64962 Federal Register / Vol. 69, No. 216 / Tuesday, November 9, 2004 / Notices 

1Under section 403(r)(6)(A) of the act (21 U.S.C. 

343(r)(6)(A)), such a statement is one that ‘‘claims 

a benefit related to a classical nutrient deficiency 

disease and discloses the prevalence of such disease 

in the United States, describes the role of a nutrient 

or dietary ingredient intended to affect the structure 

or function in humans, characterizes the 

documented mechanism by which a nutrient or 

dietary ingredient acts to maintain such structure or 

function, or describes general well-being from 

consumption for a nutrient or dietary ingredient.’’

IV. Electronic Access

An electronic version of this guidance 

is available on the Internet at http://

www.fda.gov/ora under ‘‘Compliance 

References.’’

Dated: November 2, 2004.

Steve M. Niedelman,

Acting Associate Commissioner for 

Regulatory Affairs.

[FR Doc. 04–24873 Filed 11–4–04; 8:57 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004D–0466]

Draft Guidance for Industry: 

Substantiation for Dietary Supplement 

Claims Made Under Section 403(r)(6) of 

the Federal Food, Drug, and Cosmetic 

Act; Availability

AGENCY: Food and Drug Administration, 

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance entitled 

‘‘Guidance for Industry: Substantiation 

for Dietary Supplement Claims Made 

Under Section 403(r)(6) of the Federal 

Food, Drug, and Cosmetic Act.’’ This 

draft guidance describes the amount, 

type, and quality of evidence that FDA 

recommends a manufacturer have to 

substantiate a claim under section 

403(r)(6) of the Federal Food, Drug, and 

Cosmetic Act (act). FDA is also 

announcing its decision not to publish 

additional guidance on applying the 

structure/function rule at this time.

DATES: Submit written or electronic 

comments on the draft guidance and the 

collection of information provisions by 

January 10, 2005, to ensure adequate 

consideration in preparation of any final 

guidance document. General comments 

on agency guidance documents are 

welcome at any time.

ADDRESSES: Submit written comments 

on the draft guidance document and the 

collection of information provisions to 

the Division of Dockets Management 

(HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments on the draft 

guidance and the collection of 

information to http://www.fda.gov/

dockets/ecomments. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document.

FOR FURTHER INFORMATION CONTACT:

Vickey Lutwak, Center for Food Safety 

and Applied Nutrition, Food and Drug 

Administration, 5100 Paint Branch 

Pkwy., College Park, MD 20740, 301–

436–2375, fax: 301–436–2636, e-mail: 

Vickey.Lutwak@cfsan.fda.gov

SUPPLEMENTARY INFORMATION:

I. Background—Substantiation Draft 

Guidance

Section 403(r)(6) of the act (21 U.S.C. 

343(r)(6)) requires that a manufacturer 

of a dietary supplement making a 

nutritional deficiency, structure/

function, or general well-being claim 

have substantiation that the claim is 

truthful and not misleading.1

This draft guidance document is 

intended to describe the amount, type, 

and quality of evidence FDA 

recommends a manufacturer have to 

substantiate a claim under section 

403(r)(6) of the act. This draft guidance 

document is limited to issues pertaining 

to substantiation under section 403(r)(6) 

of the act; it does not extend to 

substantiation issues that may exist in 

other sections of the act.

FDA intends to apply a standard for 

substantiating claims for dietary 

supplements that is consistent with the 

Federal Trade Commission’s (FTC’s) 

standard for dietary supplements and 

other health related products of 

‘‘competent and reliable scientific 

evidence.’’ FDA seeks comments on this 

draft guidance only as they relate to 

FDA’s use and application of the 

standard and approach that are 

described in the guidance. We (FDA) are 

not seeking comment on FTC’s 

application, use, or interpretation of 

their standard.

The agency has adopted good 

guidance practices (GGPs) that set forth 

the agency’s policies and procedures for 

the development, issuance, and use of 

guidance documents (21 CFR 10.115). 

The draft guidance document is being 

issued as a Level 1 guidance consistent 

with FDA’s GGPs. The draft guidance 

document represents the agency’s 

current thinking on the amount, type, 

and quality of evidence FDA 

recommends a manufacturer have to 

substantiate a claim under section 

403(r)(6) of the act. It does not create or 

confer any rights for or on any person 

and does not operate to bind FDA or the 

public. An alternative method may be 

used as long as it satisfies the 

requirements of the applicable statutes 

and regulations.

II. Paperwork Reduction Act of 1995—

Substantiation Draft Guidance

This draft guidance document 

contains information collection 

provisions that are subject to review by 

the Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (the PRA) (44 U.S.C. 3501–

3520). Under the PRA, Federal agencies 

must obtain approval from the OMB for 

each collection of information they 

conduct or sponsor. ‘‘Collection of 

information’’ is defined in 44 U.S.C. 

3502(3) and 5 CFR 1320.3 and includes 

agency requests or requirements that 

members of the public submit reports, 

keep records, or provide information to 

a third party. Section 3506(c)(2)(A) of 

the PRA (44 U.S.C. 3506(c)(2)(A)) 

requires Federal agencies to provide a 

60-day notice in the Federal Register

concerning each proposed collection of 

information before submitting the 

collection to OMB for approval. To 

comply with this requirement, FDA is 

hereby publishing notice of the 

proposed collection of information set 

forth in this document.

FDA invites comments on: (1) 

Whether the proposed collection of 

information is necessary for the proper 

performance of FDA’s functions, 

including whether the information will 

have practical utility; (2) the accuracy of 

FDA’s estimate of the burden of the 

proposed collection of information, 

including the validity of the 

methodology and assumptions used; (3) 

ways to enhance the quality, utility, and 

clarity of the information to be 

collected; and (4) ways to minimize the 

burden of the collection of information 

on respondents, including through the 

use of automated collection techniques, 

when appropriate, and other forms of 

information technology.

Draft Guidance for Industry: 

Substantiation for Dietary Supplement 

Claims Made Under Section 403(r)(6) of 

the Federal Food, Drug, and Cosmetic 

Act; Availability

Section 403(r)(6) of the act requires 

that a manufacturer of a dietary 

supplement making a nutritional 

deficiency, structure/function, or 

general well-being claim have 

substantiation that the statement is 

truthful and not misleading. This draft 

guidance document is intended to 

describe the amount, type, and quality 

of evidence FDA recommends a dietary 

supplement manufacturer have to 

Federal Register / Vol. 69, No. 216 / Tuesday, November 9, 2004 / Notices 64963

substantiate a claim under section 

403(r)(6) of the act. This guidance does 

not discuss the types of claims that can 

be made concerning the effect of a 

dietary supplement on the structure or 

function of the body, nor does it discuss 

criteria to determine when a statement 

about a dietary supplement is a disease 

claim.

FDA estimates the burden for this 

information collection as follows:

TABLE 1.—ESTIMATED REPORTING BURDEN1

Claim type 

No. of

Respondents

Annual Frequency

per Response

Total Annual

Responses

Hours per

Response Total Hours 

Widely known, established 667 1 667 1 667

Pre-existing, not widely established 667 1 667 120 80,040

Novel 667 1 667 120 80,040

Annual one time burden hours 160,747

1There are no capital costs or operating and maintenance costs associated with this information collection.

Dietary supplement manufacturers 

will only need to collect information to 

substantiate their product’s nutritional 

deficiency, structure/function, or 

general well-being claim if they chose to 

place a claim on their product’s label. 

Gathering evidence on their product’s 

claim is a one time burden; they collect 

the necessary substantiating information 

for their product as required by section 

403(r)(6) of the act.

The standard discussed in the 

guidance for substantiation of a claim 

on the labeling of a dietary supplement 

is consistent with standards set by the 

FTC for dietary supplements and other 

health related products that the claim be 

based on competent and reliable 

scientific evidence. This evidence 

standard is broad enough that some 

dietary supplement manufacturers may 

only need to collect peer-reviewed 

scientific journal articles to substantiate 

their claims; other dietary supplement 

manufacturers whose products have 

properties that are less well documented 

may have to conduct studies to build a 

body of evidence to support their 

claims. It is unlikely that a dietary 

supplement manufacturer will attempt 

to make a claim when the cost of 

obtaining the evidence to support the 

claim outweighs the benefits of having 

the claim on the product’s label. It is 

likely that manufacturers will seek 

substantiation for their claims in the 

scientific literature.

The time it takes to assemble the 

necessary scientific information to 

support their claims depends on the 

product and the claimed benefits. If the 

product is one of several on the market 

making a particular claim for which 

there is adequate publicly available and 

widely established evidence supporting 

the claim, then the time to gather 

supporting data will be minimal; if the 

product is the first of its kind to make 

a particular claim or the evidence 

supporting the claim is less publicly 

available or not widely established, then 

gathering the appropriate scientific 

evidence to substantiate the claim will 

be more time consuming.

FDA assumes that it will take only 

about an hour to assemble information 

needed to substantiate a claim on a 

particular dietary supplement when the 

claim is widely known and established. 

These are likely products whose 

claimed effects have been long studied 

and the results of the studies are widely 

available in credible textbook and 

reference books, therefore making the 

substantiation burden minimal. FDA 

believes it will take closer to 120 hours 

to assemble supporting scientific 

information when the claim is novel or 

when the claim is pre-existing but the 

scientific underpinnings of the claim are 

not widely established. These are claims 

that may be based on emerging science, 

where conducting literature searches 

and understanding the literature takes 

time. It is also possible that references 

for claims made for some dietary 

ingredients or dietary supplements may 

primarily be found in foreign journals 

and in foreign languages or in the older, 

classical literature where it is not 

available on computerized literature 

databases or in the major scientific 

reference databases, such as the 

National Library of Medicine’s literature 

database, all of which increases the time 

of obtaining substantiation.

In the final rule on statements made 

for dietary supplements concerning the 

effect of the product on the structure or 

function of the body (structure/function 

final rule (65 FR 1000, January 6, 2000)), 

FDA estimated that there were 29,000 

dietary supplement products marketed 

in the United States (65 FR 1000 at 

1045). Assuming that the flow of new 

products is 10 percent per year, then 

2,900 new dietary supplement products 

will come on the market each year. The 

structure/function final rule estimated 

that about 69 percent of dietary 

supplements have a claim on their 

labels, most probably a structure/

function claim (65 FR 1000 at 1046). 

Therefore, we assume that supplement 

manufacturers will need time to 

assemble the evidence to substantiate 

each of the 2,001 claims (2,900 x 69%) 

made each year. If we assume that the 

2,001 claims are equally likely to be preexisting widely established claims, 

novel claims, or pre-existing claims that 

are not widely established, then we can 

expect 667 of each of these types of 

claims to be substantiated per year. Row 

1 of Table 1 of this document shows that 

the annual burden hours associated 

with assembling evidence for claims is 

160,747 (667 x 1hr, 667 x 120 hrs, and 

667 x 120 hrs).

There are no capital costs or operating 

and maintenance costs associated with 

this information collection.

III. Guidance on Applying the 

Structure/Function Rule

On January 6, 2000, FDA published a 

final rule, often referred to as the 

‘‘structure/function rule,’’ implementing 

section 403(r)(6) of the act concerning 

the types of statements that can be made 

regarding the effect of a dietary 

supplement on the structure or function 

of the body (65 FR 1000). This rule, 

codified in § 101.93(f) (21 CFR 101.93(f) 

and (g)), distinguishes between disease 

claims and structure/function claims. 

As discussed in § 101.93, if the label or 

labeling of a product marketed as a 

dietary supplement bears a disease 

claim as defined in that rule, the 

product will be subject to regulation as 

a drug unless the claim is an authorized 

health claim for which the product 

qualifies.

64964 Federal Register / Vol. 69, No. 216 / Tuesday, November 9, 2004 / Notices 

In the preamble to the final rule, FDA 

stated that it intended to publish a 

guidance on applying this rule. In a 

notice published in the Federal Register

on February 22, 2001 (66 FR 11172), 

FDA invited public comments on the 

topics that should be included in such 

a guidance. FDA agrees with the 

comments that were submitted stating 

that the preamble to the structure/

function rule and the numerous 

courtesy letters that the agency has 

issued since the enactment of section 

403(r)(6) provide considerable guidance 

to dietary supplement manufacturers 

about the types of claims that the agency 

considers to be disease claims. 

Therefore, FDA has decided not to issue 

such a guidance at this time. FDA will 

continue to monitor dietary supplement 

manufacturers’ compliance with section 

403(r)(6) of the act and § 101.93, take 

enforcement action where appropriate, 

and reconsider the possibility of issuing 

guidance if future developments 

warrant.

IV. Comments

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding the substantiation 

draft guidance document. (FDA is not 

specifically seeking comment on its 

decision not to publish additional 

guidance on the structure/function 

rule.) Two copies of mailed comments 

are to be submitted, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. The draft 

guidance and received comments are 

available for public examination in the 

Division of Dockets Management 

between 9 a.m. and 4 p.m., Monday 

through Friday.

V. Electronic Access

Persons with access to the Internet 

may obtain the document at http://

www.cfsan.fda.gov or http://

www.fda.gov/dockets/ecomments. Once 

on this site, select 2004D–0466 

‘‘Guidance for Industry: Substantiation 

for Dietary Supplement Claims Made 

Under Section 403(r)(6) of the Federal 

Food, Drug, and Cosmetic Act’’ and 

follow the directions. Copies of this 

draft guidance may be obtained on the 

Internet from the CFSAN homepage at 

http://www.cfsan.fda.gov.

Dated: October 25, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04–24871 Filed 11–4–04; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HOMELAND 

SECURITY 

Border and Transportation Security; 

Notice to Aliens Included in the United 

States Visitor and Immigrant Status 

Indicator Technology System (US–

VISIT)

AGENCY: Border and Transportation 

Security Directorate, DHS.

ACTION: Notice.

SUMMARY: The Department of Homeland 

Security (Department or DHS) has 

established the United States Visitor 

and Immigrant Status Indicator 

Technology Program (US–VISIT), an 

integrated, automated entry-exit system 

that records the arrival and departure of 

aliens; verifies aliens’ identities; and 

authenticates aliens’ travel documents 

through comparison of biometric 

identifiers. On August 31, 2004, DHS 

implemented the second phase of US–

VISIT by publishing an interim final 

rule in the Federal Register at 69 FR 

53318 authorizing DHS to require 

certain aliens to provide fingerprints, 

photographs or other biometric 

identifiers upon arrival in the United 

States at the 50 most trafficked land 

ports of entry. The interim rule also 

authorized DHS to identify the specific 

land border ports in a separate notice 

published in the Federal Register. 

This notice identifies the 50 most 

trafficked land ports of entry where US–

VISIT will be implemented. The notice 

further provides an estimated date when 

each port will begin enrolling aliens in 

US–VISIT at the secondary inspection 

area. Pursuant to the August 31, 2004 

interim rule, all 50 ports of entry will 

begin enrolling aliens in US–VISIT no 

later than December 31, 2004. 

In addition, as stated in the August 

31, 2004 interim rule, this notice 

identifies only land ports of entry in 

which aliens will be enrolled in US–

VISIT upon entry into the United States. 

DHS will announce, through a future 

notice in the Federal Register, the 

piloting of a biometric data collection 

program at a limited number of sites as 

part of US–VISIT processing upon 

departure from the United States.

FOR FURTHER INFORMATION, CONTACT:

Michael Hardin, Senior Policy Advisor, 

US–VISIT, Border and Transportation 

Security, Department of Homeland 

Security, 1616 N. Fort Myer Drive, 18th 

Floor, Arlington, Virginia 22209, (202) 

298–5200. 

The 50 Land Border Ports of Entry 

(POEs) that will begin biometric data 

collection as part of US–VISIT 

processing no later than December 31, 

2004 are as follows: 

Estimated start date of November 15, 

2004 (6):

Port Huron POE, Blue Water Bridge, 

Highway 69 and International Border, 

Port Huron, Michigan 

Douglas POE, Rte 191 and International 

Border, Douglas, AZ 

Lincoln-Juarez Bridge POE, Laredo, TX 

Gateway to the Americas International 

Bridge POE, Laredo, TX 

Columbia Solidarity Bridge POE, 

Laredo, TX 

World Trade Bridge POE, Laredo, TX 

Estimated start date of December 6, 

2004 (11):

Niagara Falls POE (to include LewistonQueenstown, Whirlpool, and Rainbow 

Bridges), Niagara Falls, NY 

Peace Bridge POE, Moore Drive and 

International Border, Buffalo, NY 

Detroit Ambassador Bridge POE, Detroit, 

MI 

Detroit-Windsor Tunnel POE, Detroit, 

MI 

Lukeville POE, Highway 85 & 

International Border, Lukeville, AZ 

Nogales East (Deconcini POE), Nogales, 

AZ 

Nogales West (Mariposa POE), Nogales, 

AZ 

San Luis POE, Highway 95 & 

International Border, San Luis, AZ 

Andrade POE, Andrade, CA 

Calexico East-Imperial Valley POE, Rte 

111 and International Border, 

Calexico, CA 

Calexico West POE, Rte 111 and 

International Border, Calexico, CA

Estimated start date of December 13, 

2004 (11):

Fabens POE 18051, Island Guadalupe, 

Fabens, TX 

Presidio POE, Border Station Highway 

67, Presidio, TX 79845 

Santa Teresa POE, Santa Teresa, NM 

Otay Mesa POE, 9777 Via De La 

Amistad, San Diego, CA 

San Ysidro POE, Highway 5 and 

International Border, San Diego, CA 

Tecate POE, Hwy 188 and International 

Border, Tecate, CA 

Blaine-Pacific Highway POE, Rte. 543 

and International Border, Blaine, WA 

Blaine-Peace Arch POE, Interstate 5 and 

International Border, Blaine, WA 

Lynden POE, Rte. 539 and International 

Border, Lynden, WA 

Point Roberts POE, Tyee Drive and 

Roosevelt Way, Point Roberts, WA 

Sumas POE, Cherry Street and 

International Avenue, Sumas, WA 

Estimated start date of December 20, 

2004 (10):

Champlain POE, Highway 87 and 

International Border, Champlain, NY 

Massena POE, Rte. 45 and International 

Border, Rooseveltown, NY 

Thousand Islands POE, Highway 81 and 

International Border, Alexandria Bay, 

NY