cosmetic products containing sunscreen 

and clarifying that the labeling 

modifications in § 352.52(f) apply to 

both sunscreen and makeup with 

sunscreen products. Furthermore, 

because lip products with sunscreen 

have substantially less labeling space 

than the nonlip products with 

sunscreen used only on specific small 

areas of the face and sold in small 

packages, proposed § 352.52(f)(1)(vi) 

allows more labeling exemptions for lip 

products with sunscreen than other 

products that are within the scope of 

§ 352.52(f). 

(Comment 10) Several comments 

recommended changing the acronym 

‘‘SPF’’ from ‘‘sun protection factor’’ to 

‘‘sunburn protection factor’’ because the 

latter definition is more descriptive of 

the use of OTC sunscreen drug products 

and avoids giving consumers the 

impression of solar invincibility and a 

false sense of security. 

FDA agrees. In § 352.52(b) of the 

sunscreen FM, FDA included only 

indications for sunburn protection (e.g., 

‘‘helps prevent sunburn’’) (64 FR 27666 

at 27691). In this document, FDA is 

proposing to change the word ‘‘sun’’ to 

‘‘sunburn’’ in § 352.3(b)(1), (b)(2), (b)(3), 

and (d) and § 352.52(e)(1)(i), (e)(1)(ii), 

and (e)(1)(iii). 

Manufacturers can continue to use 

existing labeling until the compliance 

dates of a final rule based on this 

proposal. However, FDA encourages 

manufacturers to revise any labeling 

that states ‘‘sun protection’’ attributed to 

sunscreen active ingredient(s) to the 

new term ‘‘sunburn protection’’ as early 

as possible. 

(Comment 11) Some comments 

questioned the constitutionality of the 

FM’s labeling provisions. Specifically, 

the comments contended that the FM’s 

prohibition on the labeling of SPF 

products over 30, its restrictions on skin 

aging claims, and its limitation of the 

indications for use for OTC sunscreen 

drug products all violate the first 

amendment to the U.S. Constitution. 

The comments asserted that these bans 

on allegedly truthful labeling in the FM 

go well beyond constitutionally 

permissible restrictions on commercial 

free speech. 

One comment contended that FDA 

had failed to meet its burden to 

demonstrate that the claims at issue are 

misleading or that the restrictions on 

speech directly advance any substantial 

governmental purpose. In addition, the 

comment claimed that any interest FDA 

has asserted in restricting the speech at 

issue is served equally well, if not 

better, by regulations that do not restrict 

speech to the same extent as FDA’s 

regulations. 


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FDA disagrees with the comments for 

the following reasons. OTC drug 

monographs establish conditions under 

which ingredients for certain OTC uses 

are generally recognized as safe and 

effective (GRASE) and are not 

misbranded. General recognition of 

safety and effectiveness in an OTC drug 

monograph means that experts qualified 

by scientific training and experience 

recognize the conditions as safe and 

effective for OTC marketing for the use 

recommended or suggested in the 

product’s labeling. An OTC drug 

monograph establishes, among other 

things, specific indications that are 

appropriate for the safe and effective use 

of a drug. An OTC drug product with 

labeled indications different than those 

set forth in an applicable OTC drug 

monograph would not be considered 

GRASE. 

OTC drug monographs allow 

manufacturers to market those products 

satisfying the monograph standard 

without requiring the specific approval 

of the product by means of a new drug 

application (NDA) under section 505 of 

the act. FDA has issued numerous OTC 

drug monographs for certain categories 

of OTC drug products. If an OTC drug 

product subject to a final monograph is 

labeled for indications that differ from 

those set forth in the monograph, then 

it would be a ‘‘new drug’’ under section 

201(p) of the act. In order to be legally 

marketed and distributed in interstate 

commerce, the drug manufacturer 

would be required to obtain approval 

from FDA for that product, and those 

conditions varying from the monograph, 

in an NDA under section 505 of the act. 

All OTC drug monographs place 

limits on the conditions that have been 

found acceptable for inclusion in the 

monograph by an administrative 

rulemaking process based on scientific 

data. Here, FDA set certain limits on the 

labeling of sunscreen drug products in 

the final rule, such as the prohibition on 

specific SPF values over 30, certain skin 

aging claims, and other indications for 

use. FDA is maintaining similar labeling 

restrictions in this proposed rule with 

respect to skin aging claims and other 

indications proposed by the comments. 

Also, as described elsewhere in this 

document, the revised ‘‘sun alert’’ in the 

‘‘Warnings’’ section does not include 

any skin aging claims (see section III.G, 

comment 19 of this document). 

However, FDA is proposing to increase 

the SPF labeling limit from 30 to 50, 

based on additional data that was 

submitted subsequent to the issuance of 

the FM. FDA is also proposing that the 

term ‘‘SPF 50+’’ can be used, rather than 

the term ‘‘SPF 30+’’ allowed in the FM. 

This increase in the SPF labeling limit 

addresses, in part, the comments’

request that FDA allow specific labeled 

SPF values over 30. 

Elsewhere in this document, FDA 

explains the reasons for the specific 

labeling proposals, such as the required 

SPF labeling, revised ‘‘sun alert’’ in the 

‘‘Warnings’’ section of the Drug Facts 

box, and indications for use (see section 

III.F, comment 15 and section III.G, 

comments 16, 17, and 19 of this 

document). FDA also explains our 

denial of specific labeling claims 

suggested by the comments, including 

the prohibition on specific SPF values 

over a certain threshold (SPF 50), skin 

aging claims, and additional indications 

for use (see section III.F, comments 15 

and 17 of this document). As noted 

earlier in this comment, any variation 

from these labeling conditions in the 

monograph, if finalized, would cause an 

OTC sunscreen drug product to be a 

new drug requiring an approved NDA 

before it could be legally marketed in 

the United States. 

The labeling requirements in this 

proposed rule would not violate the first 

amendment. FDA’s requirements for the 

disclosure of information in the labeling 

of OTC sunscreen drug products are 

constitutionally permissible because 

they are reasonably related to the 

Government’s interest in promoting the 

health, safety, and welfare of consumers 

and because they are not an ‘‘unjustified 

or unduly burdensome’’ disclosure 

requirement that offends the first 

amendment (see Zauderer v. Office of 

Disciplinary Counsel, 471 U.S. 626, 651 

(1985); see also Ibanez v. Florida Dep’t 

of Bus. and Prof’l Regulation, 512 U.S. 

136, 146 (1994)). The reasonable 

relationship between the required 

labeling disclosures proposed herein 

and the Government’s interest is plain 

here. 

The proposed labeling disclosures 

addressed by the comments, such as the 

SPF value, indications for use, and 

revised ‘‘sun alert,’’ would contribute 

directly to the safe and effective use of 

OTC sunscreen drug products. The SPF 

value and indications for use are critical 

components of labeling that allow 

consumers to understand more clearly a 

sunscreen product’s use in preventing 

sunburn and relative level of UVA/UVB 

protection. As explained elsewhere in 

this document, the revised ‘‘sun alert’’

we propose to require in the 

‘‘Warnings’’ section would help 

consumers understand more clearly the 

role of sunscreens as part of a 

comprehensive sun protection program 

(see section III.F, comment 19 of this 

document). The greater consumer 

understanding resulting from all of 

these labeling conditions would 

promote directly the proper use of 

sunscreens, which, in turn, would better 

ensure the protection of public health. 

In addition, it would not be ‘‘unduly 

burdensome’’ to sunscreen 

manufacturers to require these labeling 

disclosures. Finally, it is important to 

note that a sunscreen manufacturer 

could pursue alternative labeling 

conditions for its product by filing an 

NDA with the appropriate evidence 

demonstrating the product’s safety and 

effectiveness under the proposed 

conditions. 

In any event, FDA believes that the 

labeling requirements outlined in this 

proposed rule would pass muster when 

analyzed under the four-part test for 

restrictions on commercial speech set 

fourth by the Supreme Court in Central 

Hudson Gas & Electric Corporation v. 

Public Service Commission, 447 U.S. 

557 (1980). Under the test, the first 

question is whether the commercial 

speech at issue is false, misleading, or 

concerns unlawful activity, because 

such speech is beyond the first 

amendment’s protection and may be 

prohibited. If the speech is truthful, 

nonmisleading, and concerns lawful 

activity, the Government may 

nonetheless regulate it if the 

government interest asserted to justify 

the regulation is substantial, the 

regulation directly advances the 

asserted governmental interest, and the 

regulation is no more extensive than 

necessary to serve the government 

interest (Id. at 566). The Supreme Court 

has explained that the last element of 

the test is not a ‘‘least restrictive means’’

requirement but, rather, requires narrow 

tailoring (i.e., ‘‘a fit that is not 

necessarily perfect, but reasonable’’

between means and ends) (Board of 

Trustees of the State Univ. of N.Y. v. 

Fox, 109 S.Ct. 3028, 3032–35 (1989)). In 

subsequent decisions, the Court has also 

clarified that ‘‘misleading’’ in the first 

element of the test refers to speech that 

is inherently or actually misleading. 

Thus, if the speech to be regulated 

concerns lawful activity and is not 

inherently or actually misleading, the 

remainder of the test applies (see In re 

R.M.J., 455 U.S. 191, 203 (1982)). 

Based on the data currently available, 

FDA believes that the labeling 

statements proposed by the comments 

(i.e., specific SPF values above FDA’s 

established threshold, skin aging claims, 

and certain other indications) would not 

be protected speech and may be 

prohibited under the first prong of the 

Central Hudson test. FDA has 

tentatively determined that these 

proposed labeling statements would be 

inherently misleading on OTC 

sunscreen products sold and, thus, 


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misbrand the products under section 

502(a) and 201(n) of the act. Because 

FDA believes these labeling statements 

are inherently misleading, they would 

not be subject to protection under the 

first prong of the Central Hudson test. 

With respect to the labeling 

limitations for SPF values, based on 

current data, FDA believes that the 

labeling of sunscreens with specific SPF 

values greater than 50 would be 

inherently misleading. As discussed 

elsewhere in this document, FDA is 

concerned with the accuracy and 

reproducibility of test results showing 

protection greater than SPF 50 due to 

the lack of adequate validation data (see 

section III.F, comment 15 of this 

document). FDA had the same concern 

with SPF values above 30 when we 

published the FM in 1999. At that time, 

FDA had only received data 

demonstrating that the SPF test 

produces accurate results for products 

with SPF values of 30 or less. Since 

publication of the FM, FDA has received 

additional SPF testing data for 

sunscreen products with SPF values 

between 30 and 50 (Ref. 13). However, 

FDA has not received any data for 

sunscreen products with SPF values 

greater than 50. The data submitted to 

FDA indicate that the SPF test is 

accurate and reproducible for sunscreen 

products with SPF values up to 50 (Ref. 

13). However, these data cannot be 

extrapolated to SPF values above 50. 

Thus, FDA is proposing to allow 

specific labeled SPF values only up to 

50. 

Increasing variability in test results is 

likely with increasing SPF values. If 

there is large variability in test results, 

then the SPF value determined from the 

test is not accurate (i.e., an SPF 60 

product may not actually be an SPF 60 

product). The submitted data 

demonstrated that variability is not an 

issue for sunscreen products with SPF 

values up to 50. However, FDA is 

concerned that variability will become 

an issue for sunscreen products with 

SPF values over 50. 

For those sunscreens with SPF values 

above 50, FDA is proposing that the 

labeling can denote such values by a 

‘‘50+’’ designation. As discussed 

elsewhere in this document, FDA has 

sufficient assurance that a result over 50 

from the required SPF test is, in fact, 

greater than 50 and can be labeled 

‘‘50+’’ (see section III. F, comment 15 of 

this document). Thus, FDA believes that 

the term ‘‘50+’’ is truthful and 

nonmisleading on the label of OTC 

sunscreen drug products for which the 

SPF test in the monograph has indicated 

an SPF value greater than 50. However, 

without proper validation of specific 

SPF values above 50, there is no 

assurance that the specific values 

themselves are in fact truthful and not 

misleading. Thus, labeling of specific 

values above SPF 50 without 

appropriate validation (which FDA 

currently lacks) would be inherently 

misleading. As noted elsewhere, FDA 

invited any interested parties to submit 

such validation data for consideration 

by FDA and possible inclusion of 

specific values above SPF 50 in the FM. 

With respect to anti-aging, skin 

cancer, and sun damage claims 

proposed by the comments, as discussed 

elsewhere in this proposed rule, FDA is 

concerned that these statements would 

be false or misleading due to lack of 

sufficient data in support of these 

claims (see section III.F, comment 17 of 

this document). FDA has reviewed the 

submitted articles concerning UVinduced skin damage (i.e., premature 

aging and cancer) along with the articles 

obtained from a search of scientific 

literature (Refs. 26 through 34). As 

discussed elsewhere, although FDA has 

concluded that the studies support the 

conclusion that exposure to UV rays 

increase the risk of premature skin 

aging, the study data fails to show that 

sunscreen use alone helps prevent 

premature skin aging and skin cancer 

for several reasons (see section III. F., 

comment 17 of this document). 

First, with respect to premature skin 

aging, the studies have not completely 

defined the action spectrum for the 

majority of UV radiation-induced effects 

on human skin. Second, the inability to 

identify the exact UVB and UVA 

wavelengths that induce each 

histological change in skin derives from 

the study designs. Without knowing 

which UVB and UVA wavelengths 

induce each histological change in the 

skin, FDA is unable to determine which 

wavelengths are most important to 

causing skin aging and cannot 

determine the action spectrum for aging. 

Third, the studies did not examine the 

chronic, long-term consequences of UV 

radiation exposure in human skin. 

Fourth, although the studies that 

examined the ability of sunscreens to 

protect against UV radiation-induced 

histological changes in the skin provide 

useful data, it is difficult for FDA to 

conclude that sunscreen use alone helps 

prevent skin aging based on these 

studies. 

Likewise, FDA is not aware of data 

demonstrating that sunscreen use alone 

helps prevent skin cancer. Like skin 

aging, these are studies examining the 

effects of sunscreen drug products on 

short-term factors for skin cancer, such 

as sunburn and other cellular damage. 

However, it is difficult to extrapolate 

these short-term adverse effects of UV 

radiation to a long-term, chronic effect 

such as skin cancer. In addition, like 

skin aging, the complete action 

spectrum for skin cancer is not known 

at this time. 

For all these reasons, FDA has 

tentatively concluded that the available 

evidence fails to show that sunscreen 

use alone helps prevents skin cancer or 

premature skin aging. Thus, the antiaging, skin cancer, and sun damage 

claims proposed by the comments 

would be false or misleading due to lack 

of sufficient data in support of these 

claims. For example, the statement 

proposed by one comment that 

sunscreen use ‘‘may help prevent suninduced skin damage, such as 

premature skin aging’’ would be 

inherently misleading to consumers by 

suggesting that sunscreen use alone may 

help prevent premature skin aging. As 

explained in this response, the available 

data fail to show that sunscreen use 

alone helps prevent premature skin 

aging and skin cancer. 

As described elsewhere, FDA is 

proposing a revised ‘‘sun alert’’ so that 

the labeling of OTC sunscreen drug 

products include the most accurate 

information, based on the available 

scientific evidence, concerning the 

relationship of sunscreen use to the 

prevention of sunburn, skin cancer, and 

premature skin aging caused by UV 

exposure (see section III.F, comment 19 

of this document). The revised ‘‘sun 

alert’’ also includes a statement about 

limiting sun exposure and wearing 

protective clothing because FDA has 

tentatively determined that it is critical 

for consumers to understand the role of 

sunscreen use in a comprehensive sun 

protection program. As FDA has 

explained, the available evidence 

strongly suggests that consumers rely 

more heavily on sunscreens alone 

without taking other protective 

measures against sunlight, particularly 

when the labeling of products indicates 

the potential for greater protection (see 

section III.F, comment 19 of this 

document). By indicating the potential 

for greater protection than is supported 

by the available evidence, the proposed 

anti-aging, skin cancer, and other 

related claims would mislead 

consumers into relying more heavily on 

sunscreens alone. Such excessive 

reliance would undermine consumers’

protection from the sun and, thus, 

FDA’s public health mission. 

FDA has also preliminarily 

determined that the proposed labeling 

statements would concern unlawful 

activity which are not protected speech 

under the first prong of the Central 

Hudson test. 


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FDA is proposing specific conditions 

in the monograph under which OTC 

sunscreen drug products would be 

GRASE. Elsewhere, FDA explains how 

the labeling statements proposed by the 

comments would not be appropriate 

monograph indications for these 

sunscreen products (see section III.G, 

comment 17 of this document). Thus, 

the proposed labeling statements 

outside the proposed indications of the 

final monograph, as FDA proposes to 

revise it, would promote a sunscreen 

drug product for use as an unapproved 

new drug, which is illegal. In addition, 

any variation in the statements in a 

‘‘Warnings’’ section of a final 

monograph, such as the revised ‘‘sun 

alert’’ statement in this proposed rule, 

would be outside the monograph 

conditions and, thus, would promote 

the product as an unapproved new drug. 

The marketing and distribution in 

interstate commerce of an OTC 

sunscreen drug product with such 

labeling variations would be prohibited 

under sections 301(d) and 505(a) of the 

act. Speech promoting such an illegal 

activity may be restricted without 

violating the first amendment (Central 

Hudson, 447 U.S. at 563–564). 

If a manufacturer could circumvent 

the requirements and restrictions 

imposed by a final monograph by 

including nonmonograph labeling 

statements, or excluding required 

monograph statements, based on its own 

assertions of the alleged appropriateness 

and truthfulness of the statements, then 

such activity would significantly 

undermine the monograph system and 

FDA’s assurance that OTC drugs are safe 

and effective for their labeled 

conditions. FDA has assessed the 

labeling statements proposed by the 

comments and preliminarily determined 

that they are not justified by the 

available scientific evidence as GRASE 

conditions for the monograph. Instead, 

in order to legally market a sunscreen 

drug product with such labeling 

statements, an interested manufacturer 

would have to submit an NDA to FDA 

with the appropriate evidence to show 

the safety and effectiveness of the drug 

under the proposed nonmonograph 

labeling conditions. Requiring 

premarket FDA review and 

authorization of such nonmonograph 

drug claims ensures that such claims 

will be evaluated by a public health 

agency that has scientific and medical 

expertise so that only products that are 

safe and effective will be permitted to be 

sold for therapeutic purposes. 

Although this preliminarydetermination that the labeling 

statements at issue would be inherently 

misleading and would concern unlawful 

activity would obviate the need for FDA 

to address the other three prongs of the 

Central Hudson test, we believe that the 

labeling requirements proposed in this 

document would satisfy each of the 

parts of this test. With respect to the 

second prong, FDA’s interest in the 

required labeling disclosures and 

prohibitions addressed by the comments 

would contribute directly to the safe 

and effective use of these OTC 

sunscreen drug products, which is 

critical for the protection of public 

health. FDA’s interest in protecting the 

public health has been previously 

upheld as a substantial government 

interest under Central Hudson (see 

Pearson v. Shalala, 164 F.3d 650, 656 

(D.C. Cir. 1999) (citing Rubin v. Coors 

Brewing Co., 514 U.S. 476, 484–485 

(1995)). 

The proposed labeling requirements 

would directly advance this interest, 

thereby satisfying the third prong of the 

Central Hudson test. By requiring 

labeling disclosure of the SPF value, the 

proposed revised ‘‘sun alert,’’ and 

indications for use, FDA can better 

assure that consumers understand more 

clearly the use of sunscreens in 

preventing sunburn, their relative UVA/ 

UVB protection, and their role as part of 

a comprehensive sun protection 

program. The greater consumer 

understanding resulting from all of 

these labeling conditions would 

promote directly the proper use of 

sunscreens, which, in turn, would better 

ensure the protection of the public 

health. 

Likewise, this proposed rule’s 

exclusion from the monograph of the 

labeling statements proposed by the 

comments also directly advances FDA’s 

public health interest. FDA has 

preliminarily determined from the 

available evidence that these statements 

would not be appropriate conditions for 

OTC use under the monograph. Thus, 

the statements would directly 

undermine the protection of public 

health. In addition, it is important to 

note that the Pearson court, in assessing 

whether the specific dietary supplement 

regulations at issue directly advanced 

FDA’s stated public health goals under 

the third prong of the Central Hudson 

test, explained that its findings under 

this prong did not apply to drugs, where 

‘‘the potential harm is presumably much 

greater’’ than other products (Pearson, 

164 F. 3d at 656, n 13). 

Finally, under the fourth prong of the 

Central Hudson test, there are not 

numerous and obvious (Cincinnati v. 

Discovery Network, 507 U.S. 410, 418 n. 

13 (1993)) alternatives to the required 

labeling statements or labeling 

prohibitions proposed herein. 

Consumers are accustomed to using the 

label as their primary source of 

information about a drug product’s 

contents and use. Neither a public 

education campaign, nor encouraging 

OTC drug product manufacturers to 

provide information, such as that in the 

proposed revised ‘‘sun alert,’’ to 

consumers by other means, would 

ensure that people have the information 

they need about sunscreen products at 

the point of sale or use. Likewise, with 

respect to the alternative labeling 

statements proposed by the comments, 

FDA’s proposed indications and revised 

‘‘sun alert’’ present the relevant public 

health information to consumers in the 

clearest and most direct manner. Thus, 

FDA’s proposed indications and 

prohibition of other labeling statements 

are not more extensive than necessary. 

In this way, the required labeling 

disclosures and prohibitions proposed 

in this document would meet the fourth 

prong of the test. 

Furthermore, the proposed 

prohibition of claims in a final 

monograph does not prevent such 

claims from being approved in an NDA. 

As explained previously, a final 

monograph sets forth those conditions, 

including labeling, under which an OTC 

drug product would be considered 

GRASE and not misbranded. In issuing 

monographs, FDA considers whether 

the available scientific evidence 

demonstrates that OTC drug products 

within a therapeutic category are 

GRASE. A final monograph does not 

constitute an FDA decision regarding an 

NDA for an OTC drug proposing 

variations in these conditions. Thus, 

FDA’s proposals in this document 

would not prohibit any interested 

manufacturer from filing an NDA, with 

the appropriate evidence, for any 

variations from the monograph labeling 

conditions. Because of this significant 

available option to manufacturers for 

proposing alternative labeling 

statements, FDA’s proposed labeling 

requirements and prohibitions are not 

more extensive than necessary. 

In conclusion, FDA believes it has 

complied with its burdens under the 

first amendment to support the labeling 

requirements of this proposed rule. 

(Comment 12) One comment stated 

that voluntary professional labeling can 

be provided to physicians that will 

allow them to select or recommend 

sunscreen products for their patients’

needs, based on more detailed 

information describing the quantity 

(protection factor) and the range of UV 

protection (e.g., UVB, UVA, or UVB/ 

UVA protection). Another comment 

stated that FDA should not require 

professional labeling because complete 


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and accurate product labeling should be 

available to all consumers, not just to 

their health care providers. 

FDA defines professional labeling in 

OTC drug monographs as labeling that 

is provided to health professionals but 

not to the general public (i.e., not 

directly to consumers) (for example, see 

§ 331.80 (21 CFR 331.80)). In the final 

rule, FDA stated that it would consider 

professional labeling, such as protection 

against photosensitization reactions, if 

data were received (64 FR 22666 at 

27674). FDA has not received any data 

to date. Therefore, FDA is not proposing 

any professional labeling in this 

document. FDA will consider 

professional labeling for OTC sunscreen 

drug products in the future if specific 

supportive data are provided. 

(Comment 13) Some comments 

objected to the ranges of SPF values that 

define the product category designations 

(PCDs) in § 352.3(b). Stating that 

standard public health messages 

recommend use of a sunscreen with at 

least an SPF of 15, the comments 

contended that the ‘‘moderate’’ PCD 

(SPF values of 12 to under 30) may 

cause consumers to believe that SPF 

values of less than 15 provide adequate 

protection. One comment further stated 

that if the PCD range is from SPF 12 to 

29, manufacturers will only produce the 

minimum SPF value as they can use less 

active ingredients and get the same PCD 

classification. 

As discussed in the final rule (64 FR 

27666 at 27681), the PCD ranges in 

§ 352.3(b) and § 352.52(e) reflect a 

modified, simpler, combined version of 

the previously proposed five PCDs and 

the ‘‘Recommended Product Guide.’’

However, FDA agrees with the 

comments that the current standard 

public health message from public 

health organizations generally 

recommends use of a sunscreen with an 

SPF value of at least 15 (see section 

III.G, comment 19 of this document). We 

also agree that allowing SPF values 

below 15 in any but the lowest PCD 

range may appear to contradict this 

message. Therefore, FDA is proposing to 

modify the PCD SPF value range in 

proposed § 352.3(c)(1) from ‘‘2 to under 

12’’ to ‘‘2 to under 15’’ and in proposed 

§ 352.3(c)(2) from ‘‘12 to under 30’’ to 

‘‘15 to under 30.’’ FDA is also proposing 

to replace the PCD terms ‘‘minimal’’ and 

‘‘moderate’’ with the simpler terms 

‘‘low’’ and ‘‘medium,’’ respectively, and 

to use these simpler terms for the UVA 

radiation protection categories (see 

section III.E, comment 14 of this 

document). These labeling changes will 

provide consumers with familiar and 

consistent terms describing both UVA 

and UVB radiation protection. 

FDA disagrees with the comment 

contending that manufacturers will only 

produce the minimum SPF value in a 

given PCD range because they can use 

less active ingredients and get the same 

PCD classification. Section 352.50 of the 

current FM requires the SPF value to 

appear on a sunscreen product’s PDP. 

This proposed rule would not change 

that requirement. Thus, while the PCD 

provides additional information about 

the SPF value, consumers seeking 

higher SPF values can readily identify 

such products by the SPF value stated 

on a sunscreen product’s PDP. 

E. Comments on the Labeling of 

Sunscreen Drug Products With UVA 

Protection 

(Comment 14) Many comments 

discussed ways to categorize, phrase, 

and display UVA/UVB radiation 

protection on an OTC sunscreen drug 

product label. All of the comments 

stated that the SPF value should retain 

preeminence on the label’s PDP and be 

the consumers’ criteria for choosing an 

OTC sunscreen product. Some 

comments recommended that UVA 

radiation protection be stated on the 

PDP in descriptive words or simple 

phrases, rather than numbers or 

symbols, for the following reasons: 

• Simplicity, 

• Clarity, 

• To avoid confusion with SPF, and 

• To maximize consumer 

comprehension. 

Some comments referenced consumer 

research, discussed in subsequent 

paragraphs, to support this 

recommendation (Refs. 4 and 5). 

One comment suggested the following 

labeling statements: 

• ‘‘Protects against UVA rays’’

• ‘‘screens out UVA rays’’

• ‘‘shields from UVA rays’’

• ‘‘broad spectrum sunscreen’’

• ‘‘UVA/UVB protection’’

• ‘‘provides protection against both 

UVB and UVA rays’’

• other truthful and nonmisleading 

statements describing a quantification of 

the product’s UVA radiation protection 

The comment stated that quantification 

of the UVA radiation protection should 

be allowed in labeling, but not required, 

so that consumers can have additional 

product performance information to 

help them select appropriate products. 

Another comment stated that UVA 

radiation protection should be labeled 

only as grades of effectiveness (multiple 

levels) for the following reasons: 

• UVA radiation irritation induces 

various skin reactions (e.g., erythema, 

pigment darkening, skin cancer, and 

photodermatitis), and 

• Some action spectra of damages 

have not been determined. 

This comment referred to The Japan 

Cosmetic Industry Association (JCIA) 

Measurement Standards for UVA 

Protection Efficacy (Ref. 6), which 

recommend labeling UVA protection as 

three grades: (1) PA+, (2) PA++, or (3) 

PA+++. 

Several comments recommended two 

categories of UV protection labeling 

based on the ratio of UVA radiation 

protection factor to SPF value: 

• ‘‘with UV protection’’ if ratio equals 

0.20 

• ‘‘with extra UV protection’’ if ratio 

equals 0.25 

The proposed ratio is based on the UVA 

radiation protection factor as 

determined by the persistent pigment 

darkening (PPD) test method (see 

section III.N, comment 46 of this 

document). These comments stated that, 

because the ratio of damage from solar 

UVB radiation to that of solar UVA 

radiation is 80:20 over a day, a 

sunscreen must protect against an 80:20 

ratio of UVB to UVA radiation. The 

comments also recommended that 

products labeled ‘‘with UV protection’’

or ‘‘with extra UV protection’’ exhibit 

absorbance of 360 nanometers (nm) and 

longer wavelengths. 

Another comment suggested two 

categories to state overall UV radiation 

protection: ‘‘regular’’ and ‘‘broad 

spectrum.’’ The comment proposed that 

the ratio of a sunscreen product’s SPF 

value to its UVA protection factor be the 

single criterion for the ‘‘broad 

spectrum’’ designation, with the 

maximum ratio no greater than 4:1. For 

example, an SPF 16 product would need 

to provide a UVA protection factor of at 

least 4 to be designated ‘‘broad 

spectrum.’’

One comment disagreed with the 

previous comment, stating that there is 

no supportable scientific basis for the 

relevance of the 4:1 ratio. The comment 

argued that the ratio inappropriately 

combines, in the same equation, SPF 

values obtained with a solar simulator 

and solar irradiance values at low sun 

angles. 

Another comment suggested that 

sunscreen products with an SPF value 

of 2 or greater must have a UVA 

protection factor of at least 2 to be 

labeled ‘‘UVA/UVB’’ or ‘‘broad 

spectrum protection.’’ The comment 

stated that products with SPF values of 

at least 15 and UVA protection factors 

of at least 4 may be labeled ‘‘extra (or 

extended or enhanced) UVA 

protection.’’ The comment stated that 

these criteria are independent of test 

method and should apply to any of the 

proposed UVA radiation test methods. 

Another comment proposed 

establishing PCDs based on the UVA 


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radiation protection value obtained by 

the PPD test method. The comment 

suggested four PCDs that would enable 

consumers to choose the desired levels 

of protection: 

• ‘‘moderate’’

• ‘‘high’’

• ‘‘very high’’

• ‘‘extra’’

Another comment recommended three 

PCDs: 

• ‘‘low UVA protection’’

• ‘‘moderate UVA protection’’

• ‘‘maximum UVA protection’’

Another comment suggested using the 

five PCDs proposed in the TFM (58 FR 

28194 at 28295) and added a UVA 

protection factor number for each PCD 

based on the immediate pigment 

darkening (IPD) test method. 

Two comments recommended a fourstar rating system to describe UVA 

radiation protection. The comments 

stated that this system, based on the 

ratio of UVA to UVB radiation 

absorbance, would provide a simple 

method for consumers to determine the 

protective nature of an OTC sunscreen 

drug product. The absorbance ratio 

would range from 0 for products 

exhibiting no protection against UVA 

radiation to 1 for products exhibiting 

equal absorption at all wavelengths 

throughout the UVA/UVB radiation 

spectrum. Using this ratio, products 

would be classified in one of the 

following five categories: 

• 0 to < 0.2 = no UVA radiation 

protection claim 

• 0.2 to < 0.4 = Moderate (★) 

• 0.4 to < 0.6 = Good (★★) 

• 0.6 to < 0.8 = Superior (★★★) 

• 0.8 plus = Maximum (★★★★) 

Another comment recommended a 

five point rating system using the 

‘‘critical wavelength’’ (CW) (λc) test 

method. This system uses a scale 

analogous to the star rating system to 

assign products a ‘‘broad spectrum’’

rating as follows: 

• λc < 325 = ‘‘0’’

• 325 < λc < 335 = ‘‘1’’

• 335 < λc < 350 = ‘‘2’’

• 350 < λc < 370 = ‘‘3’’

• 370 < λc = ‘‘4’’

Several comments supported a single 

claim, such as ‘‘provides broad 

spectrum protection against UVB and 

UVA radiation,’’ based on determining a 

sunscreen pass/fail CW (λc). Comments 

that supported this ‘‘broad spectrum 

protection’’ claim stated that, in 

combination with SPF, it provides 

simple and accurate labeling that is 

easily understood by consumers. The 

comments referred to a research study 

that suggested this approach to UVA 

radiation protection labeling was 

superior for consumer comprehension 

and ease of product selection (Ref. 7). 

Other comments provided consumer 

research data, discussed elsewhere in 

this comment, suggesting this approach 

was least preferred by consumers (Refs. 

4 and 8). 

One comment stated that UVA 

radiation protection claims should be 

allowed for sunscreen products with 

SPF values of 4 and higher. The 

comment added that, for products 

claiming to protect against UVA and 

UVB radiation, a minimum UVA 

protection factor of 2 should be required 

if the SPF value is less than or equal to 

12. 

Several comments stated that 

sunscreen drug products labeled as ‘‘full 

spectrum’’ or ‘‘broad spectrum’’ should 

protect consumers from substantially all 

of the harmful effects of the sun, 

including sunburn associated with UVA 

radiation. According to one comment, 

sunscreen drug products labeled ‘‘full 

spectrum’’ or ‘‘broad spectrum’’ that do 

not protect against nearly all UVB and 

UVA radiation wavelengths seriously 

risk misleading consumers into 

believing they are fully and completely 

protected from the dangers of the sun. 

One comment recommended using the 

claim ‘‘full spectrum’’ rather than 

‘‘broad spectrum’’ to describe products 

that attenuate more than 90 percent of 

UVA radiation and are at least SPF 15. 

The comment suggested no UVA 

radiation protection claims be allowed if 

the product is below SPF 15. 

In support of their proposed UVA 

labeling, a number of comments 

provided results from consumer 

research studies that assessed consumer 

labeling preferences for stating UVA 

radiation protection. One comment 

described a 1996 survey (Ref. 4) in 

which 275 subjects compared two 

labeling systems: 

• 3-level descriptive (‘‘light,’’

‘‘intermediate,’’ or ‘‘extended’’ ‘‘UVA 

protection’’) and 

• Grapho/numerical (a bar graph 

indicating a level, 0, 4, 8, or 12, with the 

corresponding number appearing 

alongside the graph). 

The comment stated that the survey data 

suggested that, while equally able to 

understand both types of labels, the 

panelists preferred the grapho/ 

numerical system over the descriptive 

system. 

Another comment described two 

consumer research studies, conducted 

in 1994 and 1995 (Ref. 9), in which 235 

subjects compared three potential UVA 

radiation labeling options: 

• Numerical (2, 3, or 5), 

• Symbolic (4 stars with 1, 2, 3, or 4 

stars filled), and 

• 3-level descriptive (labeled blank if 

no UVA radiation protection provided 

or labeled ‘‘UVA and UVB Protection’’

or ‘‘UVB Plus Extended UVA 

Protection,’’ depending on the level of 

UVA radiation protection provided). 

The studies included focus group 

discussions and indepth interviews. The 

comment stated that the data suggested 

that a numeric designation for UVA 

radiation protection (in addition to the 

SPF value) created confusion for 

consumers and that symbols (i.e., stars) 

misled consumers into giving equal or 

greater importance to the UVA radiation 

rating compared to the SPF value. The 

comment concluded that a descriptive 

approach better conveyed to consumers 

the added benefit of UVA protection 

without detracting from the SPF value. 

Another comment described two 

consumer research studies conducted in 

1999 (Ref. 7) in which 2,238 consumers 

assessed three sunscreen product 

labeling systems: 

• A pass/fail descriptive (labeled 

blank if no UVA protection provided 

(i.e., fails) or labeled ‘‘Broad Spectrum 

UVA and UVB Protection’’ if UVA 

radiation protection provided (i.e., 

passes)), 

• A 3-level descriptive (labeled blank 

if no UVA radiation protection provided 

or labeled ‘‘UVA and UVB Protection’’

or ‘‘UVB Plus Extended UVA 

Protection,’’ depending on the level of 

UVA radiation protection provided), 

and 

• A 3-level grapho/numerical (a bar 

graph indicating a level, 4, 8, or 12, with 

the corresponding number appearing 

alongside the graph). 

The comment stated that the data 

suggested the pass/fail descriptor, 

‘‘broad spectrum,’’ was significantly 

superior to the other labels and 

recommended that FDA use this 

labeling to designate UVA radiation 

protection. 

Another comment described a 

consumer research study conducted in 

2000 (Ref. 8) at 20 urban and suburban 

shopping malls in which 1,921 subjects 

ranked four labeling systems: 

• 4-level numerical, 

• 4-level symbolic, 

• 4-level descriptive, and 

• Pass/fail descriptive (‘‘with/without 

broad spectrum UVA/UVB protection’’). 

The numerical labeling system was 

shown as Arabic numerals ‘‘1, 2, 3, 4’’

with the number ‘‘2’’ highlighted. The 

descriptor labeling system was shown as 

the words ‘‘Minimum, Moderate, High, 

Maximum’’ with the word ‘‘Moderate’’

highlighted. The symbolic labeling 

system was shown as a picture of four 

stars with two stars highlighted. 


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The comment concluded that the 

subjects had a significant preference for 

a labeling system based on descriptive 

words or numbers because of clarity, 

specificity, and ease of comprehension. 

Subjects least preferred the pass/fail 

system because they found it unclear, 

nonspecific, and lacking sufficient 

information to compare sunscreen 

products. This study also revealed that 

the numerical labeling system was one 

of the top two choices because numbers 

were ‘‘clearer, more specific, and easier 

to understand.’’ Age, gender, and 

educational or ethnic background were 

reported as not affecting the study 

results. 

In the TFM for OTC sunscreen drug 

products (58 FR 28194 at 28233), FDA 

proposed to allow claims relating to 

‘‘broad spectrum protection’’ or ‘‘UVA 

radiation protection’’ for OTC sunscreen 

products that meet the following two 

criteria: 

1. Contain sunscreen active 

ingredients with absorption spectra 

extending to 360 nm or above, and 

2. Demonstrate meaningful UVA 

radiation protection using appropriate 

testing procedures to be developed. 

In the FM for OTC sunscreen drug 

products (64 FR 27666 at 27672), FDA 

stated that UVA radiation labeling of 

OTC sunscreen drug products could 

continue in accordance with the TFM 

and its amendments until addressed in 

a future issue of the Federal Register. 

Elsewhere in this document, FDA is 

proposing test methods for determining 

the UVA radiation protection potential 

of an OTC sunscreen drug product (see 

section III.N, comment 46). 

FDA believes that the existing data do 

not clearly define the relationship 

between UVA radiation and skin 

damage. The principal reason for not 

better understanding this relationship is 

that the action spectra for specific types 

of UVA radiation-induced skin damage 

(i.e., which wavelengths of UVA cause 

which types of skin damage) have not 

been established. However, most 

scientific data demonstrate that UVA 

radiation is harmful to the skin. Thus, 

until these action spectra are known, 

FDA believes that more protection 

against UVA radiation damage is better 

for consumers’ health. Therefore, FDA 

believes it is important, as with the SPF 

value, to designate UVA radiation 

protection in a straightforward manner 

that consumers clearly understand. 

FDA proposes that the UVA radiation 

protection of an OTC sunscreen drug 

product determined from these UVA 

test methods be designated on the PDP 

using a combination of category 

descriptors (i.e., ‘‘low,’’ ‘‘medium,’’

‘‘high,’’ or ‘‘highest’’) and stars (i.e., 

symbols) similar to those described by 

some of the comments. The category 

descriptors and stars will designate 

relative levels of UVA radiation 

protection as measured by the UVA 

radiation test methods. The level of 

UVA radiation protection identified on 

the label reflects the following: 

• A numerical ‘‘UVA protection 

factor’’ (from the clinical test), and 

• A numerical ratio of UVA I (340 to 

400 nm) radiation absorption to UVB/ 

UVA (290 to 400 nm) radiation 

absorption (from the in vitro test). 

The test that indicates the lowest level 

of UVA radiation protection determines 

the level identified on the label. For 

example, if the clinical test indicates 

‘‘low’’ protection and the in vitro test 

indicates ‘‘medium’’ protection for a 

product, the product is labeled as 

providing ‘‘low’’ UVA radiation 

protection. This system comprises four 

categories of UVA radiation protection 

as described in table 1 of this document. 

TABLE 1.—OVERALL UVA PROTECTION OF A SUNSCREEN DRUG

PRODUCT

Star category Category descriptor 

★✰✰✰ Low 

★★✰✰ Medium 

★★★✰ High 

★★★★ Highest 

Some of the comments argued that the 

UVB radiation protection labeling is 

more important than UVA radiation 

protection and should be emphasized in 

the labeling over UVA radiation 

protection. FDA disagrees with the 

comments and proposes that the UVA 

radiation protection designation appear 

on the PDP along with the SPF value in 

an equally prominent manner that does 

not conflict with the SPF value. Because 

action spectra for UV-induced skin 

damage have not been clearly defined, 

FDA is unable to specify labeling for 

OTC sunscreen drug products that 

indicates what ranges of UV radiation 

are most harmful to consumers. In other 

words, FDA cannot conclude whether 

UVB or UVA radiation is more harmful 

to humans based on the scientific data 

collected to date. Therefore, FDA 

considers both UVB and UVA radiation 

protection equally important at this time 

because scientific data demonstrates 

that both have harmful effects on the 

skin. 

So that consumers consider UVB and 

UVA radiation protection equally in 

selecting an OTC sunscreen drug 

product, FDA is proposing a number of 

labeling requirements. Under this 

proposal, the font size of the stars and 

category descriptors for UVA radiation 

protection must be the same size as the 

SPF value and its descriptors. All four 

stars must appear and be preceded by 

the term ‘‘UVA’’ and followed by the 

appropriate category descriptor (e.g., 

UVA ★★★✰ High). All star borders and 

the color inside a solid star must be the 

same while the color of ‘‘empty’’ stars 

must be lighter and distinctively 

different than solid stars. The color 

inside a solid star must be distinctively 

different than the background color. The 

stars must be filled in starting with the 

first star on the left and must appear in 

a straight horizontal line. 

As requested by some comments, an 

OTC sunscreen drug product that does 

not provide the minimum UVA 

protection, as determined by the 

proposed UVA test methods, may only 

display an SPF value on the PDP. An 

OTC sunscreen drug product is not 

required to provide UVA protection and 

may bear only a sunburn (UVB/SPF) 

protection claim. However, FDA is 

proposing that a sunscreen product that 

does not provide at least a ‘‘low’’ level 

of UVA protection include the following 

statement on the PDP: ‘‘no UVA 

protection.’’ This statement must be the 

same font size as the SPF value and its 

descriptor. FDA is not proposing four 

empty stars because we are concerned 

that consumers may confuse products 

providing no UVA protection (i.e., four 

empty stars) with those providing the 

highest UVA protection (i.e., four filled 

stars). 

In developing this UVA radiation 

protection labeling, FDA has 

particularly considered the label 

comprehension studies (Refs. 4, 7, 8, 

and 9). These studies used multiple 

methodologies and report a diverse 

range of preferences for each labeling 

system: 

• Category descriptors, 

• Graphics, 

• Symbols, 

• Numerics, and 

• ‘‘Pass/fail’’ descriptors. 

The diverse results and varying 

methodology make it difficult to 

identify a clear preference for one 

labeling system. However, the studies 

indicate an overall preference for 

category descriptors. 

In agreement with the studies, FDA is 

proposing category descriptors to 

indicate the relative level of UVA 

radiation protection. As discussed in 

preceding paragraphs, FDA believes 

consumers should consider UVB and 

UVA radiation protection equally when 

selecting an OTC sunscreen drug 

product. For this reason, FDA is 

proposing that stars be used with 

category descriptors. FDA believes that 


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the category descriptor and star labeling 

for UVA radiation protection will give it 

equal prominence with UVB radiation 

protection (i.e., category descriptor and 

SPF) on the PDP. 

FDA is not proposing grapho/numeric 

labeling because we are concerned that 

consumers may be confused by a second 

number on the PDP (i.e., in addition to 

the SPF value). FDA is also not 

proposing any of the simple twocategory designations suggested by the 

comments: 

• With/without UVA protection, 

• With UVA protection/with extra 

UVA protection, or 

• Regular/broad spectrum protection. 

FDA agrees with one of the comments, 

which argued that these types of 

statements are misleading. FDA does 

not consider this labeling as providing 

consumers with enough information 

about the magnitude of UVA protection 

offered by an OTC sunscreen product. 

However, FDA does not object to the use 

of the following four statements for OTC 

sunscreen drug products that satisfy the 

requirements of proposed § 352.73 for a 

labeled UVA protection value: 

• ‘‘broad spectrum sunscreen’’, 

• ‘‘provides [select one of the 

following: ‘UVB and UVA,’ or ‘broad 

spectrum’] protection’’, 

• ‘‘protects from UVB and UVA 

[select one of the following: ‘rays’ or 

‘radiation’]’’, and 

• [select one of the following: 

‘‘absorbs’’ or ‘‘protects’’] ‘‘within the 

UVA spectrum’’. 

These statements may appear elsewhere 

in product labeling outside the ‘‘Drug 

Facts’’ box or enclosure but not 

intermixed with the information 

required on the PDP under § 352.50. 

FDA agrees with some comments that 

these statements, by themselves, may be 

misleading by implying that a sunscreen 

protects against nearly all UVB and 

UVA radiation. However, FDA does not 

believe these optional statements will be 

misleading in the context of the entire 

label, because the relative level of UVB 

and UVA protection must be stated on 

sunscreen product labels (alongside 

these more general statements). 

Although none of the studies 

combined labeling systems as proposed 

in this document, FDA believes the 

studies support use of category 

descriptors and symbols together. One 

study suggested that symbols may imply 

importance over SPF values (Ref. 9). 

However, FDA believes consumers will 

not place greater importance on UVA 

protection because we are proposing a 

required statement to inform consumers 

about the importance of both UVB and 

UVA protection. We are proposing to 

require one of the following statements 

on the PDP of all OTC sunscreen drug 

products: 

• ‘‘UV rays from the sun are made of 

UVB and UVA. It is important to protect 

against both UVB & UVA rays.’’

• ‘‘UV rays from the sun are made of 

UVB and UVA. It is important to protect 

against both UVB & UVA rays to prevent 

sunburn and other skin damage.’’

FDA believes that the use of one of these 

statements, along with the proposed 

UVB and UVA radiation protection 

labeling, including the format 

requirements described in preceding 

paragraphs, will lead consumers to view 

UVB and UVA radiation protection as 

equally important. 

In addition, this statement will 

educate consumers about UVA 

radiation, which will be a new term and 

concept to many consumers. The 

proposed statement should help 

consumers better understand the new 

UVB and UVA labeling when it is 

initially introduced to the OTC market. 

Thus, FDA believes that the consumer 

label comprehension studies, along with 

the proposed educational statement 

about UVB and UVA radiation, support 

the stars and descriptor UVA radiation 

protection labeling proposed in this 

document. Moreover, a similar ‘‘star 

rating system’’ for UVA radiation 

protection (i.e., the Boots Star System) 

has been used to label sunscreen 

products throughout Europe for over 10 

years. 

To prevent consumer confusion about 

UV radiation protection, FDA is 

proposing changes to UVB radiation 

protection labeling (i.e., the SPF value). 

SPF values indicate how effective a 

sunscreen product is in protecting 

against sunburn. By displaying the 

relative level of sunburn protection on 

the sunscreen drug product PDP in 

terms of an SPF value, consumers can 

choose their desired level of UVB 

radiation protection. To further improve 

consumers’ understanding of the 

sunburn protection level provided by a 

certain sunscreen product, FDA is 

proposing to require descriptive terms 

of relative sunburn protection (i.e., 

‘‘low,’’ ‘‘medium,’’ ‘‘high,’’ and 

‘‘highest’’) to accompany the SPF value 

on the PDP. FDA is further proposing 

that the SPF value must be preceded by 

the term ‘‘UVB’’ to further differentiate 

the SPF value from the UVA symbol/ 

descriptor on the PDP. FDA believes 

that numerical labeling for UVB 

protection, symbolic labeling for UVA 

protection, and the same descriptive 

labeling for UVB and UVA protection 

will allow consumers to easily 

understand and choose from relative 

levels of UVB and UVA radiation 

protection. 

FDA is aware that consumers have 

used and become accustomed to 

choosing OTC sunscreen drug products 

based on the SPF value for many years. 

Likewise, FDA believes that, over a 

period of time, consumers will similarly 

become accustomed to the proposed 

labeling using symbols and descriptors 

to designate relative UVA radiation 

protection. Furthermore, FDA believes 

consumer familiarity with similar star 

rating systems (e.g., movies, hotels, and 

restaurants) used for many years in the 

United States provide a basis for 

consumers’ understanding of this 

proposed labeling for OTC sunscreen 

drug products. 

FDA is providing a number of 

examples of how the UVA/UVB 

protection designations could appear on 

the PDP. 


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FDA believes that, as with SPF values, 

identifying the relative level of UVA 

radiation protection provides the most 

useful information for consumers. 

Consumers who desire more protection 

from the sun will be able to identify 

products with higher UVB (SPF) and 

UVA radiation protection. FDA agrees 

with the comments that a product must 

provide at least some minimum level of 

UVA radiation protection (as with SPF 

values) to be labeled as providing UVA 

radiation protection. Therefore, FDA is 

proposing minimum criteria for the 

lowest UVA category in its proposed 

test procedures (see section III.N, 

comment 46 of this document). 

F. Comments on the Labeling of 

Sunscreen Drug Products With High SPF 

Values 

(Comment 15) Several comments 

objected to FDA limiting specific 

labeled SPF values ‘‘up to but not above 

30.’’ The comments stated that data and 

information supplied to FDA since 

publication of the sunscreen FM 

demonstrate that SPF values over 30 can 

be safely tested with accuracy. The 

comments also argued that removing the 

limit will not lead to consumers 

spending more time in the sun when 

using high SPF sunscreens in 

comparison to low SPF sunscreens. To 

address that point, one comment 

proposed labeling to help reduce 

potential consumer misuse of 

sunscreens with SPF values over 30: 

‘‘higher SPF products give more sun 

protection, but are not intended to 

extend the time spent in the sun.’’

Another comment noted that the SPF 

value, in addition to proper sunscreen 

application and reapplication, is only 

part of a comprehensive sun protection 

program. 

Other comments explained the need 

for high SPF sunscreen products. The 

comments contended that consumers 

and physicians are familiar with and 

want the many currently marketed 

sunscreens that are labeled as ‘‘SPF 45, 

SPF 50, etc.’’ Thus, the comments 

argued that U.S. consumers will be at a 

disadvantage within the international 

community, because products providing 

SPF values over 30 are available in other 

countries. In addition, the comments 

stated that many prominent medical 

authorities maintain the need for high 

SPF sunscreens for individuals at ‘‘high 

risk’’ based on medical and/or 

occupational concerns and individuals 

who desire increased protection from 

photoaging and lengthy/intensive sun 

exposure situations. The comments 

argued that the need for high SPF 

sunscreens is supported by findings that 

UV exposures in several cities are 

considerably higher than previously 

recognized and because high SPF 

products can reduce cumulative UV 

exposure. The comments stated that 

consumer desire for high SPF products 

is demonstrated by sales data showing 

that products with an SPF value of 45 

are one of the fastest growing segments 

of the total sunscreen market. 

The remaining comments discussed 

the consequences of limiting the 

specific labeled SPF value. For example, 

one comment noted that if 

manufacturers cannot state the SPF 

level above 30, they will no longer have 

an incentive to fund research for better 

sunscreens. In addition, manufacturers 

may reformulate products to reduce 

active ingredients and, thus, reduce the 

level of UV protection. A comment 

argued that another adverse 

consequence results from most 

consumers failing to achieve the labeled 

SPF value because they do not apply 

enough sunscreen and/or reapply it too 

infrequently. Because high SPF 

products can help make up for such 

improper use, limiting the specific 

labeled SPF value to 30 has a negative 

impact on UV protection. 

A foreign industry organization 

suggested an upper limit for labeled SPF 

values of 50+ and provided three 

reasons: 

• Unreasonably high SPF values will 

lead consumers to expect ‘‘too much 

effectiveness’’ from sunscreen products. 

• Higher concentrations of sunscreen 

active ingredients are not ‘‘in the 

interest of safety.’’

• Higher SPF values will invite 

excessive, meaningless competition in 

the industry. 

The comment explained that 

competition would be meaningless 

because the amount of UV protection 

provided by products with SPF values 

above 50 is not significantly greater than 

products with an SPF of 50. 

Another comment from a sunscreen 

manufacturer agreed with FDA’s 

concern about the possibility of 

increasing variability when testing high 

SPF sunscreens. The comment 

suggested a modified ‘‘binomial’’ test 

method and labeling requirements for 

SPF values over 20 that would allow for 

high SPF products. 

Another comment submitted a 

published survey of 208 sunbathers on 

Miami’s South Beach during July 2001 

with the goal of measuring UV radiation 

exposure and probable injury (Ref. 10). 

The ‘‘worst case’’ scenario identified by 

the survey was based on sunbathers 

with Type I skin (persons most sensitive 

to sunlight who burn easily and never 

tan) exposed to UV radiation near the 

longest day and highest sun angle of the 

year at the ‘‘southern-most major beach’’

in the United States. The survey was a 

followup to one conducted in 1993 with 

62 sunbathers and evaluated by FDA in 

the FM (64 FR 27666 at 27674). The 

2001 survey determined MEDs absorbed 

by the following three steps: 

1. Measuring incident UV radiation 

(using three dosimeters), 

2. Multiplying by an adjusting factor 

for skin type (using a 30 percent 


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increase in sensitivity between skin 

types), and 

3. Dividing by the SPF worn by the 

sunbather. 

The survey suggests that sunbathers 

with Type I skin might receive a 

cumulative dose of 49.5 MEDs with 8 

hours of exposure. The comment 

concluded that, while SPF values up to, 

and including, 50 are warranted, values 

over 50 are unwarranted in any 

condition for sunburn protection. 

Two comments submitted testing data 

for sunscreens with SPF values between 

30 and 50 using the test method in the 

FM. The comments concluded that the 

test method was valid for these high 

SPF values. In addition, one comment 

indicated that a very water resistant test 

for an SPF 45 to 50 sunscreen would 

take nearly 4.5 hours using the skin 

types of subjects in the SPF testing 

procedures in the FM (i.e., skin types I, 

II, and III) (Ref. 13). The comment 

concluded that it is beyond the practical 

endurance capabilities of many people 

in the test to spend more than 5 to 6 

hours in front of a UV radiation lamp 

and that fatigue can lead to errors in test 

results. The comment also noted that 

the potential for intra and 

interlaboratory variability in test results 

increases as sunscreen SPF values 

increase. 

FDA concluded in the FM (64 FR 

27666 at 27675) that test methods 

supported specific SPF label values up 

to 30. FDA invited interested persons to 

submit data in support of high SPF test 

methods and to consider proposed 

methods for communicating the level of 

protection in labeling. Data and 

information on high SPF testing and 

labeling were submitted to FDA at, and 

following, public meetings on July 22, 

1999, and October 26, 1999, and after 

reopening of the administrative record 

(65 FR 36319) (see section III.I, 

comment 24 of this document) (Refs. 11 

and 12). 

FDA continues to be aware that many 

OTC sunscreen products with specific 

labeled SPF values over 30 are currently 

marketed, both nationally and 

internationally, and are increasingly 

used by consumers and recommended 

by health professionals (64 FR 27666 at 

27675). FDA agrees that these products 

should be available for those sunsensitive consumers who require such 

products based upon personal 

knowledge, planned sun exposure, 

geographical location, or advice of a 

health professional. FDA previously 

noted the lack of any known safety 

problems for sunscreen products with 

SPF values greater than 30 (64 FR 27666 

at 27675). The comment that argued 

higher concentrations of sunscreen 

active ingredients are not ‘‘in the 

interest of safety’’ did not supply any 

new data to support its contention. FDA 

will continue to monitor adverse drug 

experience reports for sunscreen drug 

products reported to its Medwatch 

program and in the medical literature. 

As noted by one comment, some 

researchers have raised the concern that 

sunscreen use may lead to increased sun 

exposure. The ‘‘compensation 

hypothesis’’ states that consumers who 

use high SPF sunscreens spend more 

time in the sun and/or use less 

protective clothing. The only double 

blind, randomized trial that addressed 

this issue showed a significant increase 

in sun exposure time when comparing 

use of SPF 30 to SPF 10 (Ref. 14). In 

addition, two retrospective survey 

studies showed that sun exposure time 

is longer when using sunscreen 

compared to not using sunscreen (Refs. 

15 and 16). Other studies cited by the 

comment to support the premise that 

the ‘‘compensation hypothesis’’ is 

incorrect and either did not provide 

data about the length of sun exposure or 

the study method did not allow for data 

interpretation (Refs. 17 through 20). 

Based on all of this data, FDA believes 

that some consumers may increase total 

UV exposure through over-reliance on 

sunscreens. The apparent divergent 

results on the validity of the 

‘‘compensation hypothesis’’ between 

studies may indicate that sun protection 

behaviors vary greatly for each person. 

More specifically, there is a spectrum of 

attitudes about the sun, from those 

individuals who seek dark suntans to 

those who seek to avoid the sun and 

consequent UV skin damage (Ref. 21). 

Such evidence underscores the need for 

adequate labeling so consumers can 

make informed decisions regarding their 

use of OTC sunscreen drug products. 

FDA agrees that the SPF value is one 

factor in a comprehensive sun 

protection program. However, the SPF is 

only a measure of protection from 

erythema (i.e., UVB radiation-induced 

sunburn) and does not measure 

protection from other UV skin damage, 

such as that induced by UVA radiation. 

While increased short wavelength UVA 

radiation protection generally increases 

with increasing SPF values, studies 

using in vivo or in vitro UVA radiation 

testing methods demonstrate that 

sunscreen products with the same SPF 

values can have markedly different 

levels of UVA protection, especially for 

long wavelength UVA radiation (Refs. 

22 and 23). These studies also indicate 

that a specific high SPF product can 

provide much less UVA radiation 

protection than a product with a much 

lower SPF value. Elsewhere in this 

document, FDA is proposing UVA 

radiation testing methods and labeling 

that will categorize the relative levels of 

protection provided by the SPF and 

UVA values of the sunscreen product 

(see section III.E, comment 14 and 

section III.N, comment 45 of this 

document), allowing consumers to 

compare products and choose the levels 

of UVB and UVA radiation protection 

desired. 

An SPF 30 sunscreen product may 

provide adequate sunburn protection for 

many consumers. However, FDA 

believes that appropriately tested and 

labeled high SPF value sunscreen 

products should be available for 

consumers who desire or need high 

levels of UV protection, in particular, 

those who burn easily. Such products 

would do the following: 

• Help compensate for inadequate 

application and/or reapplication, 

• Provide additional sunburn 

protection during intense UV radiation 

conditions, 

• Help reduce cumulative UV 

radiation exposure (when used in 

conjunction with other measures to 

reduce overall sun exposure), and 

• Generally provide consumers 

incremental increases in sunburn 

protection. 

FDA agrees that SPF values should be 

supported by scientific evidence. In the 

FM, FDA limited the specific labeled 

SPF value to 30. At that time, FDA had 

only received data demonstrating that 

the SPF test produces accurate results 

for products with SPF values of 30 or 

less. Since publication of the FM, FDA 

has received additional SPF testing data 

for sunscreen products with SPF values 

between 30 and 50 (Ref. 13). However, 

FDA has not received any data for 

sunscreen products with SPF values 

greater than 50. The data submitted to 

FDA indicate that the SPF test is 

accurate and reproducible for sunscreen 

products with SPF values up to 50 (Ref. 

13). However, these data cannot be 

extrapolated to SPF values above 50. 

Thus, FDA proposes to allow specific 

labeled SPF values up to 50. 

FDA agrees with the sunscreen 

manufacturer that increasing variability 

in test results is likely with increasing 

SPF values. If there is large variability 

in test results, then the SPF value 

determined from the test is not accurate 

(i.e., an SPF 50 product may not 

actually be an SPF 50 product). The 

submitted data demonstrate that 

variability is not an issue for sunscreen 

products with SPF values up to 50. 

However, FDA is concerned that 

variability will become an issue for 

sunscreen products with SPF values 

over 50. 


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FDA recognizes that future data may 

demonstrate that variability may not be 

a problem for sunscreen products with 

SPF values over 50. Therefore, FDA will 

consider specific SPF values greater 

than 50 upon receipt of data 

demonstrating that accurate and 

reproducible results can be obtained 

from the SPF test for sunscreen products 

with SPF values over 50. Generally, 

such data should include results from 

multiple laboratories using the same 

sunscreen formulations and using the 

SPF test proposed in this document, 

along with a statistical analysis of the 

overall results. In addition, FDA 

believes that the modified ‘‘binomial’’

test method submitted by one comment 

has merit for high SPF sunscreens and 

is requesting others’ views on this 

method during the comment period for 

this rulemaking (see section III.I, 

comment 24 of this document). 

In the FM (64 FR 27666 at 27675), 

FDA disagreed with the comment that 

manufacturers would have no incentive 

to fund research for better sunscreens 

and may reformulate to less protective 

products if there is an upper limit to 

specific labeled SPF values. Although 

FDA would not want to decrease 

research incentive, FDA is more 

concerned about valid scientific data 

demonstrating the ability of multiple 

laboratories to accurately and 

reproducibly determine SPF values. 

However, FDA does not believe it is 

necessary to arbitrarily limit specific 

labeled SPF values. To the contrary, 

both in the FM and in this proposal, 

FDA has specifically stated that high 

SPF sunscreens should be available for 

those individuals desiring such 

products. The maximum allowable 

specific labeled SPF value, both in the 

FM and in this proposal, is based upon 

the review of data and information 

submitted to FDA. FDA purposely did 

not limit labeled SPF values at 30 in the 

FM. Instead, FDA used the value of 

‘‘30+,’’ pending the receipt of adequate 

data to support any higher specific label 

values. 

Similarly, in this document, FDA is 

proposing the collective value ‘‘50+.’’

FDA has sufficient assurance that a 

result over 50 from the required SPF test 

is, in fact, greater than 50 and can be 

labeled ‘‘50+.’’ Thus, FDA believes that 

the term ‘‘SPF 50+’’ is truthful and 

nonmisleading on the label of OTC 

sunscreen drug products for which the 

SPF test in the monograph has indicated 

an SPF value greater than 50. FDA 

believes that allowing manufacturers to 

label sunscreens as ‘‘SPF 50+’’ may 

encourage further research in human 

skin photobiology and the development 

of safe and effective sunscreen drug 

products with specific SPF values over 

50. As explained earlier in this 

comment, FDA is not proposing that the 

specific value over 50 be stated in the 

labeling because there is no data, at this 

time, demonstrating the accuracy and 

reproducibility of the specific value 

over 50. Based upon the proposed 

labeling, improvements to SPF testing 

methods, and specific high SPF test 

data, FDA is proposing to modify the 

labeled SPF values in current 

§ 352.50(a)(1) and (a)(2) by changing the 

SPF values from ‘‘30’’ to ‘‘50.’’

G. Comments on Indications for 

Sunscreen Drug Products 

(Comment 16) One comment 

requested that the ‘‘Uses’’ statement, 

‘‘higher SPF gives more sunburn 

protection,’’ be omitted except for 

products with an SPF over 30. This and 

other comments suggested that FDA’s 

labeling concerns regarding high SPF 

sunscreens could be alleviated if the 

following statement was required on 

sunscreens over SPF 30: ‘‘Higher SPF 

products give more sun protection, but 

are not intended to extend the time 

spent in the sun.’’

FDA is proposing to revise the 

sunscreen FM ‘‘Uses’’ statement ‘‘helps 

prevent sunburn’’ and delete the ‘‘Uses’’

statement ‘‘higher SPF gives more 

sunburn protection’’ in current 

§ 352.52(b). The first indication, ‘‘helps 

prevent sunburn,’’ is being revised to 

one of the following, which would be 

required on all sunscreens: 

• ‘‘low UVB sunburn protection’’

• ‘‘medium UVB sunburn protection’’

• ‘‘high UVB sunburn protection’’

• ‘‘highest UVB sunburn protection’’

The relative level of sunburn protection 

is determined from the SPF value: 

• low = SPF 2 to under 15 

• medium = SPF 15 to under 30 

• high = SPF 30 to 50 

• highest = SPF over 50 

Thus, relative descriptors (low, 

medium, high, and highest) describe 

SPF values, which are relative and not 

absolute levels of sunburn protection 

intended to help consumers determine 

differences in sunburn protection 

offered by different sunscreen products 

(see section III.I, comment 23 of this 

document). 

FDA considers it important that 

consumers be made aware of the relative 

level of sunburn protection provided by 

a product in addition to its indication 

for sunburn protection. Individuals may 

select a low, medium, high, or highest 

sunburn protection product to meet 

their specific needs. The descriptor 

‘‘UVB’’ is included to describe the 

predominant rays that are screened. The 

phrase ‘‘helps prevent’’ is being deleted 

because it is duplicative and no longer 

necessary. This phrase would only 

lengthen the ‘‘Uses’’ statement. 

Furthermore, consumers will now be 

able to equate a product’s UVB radiation 

protection rating (i.e., SPF value) 

directly to the relative level of sunburn 

protection. 

The second indication ‘‘higher SPF 

gives more sunburn protection’’ is no 

longer needed because the relative level 

of sunburn protection is provided in the 

new ‘‘Uses’’ statements. In addition, 

without clarification, the statement may 

encourage consumers to spend more 

time in the sun. Clarification is 

necessary because, as discussed in 

comment 19 of this document, surveys 

reveal that consumers spend more time 

in the sun with increasingly higher SPF 

sunscreen products (Refs. 14, 15, and 

16). Therefore, FDA is not allowing this 

statement in the ‘‘Uses’’ section. 

However, under proposed § 352.52(e)(2), 

FDA is proposing the following optional 

statement under ‘‘Other information’’ or 

anywhere outside of the ‘‘Drug Facts’’

box or enclosure: ‘‘higher SPF products 

give more sun protection, but are not 

intended to extend the time spent in the 

sun.’’ The phrase ‘‘but are not intended 

to extend the time spent in the sun’’ is 

additional information not included in 

the FM indication. FDA believes this 

revised indication statement will 

discourage consumers from spending 

more time in the sun when using a 

higher SPF product. 

FDA is proposing additional revisions 

in ‘‘Uses’’ in § 352.52(b)(1) to include 

UVA claims and other information (see 

section III.G, comments 17 and 18 of 

this document). The proposed revisions 

will help consumers to more fully 

understand the uses and expected 

results for individual sunscreen 

products. These changes are necessary 

because the PDP for a sunscreen product 

will now include two performance 

ratings (see section III.E, comment 14 of 

this document): 

• The well-accepted SPF value and 

new descriptor rating for UVB radiation 

protection, and 

• A new star/descriptor rating for 

UVA radiation protection. 

Consequently, FDA considers it 

important that the ‘‘Uses’’ statements in 

the ‘‘Drug Facts’’ box accurately reflect 

product claims related to specific 

indications, UVA and UVB radiation, 

and the level of anticipated protection 

(low, medium, high, or highest) 

determined by the UVA and UVB 

product ratings. As with the 

introduction of SPF labeling years ago, 

it will take the combined efforts of 

government, manufacturers, consumer 

organizations, and the health care 


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community to educate consumers to 

fully understand these labeling 

initiatives to enhance their safe and 

effective use of sunscreen products. 

(Comment 17) One comment stated 

that FDA’s ‘‘sun alert’’ statement in the 

FM recognized that sun-induced skin 

damage can contribute to photoaging 

and increase the risk of skin cancer. 

This statement reads: ‘‘Sun alert: 

Limiting sun exposure, wearing 

protective clothing, and using 

sunscreens may reduce the risks of skin 

aging, skin cancer, and other harmful 

effects of the sun.’’ The comment urged 

FDA to allow other truthful use 

statements, such as the following: 

• ‘‘helps protect against skin damage 

caused by the sun’’

• ‘‘helps protect against skin aging 

caused by the sun’’

• ‘‘regular use helps protect against 

certain forms of skin cancer caused by 

the sun’’

• ‘‘helps protect against fine lines and 

wrinkles caused by the sun’’

• ‘‘helps protect against pigmentary 

changes due to sun exposure’’

Another comment urged FDA to include 

the first three use statements suggested 

by the first comment, as well as ‘‘helps 

protect against the harmful effects of the 

sun’’ and ‘‘helps protect against (select 

one: ‘casual,’ ‘incidental,’ ‘intermittent,’

or ‘daily’) sun exposure.’’ The comment 

contended that, when used effectively 

as part of a sun protection program, 

sunscreens may prevent very serious 

disease conditions. 

Another comment provided citations 

from the medical literature to support 

its contention that claims of sunscreens 

preventing skin cancer induction may 

be false, deceptive, misleading, and 

unsubstantiated. The comment 

mentioned an article by Garland (Ref. 

25) that states the following: ‘‘No 

epidemiological studies were identified 

that showed a protective effect of use of 

chemical sunscreen on risk of 

melanoma or other cutaneous 

malignancies in humans.’’ The comment 

also mentioned an article by Gasparro 

(Ref. 24) that states the following: 

‘‘Although some have promoted daily 

use (of sunscreen) for the prevention of 

premature aging of the skin and the 

prevention of skin cancer, actual data 

are lacking to support these 

recommendations.’’

FDA has reviewed the submitted 

articles concerning UV-induced skin 

damage (i.e., premature aging and 

cancer) along with articles obtained 

from a search of the scientific literature 

(Refs. 26 through 34). Many of the 

articles involved preclinical data, which 

can be difficult to extrapolate to 

consumer (human) actual use 

conditions. FDA believes that the 

articles with clinical data provide more 

meaningful results, as they can be easily 

extrapolated to consumer actual use 

conditions. Therefore, FDA is focusing 

discussion in this document on the 

clinical studies. In agreement with 

Garland (Ref. 25) and Gasparro (Ref. 24), 

FDA does not believe, as a whole, that 

the studies demonstrate that sunscreens 

alone help prevent skin aging or skin 

cancer. 

Some of the clinical studies examined 

the role of UVB and UVA radiation in 

producing histological changes 

indicative of skin aging due to the sun. 

Lowe et al. demonstrated that high 

doses of UVA radiation (320 to 400 nm) 

increased melanization of human skin 

more than lower doses of UVA or solar 

simulating UV radiation at 290 to 400 

nm (Ref. 26). Seite et al. demonstrated 

that melanization of human skin 

increased with exposure to UVB/UVA 

radiation at 290 to 400 nm (Ref. 32) and 

UVA radiation at 330 to 440 nm (Ref. 

27). Seite et al. also showed that human 

skin hydration decreased after chronic 

exposure to UV radiation at the 

wavelengths studied. 

Five studies revealed stratum 

corneum thickening produced by both 

UVB and UVA radiation (Refs. 26 

through 29 and 32). Stratum granulosum 

thickening was transiently induced after 

6 weeks of exposure to UV radiation 

(UVB/UVA) at 290 to 400 nm (Ref. 32). 

The same effects were seen with solar 

simulated radiation and high and low 

doses of UVA radiation after 12 weeks 

of exposure (Ref. 26). Viable epidermal 

thickening was seen after 6 weeks of 

exposure to UV radiation at 290 to 400 

nm in one study (Ref. 32) and after 9 

days of exposure to UVA radiation at 

335 to 345 nm in another study (Ref. 

31). 

Inflammation and lysozyme 

deposition along the dermal elastic 

fibers were increased more in human 

skin exposed to UVA than UVB 

radiation (Refs. 26, 28, 29, and 31). 

Sunburn cell appearance, a typical 

response to UVB radiation, was also 

found to be present after exposure to 

different UVA radiation regimens in two 

studies (Refs. 28 and 31) but not found 

in a third study (Ref. 27). Thus, FDA 

concludes that these studies 

demonstrated that both UVB and UVA 

radiation induce histological changes 

associated with skin aging. 

Four of these studies focused on the 

histological changes within the skin 

induced by UVB and UVA radiation and 

explored the ability of sunscreens to 

protect human skin against these 

changes (Refs. 29, 30, 32, and 33). The 

first study suggested that an SPF 29 

sunscreen prevented the development of 

solar elastosis, a condition in which 

skin loses its elasticity after chronic 

exposure to the sun (Ref. 33). However, 

these method and data analyses raise 

questions about the validity of the 

reported conclusion: 

• Discrepancies were noted 

concerning demographic characteristics 

of subjects, sunscreen application, and 

compliance rates. 

• Skin biopsy data at all three time 

points in the study were available from 

only 10 of the 35 subjects. 

• The only statistically significant 

difference between the sunscreen and 

placebo treatment groups was achieved 

in a computerized evaluation of solar 

elastosis at baseline and 24 months. 

The second study demonstrated 

significant contribution of a sunscreen 

in preventing UV radiation-induced 

skin damage (Ref. 32). The use of 

sunscreens with absorption spectra 

covering the 290 to 400 nm range 

prevented all of the effects of chronic 

exposure (6 weeks) to UV radiation 

evaluated in the study. The third study 

showed a photoprotective effect of an 

SPF 15 sunscreen product from damage 

induced by short term exposure to UVB 

radiation (Ref. 30). The fourth study 

showed that a UVB only sunscreen did 

not provide protection against chronic 

exposure to UVA radiation (Ref. 29). 

The studies provide evidence that 

both UVB and UVA radiation induce 

histological changes in the skin 

consistent with skin aging. Thus, the 

studies support the conclusion that 

exposure to UV rays increases the risk 

of premature skin aging. However, the 

study data fails to show that sunscreen 

use alone helps prevent premature skin 

aging for several reasons. First, the 

studies have not completely defined the 

action spectrum for the majority of UV 

radiation-induced effects on human 

skin. While studies demonstrate that a 

given histological change, such as 

thickening of the stratum corneum, is 

induced by certain wavelengths within 

the UVB and UVA region, studies have 

not examined the ability of the 

remaining UVB and UVA regions 

outside of these wavelengths to induce 

the same change. For example, studies 

may have shown that 290 nm to 310 nm 

and 360 nm to 400 nm radiation induce 

stratum corneum thickening, but it is 

not known whether 311 nm to 359 nm 

radiation induces the same histological 

change. 

Second, the inability to identify the 

exact UVB and UVA wavelengths that 

induce each histological change in the 

skin derives from the study designs. 

Each study differed in the following 

parameters: 


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• UV radiation wavelengths, 

• UV exposure regimens, 

• Sunscreen doses, 

• Sunscreen application techniques, 

and 

• Endpoints. 

Therefore, FDA cannot combine all of 

the data from these studies to define a 

complete action spectrum for each 

histological change in the skin. 

Furthermore, the action spectrum for 

each histological change would need to 

be combined to define a single action 

spectrum for skin aging, which is a 

cumulation of these histological 

changes. Without knowing which UVB 

and UVA wavelengths induce each 

histological change in the skin, FDA is 

unable to determine which wavelengths 

are most important in causing skin aging 

and cannot determine the action 

spectrum for aging. 

Third, the studies did not examine the 

chronic, long-term consequences of UV 

radiation exposure in human skin. 

Thus, it is not possible for FDA to 

extrapolate the data to longer time 

points at which the short-term 

histological changes may cumulate to 

produce visible signs of skin aging. 

Fourth, although the studies that 

examined the ability of sunscreens to 

protect against UV radiation-induced 

histological changes in the skin provide 

useful data, it is difficult for FDA to 

conclude that sunscreens alone help 

prevent skin aging based on these 

studies. The number of participants in 

each study was relatively small, with 

only 10 to 35 subjects per study. 

Different sunscreen formulations, with 

differing absorption spectra, were used 

in each study. As explained previously, 

these studies do not identify exactly 

which UVB and UVA wavelengths 

contribute the most to skin aging (i.e., 

the studies do not define the skin aging 

action spectrum). For all of these 

reasons, the studies do not prove that 

sunscreens alone help prevent 

premature skin aging. 

Likewise, FDA is not aware of data 

demonstrating that sunscreens alone 

help prevent skin cancer. It has been 

known for many years that UV radiation 

increases the risk of skin cancer. It has 

also been known for many years that a 

higher incidence of sunburn earlier in 

life corresponds to a higher incidence of 

skin cancer later in life. However, FDA 

is not aware of any studies 

demonstrating that the use of 

sunscreens alone decreases the risk of 

skin cancer. Like skin aging, there are 

studies examining the effects of 

sunscreens on short-term factors for skin 

cancer, such as sunburn and other 

cellular damage. However, it is difficult 

to extrapolate these short-term adverse 

effects of UV radiation to a long-term, 

chronic effect such as skin cancer. In 

addition, like skin aging, the complete 

action spectrum for skin cancer is not 

known at this time. 

Unlike skin cancer and premature 

skin aging, FDA has evidence that 

sunscreens alone help prevent sunburn. 

The SPF test measures the effectiveness 

of sunscreens with sunburn (erythema) 

as the endpoint. Thus, the impact of 

sunscreens on sunburn can be measured 

directly. In contrast, it is difficult to 

measure directly the impact of 

sunscreens on skin cancer or premature 

skin aging because these are long-term, 

cumulative adverse effects of UV 

exposure. 

Thus, for all of the reasons discussed 

in this comment, FDA concludes that 

the available evidence fails to show that 

sunscreens alone help prevent skin 

cancer or premature skin aging. Based 

on this conclusion, FDA is not 

proposing the indication statements 

proposed by the first and second 

comments, because these claims are for 

protection from premature skin aging, 

skin cancer, and related factors (e.g., 

‘‘helps protect against skin aging caused 

by the sun’’). FDA also is not proposing 

claims that sunscreens protect against 

‘‘casual, incidental, intermittent, or 

daily’’ sun exposure, as proposed by the 

second comment, because the studies do 

not support these claims. Furthermore, 

FDA considers these terms as lacking 

sufficient meaning to be useful to 

consumers. 

As described elsewhere in this 

document (see section III.G, comment 

19), FDA is proposing to require a 

revised ‘‘sun alert’’ statement in the 

form of a new warning. The new 

warning statement is based on FDA’s 

review of the available evidence 

concerning UV exposure and skin 

cancer, premature skin aging, and other 

skin damage. The new warning 

statement clarifies that UV exposure 

from the sun increases the risk of skin 

cancer, premature skin aging, and other 

skin damage. In addition, the new 

warning statement specifies that 

consumers should use complementary 

sun protection measures along with 

sunscreen (i.e., limit sun exposure and 

wear protective clothing). FDA has 

concluded from the available evidence 

that it is important to adopt a complete 

sun protection program (sunscreen, sun 

avoidance, and protective clothing) to 

decrease UV exposure. In fact, the 

second comment argued for new 

indication statements by considering the 

sunscreen use as part of such a sun 

protection program (i.e., in conjunction 

with limiting time in sun and wearing 

protective clothing). Thus, the second 

comment, along with the third 

comment, seemed to agree with FDA’s 

conclusions in this proposed rule 

concerning the need for consumers to 

use sunscreens in conjunction with 

other sun protection measures. 

In addition, the reference in the new 

warning statement to sunscreen use 

combined with limiting sun exposure 

and wearing protective clothing is 

consistent with recommendations by 

other public health organizations. For 

example, the World Health 

Organization’s International Agency for 

Research on Cancer (IARC) (Ref. 21) 

makes the following assessments and 

recommendations: 

• There is inadequate evidence in 

humans for a cancer preventative effect 

of sunscreens against basal cell or 

malignant melanoma cancers. 

• There is only limited evidence for 

a preventive effect of sunscreens against 

squamous cell cancer. 

• Sunscreens should not be the first 

choice for skin cancer prevention or 

used as the sole agent for protection 

against UV radiation. 

Likewise, the CDC recommends that 

sunscreens be used as a complementary 

measure in an overall sun protection 

program (Ref. 35). 

FDA believes that additional 

information from controlled clinical 

studies is needed to better understand 

the role of sunscreens in preventing 

premature skin aging and skin cancer. 

Studies examining premature skin aging 

(using solar radiation or simulated solar 

radiation) are needed to determine the 

following in humans: 

• Measurable skin properties such as 

elasticity, collagen/elastin ratios and 

properties, wrinkling, pigmentation 

changes and visual grades, leading to 

accepted quantitative definitions of 

chronological and sun-induced skin 

aging; 

• The relationship between sunlight 

exposure and skin aging, stratified by 

skin type; 

• An action spectrum for photoaging 

of skin; 

• A dose response for UV radiationinduced skin aging; 

• Quantitative estimates of realistic 

‘‘worst case,’’ long-term exposures to 

sunlight in relevant UVA and UVB 

radiation spectral ranges (i.e., the level 

of UVB and UVA protection needed); 

and 

• How UV radiation-induced 

processes that occur at a given 

wavelength affect UV radiation-induced 

processes that occur at other 

wavelengths. 

Similar information is needed for skin 

cancer, except that studies should 

examine the different types of skin 


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cancer, rather than examining different 

skin properties. In addition, IARC has 

provided recommendations for research 

on skin cancer prevention and 

sunscreens. These recommendations 

can also be used as a guide in designing 

studies to examine the role of 

sunscreens in preventing premature 

skin aging due to the sun (Ref. 21). FDA 

encourages interested parties to submit 

study protocols to FDA for review to 

ensure that studies are as informative as 

possible. FDA also invites comments by 

interested parties on the feasibility and 

validity of surrogate endpoints for 

studies to determine whether the use of 

sunscreens alone help prevent skin 

cancer, premature skin aging, or other 

skin damage. 

(Comment 18) As discussed in section 

III.E of this document, FDA received 

several comments discussing ways to 

categorize, phrase, and display UVA/ 

UVB radiation protection on an OTC 

sunscreen drug product label. In the 

amendment to include avobenzone in 

the monograph (61 FR 48645 at 48655), 

FDA proposed the following indications 

for UVB and UVA radiation protection 

by sunscreen drug products containing 

avobenzone: 

1. ‘‘Broad spectrum sunscreen’’; 

2. ‘‘Provides’’ (select one of the 

following: ‘‘UVB and UVA,’’ or ‘‘broad 

spectrum’’) ‘‘protection’’; 

3. ‘‘Protects from UVB and UVA’’

(select one of the following: ‘‘Rays’’ or 

‘‘radiation’’); 

4. (Select one of the following: 

‘‘Absorbs,’’ ‘‘Protects,’’ ‘‘Screens,’’ or 

‘‘Shields’’) ‘‘throughout the UVA 

spectrum’’; and 

5. ‘‘Provides protection from the UVA 

rays that may contribute to skin damage 

and premature aging of the skin’’. 

Likewise, in the amendment to include 

zinc oxide in the monograph (63 FR 

56584 at 56588), FDA proposed similar 

labeling for UVA and UVB radiation 

protection for products containing zinc 

oxide (substituting the word ‘‘within’’

for the word ‘‘throughout’’ in the fourth 

statement). FDA did not include these 

indications in the FM but has allowed 

their use until the UVA portion of the 

monograph is established. 

FDA has reconsidered these UVA 

protection indications. FDA is 

proposing to allow all of them except 

the fifth statement. In proposed 

§ 352.52(e), the first four statements are 

optional statements allowed for 

products that demonstrate UVA 

protection according to the proposed 

testing (see section III.N, comment 45 of 

this document). The statements can only 

be included in labeling outside of the 

‘‘Drug Facts’’ box. Within the ‘‘Drug 

Facts’’ box, FDA is proposing one of the 

following UVA indication statements, 

depending on the level of UVA 

protection provided by a product: 

• ‘‘low UVA protection’’

• ‘‘medium UVA protection’’

• ‘‘high UVA protection’’

• ‘‘highest UVA protection’’

The level of protection (i.e., low, 

medium, high, or highest) is determined 

from the UVA rating obtained from 

product testing (see section III.N, 

comment 45 of this document). 

Manufacturers who wish to combine the 

‘‘Uses’’ statements about UVA 

protection and UVB sunburn protection 

may do so if the descriptors (i.e., levels 

of protection) are the same. For 

example, if the levels of UVA and UVB 

protection are medium, the ‘‘Use’’ may 

read: ‘‘medium UVA/UVB sunburn 

protection’’. 

FDA is not including the fifth 

indication because FDA does not 

consider ‘‘skin aging’’ or ‘‘skin damage’’

claims adequately supported at this 

time. As discussed elsewhere in this 

document (see section III.G, comment 

19), FDA is proposing a statement in the 

‘‘Drug Facts’’ box that informs 

consumers that sunscreens may reduce 

the risks of skin aging, skin cancer, and 

other harmful effects from the sun when 

used in a regular program that relies 

upon limiting sun exposure and wearing 

protective clothing. Therefore, FDA 

believes the fifth indication statement 

would mislead consumers by not 

discussing sun exposure and protective 

clothing. 

(Comment 19) As discussed in section 

III.G of this document, FDA received 

several comments concerning the ‘‘sun’’

alert statement. In § 352.52(e)(2) of the 

FM, FDA included the optional 

statement: ‘‘Sun alert: Limiting sun 

exposure, wearing protective clothing, 

and using sunscreens may reduce the 

risks of skin aging, skin cancer, and 

other harmful effects of the sun.’’ This 

statement’s emphasis of the need for a 

comprehensive sun protection program 

(64 FR 27666 at 27679) was based on the 

findings of numerous groups, including 

the following: 

• The American Academy of 

Dermatology (AAD), 

• The CDC, 

• The Australian Government; and 

• The New Zealand Government. 

These groups have recommended that 

sunscreens be considered an adjunct to 

other UV protection strategies, such as 

avoiding the sun near midday, seeking 

shade, and wearing protective clothing 

and hats. 

The FM provided that the ‘‘sun alert’’

appear under the heading ‘‘Other 

information’’ or anywhere outside of the 

‘‘Drug Facts’’ box or enclosure. At that 

time, FDA encouraged manufacturers to 

voluntarily include this statement in 

labeling, make it available at the point 

of purchase, and/or make it available 

through consumer education programs. 

FDA is now proposing a revised ‘‘sun 

alert’’ statement be required in the 

‘‘Warnings’’ section of the ‘‘Drug Facts’’

box. FDA is proposing the statement to 

read as follows: ‘‘UV exposure from the 

sun increases the risk of skin cancer, 

premature skin aging, and other skin 

damage. It is important to decrease UV 

exposure by limiting time in the sun, 

wearing protective clothing, and using a 

sunscreen. FDA is proposing that the 

statement appear in bold type as the 

first statement in the ‘‘Warnings’’

section. FDA believes the statement is 

most appropriate in the ‘‘Warnings’’

section because it warns consumers that 

effective protection from the sun does 

not involve only the application of 

sunscreens, as many consumers believe. 

In addition, it warns consumers that UV 

radiation not only increases the risk of 

sunburn but also increases the risk of 

skin cancer and premature skin aging, 

which many consumers may not know. 

FDA believes the new warning will 

encourage consumers to use sunscreen, 

limit time in the sun, and wear 

protective clothing to reduce UV 

exposure. Because of the importance of 

warning statements and the need for 

consumers to receive a uniform message 

concerning such warnings, no variations 

in wording are allowed under 

§ 330.1(c)(2). 

FDA acknowledges that the new 

warning statement differs from the 

wording of the voluntary ‘‘sun alert’’ in 

the FM. These differences are based on 

FDA’s assessment of the additional 

evidence available since publication of 

the FM in 1999. As explained in 

comment 17 of this document, FDA 

does not believe that the available data 

support a claim concerning the use of 

sunscreen and a reduction in the risk of 

premature skin aging and skin cancer. 

The revised wording of the statement 

more accurately reflects the scientific 

conclusions that can be drawn from this 

evidence. 

FDA is proposing the warning 

because we continue to be concerned 

about adequate consumer understanding 

of a sun protection program that 

includes sun avoidance and wearing 

protective clothes along with sunscreen 

use. This proposed rule provides for 

even higher SPF values and a new rating 

system for UVA protection. Consumers 

may believe that sunscreens with higher 

SPF values (especially with UVA 

protection) provide complete UV 

radiation protection. Subsequently, 

consumers may prolong sun exposure 


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because they think higher SPF values 

equate to longer times in the sun 

without burning. FDA is aware of a 

double-blind, randomized clinical study 

that showed a significant increase in 

sun exposure time of persons using high 

SPF sunscreens compared to persons 

using low SPF sunscreens (Ref. 14). In 

addition, two questionnaire-based 

surveys showed that sun exposure time 

is prolonged for persons using 

sunscreens compared to persons not 

using sunscreens (Refs. 15 and 16). By 

educating consumers about a sun 

protection program, we believe 

requiring this new proposed warning 

will decrease the likelihood of 

consumers spending more time in the 

sun when using a sunscreen. 

The new proposed warning also 

informs consumers that use of 

sunscreens alone is not the sole measure 

of protection from UV exposure, even 

with the use of high SPF products that 

provide UVA protection. Although it is 

well established that sunscreens protect 

against UV radiation, the following 

factors affect the level of protection 

provided by a sunscreen for each 

individual: 

• Variations between individuals, 

• UV radiation absorption, 

• Ability of sunscreens to adhere to 

and be absorbed by the skin, 

• Exposure conditions, and 

• Conditions of use (e.g., inadequate 

application amount or reapplication 

frequency). 

Therefore, FDA agrees with the 

numerous groups that promote 

sunscreen use as part of a total sun 

protection program. 

FDA reviewed the relationship 

between sunscreen use and skin cancer 

incidence in the scientific literature and 

did not find confirmatory evidence that 

sunscreens alone protect against the 

development of skin cancer. The 

incidence of skin cancer continues to 

rise in the United States. The incidence 

of the most serious form of skin cancer, 

malignant melanoma, grew 6.1 percent 

per year during the 1970s (Refs. 14 and 

36). The rate is still rising an average 2.8 

percent annually, with a rate of 14.3 

percent per 100,000 persons in 1997. 

Melanoma is one of the top 10 cancers, 

by incidence, for persons with white 

skin. The American Cancer Society 

(ACS) estimated the following statistics 

concerning skin cancer in 2007 (Ref. 

37): 

• More than 1 million new cases of 

curable basal cell and squamous cell 

carcinomas would be detected, 

• Approximately 59,940 new cases of 

malignant melanoma would be 

diagnosed, and 

• An estimated 8,110 persons would 

die from melanoma and 2,000 persons 

would die from other skin cancers. 

Skin cancer affects roughly the same 

number of people as all other cancers 

combined. In view of the continuing 

increase in the incidence of all types of 

skin cancer and the lack of data 

demonstrating that sunscreens alone 

prevent skin cancer, FDA considers the 

new warning important for the 

protection of the public health. 

FDA is proposing that the new 

warning be required on all OTC 

sunscreen drug products except lip 

cosmetic-drug and lip protectantsunscreen products subject to 

§ 352.52(f). FDA continues to believe 

that all sunscreen products should have 

labeling to ensure that consumers are 

adequately protected against 

overexposure to UV radiation (64 FR 

27666 at 27673). Thus, sunscreen 

products labeled for use only on specific 

small areas of the face and sold in small 

packages (i.e., sunscreen products 

subject to § 352.52(f)) must include the 

new warning. The only sunscreen 

products not required to include the 

new warning are those lip cosmeticdrug and lip protectant-sunscreen 

products subject to § 352.52(f), as 

proposed in § 352.52(f)(1)(ii). FDA is 

making this proposal because lip 

cosmetic and lip protectant products are 

often sold in packages that are 

substantially smaller than those of other 

products that fall under § 352.52(f). FDA 

believes requiring the new warning on 

lip cosmetic-sunscreen and lip 

protectant-sunscreen products may 

discourage manufacturers from 

marketing these products because it 

requires a significant amount of labeling 

space. 

FDA has limited labeling 

requirements as much as possible for 

sunscreen products subject to 

§ 352.52(f). However, FDA believes 

consumers are at great risk for UVinduced skin damage, including cancer, 

on the face. Therefore, consumers who 

purchase products specifically for use 

on the face need to be informed about 

the information contained in the new 

warning. Although these products are 

marketed in small package sizes, FDA 

has determined that the products’

labeling needs to include this important 

information in order to protect 

consumers. 

(Comment 20) One comment stated 

that consumers who use color cosmetics 

or facial moisturizers with sunscreens 

make the informed decision to purchase 

them as an additional benefit to their 

cosmetic use. The comment contended 

that a significant number of people with 

dark skin types, who do not burn easily, 

purchase sunscreens to provide 

protection from the sun damage that is 

not immediately recognizable. For these 

reasons, the comment requested claims 

such as the following: 

• ‘‘helps protect against casual or 

incidental or intermittent daily sun 

exposure’’

• ‘‘helps protect against the harmful 

effects of the sun’’

Another comment acknowledged that 

facial makeups with sunscreen provide 

protection from sunburn, but that is not 

the primary reason why consumers use 

these products. The comment 

contended that requiring the ‘‘sunburn’’

indication would be inappropriate and 

misleading labeling for most facial 

makeups with sunscreen. The comment, 

instead, requested a claim such as 

‘‘protects against the harmful rays of the 

sun.’’

FDA notes that the second comment 

acknowledged that facial makeups with 

sunscreen provide protection from 

sunburn. Not every consumer who uses 

color cosmetics or facial makeups with 

sunscreen meets the following criteria: 

• Has a dark skin type, or 

• Uses these products solely to 

provide protection from sun damage 

that is not immediately recognizable. 

As noted in section III.D, comment 9 of 

this document, many consumers use 

facial products with sunscreen as their 

primary and only source of sunscreen 

protection for that area of the body. As 

discussed in section III.G, comment 16 

of this document, sunscreen products 

will be required to bear a claim of low, 

medium, high, or highest UVB sunburn 

protection. FDA does not consider it 

inappropriate or misleading for color 

cosmetic or facial makeup products 

containing sunscreens to have this 

sunburn protection claim of low, 

medium, high, or highest. 

Sunscreen products that provide UVA 

radiation protection may also bear a 

claim about the level of protection. In 

addition, all OTC sunscreen products, 

except lip cosmetic-drug and lip 

protectant-sunscreen products subject to 

§ 352.52(f), will be required to bear the 

revised ‘‘sun alert’’ statement, which is 

now included in the ‘‘Warnings’’ section 

of the ‘‘Drug Facts’’ box. FDA considers 

the information in this new ‘‘Warnings’’

statement much more beneficial to 

consumers than the statements 

proposed by the comments. FDA 

rejected the terms ‘‘casual, incidental, 

and intermittent,’’ as explained in 

section III.G, comment 17 of this 

document. 


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49092 Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 

H. Comments on Directions for 

Sunscreen Drug Products 

(Comment 21) Several comments 

requested alternative directions for 

makeup with sunscreen products. One 

comment requested ‘‘apply smoothly or 

evenly before sun exposure and/or as 

needed.’’ The comment added that 

‘‘before sun exposure’’ may not always 

be appropriate as these makeup 

products are not exclusively or even 

primarily used for protection against 

sun exposure. A second comment 

requested ‘‘apply smoothly or evenly 

before sun exposure and reapply as 

needed.’’ A third comment did not 

suggest any specific language, but 

requested flexibility to recognize the 

product’s primary use as a makeup, 

while providing adequate information 

about the sunscreen component. This 

comment added that the direction to 

consult a doctor for children under 6 

months of age was clearly unnecessary 

for facial makeup with sunscreen 

because these products cannot 

reasonably be expected to be used on 

children that age. 

FDA agrees that flexibility is 

appropriate for the directions for 

makeup with sunscreen products. 

Elsewhere in this document, FDA is 

proposing to allow labeling 

modifications for makeup with 

sunscreen products used only on 

specific small areas of the face and sold 

in small packages (see section III.D, 

comment 9 of this document). Those 

modifications include modified 

directions for cosmetic lip products 

containing sunscreen that are within the 

scope of proposed § 352.52(f). FDA is 

not extending the proposed 

modifications to all makeup with 

sunscreen products. Makeup with 

sunscreen products not labeled only for 

specific small areas of the face may be 

applied to a large area of the face or 

other areas of the body. As explained 

later in this comment, FDA would have 

concerns with the modifications being 

applied to these products. 

Whether intentional or not, makeup 

with sunscreen products may be the 

primary sunscreen for many consumers. 

A recent study examined sunscreen use 

patterns (Ref. 48). Participants were 

instructed to apply sunscreen every day. 

Of those who used sunscreen 

infrequently, the majority spent some 

time outdoors with 11 percent spending 

the majority of their time outdoors. 

These same participants explained that 

they did not believe sunscreen was 

necessary because of their planned 

activities. The authors cited this finding 

in advocating educating consumers on 

the need for sunscreen for frequent 

incidental sun exposure in addition to 

intentional sun exposure, such as 

sunbathing. 

For these reasons, FDA considers it 

important that consumers using makeup 

with sunscreen products not labeled for 

use only on specific small areas of the 

face recognize that these products are 

sunscreens and use them appropriately 

to maximize UV protection. Therefore, 

FDA is not proposing modified 

directions for these makeup with 

sunscreen products. 

(Comment 22) One comment 

requested that FDA require sunscreen 

manufacturers to provide accurate and 

appropriate instructions about how 

much sunscreen should be applied to 

the body. The comment also suggested 

that a warning about the dangers of 

sunburn from applying suboptimal 

amounts be included in sunscreen 

product labeling. A second comment 

stated that it was not aware of any study 

indicating that consumers use adequate 

amounts of sunscreen. The comment 

supplied data and other information 

concerning the dependency of the SPF 

value on the total quantity of sunscreen 

applied (Ref. 49). 

Section 352.52(d)(1) currently 

provides manufacturers the option to 

select one or more of the following 

application terms for a sunscreen 

product: ‘‘liberally, generously, 

smoothly, or evenly.’’ Manufacturers 

may also include optional directions 

that state ‘‘[bullet] reapply as needed or 

after towel drying, swimming, or (select 

one of the following: ‘sweating’ or 

‘perspiring’).’’ In the final rule, FDA had 

concluded that the directions in 

§ 352.52(d)(1) to apply ‘‘liberally’’ or 

‘‘generously’’ convey the appropriate 

message to ensure that consumers 

adequately apply the sunscreen (64 FR 

27666 at 27679). 

Several studies suggest that, in 

practice, consumers may apply amounts 

of sunscreen below the density of 2 

milligrams/square centimeter (mg/cm2), 

which is the amount of product required 

for the SPF determination in § 352.72(e) 

(proposed § 352.71(e)). These data 

suggest that consumers may apply as 

little as 0.5 to 1.0 mg/cm2 (Refs. 50 

through 54). One comment reported 

that, to achieve the rated protection over 

the whole body, a typical adult with a 

surface area of 1.73 square meters (m2) 

would need to apply 35 milliliters (mL) 

of sunscreen, roughly one-third of a 4 oz 

bottle per application (Ref. 55). Studies 

indicate that SPF values determined at 

an application rate of 1 mg/cm2 are 

approximately 50 percent of those 

determined at 2 mg/cm2, and when 

applied at 0.65 mg/cm2, the SPF values 

are 20 to 30 percent of those determined 

at 2 mg/cm2 (Refs. 49, 50, and 51). 

Gasparro notes that statements such as 

‘‘apply liberally and frequently’’ are too 

vague to be informative (Ref. 24). 

FDA is concerned that, in practice, 

consumers may be getting less 

protection than the labeled SPF value 

and believes that further information 

should be included in the labeling for 

sunscreen drug products to reduce the 

likelihood of underapplication. FDA 

believes that this information is better 

communicated as revised product 

directions rather than a warning. FDA 

is, therefore, proposing to revise 

§ 352.52(d)(1). The directions will 

continue to state that OTC sunscreen 

drug products should be applied 

‘‘liberally’’ or ‘‘generously’’ because it 

would be cumbersome to specify 

quantitative amounts for all possible 

body areas and the various uses on the 

label. However, FDA is proposing to 

make optional the directions in 

§ 352.52(d)(1)(i) to apply ‘‘evenly.’’ FDA 

believes that this term, if used alone, 

may not convey the appropriate message 

to ensure that consumers apply 

sufficient sunscreen. In addition, FDA is 

proposing to remove the term 

‘‘smoothly’’ from § 352.52(d)(1)(i) 

because FDA considers that term to be 

vague and it may have different 

meanings to different consumers. FDA 

also believes this term is more likely to 

result in product underapplication. 

In addition to labeling directing 

consumers to apply sufficient amounts 

of sunscreen, FDA is also proposing to 

revise the labeling requirements 

concerning reapplication of the 

sunscreen product. In § 352.52(d) of the 

FM, the general reapplication statement 

‘‘and as needed’’ was the only required 

information. FDA made specific 

reapplication directions in 

§ 352.52(d)(2) of the FM optional in an 

effort to equalize requirements between 

sunscreens with and without water 

resistant claims (64 FR 27666 at 27681). 

FDA now believes that more detailed 

reapplication directions must be 

included on all OTC sunscreen 

products, because sunscreens may be 

underapplied as suggested by the 

comments. 

FDA came to this conclusion after 

reviewing studies concerning sunscreen 

reapplication as well as 

recommendations of public health 

organizations. Wright, et al. suggests 

that inadvertent sunburn may be due to 

the failure to use and reapply sunscreen 

appropriately (Ref. 56). Study subjects 

who reapplied sunscreen every 1 to 2 

hours and after swimming did not 

report sunburn. Rigel et al. reported 

that, even under intense solar 

conditions, those reapplying an SPF 15 


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Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 49093 

sunscreen every 2 hours or sooner were 

five times less likely to sunburn 

compared to those who reapplied every 

2.5 or more hours (Ref. 57). The AAD 

(Refs. 38, 58, and 59), the ACS (Ref. 60), 

and the EPA (Ref. 40) recommend 

reapplying sunscreens every 2 hours or 

sooner and also recommend application 

to all exposed areas of the body (Refs. 

60, 61, and 62). 

Because the frequency of application 

appears to be critical for proper 

protection, FDA is proposing to add the 

statement ‘‘apply and reapply as 

directed to avoid lowering protection.’’

In addition, FDA is proposing to further 

revise the directions in § 352.52(d) to 

include the following reapplication 

statement: ‘‘reapply at least every 2 

hours.’’ Likewise, for those products 

making a water resistant claim, FDA is 

proposing to include the number of 

minutes (i.e., 40 or 80) that the product 

maintains its water resistance before the 

‘‘swimming/sweating’’ term. FDA 

believes these additional proposed 

directions will alert consumers about 

the hazards of using insufficient 

amounts of sunscreen product and 

encourage reapplication after the 

appropriate time. FDA considers these 

specific, informative reapplication 

statements, instead of ‘‘and as needed,’’

to be necessary on all OTC sunscreen 

products. FDA is also proposing the 

optional direction ‘‘apply to all skin 

exposed to the sun.’’ FDA is proposing 

that this direction be optional because 

we believe most consumers know to 

apply sunscreen to all exposed skin. 

However, if a sunscreen product can 

accommodate this direction, it will 

serve to remind consumers that all 

exposed skin is susceptible to UV 

damage. These proposed directions, as a 

whole, should serve to better protect 

consumers, particularly those who tend 

to underapply sunscreen, from 

overexposure to the sun. 

Accordingly, FDA is proposing to 

change § 352.52(d) to read as follows: 

(d) Directions. * * * 

(1) For products containing any ingredient 

in § 352.10. (i) The labeling states ‘‘[bullet] 

apply [select one of the following: ‘liberally’

or ‘generously’] [and, as an option: ‘and 

evenly’] [insert appropriate time interval, if a 

waiting period is needed] before sun 

exposure’’. 

(ii) The labeling states ‘‘[bullet] apply and 

reapply as directed to avoid lowering 

protection’’. 

(iii) As an option, the labeling may state 

‘‘[bullet] apply to all skin exposed to the 

sun’’. 

(iv) The labeling states ‘‘[bullet] children 

under 6 months of age: ask a doctor’’. 

(2) For products that satisfy the water 

resistant or very water resistant testing 

procedures identified in § 352.76. The 

labeling states ‘‘[bullet] reapply after [select 

one of the following: ‘40 minutes of’ or ‘80 

minutes of’ for products that satisfy either the 

water resistant or very water resistant test 

procedures in § 352.76, respectively] 

swimming or [select one of the following: 

‘sweating’ or ‘perspiring’] and after towel 

drying. Otherwise, reapply at least every 2 

hours’’. 

(3) For products that do not satisfy the 

water resistant or very water resistant testing 

procedures identified in § 352.76. The 

labeling states ‘‘[bullet] reapply at least every 

2 hours and after towel drying, swimming, or 

[select one of the following: ‘sweating’ or 

‘perspiring’]’’. 

As discussed in the FM (64 FR 27666 at 

27679), manufacturers who have data to 

support different reapplication 

directions based on specific 

substantiation information may submit 

the information for approval of those 

directions via an NDA deviation as 

provided in § 330.11 (21 CFR 330.11). 

I. General Comments on SPF Testing 

Procedure 

(Comment 23) One comment 

suggested that the SPF test incorporate 

an amount of product that more closely 

reflects the amount applied by 

consumers. More specifically, the 

comment requested that FDA replace 

the 2 mg/cm2 required in § 352.72(e) 

(proposed § 352.70(c)(5)) to a value 

between 0.5 and 1.0 mg/cm2. The 

comment argued that the protection 

afforded during actual usage may be 

only one-quarter to one-half the labeled 

SPF value (see section III.H, comment 

22 of this document). The comment also 

suggested that SPF could be stated using 

descriptive terms, such as ‘‘light,’’

‘‘moderate,’’ or ‘‘heavy’’ protection, 

instead of a numerical value. 

FDA is not proposing the suggested 

change in test method at this time. This 

issue was discussed in detail in the 

TFM (58 FR 28194 at 28264 to 28266). 

The majority of comments advocated 

continuing the use of an application 

density of 2 mg/cm2. The current 

comment did not provide data 

demonstrating the suitability of a 

smaller test amount. FDA is concerned 

that a uniform distribution of sunscreen 

over the test area might be difficult 

using a smaller amount of sunscreen. 

Further, the standard application 

density used worldwide in the SPF test 

is 2 mg/cm2 (Ref. 63). 

FDA agrees that SPF values do not 

reflect exact levels of sunburn 

protection that consumers receive under 

actual use conditions. The required SPF 

test is a clinical test conducted with 

strict control over factors such as 

product application density. However, 

under actual use conditions, these 

factors are not controlled and vary 

greatly. The actual level of sunburn 

protection under consumer use 

conditions is affected by a number of 

factors. Some of the key factors are 

• Application density, 

• Reapplication frequency, 

• Skin type (e.g., burns easily versus 

never burns), 

• Time of day during sun exposure, 

and 

• Geographical location during sun 

exposure. 

Thus, SPF values reflect relative and not 

absolute levels of sunburn protection. 

Although SPF values do not convey 

actual levels of sunburn protection, 

when comparing multiple sunscreen 

products, SPF values enable consumers 

to determine which products provide 

the most sunburn protection. For 

example, FDA believes most consumers 

would correctly identify an SPF 20 

product as providing more sunburn 

protection than an SPF 10 product. 

Thus, lowering the sunscreen 

application density would not be 

necessary to more accurately reflect the 

degree of relative sunburn protection. 

FDA agrees that, in addition to 

bringing SPF values closer to 

representing absolute levels of 

protection, lowering the sunscreen 

application density might also reduce 

some of the inaccuracies and limitations 

encountered when testing high SPF 

sunscreen products. Thus, FDA invites 

interested parties to submit data 

supporting a smaller application density 

for SPF testing of all sunscreen dosage 

forms in accordance with § 352.77. 

However, developing a single global 

method and labeling would require a 

coordinated effort between the 

regulatory agencies in many countries 

around the world. Because FDA does 

not have data to validate the SPF test 

using a lowering sunscreen density, 

FDA is proposing directions that we 

believe will encourage consumers to 

apply greater densities of sunscreen 

(i.e., closer to 2 mg/cm2) (see section 

III.H, comment 22 of this document). 

FDA does not find that there are 

sufficient benefits for using descriptors 

instead of numerical values for SPF on 

the PDP. Consumers are familiar with 

numerical SPF values from over 20 

years of usage. As described in section 

III.G, comment 16 of this document, 

FDA believes that the use of descriptors 

in combination with numerical values 

on the PDP may be beneficial to 

consumer understanding of the level of 

sunburn protection provided by a 

product. Thus, as explained in comment 

16, FDA is proposing to include a 

descriptive term of relative sunburn 

protection (i.e., low, medium, high, or 

highest) with the proposed sunburn 

protection statement in the ‘‘Uses’’


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49094 Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 

section and on the PDP. The intent of 

this dual descriptive and numerical 

sunburn protection measure is to allow 

consumers to more easily differentiate 

the level of sunburn protection provided 

by different sunscreen products. In 

addition, this proposed labeling for 

sunburn protection is similar to the 

proposed UVA protection labeling (see 

section III.G, comment 14 of this 

document). 

FDA is also aware of sunscreen drug 

products marketed in dosage forms that 

may not be addressed by current SPF 

testing procedures. The SPF testing 

procedure described in § 352.72 

(proposed § 352.70) references oils, 

lotions, creams, gels, butters, pastes, and 

ointments. FDA invites interested 

parties to submit SPF testing 

modifications for new dosage forms 

(e.g., mousses, foams, and towelettes) in 

accordance with § 352.77. 

(Comment 24) One comment 

recommended a pass/fail (binomial) test 

to determine SPF values (Ref. 49). The 

test would demonstrate that subjects 

have no reaction to a quantity of UV 

energy equivalent to an expected SPF 

value (for products passing the test). For 

example, subjects being tested with a 

product with an expected SPF value of 

30 would be dosed only at the SPF 30 

level, and the product would either pass 

or fail. A product passing this test 

would actually have an SPF value of 30 

or over, whereas a product failing this 

test would have an SPF value below 30. 

The comment argued that while the 

monograph SPF test is probably 

adequate for products with low SPF 

values, it is not adequate for testing high 

SPF products because differences in 

solar simulators can provide as much as 

a 200 percent variation in results 

depending on the formulation. The 

comment further argued that an 

impossibly high number of subjects 

would be required for the current SPF 

method to obtain a 95 percent 

confidence level and that the test 

exposes subjects to a potentially 

dangerous condition, sunburn. 

According to the comment, the 

average MED for each skin type can be 

predicted from existing solar simulator 

calibration data. During the pass/fail 

test, each test subject is screened for 

skin type and then given a first day 

range of energy that does not exceed the 

expected MED. The comment proposed 

using a panel of five subjects. Using the 

MED information obtained on the first 

day, each subject is given four UV 

radiation exposures corresponding to 

the expected SPF value. Each subsite is 

then evaluated for erythema. If six or 

more of the 20 subsites show 

perceptible erythema, the product fails, 

as there would be less than a 95 percent 

probability the actual SPF value was 

higher than the expected SPF value. If 

less than six subsites show perceptible 

erythema, the product passes, as there 

would be greater than a 95 percent 

probability that the actual SPF value 

was more than the expected SPF value. 

The comment proposed the following: 

TABLE 2.—PROBABILITY TABLE

No. of subjects Maximum no. 

of failures Probability 

1 (n=4) 0 0.06251

2 (n=8) 2 0.0352 

3 (n=12) 3 0.0200 

4 (n=16) 5 0.0383 

5 (n=20) 5 0.0207 

1 n is not sufficient to make a 95 percent 

prediction 

The comment further proposed that if 

all eight subsites of the first two subjects 

pass, then the product passes and the 

remaining three subjects would not be 

evaluated. The probability of this 

happening would be 1/256 unless the 

product is over the expected SPF value. 

FDA agrees that, currently, there may 

not be enough experience and test data 

for products with SPF values of 30 and 

over on which to determine the sample 

size needed to obtain an acceptable 95 

percent confidence interval. As 

discussed in section III.L, comment 37 

of this document, to account for 

increased variability in SPF values for 

sunscreens with SPF values over 30, 

FDA proposes to increase the sample 

size to at least 25 subjects. Therefore, 

the comment may be correct in arguing 

that large numbers of subjects may be 

required for testing products with high 

SPF values. FDA believes that the pass/ 

fail test has merit and could provide a 

reasonable substitute for the current SPF 

method for products with expected SPF 

value of 30 or higher. However, before 

the method can be accepted, method 

validation data are required that 

demonstrate the method can be 

performed satisfactorily by multiple 

laboratories using the same sunscreen 

formulation(s). FDA invites such data. 

If the pass/fail method is accepted, 

FDA may stipulate that the method be 

used only for products with SPF values 

of 30 and higher because of the large 

number of subjects that would be 

required for high SPF products under 

the current test method. A pass/fail 

method would require fewer test 

subjects. Low SPF products can be 

adequately tested under the current 

method without large numbers of 

subjects. In addition, FDA would likely 

require that all 20 subsites be evaluated 

even if the first 2 subjects pass. Further, 

using standard probability computer 

software, FDA calculates that the values 

for the maximum number of failures in 

table 2 of this document for subjects one 

through five should be 0, 1, 2, 4, and 5, 

respectively, rather than the values 

provided by the comment. 

FDA would also consider three 

modifications to the method described 

by the comment and invites comment. 

First, each subject may have test 

successes and failures due to multiple 

subsites on each subject. Statistically, 

these will not be independent 

observations, which is a condition 

needed for a binomial probability 

calculation. Therefore, FDA is 

considering that a test panel should 

consist of 20 to 25 subjects and that only 

one site be tested on each subject. A 

pass/fail determination would be made 

for each individual. 

Second, as an alternate, a double 

sampling plan based on Taylor’s Guide 

to Acceptance Sampling may replace 

the five-layered plan proposed by the 

comment (Ref. 64). With the double 

sampling plan, two subjects are tested 

simultaneously with up to a maximum 

of four subjects, each having four 

subsites tested. If no more than one of 

the first eight subsites has perceptible 

erythema, the product passes. If three to 

eight subsites have perceptible 

erythema, the product fails. If exactly 

two of the eight subsites have 

perceptible erythema, then the second 

group of two subjects is tested. If two to 

four subsites from four subjects have 

perceptible erythema, the product 

passes. Otherwise, the product fails. 

According to this scheme, if probability 

p = 0.10 that the product tested would 

produce any recognizable erythema, 

then the probability = 0.95 that the 

product will pass. If probability p = 0.5 

that the product tested would produce 

any recognizable erythema, then the 

probability = 0.05 that the product will 

pass. 

Third, an alternative to the probability 

calculation is a margin of error 

approach. With this method, a margin of 

error for the expected SPF value is 

defined before testing. The margin of 

error is used to determine the 

tolerability interval around the expected 

SPF value. The 90 percent confidence 

interval for the product’s test result (one 

result per subject) must fall within the 

tolerability interval to be labeled with 

that SPF value. For example, if a 10 

percent margin of error is claimed for a 

product with an expected SPF value of 

40, then the tolerability interval would 

be 40 ± 4, or 36 to 44. If the related 90 

percent confidence interval is from 37 to 

43, an SPF value of 40 is assigned to the 

product. If the related 90 percent 


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confidence interval is from 35 to 45, an 

SPF value of 40 could not be assigned 

to the product and the product may be 

retested at an expected SPF of 30. 

FDA invites discussion of these 

suggested modifications to the 

comment’s pass/fail method for testing 

sunscreen drug products having an SPF 

value of 30 or higher. 

(Comment 25) One comment 

described an in vitro method it 

developed for simultaneously predicting 

SPF and assessing photostability. The 

method utilizes a 150 watt xenon arc 

lamp to irradiate sunscreen applied at a 

level of 1 to 2 mg/cm2 to a flat collagen 

membrane substrate placed in the 

opening of an integrating sphere 

attached to a spectroradiometer. The 

spectral irradiance of the source and the 

spectral irradiance of the substrate alone 

are measured from 290 to 400 nm, at 1 

nm intervals. The spectral irradiance 

transmitted by the sunscreen/substrate 

combination is measured at 1 minute 

intervals until the total erythemaleffective dose transmitted by the 

sunscreen exceeds 1 MED, where 1 MED 

equals 0.02 erythema-effective Joules (J)/ 

cm2. Each 1 minute interval represents 

two to three MEDs. The time course of 

the sunscreen’s SPF is then computed 

(Ref. 65). This information reveals the 

photostability of a sunscreen. If a 

sunscreen is photostable, it will not 

decompose when exposed to UV 

radiation, and the SPF will not change 

with increasing UV exposure. If a 

sunscreen is not photostable, it will 

decompose when exposed to UV 

radiation, and the SPF will decrease 

with increasing UV exposure. Another 

comment asked FDA to consider 

replacing the human SPF test with 

equivalent in vitro technology and 

chemical engineering, but did not 

suggest a suitable method. 

FDA does not agree that an in vitro 

method is adequate to replace the in 

vivo SPF test. In vitro tests are generally 

inadequate as the sole measure of SPF 

because substrates cannot mimic 

sweating, skin absorption, or certain 

interactions with skin that influence 

SPF. Some sunscreen ingredients do not 

behave similarly in vitro and in vivo. At 

this time, the comment’s method has 

not been validated, and the chosen 

substrate has not been demonstrated to 

possess penetration characteristics and 

surface chemistry similar to human 

skin. 

The described in vitro method does 

have potential utility for measuring 

photostability of a sunscreen product. 

Measuring the erythemal-effective dose 

transmitted through the sunscreen in 

vitro over time seems like a reasonable 

approach. However, portions of the 

method require further exploration. 

Items such as the cut-off to define 

photostability need further explanation 

and validation. It should also be pointed 

out that the current SPF test method 

does not directly measure 

photostability, but it accounts for 

photostability. More specifically, the 

SPF value is determined after a 

sunscreen is exposed to UV radiation, so 

the SPF represents UVB protection 

provided by whatever fraction of the 

sunscreen has not decomposed. 

FDA agrees that in vitro tests are 

generally rapid and less expensive than 

in vivo tests and, for SPF measurements, 

would reduce exposure of human 

subjects to UV radiation. FDA is willing 

to consider alternate methods for SPF 

testing if they are adequately supported 

with data and are shown to be 

equivalent to established in vivo 

methods by collaborative studies. If the 

methods are equivalent, then the same 

SPF values should be determined for 

each sunscreen tested according to the 

SPF method and the alternate method. 

The comments have not provided data 

from such studies. Therefore, FDA is not 

proposing to include the described in 

vitro method in the monograph at this 

time. 

(Comment 26) Several comments 

urged FDA to revise § 352.72(h) and 

reinstate the requirement for 

determining MED at 16 to 24 hours after 

exposure, rather than 22 to 24 hours. 

The comments submitted data showing 

that, for an SPF 30 product and for the 

8 percent homosalate standard, 

determining the MED at 16 or 24 hours 

does not result in any clinical or 

statistical difference in the SPF (Refs. 66 

and 67). Comments argued that 

immediate pigmentation fades rapidly 

and does not interfere with MED 

readings. One comment further argued 

that the 16 to 24 hour time is 

universally accepted by the European 

Union, Australia, and Japan and FDA 

should adopt this time in the interest of 

international harmonization. 

The Panel recommended that the 

MED be evaluated 16 to 24 hours after 

exposure (43 FR 38206 at 38262). FDA 

proposed a post exposure time of 22 to 

24 hours based upon information 

provided by comments to the Panel’s 

report that immediate pigmentation may 

persist with higher doses of UV 

radiation up to 24 hours or, in some 

cases, for 36 to 48 hours after prolonged 

exposure (58 FR 28194 at 28268 to 

28269). Comments had indicated that 

immediate pigmentation might interfere 

with an investigator’s perception of 

minimally perceptible erythema. 

FDA agrees that these new data show 

no significant difference in MED 

readings at 16 and 24 hours. Thus, FDA 

is proposing to revise the MED 

determination time in §§ 352.72(h) and 

352.73(c) (proposed §§ 352.70(c)(8) and 

352.70(d)(3), respectively) from ‘‘22 to 

24 hours’’ to ‘‘16 to 24 hours.’’

J. Comments on the Sunscreen Standard 

for SPF Testing Procedure 

(Comment 27) Several comments 

suggested that standard controls with 

SPF values of 15 or higher be developed 

to test high SPF sunscreen products. 

One comment stated that such standards 

would improve test accuracy and 

provide a consistent and adequate 

benchmark for compliance. One 

comment mentioned use of a control 

SPF 15 formula routinely in SPF 

evaluation and considered it a more 

valuable control than the 8-percent 

homosalate SPF 4 standard. Another 

comment supplied ‘‘round-robin,’’

collaborative SPF testing data from 7 

laboratories on a total of 153 subjects 

with 2 potential SPF 15 sunscreen 

standard preparations, ‘‘Formulation A’’

on 147 subjects and ‘‘Formulation B’’ on 

146 subjects (Refs. 13, 68, and 69). The 

comment concluded that differences 

between the two preparations were not 

significant (p=0.653) but ‘‘Formulation 

B’’ was preferred due to its less complex 

formula and slightly more consistent 

results. The comment added that the 

data showed that different laboratories 

can obtain valid, reproducible results 

when testing high SPF sunscreens. 

Another comment stated that it 

provided test results on 20 subjects 

using an SPF 25 product as the control 

(Ref. 70). Three comments suggested 

that the European Cosmetic, Toiletry, 

and Perfumery Association (COLIPA) 

‘‘European low SPF Standard Code 

Number COL492/1 (formerly the DIN 

standard)’’ be included in the OTC 

sunscreen drug product monograph as a 

permissible standard sunscreen 

preparation, in addition to the 8-percent 

homosalate standard, and that either 

standard should be allowed in the SPF 

testing procedures. The comments 

contended that this approach will serve 

to permit international marketing and 

eliminate duplicative testing. Another 

comment asked FDA to adopt the JCIA 

SPF 15 ‘‘P3’’ standard, but did not 

provide supporting data. 

The comment concerning the SPF 25 

control provided data from comparative 

tests on 20 subjects, using the 8-percent 

homosalate standard, an SPF 15 

sunscreen drug product, and an SPF 25 

sunscreen drug product (Ref. 70). FDA 

finds that this study is inadequate to 

support the comment’s request because 

the study did not do the following: 


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• Include sufficient numbers of 

subjects, 

• Address suitability of the standard 

across different laboratories, and 

• Document some properties required 

in a sunscreen standard to test high SPF 

sunscreen products. 

The following properties of a 

sunscreen standard were not addressed 

but need to be addressed: 

• Low level of interlaboratory 

variation, 

• Sensitivity to experimental error, 

and 

• Ease of preparation with a 

reasonable degree of accuracy. 

These data are also needed for the JCIA 

standard. 

Although comments provided data on 

20 subjects in each of 4 laboratories 

using the COLIPA COL492/1 standard, 

FDA is not proposing to include this 

standard as an alternate to the 8-percent 

homosalate standard because we do not 

believe that using the COL492/1 

standard will make the monograph 

method comparable to the European 

method, as other differences exist 

between the two methods. For example, 

the monograph method requires 20 

evaluable subjects, while the European 

method requires only 10 evaluable 

subjects. Therefore, the COL492/1 

standard is a valid standard under the 

European method but may not be a valid 

standard under the monograph method. 

Finally, FDA finds that the 8-percent 

homosalate standard is a suitable 

control for testing sunscreen drug 

products with SPF 15 or below (see 

section III.J, comment 28 of this 

document). 

FDA agrees with the comment that the 

submitted collaborative data from seven 

laboratories support ‘‘Formulation B’’ as 

an appropriate SPF 15 sunscreen 

standard. The mean SPF for 

‘‘Formulation B’’ was 16.3 in 146 

subjects tested, with 1.7 percent 

standard error of the mean, and 

laboratory means ranging from SPF 15.6 

to 18.5. Therefore, FDA is proposing to 

include the ‘‘Formulation B’’ SPF 15 

standard in the FM to be used for 

sunscreen drug products with an SPF 

value over 15 (optional for SPF values 

of 2 to 15). 

(Comment 28) One comment noted 

that there are two recognized standard 

control formulations: 

1. An 8-percent homosalate 

preparation with an SPF value of 4 

(§ 352.70(b) of the FM), and 

2. Formulation B (padimate O/ 

oxybenzone) with an SPF value of 15. 

The comment stated that the function of 

the standard formulation is quality 

assurance for method control and not as 

a calibration standard to bracket specific 

SPF ranges. The comment claimed that 

the 8-percent homosalate SPF 4 

standard is appropriate to test products 

at any SPF level and that the choice of 

whether to use the SPF 4 or SPF 15 

control formulation should rest with the 

manufacturer. Several other comments 

agreed with this comment. 

Another comment provided data 

using the 8-percent homosalate standard 

to test product formulations with 

estimated SPF values of 15, 30, and 45 

on 20 subjects (Ref. 67). The comment 

concluded that the data showed testing 

procedures in the FM can differentiate 

high SPF sunscreens using the 

homosalate SPF 4 standard. The 

comment requested that the homosalate 

SPF 4 standard be allowed to be used 

for products with an SPF value over or 

below 15. 

FDA does not consider the data 

adequate to support the suggestion that 

the 8-percent homosalate standard 

currently used to evaluate sunscreen 

drug products with SPF values up to 15 

is equally applicable to products with 

SPF values over 15 (Ref. 67). The study 

had the following deficiencies: 

• Did not include sufficient numbers 

of subjects, 

• Did not address suitability of the 

standard across different laboratories, 

and 

• Did not document certain 

properties required in a sunscreen 

standard to test high SPF sunscreen 

products. 

The following sunscreen standard 

properties were not addressed but need 

to be addressed: 

• Low level of interlaboratory 

variation, and 

• Sensitivity to experimental error. 

FDA agrees that the two standards are 

method controls rather than calibration 

tools. As such, the standard used should 

approximate the expected SPF of the 

product being tested to better verify that 

all aspects of the testing method are 

performing properly at the expected SPF 

level. 

Using the SPF 4 standard to measure 

SPF values over 15 is more likely to 

produce erroneous results than using a 

standard with an SPF of 15. In 

measuring SPF values over 15, much 

higher light energies (J/cm2) are used in 

comparison to measuring SPF values 

below 15. Problems in the accurate 

quantitation of high light intensities 

may not be detected if the SPF 4 

standard is used for SPF values over 15. 

While the SPF 4 standard may give 

acceptable results for products with SPF 

values over 15 in some studies, the 

extrapolation of these results to 

approximately 4 to 13 fold higher light 

energies used to test products with SPF 

values over 15 may be erroneous in 

other studies. Better assurance of an 

accurate SPF value is obtained by using 

a standard that is closer in SPF value to 

the sunscreen product being tested. 

The use of an SPF 15 standard would 

be reasonable to test products with SPF 

values below 15. SPF 15 is in the 

middle (geometrically) of the 4 to 50 

range. The ratio of SPF 15 to SPF 4 is 

3.75, and the ratio of SPF 50 to SPF 15 

is 3.33. Thus, there would be equal 

coverage of all ranges. Therefore, FDA is 

proposing that Formulation B may be 

used to test sunscreen drug products 

with SPF 2 and over, and is required for 

testing sunscreen drug products with 

SPF over 15 (proposed 

§ 352.70(a)(1)(ii)). The 8-percent 

homosalate standard may be used for 

testing sunscreen drug products with 

SPF of 2 to 15. 

(Comment 29) Several comments 

suggested that a modern, HPLC method 

is superior to the older 

spectrophotometric assay in § 352.70(c) 

of the FM. One comment provided 

technical information about the HPLC 

method and stated that it is now 

commonly used by analytical 

laboratories to assay sunscreen 

formulations (Ref. 71). Although this 

HPLC assay method was used in the 

study of two SPF 15 sunscreen standard 

preparations (see section III.J, comment 

27 of this document), one comment 

noted that there are limited data on this 

method with the SPF 15 control 

formulation because FDA has not yet 

published this formula as an accepted 

standard. 

FDA agrees that an HPLC method is 

superior to the spectrophotometric 

method, which was originally published 

by FDA in 1978, in specificity and 

precision. Validation data provided by 

the comment documented the following: 

• Specificity, 

• Accuracy, 

• Limit of detection, 

• Linearity, 

• Precision, and 

• Reproducibility of the method. 

The validation data included 

chromatograms and demonstrated that 

the HPLC method is suitable for both 

the SPF 4 and SPF 15 standards. 

Further, FDA validated the method in 

its laboratories and concludes that the 

method is acceptable for quality control 

and regulatory purposes (Ref. 72). 

Finally, the spectrophotometric method 

has not been validated for the SPF 15 

standard, and the HPLC method has 

been validated for both the SPF 4 and 

SPF 15 standards. Therefore, FDA is 

proposing to revise § 352.70 to replace 

the outdated spectrophotometric 

method with the HPLC method and to 


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use the HPLC method to assay both the 

SPF 4 and SPF 15 standards. 

(Comment 30) Two comments 

disagreed with the requirement in 

§ 352.70(a) for concomitant use of a 

standard sunscreen for each SPF test. 

One comment suggested that a standard 

could be run twice yearly. Another 

comment suggested that data to evaluate 

proper laboratory test procedures could 

be obtained from panels of a standard 

run as part of ‘‘the ongoing laboratory 

operation.’’ A third comment stated that 

a standard preparation should be run 

each time an SPF determination is 

made. 

FDA discussed this issue in comment 

78 of the TFM (58 FR 28194 at 28253 

to 28254). FDA disagreed with one 

comment that the standard could be run 

once or twice a year and reaffirmed the 

Panel’s recommendation that 

concomitant testing is necessary in SPF 

determinations to ensure uniform 

evaluation of OTC sunscreen drug 

products and to serve as an internal 

indicator of experimental errors. The 

comments requesting a change did not 

provide any supporting data. In the 

absence of supporting data, FDA is not 

persuaded to change the concomitant 

use requirement in § 352.70(a). 

(Comment 31) One comment 

suggested that there is a need for a 

specific source to maintain and supply 

sunscreen standards. The comment 

contended that a few testing laboratories 

are reporting differences in the tested 

SPF of the 8-percent homosalate 

standard preparation depending on 

whether the standard is prepared by the 

laboratory or purchased from one 

company that manufactured this 

standard. The comment stated that 

either the testing procedures or the 

standard itself have changed since the 

original formula was published (earlier 

standard SPF values were 3.7/3.8 to 4.2/ 

4.3 with an average of 4.1, while current 

values are 4.3 to 4.9/5.0). 

Data supporting the reliability and 

wide acceptance of the 8-percent 

homosalate standard preparation were 

previously discussed in the TFM (58 FR 

28194 at 28250 through 28252). The 

comment did not provide any data to 

support its contention concerning 

discrepancies in the SPF of 8-percent 

homosalate standard preparations and 

FDA is not aware of any new data that 

support the need for a specific source to 

maintain and supply this standard. The 

standard is a control to validate the 

testing procedure, equipment, and 

facilities rather than a calibration tool 

for setting SPF values of sunscreen 

products. FDA considers the parameters 

established in § 352.70 of the FM 

adequate to assure a uniform standard 

and is not requiring that a specific 

source maintain and supply the 

sunscreen standard at this time. 

K. Comments on Artificial Light Sources 

for SPF Testing Procedure 

(Comment 32) Several comments 

suggested that FDA replace the 

specifications in § 352.71 that state ‘‘sun 

at a zenith angle of 10°’’ and ‘‘less than 

1 percent of its total energy output 

contributed by nonsolar wavelengths 

shorter than 290 nm’’ with the COLIPA 

table of ‘‘percent erythemal 

contribution’’ as the spectral power 

distribution standard for the light source 

used in the SPF test procedures (Ref. 

73). The comments suggested that the 

spectra of currently used solar 

simulators (especially around 290 nm 

and above 350 nm) could cause 

overestimation of SPF values for high 

SPF sunscreens. Because shorter 

wavelengths can make a very large 

contribution to erythema, the comments 

stated that small errors in the 290 nm 

region of solar simulator spectra could 

have considerable effects. The 

comments noted that spectral power 

deficiencies above 350 nm may give 

artificially high SPF values for 

sunscreen drug products that absorb 

poorly in the long wavelength UVA 

region. 

The comments added that there is 

general agreement in the industry that 

§ 352.71 should be revised to permit 

compliance with the COLIPA standard 

for solar simulators. The comments 

further recommended one modification 

to the COLIPA standard: The energy for 

wavelengths below 290 nm should be 

limited to ‘‘less than 0.1 percent’’ rather 

than ‘‘less than 1.0 percent,’’ as stated 

in the COLIPA standard. The comments 

stated that a more restrictive 

specification of ‘‘0.01 percent,’’ as 

mentioned by FDA (65 FR 36319 at 

36321), would result more in testing the 

limits of the measurement 

spectroradiometer rather than the true 

output of the solar simulator. One 

comment that supported the COLIPA 

standard subsequently suggested that 

the spectral limits be further narrowed 

to prevent excessive variability of SPF 

values for certain sunscreen products 

(Ref. 74). 

One comment discussed the 

calculations to obtain the source 

spectral specification according to 

COLIPA (Ref. 73). In the COLIPA table, 

the source spectral specification is 

described in terms of cumulative 

erythemal effectiveness by successive 

wavebands. The erythemal effectiveness 

of each waveband is expressed as a 

percentage of the total erythemal 

effectiveness from 250 nm to 400 nm, or 

as the Percentage Relative Cumulative 

Erythemal Effectiveness (%RCEE). 

According to the COLIPA specifications 

and consistent with § 352.71, 

wavelengths below 290 nm should be 

excluded from any source by 

appropriate filters. Likewise, 

wavelengths above 400 nm should be 

limited as much as possible and are not 

included in the calculation of %RCEE. 

Because RCEE values are calculated as 

relative percentages, measuring the 

spectral irradiance in absolute energy 

units is not necessary. Relative units are 

sufficient. The spectral irradiance of the 

source is multiplied by the Commission 

International de L’Eclairage (CIE) (1998) 

standard skin erythemal action 

spectrum to obtain the erythemal 

effectiveness of the source. The spectral 

erythemal effectiveness values of the 

source spectrum are then integrated 

from 250 nm to the various successive 

reference wavelength values shown in 

the COLIPA table in order to produce 

the cumulative erythemal effectiveness 

for each spectral waveband, and the 

total erythemal effectiveness is 

calculated up to 400 nm. Finally, the 

%RCEE is calculated at the reference 

waveband as the percentage ratio of the 

cumulative erythemal effectiveness in 

each of these wavebands to the total 

integrated value from 250 nm to 400 

nm. 

Based on these calculations, the 

COLIPA table includes limits up to 400 

nm. In contrast, when FDA requested 

comments on this issue, we included a 

modified COLIPA table that includes 

limits up to 350 nm (65 FR 36319 at 

36321). However, the modified COLIPA 

table published by FDA was erroneous. 

FDA agrees with the comment (and 

COLIPA) that it is necessary to include 

all UV erythemal wavelengths (i.e., up 

to 400 nm) when standardizing solar 

simulator output. As argued by the 

comment, the erythemal contribution 

from long-wavelength UVA radiation 

(i.e., 350 nm to 400 nm) can become 

important when a high SPF product is 

tested. However, FDA believes that the 

limits for the 290 to 350 waveband 

should be changed from 93.5 to 99.0 

percent to 93.5 to 98.5 percent. This 

modification will address some of the 

errors in SPF that are attributed to the 

lack of match between the solar 

simulator and actual solar spectra. FDA 

invites comments on these proposed 

changes. 

FDA does not agree, at this time, with 

the comment’s suggestion to further 

narrow the COLIPA standard to the 

spectral limits that it proposed. The 

comment based its suggestion on a 

theoretical argument and did not supply 

the complete emission spectra of the 


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four solar simulators used in its two 

referenced studies. There may be 

significant differences in the 290 to 350 

nm range in these studies that can 

account for the reported differences in 

SPF test results. Further, FDA has 

concerns about the ability of currently 

used solar simulators to meet the 

comment’s suggested spectral standard 

and invites comments on the changes 

suggested by the comment. 

FDA agrees with the comments that 

the COLIPA approach provides a more 

appropriate description for solar 

simulators. FDA’s original proposal that 

solar simulators have a spectral power 

distribution ‘‘similar to sunlight at a 

zenith angle of 10°’’ is nonquantitative 

and may not be practical, considering 

the types of solar simulators that are 

generally available. Accordingly, FDA is 

proposing to revise the first part of 

§ 352.71 (proposed § 352.70(b)) as 

follows: 

(b) Light source (solar simulator)—(1) 

Emission spectrum. A solar simulator used 

for determining the SPF of a sunscreen drug 

product should be filtered so that it provides 

a continuous emission spectrum from 290 to 

400 nanometers (nm) with * * * the 

following percentage of erythema-effective 

radiation in each specified range of 

wavelengths: 

SOLAR SIMULATOR EMISSION

SPECTRUM

Wavelength range 

(nm) 

Percent erythemal 

contribution 

< 290 < 0.1 

290–310 46.0–67.0 

290–320 80.0–91.0 

290–330 86.5–95.0 

290–340 90.5–97.0 

290–350 93.5–98.5 

290–400 93.5–100.0 

(Comment 33) Several comments 

suggested the following revisions to the 

light source (solar simulator) 

requirements in § 352.71: 

• Delete the ‘‘out of band’’

specification that not more than 5 

percent of a solar simulator’s total 

energy output can be contributed by 

wavelengths longer than 400 nm. 

• In place of this 5 percent ‘‘out of 

band’’ limitation, allow a limit such as 

1,250 to 1,500 watts/square meter (W/ 

m2) on the total solar simulator 

irradiance delivered to the skin for all 

wavelengths. 

One comment provided data 

comparing solar simulators with and 

without a 50 percent neutral density 

filter to demonstrate that there is no 

measurable impact of heat load on the 

outcome of SPF testing (Ref. 13). The 

comment stated that thermal overload 

does not occur for COLIPA-compliant 

solar simulators operated at or below a 

total irradiance limit of 1,500 W/m2. 

The comments added that the ‘‘out of 

band’’ specification is not possible with 

existing solar simulators and new 

systems would need to be designed, 

tested, manufactured, and distributed to 

provide equipment capable of meeting 

this specification. The comments 

concluded that replacing the ‘‘out of 

band’’ specification with a limit would 

improve the testing of all products, 

including high SPF products. 

FDA believes that it is important to 

limit total energy delivered to the skin 

during the SPF test so that skin 

temperature does not reach a point that 

may compromise dose reciprocity. FDA 

concurs with the comments and is 

proposing to replace the ‘‘out of band’’

specification in § 352.71 (proposed 

§ 352.70(b)) with a limit of 1,500 W/m2

on total solar simulator irradiance 

between 250 and 1,400 nm. 

(Comment 34) Two comments 

recommended that FDA change the 

solar simulator specification in § 352.71 

from ‘‘good beam uniformity (within 10 

percent) in the exposure plane’’ to ‘‘the 

delivered dose to the UV exposure sites 

be within 10 percent of the prescribed 

dose with good beam uniformity’’

(without defining ‘‘good beam 

uniformity’’). The comments contended 

that although ‘‘reasonable’’ or ‘‘good’’

beam uniformity is desirable, beam 

uniformity within 10 percent is virtually 

impossible to measure or achieve for the 

vast majority of solar simulators. 

FDA agrees that ‘‘dose’’ accuracy is a 

critical variable and the delivered dose 

to the UV exposure sites should be 

within 10 percent of the prescribed 

dose. Because FDA considers 

quantification of ‘‘good beam 

uniformity’’ to be an important issue, it 

is keeping a specification for this 

parameter. However, FDA believes that 

a specification of 20 percent is more 

achievable than the proposed 10 

percent. Beam uniformity can be 

measured with broadband UV detectors 

that have been modified to provide a 

small input aperture to the detector. For 

example, for a single beam simulator 

with a subsite exposure area of 

approximately 1 cm2, an appropriate 

input aperture would be 0.25 cm2. Beam 

uniformity can then be checked by 

making a measurement in the center of 

each of the four quadrants of the 

exposure field. These readings should 

be within 20 percent of the peak 

reading. The same principle can be 

applied to larger exposure fields. 

Additionally, the average of these four 

readings should be within 10 percent of 

the prescribed dose for a given exposure 

site. In addition, FDA is proposing a 

requirement that places a quantifiable 

limit of 20 percent on time related 

fluctuations of the radiation emissions 

of the solar simulator. 

Accordingly, FDA is proposing to 

revise portions of § 352.71 (proposed 

§ 352.70(b)(2)) to read as follows: 

(2) Operation. A solar simulator should 

have no significant time related fluctuations 

(within 20 percent) in radiation emissions 

after an appropriate warmup time and good 

beam uniformity (within 20 percent) in the 

exposure plane. The average delivered dose 

to the UV exposure site must be within 10 

percent of the prescribed dose. 

(Comment 35) Several comments 

recommended that the last sentence of 

§ 352.71 be modified to include 

additional requirements for the periodic 

testing of solar simulators. The 

comments suggested that periodic 

measurements be made twice a year and 

that measurements be done after 

changes in the optical filtering 

components. 

FDA agrees with the comments and is 

proposing to revise the last part of 

§ 352.71 (proposed § 352.70(b)(3)) to 

read as follows: 

(3) Periodic measurement. To ensure that 

the solar simulator delivers the appropriate 

spectrum of UV radiation, the emission 

spectrum of the solar simulator must be 

measured every 6 months with an 

appropriate and accurately calibrated 

spectroradiometer system (results should be 

traceable to the National Institute for 

Standards and Technology). In addition, the 

solar simulator must be recalibrated if there 

is any change in the lamp bulb or the optical 

filtering components (i.e., filters, mirrors, 

lenses, collimating devices, or focusing 

devices). Daily solar simulator radiation 

intensity should be monitored with a 

broadband radiometric device that is 

sensitive primarily to UV radiation. The 

broadband radiometric device should be 

calibrated using side by side comparison 

with the spectroradiometer at the time of the 

semiannual spectroradiometric measurement 

of the solar simulator. If a lamp must be 

replaced due to failure or aging during a 

phototest, broadband device readings 

consistent with those obtained for the 

original calibrated lamp will suffice until 

measurements can be performed with the 

spectroradiometer at the earliest possible 

opportunity. 

L. Comments on the Design/Analysis of 

SPF Testing Procedure 

(Comment 36) Several comments 

contended that the series of seven 

exposure doses in § 352.73(c) should be 

modified to eliminate the two doses 

placed symmetrically around the 

middle exposure. One comment 

provided data comparing the sevenexposure series against the fiveexposure series and concluded that the 

seven-exposure series did not increase 

the precision of the test (Ref. 66). 


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Comments also argued that the sevenexposure series would require longer 

testing times, thus increasing exposure 

risk and discomfort to subjects, and that 

the five-exposure series is as accurate as 

the seven-exposure series even at high 

SPF values. 

FDA discussed its rationale for seven 

versus five exposure doses in the TFM 

(58 FR 28194 at 28269 to 28272). FDA 

sought an exposure format that would 

provide better accuracy and precision to 

SPF measurements, particularly at 

higher SPF values. FDA reasoned that 

the seven-exposure series in § 352.73(c), 

with two additional exposures 

symmetrically placed around the 

middle exposure of the geometric series, 

would increase precision and eliminate 

possible overestimation of the true SPF 

value of a product with a high SPF. 

FDA has evaluated the data and other 

information submitted by the comments 

and agrees they demonstrate that the 

additional two exposure doses do not 

make the test more precise. Therefore, 

FDA is proposing to modify § 352.73(c) 

(proposed § 352.70(d)(3)) as follows: 

* * * Administer a series of five UV 

radiation doses expressed as J/m2-eff 

(adjusted to the erythema action spectrum 

calculated according to paragraph (d)(1) of 

this section) to the subsites within each test 

site on a subject using an accurately 

calibrated solar simulator. The five UV doses 

will be a geometric series as described in 

paragraph (d)(2) of this section, where the 

middle exposure represents the expected 

SPF. For products with an expected SPF less 

than 8, use exposures that are the product of 

the initial unprotected MED times 0.64X, 

0.80X, 1.00X, 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, use exposures that are the initial 

unprotected MED times 0.69X, 0.83X, 1.00X, 

1.20X, and 1.44X, where X equals the 

expected SPF of the test product. For 

products with an expected SPF greater that 

15, use exposures that are the initial 

unprotected MED times 0.76X, 0.87X, 1.00X, 

1.15X, and 1.32X, where X equals the 

expected SPF of the test product. * * * 

(Comment 37) Several comments 

suggested changes to the number of 

subjects per test panel in § 352.72(g). 

One comment suggested deletion of the 

phrase ‘‘with the number fixed in 

advance by the investigator.’’ The 

comment reasoned that if the first 20 

subjects provided data that can be 

evaluated, risk to human subjects could 

be curtailed by not impaneling another 

5 subjects. Other comments 

recommended using 10 to 20 subjects, 

arguing that the criterion for accuracy 

should not be the number of subjects, 

but the relative deviation of individual 

SPF measurements. One comment used 

absorbance instead of the SPF value to 

calculate the number of subjects 

required for high SPF products and 

proposed a binomial test method to 

reduce the number of subjects (see 

section III.I, comment 24 of this 

document). Another comment stated 

that the 20 of 25 subject limitation may 

be an issue for products with high SPF 

values due to the high variability in the 

responses obtained and suggested that 

the number of subjects be increased 

when evaluating sunscreen products 

with high SPF values. 

As discussed in section III.I, comment 

24 of this document, the binomial test 

method deserves further investigation 

and may prove to be a reasonable 

approach as additional data and 

experience become available. In 

addition, based on the current SPF test 

method, FDA agrees with the comment 

recommending deletion of the 

requirement to fix the number of 

subjects per panel in advance. This 

requirement is unnecessary because the 

panel is limited to a range of 20 to 25 

subjects (under current § 352.72(g)). 

Thus, if 20 subjects produce valid data 

in accordance with proposed 

§ 352.70(c)(9), then it would be 

unnecessary to test additional subjects. 

In addition, some subjects may not 

produce valid data in accordance with 

proposed § 352.70(c)(9) (e.g., no 

erythema produced), requiring testing of 

additional subjects (not exceeding 25 

subjects). FDA agrees that the number of 

subjects should be based on error about 

the mean SPF, but disagrees that the 

minimum number of subjects can be 

lowered to 10. As described later in this 

comment, FDA has reevaluated the 

proposed minimum number of subjects 

based on error about the mean SPF. 

FDA agrees with one comment that 

more subjects are needed when testing 

products with high SPF values. FDA 

believes that a minimum sample size of 

20 subjects is adequate for products 

with an expected SPF value of 30 or 

less. However, current data and 

experience with products having SPF 

values over 30 are not sufficient to 

determine an appropriate sample size. 

Therefore, to account for increased 

variability in SPF values for sunscreens 

with SPF values over 30, FDA proposes 

to increase the sample size to at least 25 

subjects. FDA invites data 

demonstrating an appropriate panel size 

for sunscreens with SPF values over 30. 

At this time, FDA is proposing to revise 

§ 352.72(g) (proposed § 352.70(c)(7)) as 

follows: 

(7) Number of subjects—(i) For products 

with an expected SPF value under 30. A test 

panel shall consist of 20 to 25 subjects with 

at least 20 subjects who produce valid data 

for analysis. Data are valid unless rejected in 

accordance with paragraph (c)(9) of this 

section. If more than 5 subjects are rejected 

based on paragraph (c)(9) of this section, the 

panel is disqualified, and a new panel must 

be created. 

(ii) For products with an expected SPF of 

30 or over. A test panel shall consist of 25 

to 30 subjects with at least 25 subjects who 

produce valid data for analysis. Data are 

valid unless rejected in accordance with 

paragraph (c)(9) of this section. If more than 

5 subjects are rejected based on paragraph 

(c)(9) of this section, the panel is 

disqualified, and a new panel must be 

created. 

In the 1978 advance notice of 

proposed rulemaking (ANPRM), the 

Panel recommended that studies enroll 

at least 20 subjects, adding that ‘‘the 

standard error shall not exceed ± 5 

percent of the mean’’ (43 FR 38206 at 

38261). Following publication of the 

ANPRM, FDA held a public meeting on 

January 26, 1988 (52 FR 33598 at 33600 

to 33601). During that meeting, 

attendees argued the following four 

points related to the number of subjects: 

1. Test panels should consist of at 

least 20 subjects. 

2. The size of the test panel should be 

fixed in advance. 

3. The limitation that the standard 

error should be less than ± 5 percent 

should not apply. 

4. The testing procedures should 

make it clear that the addition of 

subjects to the test panel to achieve the 

desired minimum is acceptable under 

specific conditions (58 FR 28194 at 

28267). 

In the 1993 TFM, FDA based § 352.72(g) 

on these comments and the Panel’s 

recommendation. 

The calculations of the sample size 

and confidence interval in § 352.72(g) 

are based on the assumption that there 

is a normal distribution about the mean 

(i.e., a bell curve). Based on this 

assumption, the t-test is used for 

statistical analysis. Based on the t-test, 

FDA calculated that a panel of 20 

subjects should result in an acceptable 

error about the mean. However, in some 

cases, a panel of 10 subjects would 

probably result in an error about the 

mean that is unacceptably large. There 

is inherently higher variability in testing 

and, consequently, larger error about the 

mean for products with high SPF 

values. Therefore, FDA believes a 

greater number of subjects is necessary 

when testing products with high SPF 

values. FDA believes a panel of 25 to 30 

subjects should result in an acceptable 

error about the mean for products with 

high SPF values. FDA invites additional 

data demonstrating adequate numbers of 

subjects, especially for products with 

high SPF values. 

(Comment 38) One comment stated 

that one factor affecting the SPF of a 


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product is the erythemal threshold of 

the skin, or MED(US). The comment 

argued that SPF decreases with 

increasing erythemal threshold. The 

comment maintained that, because 

MED(US) varies only with skin type, the 

MED(US) of each subject in a test group 

should be within reasonably similar 

limits. The comment suggested that the 

MED(US) of each subject should be 50 

to 150 percent of the median MED(US). 

The comment also suggested that 

subjects with an MED(US) that is twice 

the median should be excluded 

regardless of skin type. 

FDA is not proposing the revisions 

suggested by the comment. FDA based 

§ 352.73(b), which describes 

determination of an MED(US), on the 

Panel recommendation in the ANPRM. 

The procedure for determining 

MED(US) requires irradiation of subjects 

with a geometric series of UV doses. 

When developing this procedure, the 

Panel explained that the geometric 

series provides the same relative level of 

uncertainty independent of the subject’s 

sensitivity to UV light (i.e., independent 

of skin type) (43 FR 38206 at 38266). 

Thus, the Panel disagreed that skin type 

affects MED(US). The comment did not 

provide any data or other information 

demonstrating that skin type, in fact, 

affects MED(US). FDA is not aware of 

any data demonstrating this 

phenomenon. FDA will revise the 

proposed test criteria if we receive data 

or information demonstrating that the 

criteria are not appropriate or other 

criteria are more suitable. 

(Comment 39) Several comments 

urged FDA to reduce the minimum 1 

cm2 test subsite area in § 352.72(d)(2). 

One comment proposed the minimum 

test subsite area be decreased to 0.5 cm2. 

Two comments suggested that the test 

subsite area be defined by minimum 

diameters of 0.8 cm (circular area of 0.5 

cm2) and 0.15 cm (circular area of 0.017 

cm2), respectively. 

The comment supporting the 0.5 cm2

test subsite area referenced a study 

published in 1987 (Ref. 75) that was 

mentioned in relation to artificial light 

sources in comment 86 of the TFM (58 

FR 28258 to 28261). This study was 

designed to evaluate the FDA sequential 

technique of dosing using a single-port 

solar simulator (SPSS), a series 

sequential method using a multi-port 

xenon arc solar simulator (MPSS), and 

the Deutsches Institut fu ̈r Normung 

(DIN) simultaneous technique of dosing 

using an Osram Ultravitalux lamp. Five 

sunscreen formulations with SPF values 

from 4 to 15 were tested. The authors 

suggested that there was little 

systematic difference in estimates 

obtained using the SPSS and MPSS, but 

there was a large systematic deviation 

between the FDA and DIN methods. As 

this study was not designed specifically 

to compare irradiation areas, three 

different test subsite areas were used, 

and none was 0.5 cm2. FDA cannot 

determine the suitability of a 0.5 cm2

test subsite area compared to a 1 cm2

test subsite area based on this study. 

The comment advocating the 0.8 cm 

test subsite diameter argued that setting 

a lower area limit has the following four 

benefits: 

• Does not preclude the use of larger 

irradiation areas, 

• Will not affect the accuracy of 

resulting measurements, 

• Permits lower wattage lamps as 

well as liquid light guides that have 

apertures of 0.8 cm diameter, and 

• Provides more skin area for testing. 

The comment provided statistical 

analysis of a study comparing multi-port 

and single-port solar simulators (Ref. 

66). SPF 15 or SPF 4 products were 

tested along with the homosalate 

standard sunscreen. Two subsite areas 

were exposed to the multi-port solar 

simulator, and two were exposed to the 

single-port solar simulator. The 

comment concluded that similar SPF 

values are determined using the two 

types of solar simulators. However, the 

study report did not include details 

such as subject selection, product 

application, or specifications for the 

solar simulators. More importantly, the 

study report did not specify the size of 

each subsite. Thus, FDA cannot draw 

any conclusions regarding appropriate 

test subsite area from the submitted 

study. 

The comment supporting the 0.15 cm 

test subsite diameter referenced two 

studies (Ref. 76). Significant 

discrepancies in the information 

submitted for the first study prevented 

evaluation of this study. The comment 

did not submit full details of the second 

study. Therefore, FDA could not reach 

any conclusions from the submitted 

studies. 

FDA agrees, in principle, with the 

advantages of a smaller test subsite area. 

The Panel stated that, depending on 

instrumental design, irradiation test 

subsite areas less than 1 cm2 can be 

utilized and that test subsite diameters 

greater than 0.4 cm present no difficulty 

in determining skin erythema (43 FR 

38206 at 38260). While FDA does not 

consider the information provided by 

the comments adequate to support the 

suggested test subsite areas, it 

recognizes that considerable advances 

have been made since the Panel met. 

However, FDA requires data 

demonstrating that the monograph test 

produces valid and reproducible results 

using a smaller test subsite area before 

amending the monograph test. FDA will 

consider a reduction in test subsite area 

if adequate supporting data are 

provided. The studies should do the 

following: 

• Compare the smaller subsite area to 

1 cm2 on the same subjects, 

• Utilize high SPF products as well as 

products with SPF values below 15, and 

• Demonstrate comparable results 

among several laboratories. 

(Comment 40) Several comments 

either agreed or disagreed with the 

blinding procedures for the application 

of test materials described in 

§ 352.72(e). One comment stated that 

unblinded SPF testing is bad science, 

and that exposure sites within test areas 

should always be randomized no matter 

how many products are being tested. 

Another comment stated that the 

blinding procedure is an unnecessary 

complication and does not contribute to 

the accuracy of the test. One comment 

agreed that, in order to approximate true 

blinding, the individual who grades 

erythemal responses should not be the 

same clinician who applied the test 

materials. Another comment contended 

that it is not reasonable to randomly 

irradiate test sites with varying doses of 

UV radiation. One comment 

recommended making the use of finger 

cots optional because some product 

vehicles are incompatible with finger 

cot material. Another comment 

suggested that the amount of product 

remaining on the finger cot is a source 

of variability in the SPF test and 

suggested that the extent of this 

variability be fully evaluated. 

FDA agrees with the comments that 

favor blinding and randomization and is 

not proposing to remove the blinding 

and randomization requirements from 

§ 352.72(e) (proposed § 352.70(c)(5)). 

According to § 352.72, blinding and 

randomization is required only when 

two or more sunscreen drug products 

are being evaluated at the same time. 

Because a test product is always tested 

in conjunction with the standard 

sunscreen, FDA proposes to delete the 

statement, ‘‘If only one sunscreen drug 

product is being tested, testing subsites 

should be exposed to varying doses of 

UV radiation in a randomized manner.’’

Section 352.72(h) (proposed 

§ 352.70(c)(8)) specifies that the person 

who evaluates the MED responses must 

not be the same person who applied the 

sunscreen or administered the dose of 

UV radiation. The comments that 

disagreed did not provide evidence 

demonstrating that these requirements 

are unnecessary. 

With regard to the suggestion that the 

use of finger cots be made optional, the 


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Panel’s review of data found that 

numerous investigators have obtained 

more reproducible results by spreading 

a product using a finger cot than by 

spreading with a glass or plastic rod (43 

FR 38206 at 38261). FDA agrees with 

the comment that some formulations 

may be chemically incompatible with 

latex finger cots, but there are finger cots 

composed of other materials that should 

be compatible with these sunscreens. 

Therefore, to increase reproducibility in 

sunscreen application, FDA is 

proposing to revise the application 

requirement in § 352.72(e) (proposed 

§ 352.70(c)(5)) to read as follows: 

* * * Use a finger cot compatible with the 

sunscreen to spread the product as evenly as 

possible. Pretreat the finger cot by saturating 

with the sunscreen and then wiping off 

material before application. Pretreatment is 

meant to ensure that sunscreen is applied at 

the correct density of 2 mg/cm2. 

FDA urges manufacturers of sunscreen 

drug products to investigate the extent 

of variability in the SPF test that may be 

caused by various applicators. 

(Comment 41) One comment 

addressed illumination at the test site in 

§ 352.72(h) and recommended that a 

level of at least 1,000 lux be used. The 

comment contended that 450 to 550 lux 

is too low to provide adequate 

illumination for reading erythema. 

As discussed in the TFM, the Panel 

recommended an incandescent or warm 

fluorescent illumination source but did 

not specify a required illumination level 

(58 FR 28194 at 28269). In the TFM, 

FDA agreed with the Panel about the 

illumination source. FDA also proposed 

that the illumination level be 450 to 550 

lux. The comment did not provide any 

data to support its contention that 1,000 

lux is the appropriate illumination 

level. Thus, FDA is not revising the lux 

range in § 352.72(h) (proposed 

§ 352.70(c)(8)) at this time. FDA invites 

data and information on levels of 

illumination currently used to evaluate 

MED responses in SPF testing 

laboratories and will consider 

adequately supported alternatives. 

(Comment 42) One comment stated 

that the third sentence in § 352.73(b) 

should be modified to read: ‘‘* * * 

wherein each exposure dose is 25 

percent greater than the previous 

exposure dose to maintain the same 

relative uncertainty * * *.’’ The 

comment explained that defining the 

exposure dose in terms of ‘‘time’’ is 

incorrect. 

FDA discussed the Panel’s definition 

of dose in terms of time intervals in 

comment 84 of the TFM (58 FR 28194 

at 28256 to 28257). FDA stated that it is 

more accurate to express dose as the 

‘‘erythema-effective exposure,’’ in units 

that define the total amount of 

erythema-effective energy applied to the 

testing subsite (i.e., as J/m2). FDA 

discussed replacing ‘‘exposure time 

interval’’ with ‘‘erythema-effective 

exposure (dose),’’ but inadvertently 

used ‘‘exposure time interval’’ instead of 

‘‘dose’’ in § 352.73(b). FDA agrees that 

§ 352.73(b) (proposed § 352.70(d)(2)) 

should be modified and is amending 

this section as the comment suggested. 

(Comment 43) Several comments 

suggested an alternative statistical 

procedure for calculating product SPF 

values and PCD in current § 352.73(d). 

The comments argued that the 

procedure described in the FM would 

result in significant lowering of SPF 

values. The comments advocated 

clinical equivalency testing (i.e., using a 

lower one-sided 95 percent confidence 

interval or a one-sided t test, with a 

delta of 5 percent). The comments noted 

that an upper and lower bound 

equivalency procedure with a delta of 

20 percent would be an appropriate 

procedure. The comments added that 

SPF is not a precise value, but rather a 

valid estimate of product performance. 

Another comment suggested using the 

mean of the results to find the actual 

number and then round-off (either up or 

down) to the nearest whole number. 

FDA is not proposing to modify the 

calculation of product SPF values and 

PCD in § 352.73(d) (proposed 

§ 352.70(d)(4)) at this time. The distinct 

advantage of the t-test is that it provides 

a simple computational procedure for a 

statistical test that makes inferences 

about the population. The SPF is 

determined to be the largest whole 

number that is excluded by a lower onesided 95 percent confidence interval. 

Simply finding a mean value, as one 

comment suggested, is not adequate 

because such a value does not provide 

information about the validity of the test 

(e.g., standard deviation) that should be 

taken into consideration. 

FDA’s evaluation of the equivalency 

testing approach for calculating SPF 

values indicates the method is less 

stringent than the FM method. The 

proposed equivalency test is essentially 

testing the following hypothesis: 

H0: μ ≤ 0.95L versus Ha: μ > 0.95L 

where: H0 = null hypothesis 

Ha = alternative hypothesis 

μ = population mean 

L = confidence limit 

FDA acknowledges that the equivalency 

test may be a valid method for 

determining SPF. In many cases, the 

same SPF would be determined for a 

sunscreen using either the equivalency 

test or the FM method. However, in 

some cases, a higher SPF would be 

determined for a sunscreen using the 

equivalency test than would be 

determined using the FM method. By 

contrast, a higher SPF would never be 

determined for a sunscreen using the 

FM method than would be determined 

using the equivalency test. Thus, the FM 

method results in a more conservative 

SPF value than the equivalency test. 

FDA believes it is in the best interest of 

public health to label sunscreens with 

the more conservative SPF value. If FDA 

adopted the equivalency test after over 

30 years of using the FM method, 

consumers may, in some cases, 

overestimate the protection provided by 

a sunscreen based on a higher SPF 

number resulting from the equivalency 

test. 

M. General Comments on UVA Testing 

Procedure 

(Comment 44) Many comments 

discussed UVA radiation action spectra 

and skin damage (erythema, 

photocarcinogenesis, DNA damage, 

photosensitivity reactions, photoaging, 

mutagenicity, and immunosuppression). 

Some comments described various types 

of solar-induced skin damage and the 

wavelengths contributing to the specific 

biological events. Some comments 

stated that UVA II radiation (320 to 340 

nm) is much more damaging than UVA 

I radiation (340 to 400 nm). 

Other comments stated that there is 

presently no convincing evidence that 

the action spectra for damage from UV 

radiation have been clearly defined. One 

comment stated that until the separate 

dangers and risks of each portion of the 

UVB and UVA radiation action spectra 

are precisely and scientifically 

identified and quantified, FDA should 

consider the entire UVA radiation range 

as having significant biological risk. 

Another comment stated that protection 

against all UVA radiation wavelengths 

would seem to be both desirable and 

prudent considering the present state of 

our knowledge. 

FDA agrees that the action spectra for 

various harmful effects on human skin 

from chronic UVA radiation have not 

been clearly defined and that it may be 

misleading to associate damage with 

any specific action spectrum based 

upon current knowledge. Information 

provided by comments suggests a 

relatively greater role for UVA radiation 

than UVB radiation in long-term sun 

damage even though there is little 

consensus about the amount of UVA 

radiation protection required. Therefore, 

FDA is proposing UVA radiation test 

methods that assess protection 

throughout the UVA spectrum (see 

section III.N, comment 45 of this 

document). 


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N. Comments on UVA Testing 

Procedure Design and Testing Criteria 

(Comment 45) FDA is proposing that 

both an in vitro and an in vivo test be 

conducted to determine UVA radiation 

protection. The proposed in vitro test is 

the ratio of long wavelength UVA 

absorbance (UVA I) to total UV 

absorbance (i.e., UVB + UVA). The 

proposed in vivo test is the PPD test, 

which is similar to the SPF test except 

the endpoint is pigment darkening 

rather than erythema. FDA is proposing 

that UVA labeling consist of a UVA 

rating reflecting both the in vitro and in 

vivo test results. The rating will be the 

lowest ‘‘high’’ protection, then the 

sunscreen would be labeled as 

providing ‘‘medium’’ UVA protection. 

FDA is proposing these UVA testing 

requirements based on many comments 

submitted in response to the TFM that 

contained data and information on 

possible test methods (and 

combinations or modifications of these 

methods). The comments discussed the 

following in vivo and in vitro test 

procedures: 

• IPD, 

• PPD, 

• PFA, 

• Photosensitivity methods, 

• UVA radiation protection percent, 

• Diffey/Robson method and 

modifications of that method, 

• Standards Association of Australia, 

• Diffuse reflectance method, 

• Skin2 method, and 

• Psoralen photoadduct method. 

On May 12, 1994, FDA held a public 

meeting to discuss these UVA radiation 

testing procedures (Ref. 77). 

One comment suggested using either 

or both PPD and erythema skin 

responses to measure the UVA radiation 

protection effectiveness of OTC 

sunscreen drug products. The comment 

maintained that these two test methods 

have the following similarities: 

• Same UVA radiation source, 

• Same dose range, and 

• Similar post exposure time lags for 

observation. 

The only difference is in the skin types 

used, thus giving a variable balance in 

PPD and erythema responses. The 

comment added that such a 

combination of methods has the 

following advantages: 

• Reproducibility and stability, 

• Relevance, 

• Persistence of skin response 

through 1 to 24 hours, 

• Independence of source flux and 

accuracy, 

• Utilization for static as well as for 

water resistance photoprotective 

predictions, and 

• Practicability, convenience, and 

safety. 

Stating that there is currently no 

convincing evidence that the action 

spectrum for UVA radiation damage has 

been clearly defined, another comment 

suggested that protection from UV 

radiation be measured using two factors 

based on the degree of attenuation of UV 

radiation across the full spectrum. One 

factor, the SPF value, is erythemally 

weighted and gives an indication of the 

power of protection provided by the 

product. The second factor should take 

into account the shape of the 

transmittance curve measured by either 

in vivo or in vitro means. The comment 

stated that it is potentially dangerous to 

associate skin damage with any single 

action spectrum (e.g., IPD, PPD, or PFA). 

The comment argued that all of these 

indicators are wavelength-specific and 

protection from specific wavelengths 

does not mean protection from damage. 

The comment added that if only the 

erythema action spectrum is used, it 

virtually ignores the effects of 

wavelengths over 320 nm. The comment 

contended that using an SPF value 

augmented by the shape of the 

transmission curve would give 

consumers the information necessary to 

make an effective and safe judgment 

about the protection provided by a 

sunscreen drug product. For example, 

the comment noted that a product with 

a high SPF and a uniform high level of 

attenuation across the spectrum (i.e., 

equal attenuation at all UVB and UVA 

wavelengths) will provide the most 

protection. The comment added that, at 

a later date, if sufficient evidence 

becomes available to describe a credible 

UVA radiation damage spectrum, this 

combined system could be used by 

convoluting the attenuation curve with 

the action spectrum curve. 

One comment proposed a 

modification (‘‘critical wavelength’’) of 

the Diffey/Robson test method (Refs. 78 

and 79). The comment noted that, when 

people are outdoors, they are not 

exposed to only UVB or UVA radiation 

but are exposed to solar UV radiation, 

which always contains both. In 

addition, biological effects against 

which people may wish to be protected 

are caused by all wavelengths in the 

solar UV radiation spectrum. The 

comment contended that investigators 

should not be exposing subjects to 

sources of radiation with spectra that 

have no practical application and using 

irrelevant biological effects as endpoints 

(e.g., IPD). 

The comment proposed to assess the 

UVA radiation protection potential of an 

OTC sunscreen drug product by first 

spectrophotometrically determining the 

absorption spectrum of the product 

throughout the UV radiation range. 

Then, one calculates the wavelength 

value λc (the ‘‘critical wavelength’’), 

where the area under the absorption 

spectrum from 290 nm to λc is 90 

percent of the integral of the absorption 

spectrum from 290 to 400 nm, and uses 

a five-point scale to classify products as 

follows: 

TABLE 3.—BROAD SPECTRUM RATING BASED ON CRITICAL WAVELENGTH

Critical Wavelength 

(nm) 

Broad Spectrum 

Rating 

λc < 325 0 

325 ≤ λc < 335 1 

335 ≤ λc < 350 2 

350 ≤ λc < 370 3 

370 < λc 4 

The comment concluded that this test 

method makes no underlying 

assumptions about the form of action 

spectra for either acute or chronic 

photobiological damage. Because the 

efficiency of UV radiation to induce a 

given photobiological endpoint tends to 

decrease with increasing wavelength, 

the method utilizes wavelength 

intervals for classifying the ‘‘broad 

spectrum’’ rating, which increases in an 

approximately logarithmic manner. 

One comment submitted a protocol 

for the ‘‘critical wavelength’’ (CW) 

modification of the Diffey/Robson 

method for classifying the relative 

degree of UVA radiation protection of 

sunscreen drug products (Ref. 80). The 

comment addressed product 

photostability by pre-irradiation of the 

sunscreen product with a UV radiation 

dose corresponding to one-third the 

labeled SPF value. The comment 

reported recommendations based on the 

results of a round-robin evaluation of 

the proposed CW method involving six 

laboratories using four test sunscreen 

formulations with various substrates. 

The comment concluded that the CW 

method is a convenient, reproducible in 

vitro method for measuring the 

uniformity of sunscreen absorbance 

spectra across the UV radiation 

spectrum to classify products into broad 

UVA radiation protection categories. 

In response to the June 8, 2000, 

reopening of the administrative record 

for the rulemaking for OTC sunscreen 

drug products (65 FR 36319), FDA 

received additional comments on UVA 

radiation testing methods. While all 

comments supported some type of 

testing to differentiate the UVA 

radiation protection potential of 

sunscreen products, they disagreed 


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about the use of in vivo versus in vitro 

testing methods. 

Comments from a group of sunscreen 

product manufacturers contended that 

an in vivo test method, such as PPD or 

PFA, best describes the photoprotective 

characteristics of a sunscreen drug 

product. These comments stated that an 

in vivo method measures the actual 

effect of UVA radiation on the skin and 

estimates the expected product 

performance under actual use 

conditions. 

One comment presented test data that 

suggested PPD and PFA values are 

comparable (Ref. 6). The comment 

stated that an advantage of the PFA 

method is that it allows inclusion of 

skin type I, whereas the PPD test is 

conducted on darker skin types (II and 

III). However, the comment added that 

the PPD test has been accepted since 

1996 by the JCIA for the assessment of 

UVA radiation protection efficacy of 

sunscreen products. 

One comment contended that the PPD 

test should be used for the following 

reasons: 

• It requires a relatively low dose of 

UV radiation. 

• The reaction is stabilized in 2 to 4 

hours. 

• The test subject is left with no mark 

of irradiation and receives little or no 

injury. 

• The test can be conducted with 

high precision. 

Another comment stated that PPD 

values demonstrate the same correlative 

benefits that exist for SPF values and, 

therefore, do not give false impressions 

of magnitude. Another comment stated 

that products with the same SPF can 

have different levels of UVA radiation 

protection. Thus, PFA or PPD is not 

redundant with the SPF value. 

Comments from other sunscreen 

product manufacturers opposed an in 

vivo method to determine UVA 

radiation protection. One of these 

comments stated that in vivo tests 

expose human subjects to doses of UVA 

radiation with unknown human health 

consequences. The comment added that 

because exposure to UVA radiation 

alone is never encountered in nature, 

full spectrum light is most relevant for 

product evaluations. This comment 

contended that PFA values are 

redundant with SPF testing because of 

an overemphasis on short wavelength 

UVA radiation (UVA II), and PFA values 

give a false impression of the magnitude 

of absorption differences. For example, 

the comment stated that two products 

with PFA values of 5 and 10 may 

attenuate 80 and 90 percent of UVA 

radiation, respectively. Thus, the real 

difference is small. The comment 

further stated that the proposed in vivo 

methods modeled after the SPF test 

generate protection factors that are 

protocol dependent and of 

indeterminate clinical relevance, as 

none are surrogates for long term 

concerns like cancer and photoaging. 

Another comment added that the PPD 

and PFA tests do not adequately assess 

the breadth of UVA radiation protection 

and that the biologic effects of full 

spectrum UV radiation differ from the 

effects of isolated wavelengths. 

Several comments recommended 

using an in vitro method, and most 

considered the CW method as 

appropriate. One comment stated that 

CW allows for broad spectrum activity 

regardless of SPF so that, if consumers 

use a low SPF product, they will at least 

have the option of choosing one that 

provides a wide breadth of activity. 

Another comment stated that CW 

provides a simple, reproducible, and 

adaptable method that can account for 

sunscreen photostability and insure 

UVA radiation protection that is both 

commensurate with and independent 

from the SPF value. Another comment 

added that CW accounts for 

proportionality because, in order for a 

sunscreen to maintain a given CW, 

protection from both long and short 

UVA radiation wavelengths must 

increase as UVB radiation protection 

increases. 

Several comments stated that the CW 

threshold should be 370 nm for a ‘‘broad 

spectrum’’ claim on a sunscreen. Other 

comments recommended a threshold of 

360 nm. One comment stated that if 

FDA were to arbitrarily select a standard 

higher than 360 nm, it would cause a 

major reformulation effort within the 

industry, higher prices to consumers, 

and a shortage of ‘‘broad spectrum’’

products in the OTC marketplace. The 

comments did not provide data to 

support the use of a specific threshold 

number in relation to the prevention of 

specific photobiological effects. 

Other comments opposed the CW 

method as not appropriate. One 

comment, which favored an in vivo 

method, stated that the CW method, 

based on an arbitrary, nonbiological 

criterion, fails to provide an accurate 

measure of the protection efficacy of a 

sunscreen product. This comment 

provided data to demonstrate that a 

significant failure of the CW method is 

its inherent inability to differentiate 

UVA radiation protection levels of 

sunscreen products relative to biological 

endpoints (e.g., premature skin aging) 

(Ref. 23). A second comment agreed 

with this assertion, while a third 

comment expressed concern that CW 

measurements may be misleading 

because two products can have the same 

CW with very different UVA radiation 

absorbance curves and, thus, provide 

different protection for consumers. 

Some comments stated that a 

combination of methods may be 

appropriate for assessing the complete 

UVA radiation protection potential of a 

sunscreen product. One comment 

suggested combining either the PPD or 

PFA method with an in vitro method for 

a meaningful and rigorous test of both 

the magnitude and breadth of the 

biological protection (i.e., the level of 

protection and the UVB and UVA 

wavelengths that are protected against) 

provided by a sunscreen product. 

Another comment stated that complete 

assessment of a sunscreen product’s 

UVA radiation protection must include 

both of the following: 

• An in vitro measurement of the 

absorbance above 360 nm (i.e., 

demonstrate adequate breadth of 

absorbance), and 

• An in vivo measurement of the 

quantity of UV radiation protection (i.e., 

demonstrate adequate magnitude of 

absorbance). 

Other comments stated that a 

combination of the in vivo SPF method 

and the in vitro CW method provide a 

complete description of a product’s 

inherent photoprotective characteristics 

with the SPF value describing the 

amplitude of protection and CW 

providing a reliable measure of the 

product’s spectral absorption capability. 

One comment suggested a UVA/UVB 

radiation proportionality scheme. The 

comment referred to FDA’s previous 

discussions about UVA/UVB radiation 

proportionality (Refs. 11 and 81) and a 

recommendation from the AAD that ‘‘an 

increase in SPF of a sunscreen must be 

accompanied by a proportional increase 

in the UVA protection value’’ (Ref. 82). 

The comment added that the 

proportional contribution to sunburn 

from solar UVB and UVA radiation is 80 

to 20 (4 to 1), respectively, and that this 

relationship gives the minimum UVA 

radiation attenuation needed to provide 

proportional UVA/UVB radiation 

protection for any SPF value. The 

comment concluded that a minimum 

UVA protection value of 2 should be 

required even at low SPF levels with 

proportionately higher UVA protection 

values for higher SPF values. 

One comment suggested that the UVA 

protection value should be determined 

with an in vivo method while CW is 

appropriate to determine spectral 

broadness. Another comment stated that 

CW accounts for proportionality 

because both long and short UVA 

radiation protection must increase as 

UVB radiation protection increases in 


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order for a sunscreen to maintain a 

given CW. Another comment provided 

data (Ref. 23) for two products with the 

same CW value but different SPF values 

and concluded that the product with the 

higher SPF value did not provide greater 

UVA protection. Other comments stated 

that there is no biological basis for 

establishing strict UVB/UVA radiation 

proportionality and that the 

establishment of this kind of ratio is 

arbitrary. 

The AAD (Ref. 83) referenced an 

international consensus conference on 

UVA radiation protection of sunscreens 

and recommended the following: 

1. Both an in vitro and an in vivo 

testing method must be used to measure 

UVA radiation protection. 

2. CW is the preferred method of in 

vitro testing for a broad spectrum claim 

(with a threshold for this claim at 370 

nm). 

3. CW must be combined with an in 

vivo method such as either PPD or PFA. 

4. There must be a minimum four-fold 

increase in PPD or PFA value in the 

presence of a sunscreen (relative to the 

absence of sunscreen). 

In the Federal Registers of May 12, 

1993 (58 FR 28194 at 28248 to 28250), 

September 16, 1996 (61 FR at 48645 at 

48652), and October 22, 1998 (63 FR 

56584 at 56587), FDA discussed 

photosensitivity and erythemal UVA 

radiation testing procedures for OTC 

sunscreen drug products. Criteria 

discussed for UVA radiation claims 

included the requirement for an 

absorption spectrum extending to 360 

nm or above, plus the demonstration of 

meaningful UVA radiation protection 

via testing procedures. IPD/PPD, PFA, 

photosensitivity, and in vitro UVA 

radiation testing methodologies were 

also discussed at a public meeting on 

May 12, 1994 (Ref. 77). 

The selection of an appropriate UVA 

radiation testing procedure for OTC 

sunscreen drug products has been 

difficult for a number of reasons. The 

scientific community does not agree on 

which testing procedure is most 

appropriate. For example, Cole 

discusses the virtues and shortcomings 

of a variety of in vivo and in vitro test 

methods (Ref. 84). In addition, each test 

procedure has its own distinct 

advantages and disadvantages, as 

discussed in the following paragraphs. 

FDA believes the IPD test method 

provides an appropriate endpoint for 

determining UVA protection, because 

pigment darkening is caused primarily 

by UVA (and not UVB) radiation. This 

method is advantageous over other 

suggested test methods in that it uses 

low doses of radiation and, therefore, 

exposes subjects to less risk than other 

suggested test methods. On the other 

hand, the IPD response has not been 

shown to represent a direct or surrogate 

endpoint for biological damage. The IPD 

response is also extremely difficult to 

read. 

The PFA test method uses endpoints 

that reflect actual damage that can occur 

to normal skin as a result of UVA 

radiation exposure (i.e., erythema or 

tanning). The erythema action spectra 

may be similar to the action spectra of 

known chronic skin damage (e.g., solar 

elastosis) (Ref. 85). However, the PFA 

test method may not determine 

protection against skin melanoma or 

other skin damage thought to be caused 

by chronic exposure to UVA radiation 

(Refs. 29 and 86). 

The CW method can assess how 

broadly a sunscreen can absorb across 

the UV radiation spectrum, but provides 

no information concerning product 

performance after interaction with 

human skin. While in vivo methods to 

assess UVA radiation protection may 

have possible sources of variability 

similar to the SPF test (e.g., test product 

application, differences in light sources, 

etc.), in vitro methods also possess 

possible sources of inherent variability 

(e.g., test product evaporation time, 

substrate orientation, instrumentation, 

use with color change sunscreen 

formulations, etc.). 

In general, FDA would prefer the 

standard UVA radiation test method to 

have a clinically significant endpoint. 

After reviewing the data and 

information provided by the comments, 

FDA agrees that there is no convincing 

evidence that the action spectra for all 

possible types of UVA-induced damage 

have been clearly defined and that no 

one method is without disadvantages. 

At this time, FDA agrees with the 

recommendation provided by the AAD 

and other comments that an in vivo 

method is appropriate in combination 

with an in vitro testing method to assess 

the UVA radiation protection. 

Because the action spectrum for UVAinduced skin damage is not clearly 

known, FDA considers it necessary to 

measure both the magnitude and 

breadth of UVA protection. The 

magnitude of UVA absorbance is a 

measure of how well a product absorbs 

UVA radiation. The magnitude of UVA 

absorbance is best measured by an in 

vivo method. An in vivo method 

measures a biological response on the 

skin (e.g., pigment darkening) and, 

therefore, correlates to actual use 

conditions. The breadth of the UVA 

absorbance is a measure of how broadly 

a product absorbs UVA radiation across 

the entire UVA radiation spectrum. 

Breadth can best be determined by 

appropriate in vitro test methods. 

At this time, FDA believes a 

combination of existing in vivo and in 

vitro UVA radiation testing methods 

addresses the inadequacies of either 

method when used alone and provides 

a more complete UVA radiation 

attenuation profile for use in labeling 

OTC sunscreen drug products. 

Requiring the two test methods will 

ensure that both the magnitude and 

breadth of UVA protection is 

determined. As discussed later in this 

response, the proposed UVA labeling 

will reflect the results of both tests and, 

therefore, will reflect magnitude and 

breadth of UVA protection. FDA 

believes that the methods and labeling 

currently being proposed provide the 

best assurance for consumers to receive 

adequate protection across the entire 

UVA radiation spectrum. 

FDA is proposing the PPD method as 

the in vivo part of the test to determine 

UVA radiation protection of a sunscreen 

drug product. This test assesses UVA 

radiation attenuation by measuring UVA 

radiation-induced tanning, a direct 

effect induced by UVA exposure. The 

PPD test is relatively easy to perform 

and relies on a stable, biological 

endpoint that can describe the 

magnitude of UVA radiation protection 

of sunscreen products. It is similar to 

the SPF determination as it is a ratio of 

a minimum pigmenting dose (MPD) on 

unprotected skin to that on protected 

skin. The endpoint is the PPD response, 

which is the stable, lasting residual part 

of the immediate pigment darkening or 

blue gray pigment that develops 

immediately during exposure to UVA 

radiation and quickly fades at the end 

of exposure. It provides consumers with 

a means to specifically compare the 

amount of UVA radiation protection 

between products and select an 

appropriate sunscreen product. The PPD 

test has been shown to produce reliable, 

reproducible data and to distinguish 

between varying levels of UVA radiation 

attenuation (Refs. 87 and 88). It has been 

shown to detect protection provided by 

‘‘broad spectrum’’ sunscreens against 

both short and long wavelength UVA 

radiation. The endpoint is a stable skin 

response that is linearly dependent on 

the amount of UVA radiation that enters 

the viable epidermis. FDA also agrees 

with one comment that a UVA 

protection value of 2 should define the 

lowest end of acceptable PPD test 

results relative to the consideration of 

acceptable UVA radiation claims (see 

proposed § 352.72(d)(3)). FDA considers 

it desirable to incorporate measurable 

UVA radiation protection at all SPF 


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levels for products that claim to protect 

against both UVB and UVA radiation. 

As one comment noted, the PPD test 

has been accepted and validated as the 

JCIA method since 1996 (Ref. 23) and is 

one of two in vivo methods suggested by 

the AAD (Ref. 83). Although data 

provided to FDA indicate that the PPD 

and PFA in vivo tests provide 

comparable results (Ref. 6), the PPD test 

provides the practical benefit of a 

shorter post exposure reading time. FDA 

agrees with the comments that PPD 

values are not redundant with SPF 

values as sunscreen drug products with 

the same SPF value can have very 

different levels of UVA radiation 

protection as measured by the PPD test. 

Accordingly, FDA is including the PPD 

method in proposed § 352.72 as part of 

the testing to determine the UVA 

radiation protection potential of an OTC 

sunscreen drug product. 

FDA agrees with the comments that 

suggested modifications to the PPD 

method (i.e., the JCIA standard). 

Therefore, FDA is proposing 

modifications to the PPD method. One 

group of sunscreen manufacturers 

suggested that the previously validated 

‘‘high SPF’’ padimate O/oxybenzone 

standard sunscreen under consideration 

by FDA (see section III.J, comment 27 of 

this document) should also be used as 

the control formulation for in vivo UVA 

radiation testing (Ref. 6). Based upon 

data provided by the comment, FDA is 

proposing the referenced ‘‘high SPF’’

padimate O/oxybenzone standard 

sunscreen for use as the standard 

sunscreen in the in vivo UVA radiation 

test in proposed § 352.72. FDA invites 

comment on the suitability of this 

formulation as a UVA radiation test 

standard, on alternative standards, and 

on preparation/assay/validation data for 

any suggested alternatives. 

FDA also notes that the JCIA light 

source specification states that ‘‘UV rays 

shorter than 320 nm shall be excluded 

through the use of an appropriate filter.’’

FDA considers it important to set an 

exact limit for this specification and is 

proposing that optical radiation from 

the light source between 250 and 320 

nm be less than 0.1 percent of the 

optical radiation between 320 and 400 

nm. Also, the observation of pigment 

darkening in the JCIA standard is at 2 

to 4 hours post irradiation. FDA notes 

that it appears the pigment darkening is 

most stable about 3 hours or more after 

post irradiation (Ref. 89), and is thus 

proposing that this observation occur at 

3 to 24 hours post irradiation. This time 

range provides increased flexibility in 

the test method without sacrificing 

accuracy. 

As the current state of technology 

allows for an instrumental 

measurement/quantification of skin 

color via spectral reflectance, FDA also 

invites comments regarding colorimetry 

as a method of evaluating pigment 

darkening. By avoiding the subjectivity 

of detecting pigment change by the 

human eye, the reproducibility of the 

PPD method should increase. 

Colorimetry could likewise be used in 

SPF testing if submitted data 

demonstrated increased accuracy and 

reproducibility of colorimetry over 

visual inspection. 

As the PPD method is similar, overall, 

to the SPF method, FDA is also 

proposing that the directions for the 

PPD method be similar to those for the 

SPF test for determining MPDs on 

unprotected skin, individual UVA 

protection factors, test product UVA 

protection factors, and PCDs. Further, as 

discussed in section III.L, comment 37 

of this document regarding the SPF test, 

FDA is proposing that a PPD test panel 

consist of 20 subjects who produce valid 

data, similar to the panel size for 

sunscreens having SPF values less than 

30. 

FDA is concerned, however, that use 

of the PPD method alone could result in 

some products yielding high UVA 

radiation protection factors without 

having broad absorbance throughout the 

UVA radiation spectrum due to strong 

absorbance in the UVA II region. In 

other words, a sunscreen could absorb 

high levels of UVA II but very little 

UVA I and achieve a high UVA rating 

under the PPD method. Therefore, FDA 

is proposing that an in vitro method be 

used (to assess the breadth of 

absorbance across the UV radiation 

spectrum) in conjunction with the PPD 

method to more completely assess a 

product’s UVA radiation protection. 

FDA disagrees with the comments 

that the CW method should be used as 

the in vitro testing method and proposes 

using a modification of the Boots 

adaptation of the Diffey/Robson method 

(Ref. 90). Both the CW and the in vitro 

test proposed by FDA measure the 

absorbance of a sunscreen product using 

in vitro spectrophotometry. However, 

FDA’s proposed method calculates the 

ratio of long wavelength UVA 

absorbance (UVA I) to total UV 

absorbance to provide a measure of the 

relative UVA I radiation protection 

provided by a sunscreen drug product. 

FDA believes that this test, in 

combination with the PPD method, 

provides a better assessment of overall 

UVA radiation protection. 

The Boots adaptation of the Diffey/ 

Robson test method assesses the 

absorbance of a sunscreen drug product 

over the UV radiation range from 290 to 

400 nm by measuring the quantity of UV 

radiation transmitted through surgical 

tape (TransporeTM tape) before and after 

application of a sunscreen drug product. 

The test product (2 mg/cm2) is applied 

to the textured surface of the 

TransporeTM tape. A xenon arc solar 

simulator is used as the UV radiation 

source. Transmitted UV energy is 

collected and measured at 5 nm 

intervals over the UVB and UVA 

radiation range, which provides a 

profile of UV radiation absorbance. 

Mathematical calculations are made 

separately of the areas under the UVB 

and UVA radiation parts of the curve. 

The ratio below the curve is determined 

as follows: 

As the ratio increases, the degree of 

UVA radiation protection increases. 

FDA is concerned that this method, as 

described in previous paragraphs, 

determines the ratio of the entire UVA 

to UVB radiation spectra. Therefore, a 

sunscreen drug product that absorbs 

strongly in the UVA II radiation area, 

but does not absorb strongly in the UVA 

I radiation area, might still have an 

adequate ratio of UVA to UVB radiation 

protection to fulfill the test 

requirements, but would not provide 

adequate protection in the UVA 

radiation region where absorbance is 

lacking. FDA believes that this 

deficiency can be corrected by revising 

the calculations to take into account the 

ratio of UVA I and/or UVA II 

individually to UV radiation. Some 

comments were concerned that UVA II 

radiation may be the portion of the UVA 

spectrum most represented in the PPD 

test. FDA agrees that the UVA II 

spectrum is well represented by the PPD 

test. Therefore, to provide for a more 

balanced method, FDA is proposing that 

the in vitro component of the 

monograph UVA radiation method only 

need provide a measure of the relative 

UVA I radiation absorbance. 

FDA is proposing to measure UVA I 

radiation absorbance relative to UV 

radiation absorbance rather than relative 

to UVB radiation absorbance. If UVA I 

radiation protection is measured relative 

to UVB radiation, then the test does not 

account for UVA II radiation protection. 

FDA’s proposed modification of the 

Boots adaptation of the Diffey/Robson 

method accounts for the entire UV 

radiation spectrum. Further, the ratio of 

UVA I radiation to UV radiation has a 

convenient finite range and allows for 

the use of defined values to categorize 

UVA radiation protection. 


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FDA is proposing a modified Boots 

adaptation of the Diffey/Robson method 

instead of the CW method. The CW 

determination only reveals the shortest 

wavelength at which 90 percent of total 

UVB and UVA radiation is absorbed by 

a sunscreen. Thus, this method does not 

directly reveal the breadth of UV 

absorption, whereas the modified Boots 

adaptation of the Diffey/Robson method 

does. This point is demonstrated by data 

submitted by one comment (Ref. 23). 

The comment submitted the UV 

absorption spectra of two sunscreens 

having nearly identical SPF and CW 

values. The absorption spectra 

demonstrate that two sunscreens with 

similar CWs can have significantly 

different UVA absorption spectra. The 

ratios of UVA I/UV radiation absorbance 

for these formulations were markedly 

different: 0.85 and 0.52. Thus, FDA 

believes that the ratio method generally 

allows for better discrimination of 

products with these types of absorbance 

spectra. 

FDA is also concerned that the 

activity of the sunscreen ingredients in 

the product may be diminished by 

exposure to UV radiation, i.e., that the 

sunscreen ingredients in the product 

might not be photostable. Therefore, in 

order to account for changes in 

absorbance as a function of UV radiation 

exposure, FDA is proposing to revise the 

Boots modification of the Diffey/Robson 

method by incorporating pre-irradiation 

dose (PID), which is defined as follows 

(see section III.O, comment 46 of this 

document): 

PID (J/m2-eff) = SPF * 1 MED * 2/3, 

where 1 MED = 200 J/m2-eff 

FDA is also concerned about 

specifying the use of TransporeTM tape 

(used in the original Diffey/Robson 

method), an artificial substrate that 

mimics the surface topography of 

human stratum corneum. When 

sunscreen emulsions are applied to 

TransporeTM tape (Refs. 7 and 77), the 

emulsions may experience a micro 

environment that differs from human 

skin in several key aspects, including 

the following: 

• Lack of electrolyte effect, 

• Lack of moisturization/humectant 

plasticization of the substrate, 

• Differences in pH and wetting 

effects, and 

• Different degrees of sunscreen 

penetration and retention by the 

substrate. 

The fourth aspect, different degrees of 

penetration and retention, is especially 

significant for oil soluble sunscreen 

ingredients. One comment suggested 

that either roughened quartz plates or a 

synthetic collagen should be used as the 

substrate, noting that COLIPA has used 

quartz plates for its in vitro studies and 

that quartz plates are reusable and inert. 

Diffey et al. have also used quartz plates 

as the substrate for the CW method (Ref. 

91). Accordingly, at this time, FDA is 

proposing that roughened quartz plates 

be specified as the substrate in the in 

vitro portion of its UVA test method. 

FDA requests comment regarding the 

suitability and availability of quartz 

plates and other possible substrates. 

FDA agrees with one comment that 

there is no biological basis for 

establishing a strict UVA to UVB ratio 

and that such a ratio would be arbitrary. 

FDA is proposing that data from the 

proposed in vitro and in vivo tests be 

integrated into a single labeled UVA 

rating. Similar to suggestions from some 

comments, FDA is proposing the 

categories of low, medium, high, and 

highest (corresponding to one, two, 

three, and four ‘‘stars,’’ respectively). 

Based on test data submitted by one 

comment (Ref. 6), FDA is proposing that 

test results for each in vitro or in vivo 

test be categorized as follows: 

TABLE 4.—UVA RATING CATEGORIES

Category In vitro result In vivo result 

Low 0.2 to 0.39 2 to under 4 

Medium 0.40 to 0.69 4 to under 8 

High 0.70 to 0.95 8 to under 12 

Highest greater than 0.95 12 or more 

FDA is aware of the difficulty for 

current sunscreen formulations to meet 

the ‘‘highest’’ category and believes that 

allowing such a category will foster 

additional research and development in 

this area. 

FDA is proposing that the overall 

UVA radiation category for use in 

product labeling be the lowest category 

determined by the in vitro and in vivo 

test results. For example, if the test 

results for a sunscreen indicate an in 

vitro category of ‘‘low’’ and an in vivo 

category of ‘‘high’’ (or the reverse), then 

the overall UVA classification on the 

sunscreen product label would be ‘‘low’’

(i.e., the lower of the two categories). 

FDA believes that using the lower of the 

two categories takes into account the 

following situations: 

• A product that has a high in vivo 

rating because of substantial UVA II 

absorbance, but a low in vitro rating 

because of poor UVA I absorbance, or 

• A product that has a low in vivo 

rating because of poor UVA II 

absorbance, but a high in vitro rating 

because of substantial UVA I 

absorbance. 

FDA is further proposing that each 

overall UVA radiation category 

correspond to and (on product labeling) 

be used with the following number of 

graphical representations in the form of 

solid ‘‘stars’’: 

TABLE 5.—GRAPHICAL UVA RATING

BASED ON CATEGORY

Combined Category Rating Star 

Rating 

Low ★✰✰✰ 

Medium ★★✰✰ 

High ★★★✰ 

Highest ★★★★ 

FDA invites comment on these 

proposed test methods/criteria and 

encourages the continued development 

of biologically meaningful test 

procedures. 

O. Comments on the Photostability of 

Sunscreen Drug Products 

(Comment 46) Various comments 

discussed the photostability of OTC 

sunscreen formulations and active 

ingredients. One comment stated that 

photostability is important because 

many sunscreen ingredient 

combinations with avobenzone are not 

believed to be photostable. This 

comment stressed that a sunscreen drug 

product should maintain most of its 

UVA and UVB radiation protection 

throughout the expected consumer time 

in the sun. Another comment stated that 

the integrity of a sunscreen drug 

product depends on its degree of 

photostability and that a photostable 

product should maintain its protection 

over a wide range of UV radiation 

spectra. 

Some comments supported a standard 

method using pre-irradiation to account 

for photostability of sunscreen 

ingredients. One comment favoring the 

CW method for measuring UVA 

radiation protection submitted a 

formula to establish a pre-irradiation 

dose to assess photostability (Ref. 7). 

This comment stated that pre-irradiation 

provides a reasonable estimate of what 

a consumer might expect when using 

the product and stressed that the dose 

should be both full spectrum (290 to 400 

nm) and sufficient to detect significant 

changes in CW as a function of UV 

radiation exposure. This comment 

considered its pre-irradiation dose of 

solar-simulated UV radiation to be 

equivalent to about 1 1/2 hours of 

noonday sun or 3 hours of sun exposure 

in the early morning or late afternoon. 

One comment noted that avobenzonecontaining formulations can be 

photostabilized by the addition of 

suitable ingredients and supported a 

protocol developed by Sayre and Dowdy 

for measuring UVA radiation protection 


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following a measured exposure of the 

test formulation to solar radiation (290 

to 400 nm) (Ref. 92). 

Another comment stressed the 

importance of a standard pre-irradiation 

dose and included data suggesting that 

a ‘‘UVB-only’’ sunscreen product 

formulation, at high pre-irradiation 

doses, could qualify for UVA ‘‘broad 

spectrum’’ labeling by the CW method 

(Ref. 23). This comment concluded that 

pre-irradiation does not always account 

for photostability and appears to be very 

formulation specific. 

Another comment submitted an in 

vitro method for simultaneously 

predicting SPF and assessing 

photostability of sunscreen formulas 

(Ref. 65). The comment stated that preirradiation with measured UV radiation 

doses has permitted more accurate in 

vitro estimates of SPF. 

FDA agrees that it is important to 

address the photostability for sunscreen 

drug product formulations. Unstable 

product formulations present the 

problem of degradation of product 

effectiveness during actual use. The 

assessment of overall protection 

provided by such formulations is 

difficult due to product effectiveness 

being heavily dependent on the UV 

radiation exposure dose. Sayre and 

Dowdy demonstrated, through a series 

of in vitro studies, how the UV radiation 

transmission of an avobenzone 

containing formula changes with UV 

radiation exposure and that most of the 

loss of protection occurred in the UVA 

radiation spectrum (Ref. 92). 

FDA is proposing to address 

photostability by adding a preirradiation step to the in vitro test 

method for measuring UVA radiation 

protection (see section III.N, comment 

45 of this document). As noted in the 

scientific literature, the choice of a pre 

irradiation dose is ‘‘somewhat arbitrary, 

yet critical to the outcome of the test’’

(Ref. 84). FDA received one comment 

with supporting data for a proposed preirradiation dose (Ref. 7). The comment 

suggested using a dose equivalent to the 

SPF times 2 J/cm2 multiplied by a factor 

of 2/3. The comment stated that 2 J/cm2

from a xenon arc solar simulator with 1 

millimeter (mm) WG-320 and 1 mm UG5 filters was equivalent to one MED. 

Because all solar simulators used by the 

industry may not use this exact filter 

combination and the spectral 

transmittance of filters can vary from lot 

to lot, FDA is proposing to specify the 

pre-irradiation dose in terms of 

‘‘erythemal effective dose.’’ The 

erythemal effective dose of a solar 

simulator can by calculated as described 

in proposed § 352.70(d) by weighting 

the output spectrum of the solar 

simulator with the reference action 

spectrum for erythema as defined by 

CIE. A typical weighted value (J/m2-eff) 

for an MED in a Skin Type II individual 

is 200 J/m2-eff (Ref. 93). Thus, FDA is 

proposing to use the following formula 

to determine the required preirradiation dose: 

PID (J/m2-eff) = SPF * 1 MED * 2/3 

where 1 MED = 200 J/m2-eff 

In considering the selection of the 

appropriate pre-irradiation dose of 

solar-simulated UV radiation, FDA 

agrees that the maximum pre-irradiation 

exposure would be a dose of UV 

radiation that equaled the SPF of the 

product times the MED. However, FDA 

believes that this calculated dose is 

probably greater than the dose that a 

sunscreen product would incur during 

typical consumer usage. Thus, the dose 

was reduced by a factor of one-third to 

represent a more reasonable exposure 

condition. 

IV. FDA’s Tentative Conclusions and 

Proposals 

FDA tentatively concludes that the 

FM for OTC sunscreen drug products 

should be amended to include the 

combinations of avobenzone with 

ensulizole and avobenzone with zinc 

oxide when used in the concentrations 

established for each ingredient in 

§ 352.10 (see section III.C, comment 7 of 

this document). However, before 

marketing may begin, the comment 

period for this proposal must end and 

FDA must publish another Federal 

Register notice setting forth our 

determination concerning interim 

marketing before publication of the final 

rule for OTC sunscreen drug products. 

FDA followed this procedure previously 

for avobenzone as a single active 

ingredient and in combination with 

some GRASE active ingredients other 

than ensulizole or zinc oxide (62 FR 

23350). 

FDA considers the UVA-related 

labeling in this proposal to supersede 

the labeling proposed in the TFM and 

its amendments of September 16, 1996, 

and October 22, 1998. While the prior 

proposed labeling can continue to be 

used until a FM is issued, FDA 

encourages manufacturers of OTC 

sunscreen drug products to voluntarily 

implement the UVA-related labeling 

changes as soon as possible after 

publication of this proposal, especially 

if product relabeling occurs in the 

normal course of business. We note, 

though, that any relabeling prior to 

issuance of the FM is subject to the 

possibility that FDA may change some 

of the labeling requirements as a result 

of comments filed in response to this 

proposal. 

Mandating warnings in an OTC drug 

monograph does not require a finding 

that any or all of the OTC drug products 

covered by the monograph actually 

caused an adverse event, and FDA does 

not so find. Nor does FDA’s requirement 

of warnings repudiate the prior OTC 

drug monographs and monograph 

rulemakings under which the affected 

drug products have been lawfully 

marketed. Rather, as a consumer 

protection agency, FDA has determined 

that warnings are necessary to ensure 

that these OTC drug products continue 

to be safe and effective for their labeled 

indications under ordinary conditions 

of use as those terms are defined in the 

act. This judgment balances the benefits 

of these drug products against their 

potential risks (see 21 CFR 330.10(a)). 

FDA’s decision to act in this instance 

need not meet the standard of proof 

required to prevail in a private tort 

action (Glastetter v. Novartis 

Pharmaceuticals Corp., 252 F.3d 986, 

991 (8th Cir. 2001)). To mandate 

warnings, or take similar regulatory 

action, FDA need not show, nor do we 

allege, actual causation. For an 

expanded discussion of the case law 

supporting FDA’s authority to require 

such warnings without evidence of 

actual causation, see Labeling of 

Diphenhydramine-Containing Drug 

Products for Over-the-Counter Human 

Use, final rule (67 FR 72555, December 

6, 2002). 

V. Analysis of Impacts 

FDA has examined the impacts of this 

proposed rule under Executive Order 

12866, the Regulatory Flexibility Act (5 

U.S.C. 601–612), and the Unfunded 

Mandates Reform Act of 1995 (2 U.S.C. 

1501 et seq.). Executive Order 12866 

directs agencies to assess all costs and 

benefits of available regulatory 

alternatives and, when regulation is 

necessary, to select regulatory 

approaches that maximize net benefits 

(including potential economic, 

environmental, public health and safety, 

and other advantages; distributive 

impacts; and equity). Under the 

Regulatory Flexibility Act, if a rule has 

a significant economic impact on a 

substantial number of small entities, an 

agency must analyze regulatory options 

that would minimize any significant 

impact of the rule on small entities. 

Section 202(a) of the Unfunded 

Mandates Reform Act requires that 

agencies prepare a written statement of 

anticipated costs and benefits before 

proposing any rule that may result in an 

expenditure in any one year by State, 

local, and tribal governments, in the 

aggregate, or by the private sector, of 


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1We did not select the midpoint of the ranges 

because of the large number of private label 

products that have lower design and administrative 

costs than branded goods. 

$100 million (adjusted annually for 

inflation). 

FDA believes that this proposed rule 

is consistent with the principles set out 

in the Executive Order 12866 and in 

these two statutes. The proposed rule is 

not a significant regulatory action as 

defined by the Executive order and, 

therefore, is not subject to review under 

the Executive order. Further, because 

this proposed rule is not expected to 

result in any 1-year expenditure that 

would exceed $100 million adjusted for 

inflation, FDA need not prepare 

additional analyses under the Unfunded 

Mandates Reform Act. Because the rule 

may have a significant economic impact 

on a substantial number of small 

entities, this section of the preamble 

constitutes FDA’s regulatory flexibility 

analysis. 

An analysis of the costs and benefits 

of this regulation, conducted under 

Executive Order 12866, was discussed 

in the FM (64 FR 27666 at 27683 to 

27686), which was later stayed (66 FR 

67485). This analysis reflects the 

incremental costs of the revised or new 

requirements in this proposed 

amendment of the FM. 

A. Background 

The purpose of this document is to 

amend the conditions under which OTC 

sunscreen drug products are generally 

recognized as safe and effective 

(GRASE) and not misbranded. This 

amendment addresses formulation, 

labeling, and testing requirements for 

both UVB and UVA radiation 

protection. 

Manufacturers would not need to 

reformulate their sunscreen products to 

comply with the proposed 

requirements. Manufacturers also would 

not need to retest their sunscreen 

products for UVB protection (i.e., they 

would not need to retest for SPF). The 

labeled SPF value determined from the 

SPF test in the FM would not likely 

change if a sunscreen product was 

retested using the modifications to the 

SPF test proposed in this document. In 

addition, manufacturers who have 

tested and labeled their sunscreen 

products as ‘‘SPF 30+’’ can relabel their 

products with the specific SPF value 

above 30 (but no greater than 50) 

without retesting. 

However, all manufacturers would 

incur some relabeling costs due to 

proposed revisions to both the PDP and 

the Drug Facts section of the product 

label. If manufacturers wish to label 

their sunscreen products as providing 

UVA protection, then manufacturers of 

those sunscreen products would also 

incur UVA testing costs. Because UVA 

testing is not required, some 

manufacturers will choose not to test for 

UVA protection and the labeling for 

those sunscreens will state, ‘‘No UVA 

Protection.’’

B. Number of Products Affected 

Estimating the number of products 

affected is difficult because we lack data 

on the number of products currently 

marketed. Our Drug Listing System 

currently does not have accurate 

information on the number of marketed 

OTC sunscreen products, especially the 

drug-cosmetic combination products. 

Proprietary databases that track retail 

sales of OTC drugs and other products 

do not distinguish cosmetics containing 

sunscreens from other cosmetic 

products and their surveys do not 

include many of the outlets where 

sunscreen products are sold. Based on 

earlier estimates (64 FR 27666 at 27684) 

and our knowledge of the industry, we 

assume there are about 3,000 OTC 

sunscreen drug products (different 

formulations, not including products 

that differ only by color), including 

drug-cosmetic combinations, and about 

12,000 individual stock keeping units 

(SKUs) (individual products, packages, 

and sizes). All 12,000 SKUs will need to 

be relabeled, but manufacturers can 

choose whether to test their sunscreen 

products for UVA protection. We 

assume that about 75 percent (2,250) of 

the sunscreen products would be tested 

for UVA protection. We request 

comment on the accuracy of this 

assumption. 

C. Cost to Relabel 

The cost to relabel varies greatly 

depending on the printing method and 

number of colors used. The majority of 

sunscreen products are packaged in 

plastic bottles or tubes with the label 

printed directly on the container or 

applied as a decal or paper label during 

the packaging process. The proposed 

labeling requirements impact both the 

PDP and the Drug Facts section of the 

package and would be considered a 

major redesign. 

Frequent label redesigns are typical 

for OTC sunscreen products, with 

redesigns generally implemented every 

1 to 2 years for a product. To the extent 

that a scheduled redesign coincides 

with the regulatory-mandated 

relabeling, the impact on the 

manufacturer will be negligible. 

We used a model developed for FDA 

by the consulting firm RTI to derive an 

estimate of the cost to relabel sunscreen 

products (Ref. 94). The model was 

developed to estimate the cost of food 

labels. However, we believe that the 

graphic and design estimates from that 

study are an appropriate proxy for the 

costs that would be incurred by OTC 

sunscreen manufacturers. RTI estimated 

that graphic design and prepress and 

engraving costs would range from 

$1,970 to $13,800 per SKU depending 

on the type of packaging and printing 

method used. There would also be 

administrative costs to account for 

contracting costs and obtaining final 

approvals for the new labels. RTI 

estimated administrative costs to range 

from $360 to $880 depending on the 

size of the firm. For this analysis, we are 

assuming an average design price of 

$7,000 per SKU and average 

administrative costs of $600 per SKU.1

Therefore, the total relabeling cost per 

SKU would be $7,600 (i.e., $600 + 

$7,000). 

While all sunscreen SKUs would need 

to be relabeled to comply with the 

proposed rule, we estimate that the 

timing of the scheduled relabeling 

would coincide with the regulatorymandated changes for 50 percent of the 

SKUs (i.e., 6,000 SKUs). We estimate the 

total labeling cost of the proposed 

labeling changes for the SKUs with the 

coinciding scheduled redesign would be 

50 percent of the administrative cost 

(i.e., $300). Therefore, the total one-time 

cost to industry for relabeling would be 

about $47.5 million (i.e., (6,000 x 

$7,600) + (6,000 x $300)). 

D. Cost to Test or Retest Products for 

UVA Protection 

This proposed rule will result in 

testing costs for products that make 

UVA protection claims. The 

approximate costs are $2,200 for in vivo 

UVA testing and $200 for in vitro UVA 

testing. Based on the number of 

sunscreen products currently labeled as 

providing UVA protection, we estimate 

that 75 percent (2,250) of the sunscreen 

products will be tested according to the 

proposed UVA tests. Therefore, FDA 

estimates a one-time UVA testing cost of 

approximately $5.4 million (i.e., 2,250 x 

$2,400). 

E. Total Incremental Costs 

The estimated total one-time 

incremental cost of this proposed rule is 

$53 million (i.e., $47.5 million + $5.4 

million). The incremental cost for the 

UVA testing could be less should the 

rule become final because many 

manufacturers may voluntarily comply 

with the proposed rule when 

reformulating current products or 

marketing new products. Although the 

FM is not effective, manufacturers of 

sunscreen products comply with the 


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UVB (SPF) test in the FM for nearly all 

sunscreen products. Therefore, it is 

likely that manufacturers of sunscreen 

products will also voluntarily comply 

with the proposed UVA tests in this 

document. 

It should also be noted that sunscreen 

products that are already distributed by 

the effective date of the FM will not be 

required to be relabeled or retested in 

conformity with these FM conditions, 

unless these products are subsequently 

relabeled or repackaged after the 

effective date. Therefore, there is no 

one-time cost associated with disposing 

of sunscreens that are already on the 

market at the time of the rule’s effective 

date. 

F. Small Business Impact 

In the FM (64 FR 27666 at 27685), 

FDA estimated that 78 percent of the 

180 domestic companies that 

manufacture OTC sunscreen products 

would be considered a small business 

(defined as fewer than 750 employees). 

FDA cannot estimate with certainty the 

number of small firms that will need to 

test or retest their OTC sunscreen 

products to provide for UVA protection 

claims, but projects that approximately 

75 percent of all products may need to 

be tested for UVA protection. Costs will 

vary by firm, depending on the number 

of products requiring testing. The firmspecific impact may vary inversely with 

the volume of product sales, because per 

unit costs will be lower for products 

with high volume sales. Thus, the 

relative economic impact of product 

retesting may be greater for small firms 

than for large firms. Because the OTC 

drug industry is highly regulated, all 

firms are expected to have access to the 

necessary professional skills on staff or 

to have contractual arrangements to 

comply with the testing requirements of 

this rule. 

G. Analysis of Alternatives 

FDA could have proposed only an in 

vivo or an in vitro test for UVA. FDA 

recognizes that requiring only the in 

vitro test would mean significantly less 

cost to manufacturers. However, the 

proposed in vivo test measures the 

magnitude of UVA protection. The 

proposed in vitro test measures the 

breadth of UVA protection. FDA 

believes it is important to conduct both 

tests to determine the magnitude and 

breadth of UVA protection. 

FDA plans to grant an extended 

compliance period when this proposed 

rule is finalized. Given the seasonal 

nature of these products, FDA is 

concerned that some manufacturers may 

not have sufficient time to incorporate 

labeling changes without disrupting 

their production schedules. By 

providing an additional 6 months to 

implement the changes, compliance 

costs to manufacturers will be reduced. 

In addition, FDA reduced compliance 

costs when we chose to stay the labeling 

requirements for the FM (64 FR 27666), 

sparing industry the cost of an 

additional regulatory-mandated label 

change. In the stay, FDA estimated a 

cost savings of $1.5 million to industry. 

It should be noted that labeling costs 

were significantly less in the FM than in 

this proposed rule primarily because we 

assumed in the FM that the majority of 

relabeling would coinside with 

scheduled voluntary label redesigns at 

no additional cost. Manufacturers were 

also able to avoid or postpone incurring 

an additional industry total of $5 

million when FDA chose to stay the 

UVB testing requirements of the FM. 

FDA invites public comment 

regarding any substantial or significant 

economic impact that this proposed rule 

would have on manufacturers of OTC 

sunscreen drug products. Comments 

regarding the impact of this rulemaking 

on such manufacturers should be 

accompanied by appropriate 

documentation. FDA is providing a 

period of 90 days from the date of 

publication of this proposed rule in the 

Federal Register for comments to be 

developed and submitted. FDA will 

evaluate any comments and supporting 

data that are received and will reassess 

the economic impact of this rulemaking 

in the final rule. 

VI. Paperwork Reduction Act of 1995 

FDA tentatively concludes that the 

labeling requirements in this document 

are not subject to review by the Office 

of Management and Budget because 

they do not constitute a ‘‘collection of 

information’’ under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501 

et seq.). Rather, the proposed labeling 

statements are a ‘‘public disclosure of 

information originally supplied by the 

Federal Government to the recipient for 

the purpose of disclosure to the public’’

(5 CFR 1320.3(c)(2)). 

VII. Environmental Impact 

FDA has determined under 21 CFR 

25.31(a) that this action is of a type that 

does not individually or cumulatively 

have a significant effect on the human 

environment. Therefore, neither an 

environmental assessment nor an 

environmental impact statement is 

required. 

VIII. Federalism 

FDA has analyzed this proposed rule 

in accordance with the principles set 

forth in Executive Order 13132. FDA 

has determined that the proposed rule, 

if finalized as proposed, would have a 

preemptive effect on State law. Section 

4(a) of the Executive order requires 

agencies to ‘‘construe * * * a Federal 

statute to preempt State law only where 

the statute contains an express 

preemption provision or there is some 

other clear evidence that the Congress 

intended preemption of State law, or 

where the exercise of State authority 

conflicts with the exercise of Federal 

authority under the Federal statute.’’

Section 751 of the Federal Food, Drug, 

and Cosmetic Act (the act) (21 U.S.C. 

379r) is an express preemption 

provision. Section 751(a) of the act (21 

U.S.C. 379r(a)) provides that ‘‘no State 

or political subdivision of a State may 

establish or continue in effect any 

requirement—* * * (1) that relates to 

the regulation of a drug that is not 

subject to the requirements of section 

503(b)(1) or 503(f)(1)(A); and (2) that is 

different from or in addition to, or that 

is otherwise not identical with, a 

requirement under this Act, the Poison 

Prevention Packaging Act of 1970 (15 

U.S.C. 1471 et seq.), or the Fair 

Packaging and Labeling Act (15 U.S.C. 

1451 et seq.).’’ Currently, this provision 

operates to preempt States from 

imposing requirements related to the 

regulation of nonprescription drug 

products. Section 751(b) through (e) of 

the act outlines the scope of the express 

preemption provision, the exemption 

procedures, and the exceptions to the 

provision. 

This proposed rule, if finalized as 

proposed, would amend the labeling 

and include new UVA testing for OTC 

sunscreen drug products. Any final rule 

would have a preemptive effect in that 

it would preclude States from issuing 

requirements related to the labeling and 

testing of OTC sunscreen drug products 

that are different from or in addition to, 

or not otherwise identical with a 

requirement in the final rule. This 

preemptive effect is consistent with 

what Congress set forth in section 751 

of the act. Section 751(a) of the act 

displaces both State legislative 

requirements and State common law 

duties. We also note that even where the 

express preemption provision in section 

751(a) of the act is not applicable, 

implied preemption may arise (see Geier 

v. American Honda Co., 529 US 861 

(2000)). 

FDA believes that the preemptive 

effect of the proposed rule, if finalized 

as proposed, would be consistent with 

Executive Order 13132. Section 4(e) of 

the Executive order provides that ‘‘when 

an agency proposes to act through 

adjudication or rulemaking to preempt 

State law, the agency shall provide all 


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49110 Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 

affected State and local officials notice 

and an opportunity for appropriate 

participation in the proceedings.’’ FDA 

is providing an opportunity for State 

and local officials to comment on this 

rulemaking. 

IX. Request for Comments 

In the Federal Register of January 10, 

2005 (70 FR 1721), FDA announced the 

availability of a final guidance for 

industry entitled ‘‘Labeling for 

Topically Applied Cosmetic Products 

Containing Alpha Hydroxy Acids as 

Ingredients.’’ The purpose of this 

guidance is twofold: 

• To educate consumers about the 

potential for increased skin sensitivity 

to the sun from the topical use of 

cosmetics containing alpha hydroxy 

acids (AHAs) as ingredients. 

• To educate manufacturers to help 

ensure that their labeling for cosmetic 

products containing AHAs as 

ingredients is not false or misleading. 

As discussed in the guidance, AHAs 

may increase skin sensitivity to UV 

radiation. Therefore, FDA recommends 

that manufacturers of cosmetic products 

containing AHAs include the following 

warning: 

Sunburn Alert: This product contains an 

alpha hydroxy acid (AHA) that may increase 

your skin’s sensitivity to the sun and 

particularly the possibility of sunburn. Use a 

sunscreen and limit sun exposure while 

using this product and for a week afterwards. 

The guidance addresses only cosmetic 

products containing AHAs and does not 

address sunscreen drug products 

containing AHAs (i.e., drug-cosmetic 

products). FDA is considering an 

additional warning or direction for 

sunscreen drug products containing 

AHAs similar to the warning for the 

cosmetic products described in the 

guidance for industry. However, FDA 

invites interested parties to submit 

comments and data regarding such 

labeling. In particular, FDA would like 

the following questions addressed: 

1. Does the body of existing evidence 

on AHAs and skin sensitivity warrant 

voluntary or mandatory labeling on OTC 

sunscreen drug products containing 

AHAs regarding possible risks of 

increased sun damage (e.g., sunburn)? 

2. If additional labeling is warranted, 

what information should be conveyed in 

the labeling and why? 

Comments along with supporting data 

will help enable FDA to determine how 

and what information, if any, related to 

UV hypersensitivity due to AHAs in 

sunscreen-cosmetic products should be 

communicated to consumers. FDA will 

also be evaluating any comments or data 

submitted in response to the final 

guidance for cosmetic products 

containing AHAs. 

In addition to AHAs, FDA seeks 

comment on titanium dioxide and zinc 

oxide formulated in particle sizes as 

small as a few nanometers. FDA 

addressed issues concerning micronized 

sunscreen ingredients in the FM (64 FR 

27666 at 27671 to 27672). The FM stated 

that FDA did not consider micronized 

titanium dioxide to be a new ingredient 

but rather a specific grade of the same 

active ingredient. The FM also stated 

that FDA was aware of concerns about 

potential risks associated with increased 

dermal penetration of such small 

particles. However, the FM explained 

that, based on the safety data submitted 

to FDA before publication of the FM, 

FDA was not aware of any evidence at 

that time demonstrating a safety concern 

from the use of micronized titanium 

dioxide in sunscreen products (64 FR 

27666 at 27671 to 27672). 

FDA recognizes that more sunscreens 

containing small particle size titanium 

dioxide and zinc oxide ingredients enter 

the market each year. FDA is interested 

in receiving comments and data about 

these sunscreen ingredients and 

products that contain these ingredients, 

their safety and effectiveness, and how 

they should be regulated. FDA received 

a citizen petition shortly before 

publication of this document that, 

among other things, raises these issues. 

FDA is currently evaluating the citizen 

petition, which is filed as CP17 in 

Docket No. 1978N–0038. FDA 

encourages other parties to submit 

additional data or information on the 

safety and effectiveness of sunscreen 

ingredients formulated in particle sizes 

as small as a few nanometers. 

On April 14, 2006, FDA announced in 

the Federal Register that we were 

planning a public meeting on FDAregulated products containing 

nanotechnology materials (71 FR 

19523). As explained in the notice, the 

purpose of the meeting was to help FDA 

further its understanding of 

developments in nanotechnology 

materials that pertain to FDA-regulated 

products. The meeting was held on 

October 10, 2006, and FDA has received 

comments from interested members of 

the public which have been filed in the 

docket for this public meeting (Docket 

No. 2006N– 0107). Some of these 

comments concern sunscreen 

ingredients formulated with 

nanotechnology materials. FDA will file 

any comments concerning sunscreen 

ingredients formulated in nanometer 

particle sizes received in response to 

this proposed rule in the docket for this 

rulemaking and the citizen petition 

(Docket No. 1978N–0038) and the 

docket for the nanotechnology meeting. 

X. Proposed Effective and Compliance 

Dates 

FDA is proposing that any final rule 

that may issue based on this proposal 

become effective 18 months after its 

date of publication in the Federal 

Register. The compliance date for 

products with annual sales less than 

$25,000 would be 24 months after 

publication of the final rule in the 

Federal Register. 

XI. References 

The following references are on 

display in the Division of Dockets 

Management (see ADDRESSES) under 

Docket No. 1978N–0038 and may be 

seen by interested persons between 9 

a.m. and 4 p.m., Monday through 

Friday. 

1. Comment No. CP6. 

2. Comment Nos. CP8, C548, SUP22, and 

C555. 

3. Comment Nos. LET166 and LET169. 

4. Comment No. C538. 

5. Comment No. C576. 

6. Comment No. C565. 

7. Comment No. C581. 

8. Comment No. C567. 

9. Comment No. C515. 

10. Comment No. C597. 

11. Comment No. MM22. 

12. Comment No. MM21. 

13. Comment No. C573. 

14. Autier, P. et al., ‘‘Sunscreen Use and 

Duration of Sun Exposure: a Double-blind, 

Randomized Trial,’’ Journal of the National 

Cancer Institute, 91(15):1304–1309, 1999. 

15. Reynolds, K.D. et al., ‘‘Predictors of 

Sun Exposure in Adolescents in a 

Southeastern U.S. Population,’’ Journal of 

Adolescent Health, 19(6):409–415, 1996. 

16. Robinson, J.K., D.S. Rigel, and R.A. 

Amonette, ‘‘Summertime Sun Protection 

Used by Adults for Their Children,’’ Journal 

American Academy of Dermatology, 

42(5):746–753, 2000. 

17. Gallagher, R.P. et al., ‘‘Broad-spectrum 

Sunscreen Use and the Development of New 

Nevi in White Children: A Randomized 

Controlled Trial,’’ Journal of the American 

Medical Association, 283(22):2955–2960, 

2000. 

18. Stender, I.M., J.L. Andersen, and H.C. 

Wulf, ‘‘Sun Exposure and Sunscreen Use 

among Sunbathers in Denmark,’’ Acta 

Dermato-Venereologica, 76:31–33, 1996. 

19. Zitser, B.S. et al., ‘‘A Survey of 

Sunbathing Practices on Three Connecticut 

State Beaches,’’ Connecticut Medicine, 

60(10):591–594, 1996. 

20. Green, A. et al., ‘‘Daily Sunscreen 

Application and Betacarotene 

Supplementation in Prevention of Basal-cell 

and Squamous-cell Carcinomas of the Skin: 

a Randomized Controlled Trial,’’ The Lancet, 

354:723–729, 1999. 

21. IARC Handbooks of Cancer Prevention 

Volume 5 Sunscreens, H. Vainio, ed., 

International Agency for Research on Cancer, 

Lyon, France, p. 62, 2001. 

22. Diffey, B.L. et al., ‘‘In Vitro Assessment 

of the Broad-spectrum Ultraviolet Protection 

of Sunscreen Products,’’ Journal of the 


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Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 49111 

American Academy of Dermatology, 

43(6):1024–1035, 2000. 

23. Comment No. C572. 

24. Gasparro, F.P., ‘‘Sunscreens, Skin 

Photobiology, and Skin Cancer: the Need for 

UVA Protection and Evaluation of Efficacy,’’

Environmental Health Perspectives, 108 

Suppl 1:71–78, 2000. 

25. Garland, C.F., F.C. Garland, and E.D. 

Gorham, ‘‘Lack of Efficacy of Common 

Sunscreens in Melanoma Prevention’’ in 

Epidemiology, Causes and Prevention of Skin 

Diseases, Grob, J.J. et al. eds., Blackwell 

Science Ltd., Malden, MA, pp. 151–159, 

1997. 

26. Lowe, N.J. et al., ‘‘Low Doses of 

Repetitive Ultraviolet A Induce Morphologic 

Changes in Human Skin,’’ Journal of 

Investigative Dermatology, 105(6):739–743, 

1995. 

27. Seite, S. et al., ‘‘Effects of Repeated 

Suberythemal Doses of UVA in Human 

Skin,’’ European Journal of Dermatology, 

7:204–209, 1997. 

28. Lavker, R.M. et al., ‘‘Quantitative 

Assessment of Cumulative Damage from 

Repetitive Exposures to Suberythemogenic 

Doses of UVA in Human Skin,’’

Photodermatology, Photoimmunology, and 

Photomedicine, 62(2):348–352, 1995. 

29. Lavker, R.M. et al., ‘‘Cumulative Effects 

from Repeated Exposures to Suberythemal 

Doses of UVB and UVA in Human Skin,’’

Journal of the American Academy of 

Dermatology, 32(1):53–62, 1995. 

30. Elmets, C.A., A. Vargas, and C. Oresajo, 

‘‘Photoprotective Effects of Sunscreens in 

Cosmetics on Sunburn and Langerhans Cell 

Photodamage,’’ Photodermatology, 

Photoimmunology, and Photomedicine, 

9(3):113–120, 1992. 

31. Lavker, R., and K. Kaidbey, ‘‘The 

Spectral Dependence for UVA-induced 

Cumulative Damage in Human Skin,’’ Journal 

of Investigative Dermatology, 108(1):17–21, 

1997. 

32. Seite, S. et al., ‘‘A Full-UV Spectrum 

Absorbing Daily Use Cream Protects Human 

Skin Against Biological Changes Occurring in 

Photoaging,’’ Photodermatology, 

Photoimmunology, and Photomedicine, 

16(4):147–155, 2000. 

33. Boyd, A.S. et al., ‘‘The Effects of 

Chronic Sunscreen Use on the Histologic 

Changes of Dermatoheliosis,’’ Journal of the 

American Academy of Dermatology, 

33(6):941–946, 1995. 

34. Comment No. CP15. 

35. Center for Disease Control and 

Prevention, ‘‘Guidelines for School Programs 

To Prevent Skin Cancer’’ in Morbidity and 

Mortality Weekly Report, 1–18, 2002. 

36. Ries, A.G. et al., ‘‘The Annual Report 

to the Nation on the Status of Cancer, 1973–

1997, with a Special Section on Colorectal 

Cancer,’’ Cancer, 88(10):2398–2424, 2000. 

37. Cancer Facts and Figures 2007, 

American Cancer Society, Inc., 2007. 

38. Sun Safety Tips, The American 

Academy of Dermatology, 1999. 

39. Skin Cancer: Preventing America’s 

Most Common Cancer 2001 Choose Your 

Cover, Centers for Disease Control and 

Prevention, 2001. 

40. The Sun, UV, and You: A Guide to 

SunWise Behavior, Environmental Protection 

Agency, 1999. 

41. Sun Protection Facts to Help You 

Prevent Skin Cancer, American Cancer 

Society, 2000. 

42. What You Need to Know About Skin 

Cancer, National Cancer Institute, 1998. 

43. Committee on Environmental Health, 

American Academy of Pediatrics, 

‘‘Ultraviolet Light: A Hazard to Children,’’

Pediatrics, 104:328–333, 1999. 

44. Green, A. et al., ‘‘Site Distribution of 

Cutaneous Melanoma in Queensland,’’

International Journal of Cancer, 53:232–236, 

1992. 

45. Franceschi, S. et al., ‘‘Site Distribution 

of Different Types of Skin Cancer: New 

Aetiological Clues,’’ International Journal of 

Cancer, 67:24–28, 1996. 

46. Raasch, B. et al., ‘‘Body Site Specific 

Incidence of Basal and Squamous Cell 

Carcinoma in an Exposed Population, 

Townsville, Australia,’’ Mutation Research, 

422:101–106, 1998. 

47. Osterlind, A., K. Hou-Jensen, and O.M. 

Jensen, ‘‘Incidence of Cutaneous Malignant 

Melanoma in Denmark 1978–1982. Anatomic 

Site Distribution, Histologic Types, and 

Comparison with Non-melanoma Skin 

Cancer,’’ British Journal of Cancer, 58:385–

391, 1988. 

48. Neale, R., G. Williams, and A. Green, 

‘‘Application Patterns Among Participants 

Randomized to Daily Sunscreen Use in a 

Skin Cancer Prevention Trial,’’ Archives of 

Dermatology, 138:1319–1325, 2002. 

49. Comment No. C584. 

50. Steinberg, C., and O. Larko, ‘‘Sunscreen 

Application and its Importance for Sun 

Protection Factor,’’ Archives of Dermatology, 

121:1400–1402, 1985. 

51. Stokes, R., and B. Diffey, ‘‘How Well 

Are Sunscreen Users Protected?,’’

Photodermatology, Photoimmunology, and 

Photomedicine, 13:186–188, 1997. 

52. Sayre, R.M. et al., ‘‘Product Application 

Technique Alters the Sun Protection Factor,’’

Photodermatology, Photoimmunology, and 

Photomedicine, 8:222–224, 1991. 

53. Azurda, R.M. et al., ‘‘Sunscreen 

Application Technique in Photosensitive 

Patients: a Quantitative Assessment and the 

Effect of Education,’’ Photodermatology, 

Photoimmunology and Photomedicine, 

16:53–66, 2000. 

54. Bech-Thomsen, N., and H.C. Wulf, 

‘‘Sunbather’s Application of Sunscreen is 

Probably Inadequate to Obtain Sun 

Protection Factor Assigned to the 

Preparation,’’ Photodermatology, 

Photoimmunolology and Photomedicine, 

9:242–244, 1992. 

55. Diffey, B., ‘‘People Do Not Apply 

Enough Sunscreen for Protection,’’ British 

Medical Journal, 313:942, 1996. 

56. Wright, M.W. et al., ‘‘Mechanisms of 

Sunscreen Failure,’’ Journal of the American 

Academy of Dermatology, 44:781–784, 2001. 

57. Rigel, D. et al., ‘‘American Academy of 

Dermatology’s Melanoma/Skin Cancer 

Detection and Prevention Month Press 

Release,’’ April 25, 2001. 

58. The ABCs for Fun in the Sun 

Educational Pamphlet, The American 

Academy of Dermatology, 1999. 

59. Ultraviolet Index—What You Need to 

Know, The American Academy of 

Dermatology, 1996. 

60. Sun Basics-Skin Protection Made 

Simple for Everyone Under the Sun, 

American Cancer Society, Inc., 1999. 

61. Skin Protection Guide for Everyone 

Under the Sun. A Parents Guide to Sun 

Protection, American Cancer Society, Inc., 

1999. 

62. Can Melanoma Be Prevented?, 

American Cancer Society, Inc., 2001. 

63. Diffey, B., ‘‘Has the Sun Protection 

Factor Had Its Day?,’’ British Medical Journal, 

320:176–177, 2000. 

64. Taylor, W.A., ‘‘Double Sampling Plan’’

in Guide to Acceptance Sampling, R. R. 

Donnelly & Sons, U.S.A., pp. 117–142, 1992. 

65. Comment No. C574. 

66. Comment No. C405. 

67. Comment No. C404. 

68. Comment No. C111. 

69. Comment No. RPT7. 

70. Comment No. C442. 

71. Comment No. SUP29. 

72. Memorandum from W.H. DeCamp, 

FDA, to C. Ganley, FDA, July 7, 2000. 

73. Comment No. CP12. 

74. Comment No. SUP33. 

75. Gabriel, K.L. et al., ‘‘Sun Protection 

Factor Testing: Comparison of FDA and DIN 

Methods,’’ Journal of Toxicology-Cutaneous 

and Ocular Toxicology, 6:357–370, 1987. 

76. Comment No. C491. 

77. Comment No. TR2. 

78. Diffey, B.L., ‘‘A Method for Broad 

Spectrum Classification of Sunscreens,’’

International Journal of Cosmetic Science, 

16:47–52, 1994. 

79. Diffey, B.L., and J. Robson, ‘‘A New 

Substrate to Measure Sunscreen Protection 

Factors Throughout the Ultraviolet 

Spectrum,’’ Journal of the Society of 

Cosmetic Chemists, 40:127–133, 1989. 

80. Comment No. RPT9. 

81. Comment No. LET170. 

82. Press Release: ‘‘The Future of 

Sunscreen Labeling: Recommendations of the 

Consensus Conference on UVA Protection of 

Sunscreens Convened by the American 

Academy of Dermatology,’’ New York, NY, 

April 26, 2000. 

83. Lim, H.W. et al., ‘‘American Academy 

of Dermatology Consensus Conference on 

UVA Protection of Sunscreens: Summary and 

Recommendations,’’ Journal of the American 

Academy of Dermatology, 44:505–508, 2001. 

84. Cole, C., ‘‘Sunscreen Protection in the 

Ultraviolet A Region: How to Measure 

Effectiveness,’’ Photodermatology, 

Photoimmunology, and Photomedicine, 17:2–

10, 2001. 

85. Comment No. C137. 

86. Setlow, R.B., et al., ‘‘Wavelengths 

Effective in Induction of Malignant 

Melanoma,’’ Proceedings of the American 

Academy of Science, U.S.A., 90:6666–6670, 

1993. 

87. Moyal, D. et al., ‘‘UVA Protection 

Efficacy of Sunscreens Can Be Determined by 

the Persistent Pigment Darkening (PPD) 

Method (Part 2),’’ Photodermatology, 

Photoimmunology, and Photomedicine, 

16:250–255, 2000. 

88. Moyal, D. et al., ‘‘Determination of 

UVA Protection Factors Using the Persistent 

Pigment Darkening (PPD) Method as the 

Endpoint (Part 1) Calibration of the Method,’’

Photodermatology, Photoimmunology, and 

Photomedicine, 16:245–249, 2000. 


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49112 Federal Register / Vol. 72, No. 165 / Monday, August 27, 2007 / Proposed Rules 

89. Chardon, A. et al., ‘‘Persistent PigmentDarkening Response as a Method for 

Evaluation of Ultraviolet A Protection 

Assays’’ in Sunscreens: Development, 

Evaluation, and Regulatory Aspects, 2nd 

edition, Marcel Dekker, Inc., New York, NY, 

pp. 559–582, 1997. 

90. Comment No. TS3. 

91. Diffey, B.L. et al., ‘‘Suncare Product 

Photostability: a Key Parameter for a More 

Realistic In Vitro Efficacy Evaluation,’’

European Journal of Dermatology, 7:226–228, 

1997. 

92. Sayre, R.M., and J. Dowdy, 

‘‘Photostability Testing of Avobenzone,’’

Cosmetics and Toiletries, 114:85–86, 88, 90–

91, 1999. 

93. Urbach, F., ‘‘Man and Ultraviolet 

Radiation’’ in Human Exposure to Ultraviolet 

Radiation: Risks and Regulations, Passchier, 

W.F. and Bosnjakovic, B.F.M. (eds.), Elsevier 

Science, New York, NY, pp. 3–6, 1987. 

94. RTI International, ‘‘FDA Labeling Cost 

Model, Final Report,’’ prepared by Mary 

Muth, Erica Gledhill, and Shawn Karns, RTI. 

Prepared for Amber Jessup, FDA Center for 

Food Safety and Applied Nutrition, Revised 

January 2003. 

List of Subjects 

21 CFR Part 347 

Labeling, Over-the-counter drugs. 

21 CFR Part 352 

Labeling, Over-the-counter drugs, 

Incorporation by reference. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act, and under 

authority delegated to the Commissioner 

of Food and Drugs, it is proposed that 

21 CFR parts 347 and 352 be amended 

as follows: 

PART 347—SKIN PROTECTANT DRUG 

PRODUCTS FOR OVER-THECOUNTER HUMAN USE 

1. The authority citation for 21 CFR 

part 347 continues to read as follows: 

Authority: 21 U.S.C. 321, 351, 352, 353, 

355, 360, 371. 

2. FDA is proposing to lift the stay of 

§ 347.20(d) as published at 68 FR 33362, 

June 4, 2003. 

PART 352—SUNSCREEN DRUG 

PRODUCTS FOR OVER THE COUNTER 

HUMAN USE 

3. The authority citation for 21 CFR 

part 352 continues to read as follows: 

Authority: 21 U.S.C. 321, 351, 352, 353, 

355, 360, 371. 

4. FDA is proposing to lift the stay of 

21 CFR part 352 as published at 68 FR 

33362, June 4, 2003. 

5. Section 352.3 is amended by 

redesignating paragraphs (b) through (d) 

as (c) through (e), respectively; revising 

newly redesignated paragraphs (c) and 

(e); and adding new paragraph (b) to 

read as follows: 

§ 352.3 Definitions. 

* * * * * 

(b) Minimal pigmenting dose (MPD). 

The quantity of erythema-effective 

energy (expressed as Joules per square 

meter) required to produce the first 

perceptible pigment darkening. 

(c) Product category designation 

(PCD). A labeling designation for 

sunscreen drug products to aid in 

selecting the type of product best suited 

to an individual’s complexion 

(pigmentation) and desired response to 

ultraviolet (UV) radiation. 

(1) Low UVB sunburn protection 

product. A sunscreen product that 

provides a sunburn protection factor 

(SPF) value of 2 to under 15. 

(2) Medium UVB sunburn protection 

product. A sunscreen product that 

provides an SPF value of 15 to under 30. 

(3) High UVB sunburn protection 

product. A sunscreen product that 

provides an SPF value of 30 to 50. 

(4) Highest UVB sunburn protection 

product. A sunscreen product that 

provides an SPF value over 50. 

* * * * * 

(e) Sunburn protection factor (SPF) 

value. The UV energy required to 

produce an MED on protected skin 

divided by the UV energy required to 

produce an MED on unprotected skin, 

which may also be defined by the 

following ratio: SPF value = MED 

(protected skin (PS))/MED (unprotected 

skin (US)), where MED(PS) is the 

minimal erythema dose for protected 

skin after application of 2 milligrams 

per square centimeter of the final 

formulation of the sunscreen product, 

and MED(US) is the minimal erythema 

dose for unprotected skin (i.e., skin to 

which no sunscreen product has been 

applied). In effect, the SPF value is the 

reciprocal of the effective transmission 

of the product viewed as a UV radiation 

filter. 

6. Section 352.20 is amended by 

revising paragraph (a)(2) to read as 

follows: 

§ 352.20 Permitted combinations of active 

ingredients. 

* * * * * 

(a) * * * 

(2) Avobenzone in § 352.10(b) may be 

combined with one or more sunscreen 

active ingredients identified in 

§ 352.10(c), (e), (f), (i) through (l), (n), 

(o), (q), and (r) in a single product when 

used in the concentrations established 

for each ingredient in § 352.10. The 

concentration of each active ingredient 

must be sufficient to contribute a 

minimum SPF of not less than 2 to the 

finished product. The finished product 

must have a minimum SPF of not less 

than the number of sunscreen active 

ingredients used in the combination 

multiplied by 2. 

* * * * * 

7. Section 352.50 is revised to read as 

follows: 

§ 352.50 Principal display panel of all 

sunscreen drug products. 

(a) UVB sunburn protection 

designation—(1) For products with an 

SPF of 2 to under 15. The labeling states 

‘‘UVB SPF [insert tested SPF value of 

the product] low’’. 

(2) For products with an SPF of 15 to 

under 30. The labeling states ‘‘UVB SPF 

[insert tested SPF value of the product] 

medium’’. 

(3) For products with an SPF of 30 to 

50. The labeling states ‘‘UVB SPF [insert 

tested SPF value of the product] high’’. 

(4) For products with an SPF over 50. 

The labeling states ‘‘UVB SPF 50 [select 

one of the following: ‘plus’ or ‘+’] 

highest’’. Any statement accompanying 

the marketed product that states a 

specific SPF value over 50 or similar 

language indicating a person can stay in 

the sun more than 50 times longer than 

without sunscreen will cause the 

product to be misbranded under section 

502 of the Federal Food, Drug, and 

Cosmetic Act (the act) (21 U.S.C. 352). 

(b) UVA protection designation—(1) 

For products not providing UVA 

protection according to § 352.73. The 

labeling states ‘‘no UVA protection’’. 

(i) The UVA protection designation 

shall appear on the principal display 

panel along with the UVB protection 

designation in an equally prominent 

manner that does not conflict with the 

UVB protection designation. 

(ii) The font size of the UVA 

protection designation shall be the same 

size as the UVB protection designation. 

(2) For products providing UVA 

protection according to § 352.73. The 

labeling states ‘‘UVA [select one of the 

following in accordance with § 352.73: 

‘★✰✰✰ Low,’ ‘★★✰✰ Medium,’

‘★★★✰ High,’ or ‘★★★★ Highest’]’’. 

(i) The UVA protection designation 

shall appear on the principal display 

panel along with the UVB protection 

designation in an equally prominent 

manner that does not conflict with the 

UVB protection designation. 

(ii) The font size of the UVA 

protection designation shall be the same 

size as the UVB protection designation. 

(iii) All star borders and the color 

inside a solid star shall be the same 

while the color of ‘‘empty’’ stars must be 

lighter and distinctly different than 

solid stars. The color inside a solid star 

should be distinctly different than the 

background color. 

(iv) The stars are to be filled in 

starting with the first star on the left and 


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1See § 201.66(b)(4) of this chapter for definition 

of bullet symbol. 

are to appear in a straight horizontal 

line. 

(c) Select one of the following: ‘‘UV 

rays from the sun are made of UVB and 

UVA. It is important to protect against 

both UVB & UVA rays.’’ or ‘‘UV rays 

from the sun are made of UVB and 

UVA. It is important to protect against 

both UVB & UVA rays to prevent 

sunburn and other skin damage.’’

(d) For products that satisfy the water 

resistant sunscreen product testing 

procedures in § 352.76. The labeling 

states (select one of the following: 

‘‘water,’’ ‘‘water/sweat,’’ or ‘‘water/ 

perspiration’’) ‘‘resistant.’’

(e) For products that satisfy the very 

water resistant sunscreen product 

testing procedures in § 352.76. The 

labeling states ‘‘very’’ (select one of the 

following: ‘‘water,’’ ‘‘water/sweat,’’ or 

‘‘water/perspiration’’) ‘‘resistant.’’

8. Section 352.52 is amended by 

revising paragraphs (b), (c), (d), (e), the 

heading of paragraph (f), paragraphs 

(f)(1)(ii) through (f)(1)(vi) to read as 

follows: 

§ 352.52 Labeling of sunscreen drug 

products. 

* * * * * 

(b) Indications. The labeling of the 

product states, under the heading 

‘‘Uses,’’ all of the phrases listed in 

paragraph (b)(1) of this section that are 

applicable to the product and may 

contain any of the additional phrases 

listed in paragraph (b)(2) of this section, 

as appropriate. Other truthful and 

nonmisleading statements, describing 

only the uses that have been established 

and listed in this paragraph (b), may 

also be used, as provided in § 330.1(c)(2) 

of this chapter, subject to the provisions 

of section 502 of the act (21 U.S.C. 352) 

relating to misbranding and the 

prohibition in section 301(d) of the act 

(21 U.S.C. 331(d)) against the 

introduction or delivery for introduction 

into interstate commerce of unapproved 

new drugs in violation of section 505(a) 

of the act (21 U.S.C. 355(a)). 

(1) For products containing any 

ingredient in § 352.10. (i) For products 

with an SPF of 2 to under 15. The 

labeling states ‘‘[bullet]1 low UVB 

sunburn protection’’. 

(ii) For products with an SPF of 15 to 

under 30. The labeling states ‘‘[bullet] 

medium UVB sunburn protection’’. 

(iii) For products with an SPF of 30 

to 50. The labeling states ‘‘[bullet] high 

UVB sunburn protection’’. 

(iv) For products with an SPF over 50. 

The labeling states ‘‘[bullet] highest 

UVB sunburn protection’’. 

(v) For products not providing UVA 

protection according to § 352.73. The 

labeling states ‘‘[bullet] no UVA 

protection.’’

(vi) For products providing UVA 

protection according to § 352.73. The 

labeling states ‘‘[bullet] [select one of 

the following in accordance with 

§ 352.73: ‘Low,’ ‘medium,’ ‘high,’ or 

‘highest’] UVA protection’’. 

(vii) For products that satisfy the 

water resistant testing procedures 

identified in § 352.76. The labeling 

states ‘‘[bullet] retains SPF after 40 

minutes of [select one or more of the 

following: ‘activity in the water,’

‘swimming,’ ‘sweating,’ ‘perspiring,’

‘swimming/sweating,’ or ‘swimming/ 

perspiring’]’’. 

(viii) For products that satisfy the very 

water resistant testing procedures 

identified in § 352.76. The labeling 

states ‘‘[bullet] retains SPF after 80 

minutes of [select one or more of the 

following: ‘activity in the water,’

‘swimming,’ ‘sweating,’ ‘perspiring,’

‘swimming/sweating,’ or ‘swimming/ 

perspiring’]’’. 

(2) Additional indications. In addition 

to the indications provided in paragraph 

(b)(1) of this section, the following may 

be used for products containing any 

ingredient in § 352.10: 

(i) For products with an SPF of 2 to 

under 15. Select one or both of the 

following: ‘‘[Bullet] provides low 

protection against [select one of the 

following: ‘sunburn’ or ‘sunburn and 

tanning’]’’ or ‘‘[bullet] for skin that 

sunburns minimally’’. 

(ii) For products with an SPF of 15 to 

under 30. Select one or both of the 

following: ‘‘[Bullet] provides medium 

protection against [select one of the 

following: ‘sunburn’ or ‘sunburn and 

tanning’]’’ or ‘‘[bullet] for skin that 

sunburns moderately’’. 

(iii) For products with an SPF of 30 

to 50. Select one or both of the 

following: ‘‘[Bullet] [select one of the 

following: ‘provides high’ or ‘high’] 

protection against [select one of the 

following: ‘sunburn’ or ‘sunburn and 

tanning’]’’ or ‘‘[bullet] for skin highly 

sensitive to sunburn’’. 

(iv) For products with an SPF over 50. 

Select one or both of the following: 

‘‘[Bullet] [select one of the following: 

‘provides highest’ or ‘highest’] 

protection against [select one of the 

following: ‘sunburn’ or ‘sunburn and 

tanning’]’’ or ‘‘[bullet] for skin extremely 

sensitive to sunburn’’. 

(v) If the UVA descriptor in 

§ 352.52(b)(1)(vi) is the same as the SPF 

descriptor in § 352.52(b)(1)(i) through 

(b)(1)(iv), then the statement in 

§ 352.52(b)(1)(i) through (b)(1)(iv) may 

be combined with the statement in 

§ 352.52(b)(1)(vi) as follows: ‘‘[Bullet] 

[select one of the following descriptors 

in accordance with §§ 352.70 and 

352.73: ‘low,’ ‘medium,’ ‘high,’ or 

‘highest’] UVB sunburn/UVA 

protection’’. 

(c) Warnings. The labeling of the 

product contains the following warnings 

under the heading ‘‘Warnings:’’

(1) The labeling states in bold type 

‘‘UV exposure from the sun increases 

the risk of skin cancer, premature skin 

aging, and other skin damage. It is 

important to decrease UV exposure by 

limiting time in the sun, wearing 

protective clothing, and using a 

sunscreen.’’

(2) The labeling states ‘‘When using 

this product [bullet] keep out of eyes. 

Rinse with water to remove.’’

(3) The labeling states ‘‘Stop use and 

ask a doctor if [bullet] skin rash occurs’’. 

(d) Directions. The labeling of the 

product contains the following 

statements, as appropriate, under the 

heading ‘‘Directions.’’ More detailed 

directions applicable to a particular 

product formulation (e.g., cream, gel, 

lotion, oil, spray, etc.) may also be 

included. 

(1) For products containing any 

ingredient in § 352.10. (i) The labeling 

states ‘‘[bullet] apply [select one of the 

following: ‘liberally’ or ‘generously’] 

[and, as an option: ‘and evenly’] [insert 

appropriate time interval, if a waiting 

period is needed] before sun exposure’’. 

(ii) The labeling states ‘‘[bullet] apply 

and reapply as directed to avoid 

lowering protection’’. 

(iii) As an option, the labeling may 

state ‘‘[bullet] apply to all skin exposed 

to the sun’’. 

(iv) The labeling states ‘‘[bullet] 

children under 6 months of age: ask a 

doctor’’. 

(2) For products that satisfy the water 

resistant or very water resistant testing 

procedures identified in § 352.76. The 

labeling states ‘‘[bullet] reapply after 

[select one of the following: ‘40 minutes 

of’ or ‘80 minutes of’ for products that 

satisfy either the water resistant or very 

water resistant test procedures in 

§ 352.76, respectively] swimming or 

[select one or more of the following: 

‘sweating’ or ‘perspiring’] and after 

towel drying. Otherwise, reapply at least 

every 2 hours’’. 

(3) For products that do not satisfy the 

water resistant or very water resistant 

testing procedures identified in § 352.76. 

The labeling states ‘‘[bullet] reapply at 

least every 2 hours and after towel 

drying, swimming, or [select one of the 

following: ‘sweating’ or ‘perspiring’]’’. 

(e) Statement on product 

performance—(1) For products 

containing any ingredient identified in 


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§ 352.10. The following product 

category designation (PCD) labeling 

claims may be used under the heading 

‘‘Other information’’ or anywhere 

outside of the ‘‘Drug Facts’’ box or 

enclosure and shall not be intermixed 

with the information required under 

§ 352.50(a). 

(i) For products with an SPF of 2 to 

under 15. The labeling states ‘‘low 

sunburn protection product’’. 

(ii) For products with an SPF of 15 to 

under 30. The labeling states ‘‘medium 

sunburn protection product’’. 

(iii) For products with an SPF of 30 

to 50. The labeling states ‘‘high sunburn 

protection product’’. 

(iv) For products with an SPF over 50. 

The labeling states ‘‘highest sunburn 

protection product’’. 

(2) For products containing any 

ingredient identified in § 352.10. The 

following labeling statement may be 

used under the heading ‘‘Other 

information’’ or anywhere outside of the 

‘‘Drug Facts’’ box or enclosure and shall 

not be intermixed with the information 

required under § 352.50(a). The labeling 

states ‘‘higher SPF products give more 

sun protection, but are not intended to 

extend the time spent in the sun’’. 

(3) For products containing any 

ingredient identified in § 352.10 and 

that satisfy the requirements in § 352.73 

for a labeled UVA protection value. The 

following labeling statements may be 

used anywhere outside of the ‘‘Drug 

Facts’’ box or enclosure and shall not be 

intermixed with the information 

required under § 352.50(a). 

(i) The labeling states ‘‘broad 

spectrum sunscreen’’. 

(ii) The labeling states ‘‘provides 

[select one of the following: ‘UVA and 

UVB,’ or ‘broad spectrum’] protection’’. 

(iii) The labeling states ‘‘protects from 

UVA and UVB [select one of the 

following: ‘rays’ or ‘radiation’]’’. 

(iv) The labeling states ‘‘[select one of 

the following: ‘absorbs’ or ‘protects’] 

within the UVA spectrum’’. 

(f) Products, including cosmetic-drug 

products, containing any ingredient 

identified in § 352.10 labeled for use 

only on specific small areas of the face 

(e.g., lips, nose, ears, and/or around the 

eyes) and that meet the criteria 

established in § 201.66(d)(10) of this 

chapter. * * * 

(1) * * * 

* * * * * 

(ii) The indication required by 

§ 201.66(c)(4) of this chapter may be 

limited to the following: ‘‘Use [in bold 

type] helps prevent sunburn.’’

(iii) The warnings required by 

§ 201.66(c)(5)(i) through (c)(5)(ix) of this 

chapter may be limited to the following: 

‘‘UV exposure from the sun increases 

the risk of skin cancer, premature skin 

aging, and other skin damage. It is 

important to decrease UV exposure by 

limiting time in the sun, wearing 

protective clothing, and using a 

sunscreen. [in bold type]’’ ‘‘[bullet] keep 

out of eyes’’ ‘‘[bullet] stop use if skin 

rash occurs.’’

(iv) The warning in § 201.66(c)(5)(x) 

of this chapter may be limited to the 

following: ‘‘Keep out of reach of 

children.’’

(v) For lip protectant products 

containing any ingredient identified in 

§ 352.10. The heading and the 

indication required by § 201.66(c)(4) of 

this chapter may be limited to ‘‘Use [in 

bold type] helps prevent sunburn and 

chapped lips’’. The warnings required 

in paragraph (f)(1)(iii) of this section 

may be limited to the following: ‘‘Stop 

use if skin rash occurs.’’ The warning 

required in paragraph (f)(1)(iv) of this 

section may be omitted. The directions 

in paragraphs (d)(2) and (d)(3) of this 

section may be limited to the following: 

‘‘apply liberally and reapply at least 

every 2 hours for sunburn protection’’. 

(vi) For lipsticks, lip products to 

prolong wear of lipstick, lip gloss, and 

lip balm containing any ingredient 

identified in § 352.10 and identified in 

§ 720.4(c)(7) of this chapter. The 

labeling is identical to that in paragraph 

(f)(1)(v) of this section except the 

heading and the indication required by 

§ 201.66(c)(4) of this chapter are limited 

to ‘‘Use [in bold type] helps prevent 

sunburn’’. 

* * * * * 

9. Section 352.60 is amended by 

revising paragraphs (c) and (d) to read 

as follows: 

§ 352.60 Labeling of permitted 

combinations of active ingredients. 

* * * * * 

(c) Warnings. The labeling of the 

product states, under the heading 

‘‘Warnings,’’ the warning(s) for each 

ingredient in the combination, as 

established in the warnings section of 

the applicable OTC drug monographs, 

except that the warning for skin 

protectants in § 347.50(c)(3) of this 

chapter is not required for permitted 

combinations containing a sunscreen 

and a skin protectant identified in 

§ 352.20(b). For products marketed as a 

lip protectant with sunscreen, 

§ 352.52(f)(1)(vi) applies. 

(d) Directions. The labeling of the 

product states, under the heading 

‘‘Directions,’’ directions that conform to 

the directions established for each 

ingredient in the directions sections of 

the applicable OTC drug monographs, 

unless otherwise stated in this 

paragraph. When the time intervals or 

age limitations for administration of the 

individual ingredients differ, the 

directions for the combination product 

may not contain any dosage that 

exceeds those established for any 

individual ingredient in the applicable 

OTC drug monograph(s), and may not 

provide for use by any age group lower 

than the highest minimum age limit 

established for any individual 

ingredient. For permitted combinations 

containing a sunscreen and a skin 

protectant identified in § 352.20(b), the 

directions for sunscreens in § 352.52(d) 

must be used. For products marketed as 

a lip protectant with sunscreen, 

§ 352.52(f)(1)(vi) applies. 

10. Sections 352.70 through 352.73 

are revised as follows: 

Subpart D—Testing Procedures 

Sec. 

352.70 SPF testing procedure. 

352.71 UVA in vitro testing procedure. 

352.72 UVA in vivo testing procedure. 

352.73 Determination of the labeled UVA 

protective value. 

* * * * * 

§ 352.70 SPF testing procedure. 

(a) Standard sunscreens—(1) 

Laboratory validation. A standard 

sunscreen shall be used concomitantly 

in the testing procedures for 

determining the SPF value of a 

sunscreen drug product to ensure the 

uniform evaluation of sunscreen drug 

products. 

(i) For products with an SPF of 2 to 

15. The standard sunscreen shall be an 

8-percent homosalate preparation with a 

mean SPF value of 4.47 (standard 

deviation = 1.28). In order for the SPF 

determination of a test product to be 

considered valid, the SPF of the 

standard sunscreen must fall within the 

standard deviation range of the expected 

SPF (i.e., 4.47 ± 1.28). Optionally, the 

standard sunscreen in paragraph 

(a)(1)(ii) of this section may be used. 

(ii) For products with an SPF over 15 

(optional for SPF values of 2 to 15). The 

standard sunscreen shall be an SPF 15 

formulation containing 7 percent 

padimate O and 3 percent oxybenzone 

with a mean SPF value of 16.3 (standard 

deviation = 3.43). In order for the SPF 

determination of a test product to be 

considered valid, the SPF of the 

standard sunscreen must fall within the 

standard deviation range of the expected 

SPF (i.e., 16.3 ± 3.43). 

(2) Standard homosalate sunscreen—

(i) Preparation of the standard 

homosalate sunscreen. (A) The standard 

homosalate sunscreen is prepared from 

two different preparations (preparation 


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A and preparation B) with the following 

compositions: 

COMPOSITION OF PREPARATION A AND

PREPARATION B OF THE HOMOSALATE

STANDARD SUNSCREEN

Ingredients Percent by 

weight 

Preparation A 

Lanolin 5.00 

Homosalate 8.00 

White petrolatum 2.50 

Stearic acid 4.00 

Propylparaben 0.05 

Preparation B 

Methylparaben 0.10 

Edetate disodium 0.05 

Propylene glycol 5.00 

Triethanolamine 1.00 

Purified water USP 74.30 

(B) Preparation A and preparation B 

are heated separately to 77 to 82 °C, 

with constant stirring, until the contents 

of each part are solubilized. Add 

preparation A slowly to preparation B 

while stirring. Continue stirring until 

the emulsion formed is cooled to room 

temperature (15 to 30 °C). Add sufficient 

purified water to obtain 100 grams of 

standard sunscreen preparation. 

(ii) High performance liquid 

chromatography (HPLC) assay of the 

standard homosalate sunscreen. Assay 

the standard homosalate sunscreen 

preparation by the following method to 

ensure proper concentration: 

(A) Reagents. (1) Acetic acid, glacial, 

ACS grade. 

(2) Isopropanol, HPLC grade. 

(3) Methanol, HPLC grade. 

(4) Homosalate, USP reference 

standard. 

(B) Instrumentation. Equilibrate a 

suitable liquid chromatograph to the 

following or equivalent conditions: 

Column .............. Ultrasphere ODS 150 x 4.6 

millimeters (5 microns), or 

Ultrasphere ODS 250 x 4.6 

millimeters (5 microns) 

Mobile Phase ..... 85:15:0.5 methanol:water:acetic acid 

Flow Rate .......... 1.5 milliliters per minute 

Temperature ...... Ambient 

Detector ............. UV spectrophotometer at 308 

nanometers 

Attenuation ........ As needed 

Injection Amount 10 microliters 

(C) Standard preparation. (1) 

Accurately weigh 0.50 gram of 

homosalate USP reference standard into 

a 250-milliliter volumetric flask. 

Dissolve and dilute to volume with 

isopropanol. Mix well. 

(2) Accurately pipet 20.0 milliliters of 

the homosalate solution (described in 

paragraph (a)(2)(ii)(C)(1) of this section) 

into a 100-milliliter volumetric flask. 

Dilute to volume with isopropanol and 

mix well. This is the standard 

preparation. 

(D) Sample preparation. (1) 

Accurately weigh 2.0 grams of sample 

into a 100-milliliter volumetric flask. 

(2) Add approximately 75 milliliters 

of isopropanol and heat with swirling 

until the sample is evenly dispersed. 

(3) Cool to room temperature (15 to 30 

°C) and dilute to volume with 

isopropanol. Mix well. 

(4) Pipet 25.0 milliliters of this sample 

preparation into a 100-milliliter 

volumetric flask and dilute to volume 

with isopropanol. Mix well. 

(E) System suitability. (1) Three 

replicate injections of the standard 

preparation (described in paragraph 

(a)(2)(ii)(C)(2) of this section) will yield 

a relative standard deviation of not more 

than 2.0 percent calculated on peak 

areas for homosalate. 

(2) In case a system fails to meet this 

criterion, adjusting the mobile phase or 

replacing the column may be necessary 

to obtain suitable chromatography. 

(F) Analysis. (1) Inject 10 microliters 

of the standard preparation (described 

in paragraph (a)(2)(ii)(C) of this section) 

in triplicate and collect data for about 

15 minutes or until both homosalate 

(two isomers) peaks have completely 

eluted. 

(2) Similarly inject 10 microliters of 

each sample preparation. 

(3) The system suitability 

requirements must be met. 

(G) Calculation. Sum the peak areas of 

the two homosalate isomers for each 

injection and calculate the percent 

(weight/weight) homosalate content in 

the sample preparation as follows: 

(3) Standard padimate O/oxybenzone 

sunscreen—(i) Preparation of the 

standard padimate O/oxybenzone 

sunscreen. The standard sunscreen is 

prepared from four different parts (parts 

A, B, C, and D) with the following 

compositions: 

COMPOSITION OF THE PADIMATE O/ 

OXYBENZONE STANDARD SUNSCREEN

Ingredients 

Percent 

by 

weight 

Part A 

Lanolin ..................................... 4.50 

Cocoa butter ............................ 2.00 

Glyceryl monostearate ............. 3.00 

Stearic acid .............................. 2.00 

Padimate O .............................. 7.00 

COMPOSITION OF THE PADIMATE O/ 

OXYBENZONE STANDARD SUNSCREEN—Continued 

Ingredients 

Percent 

by 

weight 

Oxybenzone ............................. 3.00 

Propylparaben ......................... 0.10 

Part B 

Purified water USP .................. 71.60 

Sorbitol solution ....................... 5.00 


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COMPOSITION OF THE PADIMATE O/ 

OXYBENZONE STANDARD SUNSCREEN—Continued 

Ingredients 

Percent 

by 

weight 

Triethanolamine, 99 percent .... 1.00 

Methylparaben ......................... 0.30 

Part C 

Benzyl alcohol ......................... 0.50 

Part D 

Purified water USP .................. QS1 

1Quantity sufficient to make 100 grams 

(A) Step 1. Add the ingredients of Part 

A into a suitable stainless steel kettle 

equipped with a propeller agitator. Mix 

at 77 to 82 °C until uniform. 

(B) Step 2. Add the water of Part B 

into a suitable stainless steel kettle 

equipped with a propeller agitator and 

begin mixing and heating to 77 to 82 °C. 

Add the remaining ingredients of Part B 

and mix until uniform. Maintain 

temperature at 77 to 82 °C. 

(C) Step 3. Add the batch of Step 1 at 

77 to 82 °C to the batch of Step 2 at 77 

to 82 °C, and mix until smooth and 

uniform. Slowly cool the batch to 49 to 

54 °C. 

(D) Step 4. Add the benzyl alcohol of 

Part C to the batch of Step 3 at 49 to 54 

°C. Mix until uniform. Continue to cool 

batch to 35 to 41 °C. 

(E) Step 5. Add sufficient water of 

Part D to the batch of Step 4 at 35 to 41 

°C to obtain 100 grams of standard 

sunscreen preparation. Mix until 

uniform. Cool batch to 27 to 32 °C. 

(ii) HPLC assay of the standard 

padimate O/oxybenzone sunscreen. To 

ensure that the standard sunscreen 

contains proper amounts of padimate O 

and oxybenzone, analyze it against USP 

reference standards for padimate O and 

oxybenzone in a high performance 

liquid chromatography procedure using 

the following parameters: 

(A) Reagents. (1) Acetic acid, glacial, 

ACS grade. 

(2) Isopropanol, HPLC grade. 

(3) Methanol, HPLC grade. 

(4) Oxybenzone, USP reference 

standard. 

(5) Padimate O, USP reference 

standard. 

(B) Instrumentation. Equilibrate a 

suitable liquid chromatograph to the 

following or equivalent conditions: 

Column .............. Ultrasphere ODS 250 x 4.6 

millimeters (5 microns), or 

Supelcosil LC-18 DB 250 x 

4.6 millimeters (5 microns) 

Mobile Phase ..... 85:15:0.5 methanol:water:acetic acid 

Flow Rate .......... 1.5 milliliters per minute 

Temperature ...... Ambient 

Detector ............. UV spectrophotometer at 308 

nanometers 

Attenuation ........ As needed 

Injection Amount 10 microliters 

(C) Standard preparation. (1) Weigh 

0.50 gram of oxybenzone reference 

standard into a 250-milliliter volumetric 

flask. Dissolve and dilute to volume 

with isopropanol. Mix well. 

(2) Weigh 0.50 gram of padimate O 

reference standard into a 250-milliliter 

volumetric flask. Dissolve and dilute to 

volume with isopropanol. Mix well. 

(3) Pipet 3.0 milliliters of the 

oxybenzone solution and 7.0 milliliters 

of the padimate O solution into a 100- 

milliliter volumetric flask. Dilute to 

volume with isopropanol and mix well. 

This is the standard preparation. 

(D) Sample preparation. (1) Weigh 1.0 

gram of sample into a 50-milliliter 

volumetric flask. 

(2) Add approximately 30 milliliters 

of isopropanol and heat with swirling 

until the sample is evenly dispersed. 

(3) Cool to room temperature (15 to 30 

°C) and dilute to volume with 

isopropanol. Mix well. 

(4) Pipet 5.0 milliliters of this sample 

preparation into a 50-milliliter 

volumetric flask and dilute to volume 

with isopropanol. Mix well. 

(E) System suitability. (1) Three 

replicate injections of the standard 

preparation (described in paragraph 

(a)(3)(ii)(C) of this section) will yield a 

relative standard deviation of not more 

than 2.0 percent calculated on peak 

areas for oxybenzone and padimate O. 

(2) A calculated resolution between 

the oxybenzone and padimate O peaks 

will be not less than 3.0. 

(3) In case a system fails to meet this 

criterion, adjusting the mobile phase or 

replacing the column may be necessary 

to obtain suitable chromatography. 

(F) Analysis. (1) Inject 10 microliters 

of the standard preparation (described 

in paragraph (a)(3)(ii)(C) of this section) 

in triplicate and collect data for about 

15 minutes or until the padimate O peak 

has completely eluted. Elution order is 

oxybenzone, then padimate O. 

(2) Similarly inject 10 microliters of 

each sample preparation. 

(3) The system suitability 

requirements must be met. 

(G) Calculation. Calculate the percent 

(weight/weight) of each sunscreen 

ingredient in the sample preparation as 

follows: 

(1) Oxybenzone (percent weight) 

(2) Padimate O (percent weight) 

(b) Light source (solar simulator)—(1) 

Emission spectrum. A solar simulator 

used for determining the SPF of a 

sunscreen drug product should be 

filtered so that it provides a continuous 

emission spectrum from 290 to 400 

nanometers (nm) with a limit of 1,500 

watts per square meter (W/m2) on total 

solar simulator irradiance for all 

wavelengths between 250 and 1400 nm 

and the following percentage of 

erythema-effective radiation in each 

specified range of wavelengths: 


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SOLAR SIMULATOR EMISSION

SPECTRUM

Wavelength range 

(nm) 

Percent erythemal 

contribution 

< 290 < 0.1 

290–310 46.0–67.0 

290–320 80.0–91.0 

290–330 86.5–95.0 

290–340 90.5–97.0 

290–350 93.5–98.5 

290–400 93.5–100.0 

(2) Operation. A solar simulator 

should have no significant time related 

fluctuations (within 20 percent) in 

radiation emissions after an appropriate 

warmup time and good beam uniformity 

(within 20 percent) in the exposure 

plane. The average delivered dose to the 

UV exposure site must be within 10 

percent of the prescribed dose. 

(3) Periodic measurement. To ensure 

that the solar simulator delivers the 

appropriate spectrum of UV radiation, 

the emission spectrum of the solar 

simulator must be measured every 6 

months with an appropriate and 

accurately calibrated spectroradiometer 

system (results should be traceable to 

the National Institute for Standards and 

Technology). In addition, the solar 

simulator must be recalibrated if there is 

any change in the lamp bulb or the 

optical filtering components (i.e., filters, 

mirrors, lenses, collimating devices, or 

focusing devices). Daily solar simulator 

radiation intensity should be monitored 

with a broadband radiometric device 

that is sensitive primarily to UV 

radiation. The broadband radiometric 

device should be calibrated using side 

by side comparison with the 

spectroradiometer at the time of the 

semiannual spectroradiometric 

measurement of the solar simulator. If a 

lamp must be replaced due to failure or 

aging during a phototest, broadband 

device readings consistent with those 

obtained for the original calibrated lamp 

will suffice until measurements can be 

performed with the spectroradiometer at 

the earliest possible opportunity. 

(c) General testing procedures—(1) 

Medical history. Obtain a medical 

history from each subject with emphasis 

on the effects of sunlight on his/her 

skin. Determine that each subject is in 

good general health with skin type I, II, 

or III (as described in this paragraph). 

Skin Type and Sunburn and Tanning 

History (Based on first 30 to 45 minutes 

of sun exposure after a winter season of 

no sun exposure). 

I: Always burns easily; never tans (sensitive). 

II: Always burns easily; tans minimally 

(sensitive). 

III: Burns moderately; tans gradually (light 

brown) (normal). 

IV: Burns minimally; always tans well 

(moderate brown) (normal). 

V: Rarely burns; tans profusely (dark brown) 

(insensitive). 

VI: Never burns; deeply pigmented 

(insensitive). 

Determine that the subject is not taking 

topical or systemic medication that is 

known to alter responses to ultraviolet 

radiation and that the subject has no 

history of sensitivities to topical 

products and/or abnormal responses to 

sunlight, such as a phototoxic or 

photoallergic response. 

(2) Physical examination. Conduct a 

physical examination to determine the 

presence of sunburn, suntan, scars, 

active dermal lesions, and uneven skin 

tones on the areas of the back to be 

tested. A suitable source of low power 

UVA, such as a Woods lamp, is helpful 

in this process. If any of these 

conditions are present, the subject is not 

qualified to participate in the study. The 

presence of nevi, blemishes, or moles 

will be acceptable if in the physician’s 

judgment they will neither compromise 

the study, nor jeopardize subject safety. 

Subjects with dysplastic nevi should not 

be enrolled. Excess hair on the back is 

acceptable if the hair is clipped. 

Shaving is unacceptable because it may 

remove a significant portion of the 

stratum corneum and temporarily 

increase skin permeability to ultraviolet 

radiation. 

(3) Informed consent. Obtain legally 

effective written informed consent from 

all subjects. 

(4) Test site delineation—(i) Test site. 

A test site is the location on the back for 

determining the subject’s initial and 

final minimal erythema dose (MED) for 

unprotected skin and for determining 

SPF values after application of the 

sunscreen standard and the test 

sunscreen product(s). There typically 

are 4 to 6 test sites for each subject. Test 

sites should be located on the back 

between the beltline and the shoulder 

blades (scapulae) and lateral to the 

midline. Each test site shall be a 

minimum of 50 square centimeters, e.g., 

5 x 10 centimeters. Outline the test sites 

to which the sunscreen standard and the 

test sunscreen product(s) will be 

applied with indelible ink. If the subject 

is to receive the doses of ultraviolet 

radiation in an upright (seated) position, 

draw the lines on the skin with the 

subject upright (seated). If the subject is 

to receive the doses of ultraviolet 

radiation while prone, draw the lines 

with the subject prone. 

(ii) Test subsite. Test subsites are the 

locations to which ultraviolet radiation 

is administered within a test site. At 

least 5 test subsites will receive UV 

doses within each test site. Test subsites 

will be at least 1 square centimeter 

(cm2) in area and will be separated from 

each other by at least 1 cm. Mark the 

location of each test subsite with 

indelible ink. 

(5) Application of test materials. 

Apply the test sunscreen product and 

the standard sunscreen at 2 milligrams 

per square centimeter (mg/cm2) to their 

respective test sites to establish standard 

films. Test sites will be randomly 

located on the back in a blinded 

manner. Use a finger cot compatible 

with the sunscreen to spread the 

product as evenly as possible. Pretreat 

the finger cot by saturating with the 

sunscreen and then wiping off material 

before application. Pretreatment is 

meant to ensure that sunscreen is 

applied at the correct density of 2 mg/ 

cm2. 

(6) Waiting period. Before exposing 

the test site areas after applying a 

product, wait at least 15 minutes. 

(7) Number of subjects—(i) For 

products with an expected SPF under 

30. A test panel shall consist of 20 to 25 

subjects with at least 20 subjects who 

produce valid data for analysis. Data are 

valid unless rejected in accordance with 

paragraph (c)(9) of this section. If more 

than 5 subjects are rejected based on 

paragraph (c)(9) of this section, the 

panel is disqualified, and a new panel 

must be created. 

(ii) For products with an expected 

SPF of 30 or over. A test panel shall 

consist of 25 to 30 subjects with at least 

25 subjects who produce valid data for 

analysis. Data are valid unless rejected 

in accordance with paragraph (c)(9) of 

this section. If more than 5 subjects are 

rejected based on paragraph (c)(9) of this 

section, the panel is disqualified, and a 

new panel must be created. 

(8) Response criteria. In order that the 

person who evaluates the MED 

responses is not biased, he/she must not 

be the same person who applied the 

sunscreen drug product to the test site 

or administered the doses of UV 

radiation. After UV radiation exposure 

from the solar simulator is completed, 

all immediate responses shall be 

recorded. These may include an 

immediate darkening or tanning, 

typically grayish or purplish in color, 

which fades in 30 to 60 minutes; an 

immediate reddening at the subsite, due 

to heating of the skin, which fades 

rapidly; and an immediate generalized 

heat response, spreading beyond the 

subsite, which fades in 30 to 60 

minutes. After the immediate responses 

are noted, each subject shall shield the 

exposed area from further UV radiation 

until the MED response is evaluated. 

Determine the MED 16 to 24 hours after 

exposure. Evaluate the erythema 


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responses of each test site using either 

tungsten or warm white fluorescent 

lighting that provides 450 to 550 lux of 

illumination at the test site. For the 

evaluation, the test subject should be in 

the same position used when the test 

site was irradiated. For each test site, 

determine the smallest UV dose that 

produced redness reaching the borders 

of the test subsite. The MED is the 

quantity of erythema-effective energy 

required to produce the first perceptible, 

redness reaction with clearly defined 

borders at 16 to 24 hours post-exposure. 

To determine the MED, there must be at 

least one subsite that received a smaller 

UV dose and does not produce redness 

as well as a subsite(s) with somewhat 

more intense redness. For subsites 

showing an erythema response, the 

maximal exposure should be no more 

than twice the total energy of the 

minimal exposure. 

(9) Rejection of test data. Reject test 

data if the exposure series fails to elicit 

an MED response on either the treated 

or unprotected skin sites; or all subsites 

within a test site show more intense 

responses than the threshold erythema 

response; or the responses are 

inconsistent with the series of UV doses 

administered; or the subject was 

noncompliant, e.g., the subject 

withdraws from the test due to illness 

or work conflicts or does not shield the 

exposed testing sites from further UV 

radiation until the MED is read. 

(d) Determination of SPF—(1) 

Determination of erythema action 

spectrum. (i) Use the following 

erythema action spectrum as weighting 

factors to calculate the erythemaeffective exposure produced by a solar 

simulator: 

Vi (λ) = 1.0 (250 < λ < 298 nm) 

Vi (λ) = 100.094 * (298 - l) (298 < λ < 328 

nanometers) 

Vi (λ) = 100.015 * (140 - l) (328 < λ < 400 

nanometers) 

(ii) Integrate the erythemally-effective 

spectral irradiance over wavelength and 

time to calculate the erythema-effective 

UV dose delivered by a solar simulator 

as follows: 

(iii) The erythema action spectrum 

may be determined using a handheld 

radiometer with a response weighted to 

match the spectrum in ‘‘CIE S 007/E 

Erythemal Reference Action Spectrum 

and Standard Erythema Dose,’’ dated 

1998, which is incorporated by 

reference in accordance with 5 U.S.C. 

552(a) and 1 CFR part 51. Copies are 

available from CIE Central Bureau, 

Kegelgasse 27, A–1030, Vienna, Austria, 

or may be examined at the Center for 

Drug Evaluation and Research, 10903 

New Hampshire Ave., Bldg. 22, Silver 

Spring, MD, or at the Office of the 

Federal Register, 800 North Capitol St. 

NW., suite 700, Washington, DC. It is 

advisable to measure the solar simulator 

output before and after each phototest 

or, at a minimum, at the beginning and 

end of each test day. This radiometer 

should be calibrated using side by side 

comparison with the spectroradiometer 

(using the weighting factors determined 

according to paragraph (d)(1)(i) of this 

section) at the time of the semiannual 

spectroradiometric measurement of the 

solar simulator. 

(2) Determination of MED of 

unprotected skin. Administer a series of 

five UV radiation doses expressed as J/ 

m2-eff (adjusted to the erythema action 

spectrum calculated according to 

paragraph (d)(1) of this section) to the 

subsites within each test site on a 

subject using an accurately calibrated 

solar simulator. Use the series of five 

exposures to the unprotected test site to 

determine the initial unprotected MED. 

Select the doses that are a geometric 

series represented by (1.25n), wherein 

each exposure dose is 25 percent greater 

than the previous exposure dose to 

maintain the same relative uncertainty 

(expressed as a constant percentage), 

independent of the subject’s sensitivity 

to UV radiation. Usually, the UV 

radiation for determining the initial 

unprotected MED is administered the 

day prior to applying the sunscreen 

product and standard sunscreen, and 

the responses then are evaluated 

immediately prior to applying the 

sunscreen product and sunscreen 

standard. Determine the final 

unprotected MED on the same day that 

UV radiation is administered to the 

sunscreen-protected test sites. Use the 

final unprotected MED (MED(US)) in 

calculating SPF. 

(3) Determination of individual SPF 

values. Administer a series of five UV 

radiation doses expressed as J/m2-eff 

(adjusted to the erythema action 

spectrum calculated according to 

paragraph (d)(1) of this section) to the 

subsites within each test site on a 

subject using an accurately calibrated 

solar simulator. The five UV doses will 

be a geometric series as described in 

paragraph (d)(2) of this section, where 

the middle exposure represents the 

expected SPF. For products with an 

expected SPF less than 8, use exposures 

that are the product of the initial 

unprotected MED times 0.64X, 0.80X, 

1.00X, 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, use exposures 

that are the initial unprotected MED 

times 0.69X, 0.83X, 1.00X, 1.20X, and 

1.44X, where X equals the expected SPF 

of the test product. For products with an 

expected SPF greater that 15, use 

exposures that are the initial 

unprotected MED times 0.76X, 0.87X, 

1.00X, 1.15X, and 1.32X, where X 

equals the expected SPF of the test 

product. The MED is the smallest 

erythemally-effective UV dose required 

to produce mild redness within the 

subsite border at 16 to 24 hours postexposure. Calculate the SPF value of 

each sunscreen product and sunscreen 

standard using the MED of sunscreenprotected skin (MED(PS)) and the final 

unprotected skin MED (MED(US)) as 

follows: 

(4) Determination of the test product 

SPF and PCD. Use data from at least 20 

test subjects with n representing the 

number of subjects used. First, compute 

the SPF value for each subject as stated 

in paragraphs (d)(2) and (d)(3) of this 

section. Second, compute the mean SPF 

value, x ̄, and the standard deviation, s, 

for these subjects. Third, obtain the 

upper 5-percent point from Student’s t 

distribution table with n-1 degrees of 

freedom. Denote this value by t. Fourth, 

compute ts/√n. Denote this quantity by 

A (i.e., A = ts/√n). Fifth, calculate the 

SPF value to be used in labeling as 


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follows: The label SPF equals the largest 

whole number less than x ̄ - A. Sixth and 

last, the sunscreen product is classified 

into a PCD as follows: If 50 + A < x ̄, the 

PCD is Highest; if 30 + A ≤ x ̄ ≤ 50 + A, 

the PCD is High; if 15 + A ≤ x ̄ < 30 + 

A, the PCD is Medium; if 2 + A ≤ x ̄ < 

15 + A, the PCD is Low; if x ̄ < 2 + A, 

the product shall not be labeled as an 

OTC sunscreen drug product and may 

not display an SPF value. 

§ 352.71 UVA in vitro testing procedure. 

(a) Light source for transmittance/ 

absorbance measurements. The light 

source should satisfy the requirements 

for solar simulators described in 

§ 352.70(b). 

(b) Substrate. Use optical-grade quartz 

plate suitable for substrate 

spectrophotometry that has been 

roughened on one side. 

(c) Sample holder. The sample holder 

should hold the substrate in a horizontal 

position to avoid flowing of the 

sunscreen drug product from one edge 

of the substrate to the other. It should 

be mounted as close as possible to the 

input optics of the spectroradiometer to 

maximize capture of forward scattered 

radiation. The sample holder should be 

a thin, flat plate with a suitable aperture 

through which UV radiation can pass. 

The substrate will be placed on the 

upper surface of the sample holder. 

(d) Spectroradiometer input optics. 

Unless the spectroradiometer is 

equipped with an integrating sphere, an 

ultraviolet radiation diffuser should be 

placed between the sample and the 

input optics of the spectroradiometer. 

The diffuser will be constructed from 

any UV radiation transparent material 

(e.g., Teflon or quartz). The diffuser 

ensures that the radiation received by 

the spectroradiometer is not collimated. 

The spectroradiometer input slits 

should be set to provide a bandwidth 

that is less than or equal to 5 

nanometers. 

(e) Sunscreen drug product 

application to substrate. The accuracy 

of the test depends upon the application 

of a precisely controlled amount of 

sunscreen product with a uniform 

distribution over the application area of 

the substrate. The product is applied at 

2 milligrams per square centimeter to 

the substrate. To achieve uniform 

distribution over the substrate, the 

sunscreen product should be applied in 

a series of small dots over the 

application area of the substrate and 

then spread evenly using a gloved 

finger. A very light spreading action for 

a short period of time (approximately 10 

seconds) should be used when 

distributing the product to ensure 

complete coverage without excessive 

buildup of product in the troughs of the 

substrate. 

(f) Pre-irradiation to account for 

differences in photostability. To account 

for potentially varying degrees of 

photostability between sunscreen drug 

products, irradiate the sunscreen 

product on the substrate with a dose of 

UV radiation equal to the SPF of the 

sunscreen product multiplied by 200 J/ 

m2-eff multiplied by 2/3. A UV 

radiation dose of 200 J/m2-eff is 

equivalent to one minimal erythema 

dose (MED). The UV dose to be 

delivered is determined by multiplying 

the light source spectral irradiance 

action spectrum for erythema in ‘‘CIE S 

007/E Erythemal Reference Action 

Spectrum and Standard Erythema 

Dose,’’ at each wavelength, integrating 

over wavelength, and multiplying the 

integral by the exposure time. ‘‘CIE S 

007/E Erythemal Reference Action 

Spectrum and Standard Erythema 

Dose,’’ dated 1998, is incorporated by 

reference in accordance with 5 U.S.C. 

552(a) and 1 CFR part 51. Copies are 

available from CIE Central Bureau, 

Kegelgasse 27, A–1030, Vienna, Austria, 

or may be examined at the Center for 

Drug Evaluation and Research, 10903 

New Hampshire Ave., Bldg. 22, Silver 

Spring, MD 20993, or at the Office of the 

Federal Register, 800 North Capitol St. 

NW., suite 700, Washington, DC. 

(g) Calculation of the spectral 

transmittance at each wavelength 

interval. The dynamic range of the 

measurement system and the intensity 

of the light source should be sufficiently 

high that signals measured at all UV 

wavelengths (290 to 400 nanometers) 

through a highly absorbing sunscreen 

product are above the noise level of the 

measurement system. Spectral 

irradiance will be measured at 5 

nanometer intervals, from 290 to 400 

nanometers. At least 12 measurements 

of spectral irradiance transmitted 

through the substrate without sunscreen 

drug product present will be obtained 

from different locations on the substrate 

surface (C(λ)1, C(λ)2, C(λ)3, . . . C(λ)12). 

In addition, a minimum of 12 

measurements of spectral irradiance 

transmitted through the substrate with 

the sunscreen drug product present will 

be similarly obtained after preirradiation of the sunscreen drug 

product (P(λ)1, P(λ)2, P(λ)3, . . . P(λ)12). 

The mean transmittance for wavelength 

λ, T(λ), is the ratio of the mean of the 

C(λ) values to the mean of the P(λ) 

values, as follows: 

The standard deviation, s, associated 

with the spectral transmittance is 

evaluated using Taylor’s approximation, 

as follows: 

where C(λ) = mean of the measurements 

of C at wavelength λ. 

P(λ) = mean of the measurements of P 

at wavelength λ. 

s(C(λ)) = standard deviation of the 

measurements of C at wavelength λ. 

s(P(λ)) = standard deviation of the 

measurements of P at wavelength λ. 

s(C(λ)) is calculated as follows: 

s(P(λ)) is calculated as follows: 

This calculation gives 23 spectral 

transmittance values with associated 

standard deviations, one for each 5 

nanometer wavelength increment from 

290 to 400 nanometers. The standard 

deviation values will provide an 

indication of the uniformity of 

sunscreen drug product spreading 

during application to the substrate. The 

coefficient of variation, which is the 

standard deviation divided by the mean, 

and expressed as a percentage, should 

be less than 10 percent. 

(h) Calculation of the UVA I/UV ratio. 

(1) Spectral transmittance values, T(λ), 

are converted into absorbance values, 

A(λ), by taking the negative logarithm of 


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the spectral transmittance value as 

follows: 

A(λ) = -log T(λ) 

The calculation yields 23 

monochromatic absorbance values in 5 

nanometer increments from 290 to 400 

nanometers. 

(2) The index of UVA I protection is 

calculated as the area (per unit 

wavelength) under the UVA I portions 

of a plot of wavelength versus A(λ), 

divided by the area (per unit 

wavelength) under the total curve, as 

follows: 

UVA I area per unit λ is given as: 

UV area per unit λ is given as: 

where: A(λ) = effective absorbance given 

as -log T(λ) 

d(λ) = wavelength interval between 

measurements 

B(λ) = any biological action spectrum 

factor 

Because no appropriate biological action 

spectrum for UVA radiation damage has 

been universally accepted, no action 

spectrum is specified. The value of B(λ) 

is, therefore, equal to 1.0 for all 

wavelengths. 

(3) The integrals in the formulae in 

paragraphs (h)(1) and (h)(2) of this 

section are evaluated using Simpson’s 

Rule for irregular areas, which states: 

Area = h/3 x [Y0 + Y2m + 4(Y1 + Y3 . . . + 

Y2m-1) + 2(Y2 + Y4 + . . . Y2m-2)] 

In this equation, Y0, Y1, Y2, . . . Y2m are 

the lengths of 2m parallel lines drawn 

vertically to divide the area under the 

curve of a graph into 2m-1 segments of 

equal width, h. In practice, the values of 

Y0, Y1, Y2, . . . Y2m are the A(λ) values 

determined and h is the wavelength 

interval at which the spectral 

transmittance is determined (i.e., 5 

nanometers). 

(4) UVA I area per unit wavelength 

(aUVA I/λ) is calculated as follows: 

aUVA I/λ = 5/3 x [A340 + A400 + 4(A345 + ... 

+ A395) + 2(A350 + A360 + A370 + ... + A390)]/ 

60 

UV area per unit wavelength (aUV/λ) is 

calculated as follows: 

aUV/λ = 5/3 x [A290 + A400 + 4(A295 + A305

+ A315 + ... + A395) + 2(A300 + A310 + ... + 

A390)]/110 

UVA I/UV ratio is calculated as follows: 

(i) Category determination of the UVA 

I/UV ratio. Perform at least 5 separate 

determinations of the UVA I/UV ratio, 

from which the mean can be calculated. 

Using the mean, the sunscreen drug 

product is classified by in vitro UVA I/ 

UV ratio as follows: 

UVA I/UV Ratio Category 

0.20 to 0.39 Low 

0.40 to 0.69 Medium 

0.70 to 0.95 High 

greater than 0.95 Highest 

§ 352.72 UVA in vivo testing procedure. 

(a) Standard sunscreen. A standard 

sunscreen shall be tested concomitantly 

in the procedure for determining the 

UVA protection factor (UVA–PF) value 

by means of persistent pigment 

darkening to ensure the uniform 

evaluation of sunscreen drug products. 

The standard sunscreen shall be a 

preparation containing 7 percent 

padimate O and 3 percent oxybenzone 

as specified in § 352.70(a)(3). For the 

test to be valid, the measured mean 

UVA–PF value of the standard 

preparation shall be 3.2 with a standard 

deviation less than or equal to 0.5. 

(b) Light source. The light source used 

for determining the UVA–PF value of a 

sunscreen drug product shall provide a 

continuous emission spectrum in the 

range of 320 to 400 nanometers. The 

ratio of UVA I (340 to 400 nanometers) 

to UVA II (320 to 340 nanometers) in the 

final beam shall be close to that of 

sunlight, i.e., emitted UVA II shall be 8 

to 20 percent of the total UVA radiation. 

Optical radiation from 250 to 320 

nanometers shall be less than 0.1 

percent of the optical radiation between 

320 to 400 nanometers. Exclude visible 

and infrared light to avoid the darkening 

effects of visible light and the effect of 

heat. Perform monitoring and 

maintenance of the light source as 

specified in § 352.70(b)(3). 

(c) General testing procedures—(1) 

Medical history. Obtain a medical 

history from each subject with emphasis 

on the effects of sunlight on his/her 

skin. Determine that each subject is in 

good general health and has skin type II 

or III (as described in this paragraph). 

Skin Type and Sunburn and Tanning 

History (Based on first 30 to 45 minutes 

of sun exposure after a winter season of 

no sun exposure). 

I: Always burns easily; never tans 

(sensitive). 

II: Always burns easily; tans minimally 

(sensitive). 

III: Burns moderately; tans gradually 

(light brown) (normal). 

IV: Burns minimally; always tans well 

(moderate brown) (normal). 

V: Rarely burns; tans profusely (dark 

brown) (insensitive). 

VI: Never burns; deeply pigmented 

(insensitive). 

Determine that the subject is not taking 

topical or systemic medication that is 

known to alter responses to ultraviolet 

radiation and that the subject has no 

history of sensitivities to topical 

products and/or abnormal responses to 

sunlight, such as a phototoxic or 

photoallergic response. 

(2) Physical examination. The 

physical examination shall be 

conducted as specified in § 352.70(c)(1). 

(3) Informed consent. Obtain legally 

effective written informed consent from 

all subjects. 

(4) Test site delineation—(i) Test site. 

A test site is the location on the back for 

determining the subject’s initial and 

final minimal pigmenting dose (MPD) 

for unprotected skin and for 

determining UVA–PF values after 

application of the sunscreen standard 

and the test sunscreen product(s). There 

typically are 4 to 6 test sites for each 

subject. Test sites should be located on 

the back between the beltline and the 

shoulder blades (scapulae) and lateral to 

the midline. Each test site shall be a 

minimum of 50 square centimeters 

(cm2) (i.e., 5 x 10 centimeters). Outline 

the test sites to which the sunscreen 

standard and the test sunscreen 

product(s) will be applied with 

indelible ink. If the subject is to receive 

the doses of ultraviolet radiation in an 

upright (seated) position, draw the lines 

on the skin with the subject upright 

(seated). If the subject is to receive the 

doses of ultraviolet radiation while 

prone, draw the lines with the subject 

prone. 

(ii) Test subsite. Test subsites are the 

locations to which ultraviolet radiation 

is administered within a test site. At 

least 5 test subsites will receive UV 

doses within each test site. Test subsites 

will be at least 1 cm2 in area and will 

be separated from each other by at least 

1 cm. Mark the location of each test 

subsite with indelible ink. 

(5) Application of test materials. 

Apply the test sunscreen product and 

the standard sunscreen as specified in 

§ 352.70(c)(5). 

(6) Waiting period. Before exposing 

the test site areas after applying a 

product, wait at least 15 minutes. 

(7) Number of subjects. A test panel 

shall consist of 20 to 25 subjects with 

at least 20 subject who produce valid 

data for analysis. Data is valid unless 

rejected in accordance with 

§ 352.70(c)(9). If more than 5 subjects 

are rejected based on § 352.70(c)(9), the 

panel is disqualified, and a new panel 

must be created. 


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(8) Response criteria. In order that the 

person who evaluates the MPD 

responses is not biased, he/she must not 

be the same person who applied the 

sunscreen drug product to the test site 

or administered the doses of UV 

radiation. After UV radiation exposure 

from the solar simulator is completed, 

all immediate responses shall be 

recorded. These may include an 

immediate darkening or tanning, 

typically grayish or purplish in color, 

which fades in 30 to 60 minutes; an 

immediate reddening at the subsite, due 

to heating of the skin, which fades 

rapidly; and an immediate generalized 

heat response, spreading beyond the 

subsite, which fades in 30 to 60 

minutes. After the immediate responses 

are noted, each subject shall shield the 

exposed area from further UV radiation 

until the MPD response is evaluated. 

Determine the MPD 3 to 24 hours after 

exposure. Evaluate the pigmentation 

responses of each test site using either 

tungsten or warm white fluorescent 

lighting that provides 450 to 550 lux of 

illumination at the test site. For the 

evaluation, the test subject should be in 

the same position used when the test 

site was irradiated. For each test site, 

determine the smallest UV dose that 

produced mild pigmentation reaching 

the borders of the test subsite. The MPD 

is the smallest UV dose required to 

produce the first perceptible pigment 

darkening at 3 to 24 hours postexposure. To determine the MPD, there 

must be at least one subsite that 

received a smaller UV dose and does not 

produce pigmentation as well as a 

subsite(s) with somewhat more intense 

pigmentation. For subsites showing 

pigmentation, the maximal exposure 

should be no more than twice the total 

energy of the minimal exposure. 

(9) Rejection of test data. Reject test 

data if the exposure series fails to elicit 

an MPD response on either the treated 

or unprotected skin sites, or all subsites 

within a test site show more intense 

responses than the threshold 

pigmentation response, or the responses 

are inconsistent with the series of UV 

doses administered, or the subject was 

noncompliant, e.g., the subject 

withdraws from the test due to illness 

or work conflicts or does not shield the 

exposed testing sites from further UV 

radiation until the MPD is read. 

(d) Determination of UVA–PF 

values—(1) Determination of MPD of 

unprotected skin. Administer a series of 

five UV radiation doses expressed as 

Joules per square meter to the subsites 

within each test site on a subject using 

the light source described in paragraph 

(b) of this section. Use the series of five 

exposures to the unprotected test site to 

determine the initial unprotected MPD. 

Select the doses that are a geometric 

series represented by (1.25n), wherein 

each exposure dose is 25 percent greater 

than the previous exposure dose to 

maintain the same relative uncertainty 

(expressed as a constant percentage), 

independent of the subject’s sensitivity 

to UV radiation. Usually, the UV 

radiation for determining the initial 

unprotected MPD is administered the 

day prior to applying the sunscreen 

product and standard sunscreen, and 

the responses are then evaluated 

immediately prior to applying the 

sunscreen product and sunscreen 

standard. Determine the final 

unprotected MPD on the same day that 

UV radiation is administered to the 

sunscreen-protected test sites. Use the 

final unprotected MPD (MPD(US)) in 

calculating UVA–PF. 

(2) Determination of individual UVA–

PF values. Administer a series of five 

UV radiation doses expressed as Joules 

per square meter to the subsites within 

each test site on a subject using the light 

source described in paragraph (b) of this 

section. The five UV doses will be a 

geometric series as described in 

paragraph (d)(1) of this section, where 

the middle exposure represents the 

expected UVA–PF. Use exposures that 

are the product of the initial 

unprotected MPD times 0.64X, 0.80X, 

1.00X, 1.25X, and 1.56X, where X 

equals the expected UVA–PF of the test 

product. The MPD is the smallest UV 

dose required to produce pigmentation 

at 3 to 24 hours post-exposure. Calculate 

the UVA–PF value of each sunscreen 

product and sunscreen standard using 

MPD of sunscreen-protected skin 

(MPD(PS)) and the final unprotected 

MPD (MPD(US)) as follows: 

(3) Determination of test product 

UVA–PF and UVA product category 

designation (PCD). Use data from at 

least 20 test subjects with n representing 

the number of subjects used. First, 

compute the UVA–PF value for each 

subject as stated in paragraph (d)(2) of 

this section. Second, compute the mean 

UVA–PF value, x, and the standard 

deviation, s, for these subjects. Third, 

obtain the upper 5-percent point from 

Student’s t distribution table with n-1 

degrees of freedom. Denote this value by 

t. Fourth, compute ts/√n. Denote this 

quantity by A (i.e., A = ts/√n). Fifth, 

calculate the UVA–PF value to be used 

in labeling as follows: The label UVA–

PF equals the largest whole number less 

than x - A. Sixth and last, the drug 

product is classified into a PCD as 

follows: If 12 + A ≤ x, the PCD is 

Highest; if 8 + A ≤ x < 12 + A, the PCD 

is High; if 4 + A < x < 8 + A, the PCD 

is Medium; if 2 + A ≤ x < 4 + A, the 

PCD is Low; if x < 2 + A, the product 

shall not display a UVA–PF value. 

§ 352.73 Determination of the labeled UVA 

protection value. 

Test the sunscreen product in 

accordance with §§ 352.71 and 352.72. 

The UVA category on the principal 

display panel (PDP) of the tested 

sunscreen product, as specified in 

§ 352.50, shall be the lower of either the 

UVA I/UV ratio category determined in 

§ 352.71(j) or the UVA–PF product 

category designation (PCD) determined 

in § 352.72(d)(3). If the product does not 

attain at least a ‘‘low’’ category rating for 

both the UVA–PF and the UVA I/UV 

ratio, the product shall not display a 

UVA claim. State the final combined 

category rating (i.e., the lower of either 

the UVA I/UV ratio or UVA–PF PCD 

categories) on the PDP of the product 

along with the corresponding number of 

stars for that combined category rating 

as follows: 

Combined Category Rating Star Rating 

Low ★✰✰✰ 

Medium ★★✰✰ 

High ★★★✰ 

Highest ★★★★ 

11. Section 352.76 is amended by 

revising the introductory paragraph and 

paragraphs (a) introductory text, (a)(6), 

(b) introductory text, and (b)(10) to read 

as follows: 

§ 352.76 Determination if a product is 

water resistant or very water resistant. 

The general testing procedures in 

§ 352.70(c) shall be used as part of the 

following tests, except where modified 

in this section. An indoor fresh water 

pool, whirlpool, and/or jacuzzi 

maintained at 23 to 32 °C shall be used 

in these testing procedures. Fresh water 

is clean drinking water that meets the 

standards in 40 CFR part 141. The pool 

and air temperature and the relative 

humidity shall be recorded. 

(a) Procedure for testing the water 

resistance of a sunscreen product. For 

sunscreen products making the claim of 

‘‘water resistant,’’ the label SPF and, if 

appropriate, UVA values shall be the 

label SPF and UVA values determined 

after 40 minutes of water immersion 

using the following procedure for the 

water resistance test: 

* * * * * 

(6) Begin light source exposure to test 

site areas as described in § 352.70(b) 

and, if appropriate, § 352.72(b). 

(b) Procedure for testing a very water 

resistant sunscreen product. For 


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sunscreen products making the claim of 

‘‘very water resistant,’’ the label SPF 

and, if appropriate, UVA values shall be 

the label SPF and UVA values 

determined after 80 minutes of water 

immersion using the following 

procedure for the water resistance test: 

* * * * * 

(10) Begin light source exposure to 

test site areas as described in § 352.70(b) 

and, if appropriate, § 352.72(b). 

Dated: August 10, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 07–4131 Filed 8–23–07; 8:45 am] 

BILLING CODE 4160–01–S 


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