34092 Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 98N–0428]

Food Labeling: Health Claims;

Antioxidant Vitamin A and BetaCarotene and the Risk in Adults of

Atherosclerosis, Coronary Heart

Disease, and Certain Cancers

AGENCY: Food and Drug Administration,

HHS.

ACTION: Interim final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing an

interim final rule to prohibit the use on

foods of a claim relating to the

relationship between antioxidant

vitamin A and beta-carotene and the

risk in adults of atherosclerosis,

coronary heart disease, and certain

cancers. This interim final rule is in

response to a notification of a health

claim submitted under section 303 of

the FDA Modernization Act of 1997

(FDAMA). FDA has reviewed statements

that the petitioner submitted in that

notification, and, in conformity with the

requirements of FDAMA, the agency is

prohibiting the claim because the

statements submitted as the basis of the

claim are not ‘‘authoritative statements’’

of a scientific body, as required by

FDAMA; therefore, section 303 of

FDAMA does not authorize use of this

claim. As provided for in section 301 of

FDAMA, this interim final rule is

effective immediately upon publication.

DATES: The interim final rule is effective

June 22, 1998; comments by September

8, 1998.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Christine J. Lewis, Center for Food

Safety and Applied Nutrition (HFS–

451), Food and Drug Administration,

200 C St. SW., Washington, DC 20204,

202–205–4168.

SUPPLEMENTARY INFORMATION:

I. The FDA Modernization Act of 1997

On November 21, 1997, the President

signed FDAMA into law (Pub. L. 105–

115), which amended the Federal Food,

Drug, and Cosmetic Act (the act).

Sections 303 and 304 of FDAMA

amended section 403(r)(2) and (r)(3) of

the act (21 U.S.C. 343(r)(2) and (r)(3)) by

adding new paragraphs (r)(2)(G),

(r)(2)(H), (r)(3)(C), and (r)(3)(D) to

section 403 of the act (21 U.S.C.

343(r)(2)(G), (r)(2)(H), (r)(3)(C), and

(r)(3)(D), respectively), which provide

for the use in food labeling of nutrient

content claims and health claims,

respectively, based on authoritative

statements. FDAMA requires that a

notification of the prospective nutrient

content claim or the prospective health

claim be submitted to FDA at least 120

days before a food bearing the claim

may be introduced into interstate

commerce. FDAMA and its

requirements are discussed in more

detail in ‘‘Food Labeling: Health Claims;

Antioxidant Vitamins C and E and the

Risk in Adults of Atherosclerosis,

Coronary Heart Disease, Certain

Cancers, and Cataracts’’ (hereinafter

referred to as ‘‘Health Claims; Vitamins

C and E’’), which is published

elsewhere in this issue of the Federal

Register. In particular, aspects of the

requirements for an ‘‘authoritative

statement’’ that are relevant to this

rulemaking and FDA’s review process

for notifications are discussed in

sections I.A and I.B, respectively, of that

document.

II. The Notification

Section 403(r)(2)(G) and (r)(3)(C) of

the act became effective on February 19,

1998. On February 23, 1998, the agency

received a notification from Weider

Nutrition International, Inc., containing

nine prospective claims that were

identified in the text of the notification

as health claims (Ref. 1). The

notification included statements that the

submitter described as authoritative

statements and a scientific literature

review for each claim. FDA has created

nine separate dockets, one for each of

the nine claims and is issuing a separate

interim final rule responding to each

claim.

This interim final rule addresses the

second claim in the notification. The

notification included 11 statements that

the petitioner identified as authoritative

statements on which the following

claim is based: ‘‘Antioxidant vitamin A

and beta-carotene may reduce the risk in

adults of atherosclerosis, coronary heart

disease and certain cancers. Sources of

Vitamin A and beta-carotene include

red, yellow and green leafy vegetables,

dairy products, and dietary

supplements.’’

The first sentence of this claim will be

discussed in greater detail in section III

of this document. FDA notes that this

claim describes the relationship

between vitamin A and beta-carotene

and a number of different diseases and,

thus, in point of fact, reflects several

prospective health claims. The second

sentence, ‘‘Sources of Vitamin A and

beta-carotene include red, yellow and

green leafy vegetables, dairy products,

and dietary supplements,’’ is not a

health claim. Given that the notification

indicated that it was intended to be a

notification for health claims, this

statement was not reviewed by FDA.

The submitter did not separately

identify this statement as any particular

type of claim.

Nonetheless, as a point of

information, the agency wishes to

highlight that statements that

appropriately constitute nutrient

content claims are allowed on labels

and in the labeling of foods and dietary

supplements. Moreover, statements that

constitute dietary guidance are also

allowed provided the information is

truthful and not misleading as required

by sections 403(a) and 201(n) of the act

(21 U.S.C. 321(n)). These aspects of

nutrient content claims and dietary

guidance are discussed in more detail in

‘‘Health Claims; Vitamins C and E,’’

which is published elsewhere in this

issue of the Federal Register.

III. Basis for the Action

FDA has reviewed the notification

submitted in support of the prospective

claim: ‘‘Antioxidant vitamin A and betacarotene may reduce the risk in adults

of atherosclerosis, coronary heart

disease and certain cancers.’’ The

agency has determined that none of the

11 statements submitted as the basis for

this claim meets the requirements in

section 403(r)(3)(C) of the act to be an

‘‘authoritative statement.’’ Because the

prospective claim is not based on an

authoritative statement, it is not

appropriate for the claim to appear on

food labels and labeling. Consequently,

FDA is issuing this interim final rule to

prohibit the use of this claim. A

discussion of the basis for the agency’s

action on the notification follows:

First, FDA determined that the

components required by section

403(r)(3)(C) of the act were present in

the notification submitted to support

this claim. Second, FDA determined

that, as a threshold matter, each of the

11 statements cited in support of the

claim may be attributable either to an

appropriate Federal scientific body or to

an employee or employees of such a

body.

The notification in support of the

claim that is the subject of this

document cites statements from: (1) A

report on nutrition monitoring prepared

for the Department of Health and

Human Services (DHHS) and the U.S.

Department of Agriculture (USDA); (2)

an electronic version provided on the

Internet of ‘‘Nutrition and Your Health:

Dietary Guidelines for Americans,’’
Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations 34093

recommendations developed by a group

of Federal agencies and issued jointly by

DHHS and USDA; (3) electronic

versions provided on the Internet of four

quarterly reports from USDA’s

Agricultural Research Service (ARS)

(statement 3, 7, 9, and 11); (4) electronic

versions provided on the Internet of two

interpretative summaries from USDA/

ARS Technology Transfer Information

Center (statements 4 and 10); (5) public

information provided on the Internet by

an institute of the National Institutes of

Health (NIH); (6) public information

provided on the Internet by USDA/ARS

Beltsville Human Nutrition Research

Center; and (7) public information

provided on the Internet by the National

Cancer Institute (NCI), an institute

within NIH. Thus, nine statements in

the notification are attributable to either

NIH or USDA/ARS. A 10th statement is

attributable to USDA and DHHS and is

intended for use by Federal agencies

including NIH, the Centers for Disease

Control and Prevention (CDC), and

USDA/ARS. An 11th statement from the

Dietary Guidelines for Americans is

attributable to a group of Federal

agencies that included NIH, CDC, and

USDA/ARS. Two of the agencies, NIH

and CDC, are highlighted in the statute

as Federal scientific bodies. FDA

believes that USDA/ARS is also a

scientific body of the U.S. Government

with official responsibility for public

health protection or research directly

relating to human nutrition for the

purposes of section 403(r)(2)(G) and

(r)(3)(C) of the act. The agencies that

were identified as users of the

‘‘Nutrition Monitoring Report’’ as well

as the group that developed the dietary

guidelines included Federal agencies

that are such scientific bodies, including

NIH, CDC, and USDA/ARS.

Accordingly, the statements provided in

the notification in support of the claim

may be attributable to appropriate

Federal scientific bodies or to their

employees.

Finally, however, none of the 11

statements discussed in sections III.A

through III.K of this document was

found to be an authoritative statement.

A. Statement 1

Statement 1 reads: ‘‘Beta-carotene and

other pro-vitamin a carotenoids can be

converted to vitamin A in the body.

Interest in the carotenoids has increased

in recent years because of the

accumulation of a large body of

evidence that foods high in carotenoids

are protective against a variety of

epithelial cancers.’’ The notification

identified statement 1 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found in a discussion on vitamins that

is contained in ‘‘Nutrition Monitoring in

the United States—An Update Report on

Nutrition Monitoring’’ that was

prepared for USDA and the Public

Health Service of DHHS by the Life

Sciences Research Office (SRO) of the

Federation of American Societies for

Experimental Biology (FASEB) (DHHS

Publication No. (PHS) 89–1255,

September 1989, 71). The notification

provided a photocopy of selected pages

from the report.

The statement indicates that there is

interest in the relationship because of a

growing body of evidence, but does not

confirm that the relationship is

considered scientifically valid or well

established. Rather, the context suggests

that further research would be

worthwhile and that the scientific

evidence about the relationship is

preliminary or inconclusive, as

described in section I.A.3 of ‘‘Health

Claims; Vitamins C and E,’’ which is

published elsewhere in this issue of the

Federal Register.

The agency notes that the report was

prepared under a DHHS contract by

LSRO/FASEB, an organization that is

neither a Federal Government agency

nor affiliated with the National

Academy of Sciences (NAS).

Contractual activities involved in the

preparation of the report were overseen

by several Federal agencies that

participate in the National Nutrition

Monitoring System (NNMS). The report

provides an independent expert panel’s

review of the dietary and nutritional

status of the U.S. population, as well as

the factors that determine status, based

on information available through the

NNMS; the report is an advisory

document for the Government agencies.

A disclaimer that appears on the inside

front cover of the report, which was not

included in the notification, states that,

although the report was printed and

distributed as part of a series of reports

from the NNMS, ‘‘the interpretations

contained in this report do not

necessarily express the views or policies

of the U.S. Government and its

constituent agencies’’ (Ref. 2).

Additionally, as noted in the foreword

of the report (page vii), representatives

of participating Federal Government

agencies ‘‘reviewed final drafts of the

report for technical accuracy and

satisfaction of the scope of work’’ (Ref.

2).

Given this disclaimer and the

statement from the foreword, the

component of the submitter’s

notification that provided ‘‘a concise

description of the basis upon which [the

submitter] relied for determining that

the requirements of [403(r)(3)(C)(i)] have

been satisfied’’ (as required by

403(r)(3)(C)(ii)(I) of the act) needed to

address why this statement was in fact

an authoritative statement. It did not.

The disclaimer indicates that Federal

Government agencies cannot be

considered to have ‘‘published’’ the

report in the sense that it represents

official policy of the agencies, as

discussed in section I.A.2 of ‘‘Health

Claims; Vitamins C and E,’’ which is

published elsewhere in this issue of the

Federal Register. The foreword of the

report indicates that it may involve a

deliberative review of the scientific

evidence about the dietary and

nutritional status of the U.S. population,

but that it does not involve a

deliberative review of the scientific

evidence about diet/disease

relationships. Further, the foreword

indicates that the Federal agencies did

not themselves conduct a deliberative

review of the scientific evidence

necessary for the statements in the

report to be ‘‘authoritative statements,’’

as described in section I.A.3 of ‘‘Health

Claims; Vitamins C and E,’’ which is

published elsewhere in this issue of the

Federal Register, but rather only a

review for technical accuracy of a final

draft of the report itself.

FDA concludes that the statement is

not an ‘‘authoritative statement’’

because it indicates that the scientific

evidence is preliminary or inconclusive,

that it does not reflect the official policy

of an appropriate scientific body, and

that no appropriate scientific body has

conducted a deliberative review of the

scientific evidence.

B. Statement 2

Statement 2 reads: ‘‘The antioxidant

nutrients found in plant foods (e.g.,

vitamin C, carotenoids, vitamin E, and

certain minerals) are presently of great

interest to scientists and the public

because of their potentially beneficial

role in reducing the risk of cancer and

certain other chronic diseases.’’ The

notification identified statement 2 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

from an electronic version of ‘‘Nutrition

and Your Health: Dietary Guidelines for

Americans’’ (Home and Garden Bulletin

No. 232, Fourth Ed., 1995), hereinafter

referred to as the ‘‘dietary guidelines,’’

issued jointly by DHHS and USDA and

provided on the Internet

(‘‘http:www.usda.gov/fcs/library/0102-

1.txt’’ accessed on 12/5/97). The

submitted material consists of selected

pages reprinted from the Internet

information, which identifies the seven

dietary guidelines and gives background
34094 Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations

information on the use of, and reasons

for, the guidelines. The dietary

guidelines reflect the findings of a panel

of scientists concerning the dietary

recommendations to be made to the U.S.

population, and the guidelines are based

on a deliberative review of the scientific

evidence about the nutrient/disease

relationships that the guidelines

address. The subject statement is found

within the discussion that accompanies

the recommendation to ‘‘Choose a diet

with plenty of grain products,

vegetables, and fruits.’’

The statement indicates that a

relationship between antioxidant

nutrients and cancer and other chronic

disease is ‘‘of great interest’’ because of

a ‘‘potentially beneficial role.’’ The

statement points to the need for future

research and suggests that whether a

relationship exists should be the subject

of scientific study, but does not indicate

that there exists a scientifically sound

relationship that should be accorded a

presumption of validity. This

assessment is further supported by the

fact that the subject of the dietary

guideline is the dietary importance of

grain products, vegetables, and fruits,

not the specific impact of antioxidant

nutrients, vitamin A and beta-carotene,

per se. FDA notes that, consistent with

the dietary guidelines, the agency has

authorized a health claim for the

relationship between cancer and fruits

and vegetables that contain vitamins A

(as beta-carotene) as well as vitamin C

and dietary fiber (21 CFR 101.78).

On this basis, FDA has concluded that

the statement is not an ‘‘authoritative

statement’’ under section 403(r)(3)(C) of

the act because the statement indicates

that the scientific evidence about the

relationship in question is preliminary

or inconclusive, as discussed in section

I.A.3 of the Federal Register ‘‘Health

Claims; Vitamins C and E,’’ which is

published elsewhere in this issue of the

Federal Register.

The dietary guidelines is the product

of a periodic review by a group of

Federal agencies, the most recent review

having been completed in 1995. FDA

did not attempt to reconvene this group

of Federal agencies to consult with it

about whether the statement is an

authoritative statement because, as

discussed previously, the wording and

context of the statement show that it is

not an authoritative statement under

section 403(r)(3)(C) of the act.

C. Statement 3

Statement 3 reads: ‘‘If the findings

hold up in further research, eating more

vegetables rich in beta-carotene and

related carotenoids–lutein and

lycopene–may help people ward off a

cold or flu as well as protect from

cancer * * *. The findings also suggest

that carotenoid-rich vegetables also

stimulate the immune system.’’ The

notification identified statement 3 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found in Human Nutrition (quarterly

reports of selected research projects, 4th

quarter 1996) issued by the USDA’s ARS

and provided on the Internet (‘‘http://

www.ars.usda.gov/is/qtr/q496/

hn496.htm’’ accessed on 12/3/97).

Human Nutrition is a periodic

compilation of brief (one paragraph)

descriptions of ongoing research being

conducted within the various ARS

facilities. The subject statement

(submitted to the agency as a hardcopy

reprint from the Internet) appears in a

description of research entitled: ‘‘Daily

servings of dark green and deep yellow

vegetables and tomatoes boost immune

response, a preliminary study suggests.’’

The paragraph describes the nature and

outcome of one ARS study and is

attributed to Tim R. Kramer and Beverly

Clevidence of the USDA Beltsville

Human Nutrition Research Center in

Beltsville, MD. The agency notes that

the research is identified as a

‘‘preliminary study.’’

The context of the paragraph, as well

as the wording of the statement (i.e., ‘‘if

the findings hold up’’), suggests that the

statement is based on preliminary

research and that further study is

needed. As such, the statement appears

to indicate that the scientific evidence

about the relationship is preliminary or

inconclusive.

The agency asked USDA whether the

statement is an ‘‘authoritative

statement’’ under FDAMA. USDA

responded to FDA that the statement is

not an authoritative statement of USDA

because it was not based upon a

deliberative review of the scientific

evidence regarding a relationship

between the nutrient and the disease in

question (Ref. 3). USDA explained that

the ARS quarterly reports describe

progress on individual projects without

a deliberative review of all relevant

scientific evidence. Therefore, FDA has

concluded that the statement is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act because it is not

based on a deliberative review of the

scientific evidence.

D. Statement 4

Statement 4 reads: ‘‘This research

involving cells provides data which

supports the general hypothesis that

beta-carotene and lutein protect cells by

serving as antioxidants.’’ The

notification identified statement 4 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found in a one paragraph interpretative

summary of a research report from

Technology Transfer Information

Center, TEKTRAN of USDA/ARS

entitled ‘‘Beta-carotene and Lutein

Protect the Plasma Membrane of HEPG2

Human Liver Cells Against Oxidantinduced Damage,’’ and provided on the

Internet (‘‘http://www.nalusda.gov/ttic/

tektran/data/000006/92/

0000069264.html’’ accessed on 12/3/97)

(ARS Report Number 69264). It

describes the nature and outcome of one

study, which is attributed to Keith J.

Martin, Mark L. Failla, and James C.

Smith, Jr.

The statement is not ‘‘about the

relationship between a nutrient and a

disease or health-related condition’’

because no disease is identified in the

statement. Therefore, FDA has

concluded that the statement does not

address a disease or health-related

condition and therefore is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act, as described in

section I.A.1 of ‘‘Health Claims;

Vitamins C and E,’’ which is published

elsewhere in this issue of the Federal

Register.

E. Statement 5

Statement 5 reads: ‘‘[Antioxidants]

may help prevent disease. Antioxidants

fight harmful molecules called oxygen

free radicals, which are created by the

body as cells go about their normal

business of producing energy * * *.

[S]ome studies show that antioxidants

may help prevent heart disease, some

cancers, cataracts, and other health

problems that are more common as

people get older.’’ The notification

identified statement 5 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found within an information piece

entitled: ‘‘Life Extension: Science or

Fiction?’’ that is provided on the

Internet by the Administration on Aging

and which includes statements from the

‘‘Age Page’’ of the National Institute on

Aging (an Institute of the NIH) (‘‘http:/

/www.aoa.dhhs.gov/aoa/pages/

agepages/lifextsn.html’’ accessed on 12/

2/97). This electronically available

information (submitted to the agency as

a hardcopy reprint from the Internet

information) is dated 1994, is

approximately two standard printed

pages in length, and is described as

being intended to inform the reader

about chemicals being studied that may

play a role in aging and what scientists

have learned about them so far. Topics
Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations 34095

covered include: Antioxidants, DNA,

DHEA, and other hormones. Ten tips for

healthy aging are also included. The

section on antioxidants is 14 sentences

in length and includes the 3 sentences

identified as the subject statement. The

agency notes that the last sentence of

the antioxidant section is: ‘‘More

research is needed before specific

recommendations can be made.’’

FDA asked NIH whether the statement

is an ‘‘authoritative statement’’ under

FDAMA. NIH responded to FDA that

the statement is not an authoritative

statement of NIH because it was

prepared by an individual from the

National Institute on Aging and is not

based on a deliberative review of

scientific evidence regarding the

nutrient-disease relationship in question

(Ref. 4). Therefore, FDA has concluded

that the statement is not an

‘‘authoritative statement’’ under section

403(r)(3)(C) of the act because it is not

based on a deliberative review of the

scientific evidence.

F. Statement 6

Statement 6 reads: ‘‘As potent

antioxidants, [lutein and lycopene] are

thought to contribute to the lower rates

of heart disease, cancer and other

diseases of aging among populations

that eat a lot of fruits and vegetables.’’

The notification identified statement 6

as an ‘‘authoritative statement’’ for

purposes of making the claim that is the

subject of this rulemaking. The

statement is found within an

information piece, ‘‘BHNRC Success

Stories,’’ provided on the Internet by

USDA/ARS Beltsville Human Nutrition

Research Center and entitled:

‘‘Carotenoids Show Their Real Colors’’

(‘‘http://www.barc.usda.gov/bhnrc/

success.htm’’ accessed on 12/4/97). This

electronically available information

(submitted to the agency as a hardcopy

reprint from the Internet information) is

undated. The section on carotenoids is

three brief paragraphs in length and

describes the nature and outcome of a

single ARS study attributed to Tim

Kramer and Beverly Clevidence. The

same study was also referenced in

ARS’s Human Nutrition quarterly report

as noted in the discussion of statement

3 in section III.C of this document.

The context of the section, as well as

the wording of the statement (i.e., ‘‘are

thought’’), suggests that the statement is

based on preliminary research and that

further study is needed. As such, the

statement appears to indicate that the

scientific evidence about the

relationship is preliminary or

inconclusive.

The agency asked USDA whether the

statement is an ‘‘authoritative

statement’’ under FDAMA. USDA

responded to FDA that the statement is

not an authoritative statement of USDA

because it was not based upon a

deliberative review of the scientific

evidence regarding a relationship

between the nutrient and the disease in

question (Ref. 3). USDA explained that

the ARS ‘‘BHNRC Success Stories’’

describe progress on individual projects

without a deliberative review of all

relevant scientific evidence. Therefore,

FDA has concluded that the statement is

not an ‘‘authoritative statement’’ under

section 403(r)(C)(3) of the act because it

is not based on a deliberative review of

the scientific evidence.

G. Statement 7

Statement 7 reads: ‘‘Researchers also

found more evidence suggesting that

carotenes act as antioxidants to protect

the body from harmful oxidation.

Antioxidants are thought to help

prevent heart attack, stroke and cancer.

During the low-carotene stints,

researchers recorded several

biochemical signs of oxidative damage.’’

The notification identified statement 7

as an ‘‘authoritative statement’’ for

purposes of making the claim that is the

subject of this rulemaking. The

statement is found in Human Nutrition

(quarterly reports of selected research

projects, 4th quarter 1996) (see

discussion of statement 3 in section III.C

of this document), which is issued by

the USDA’s ARS and provided on the

Internet (‘‘http://www.ars.usda.gov/is/

qtr/q496/hn496.htm’’ accessed on 12/3/

97) in a description of research entitled:

‘‘Do carotenoids—the bright red, yellow

and orange pigments in fruits and

vegetables—warrant a Recommended

Dietary Allowance?’’ The paragraph

describes the nature and outcome of two

ARS studies and is attributed to Betty

Burri of the Western Human Nutrition

Research Center in San Francisco, CA.

The agency notes that the final sentence

states: ‘‘Further ARS studies will try to

shed more light on whether a specific

minimum daily intake of carotenoids is

important for good health.’’

The context of the paragraph, as well

as the wording of the statement (i.e.,

‘‘are thought’’), suggests that the

statement is based on preliminary

research and that further study is

needed. As such, the statement appears

to indicate that the scientific evidence

about the relationship is preliminary or

inconclusive.

The agency asked USDA whether the

statement is an ‘‘authoritative

statement’’ under FDAMA. USDA

responded to FDA that the statement is

not an authoritative statement of USDA

because it was not based upon a

deliberative review of the scientific

evidence regarding a relationship

between the nutrient and the disease in

question (Ref. 3). Therefore, FDA has

concluded that the statement is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act because it is not

based on a deliberative review of the

scientific evidence.

H. Statement 8

Statement 8 reads: ‘‘[H]igh dietary

carotene and possibly vitamins C and E

and folate are associated with reduced

risk for cervical cancer.’’ The

notification identified statement 8 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found in information provided on the

Internet by the NCI, an institute of NIH,

in an article entitled: ‘‘Prevention of

Cervical Cancer’’ and disseminated as

part of ‘‘PDQ—Detection & Prevention—

Health Professionals’’ (PDQ stands for

physicians data query) (‘‘http://

cancernet.nci.nih.gov/ clinpdq/

screening/ Preventionloflcervicall

cancerlPhysician.html’’ accessed on

12/1/97). This electronically available

information (submitted as a hardcopy

reprint from the Internet information) is

undated, approximately nine standard

printed pages in length, and is described

as intended for use by doctors and other

health care professionals. The subject

sentence is one of several sentences

summarizing research on the intake of

micronutrients and the risk of squamous

intraepithelial lesion (SIL) and cervical

cancer.

FDA asked NIH whether this was an

‘‘authoritative statement’’ under

FDAMA. NIH responded that the

statement was not an authoritative

statement of NIH and does not reflect

consensus within NIH (Ref. 4). NIH

explained that the evidence was

reviewed by an editorial board for PDQ,

and the majority of the members are not

Federal employees. The statements

contained in PDQ were reported by NIH

to be ‘‘state of the art’’ educational

statements developed by an editorial

board that assesses the levels of

scientific evidence supporting the

statements. In this instance, the

scientific evidence for the nutrientdisease relationship was not considered

to be strong since it was based on

observational studies. NIH reiterated

that the statement is not the product of

consensus process within the NCI and

the statement has not undergone formal

review and clearance by the Director of

the National Institutes of Health.

Therefore, FDA has concluded that

the statement is not an ‘‘authoritative

statement’’ under section 403(r)(C)(3) of
34096 Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations

the act because it does not reflect

consensus within NIH, as discussed in

section I.A.2 of ‘‘Health Claims: Vitamin

C and E,’’ which is published elsewhere

in this issue of the Federal Register.

I. Statement 9

Statement 9 reads: ‘‘[B]eta carotene or

vitamin A supplements have reversed

pre-cancerous conditions in people’s

mouths.’’ The notification identified

statement 9 as an ‘‘authoritative

statement’’ for purposes of making the

claim that is the subject of this

rulemaking. The statement is found in

Human Nutrition (quarterly reports of

selected research projects, 3rd quarter

1995) (see discussion of statement 3 in

section III.C of this document), which is

issued by the USDA’s ARS and

provided on the Internet (‘‘http://

www.ars.usda.gov/is/qtr/q395/

hn395.htm’’ accessed on 12/3/97) in a

description of research entitled: ‘‘A

daily dose of blue-green algae Spirulina

may help prevent cancer of the mouth,

a study shows.’’ The paragraph

describes the nature and outcome of an

ARS study and is attributed to

Padmanabhan P. Nair of the Beltsville

Human Nutrition Research Center,

Beltsville, MD.

The agency asked USDA whether the

statement is an ‘‘authoritative

statement’’ under FDAMA. USDA

responded to FDA that the statement is

not an authoritative statement of USDA

because it was not based upon a

deliberative review of the scientific

evidence regarding a relationship

between the nutrient and the disease in

question (Ref. 3). Therefore, FDA has

concluded that the statement is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act because it is not

based on a deliberative review of the

scientific evidence.

J. Statement 10

Statement 10 reads: ‘‘Carotenoids or

other plant components appear to boost

the immune system.’’ The notification

identified statement 10 as an

‘‘authoritative statement’’ for purposes

of making the claim that is the subject

of this rulemaking. The statement is

found in a one-paragraph interpretative

summary of a research report from

Technology Transfer Information

Center, TEKTRAN of USDA/ARS

entitled: ‘‘Consumption of CarotenoidRich Vegetables Increases TLymphocyte Proliferation and Plasma

Levels of Carotenoid Oxidation

Products’’ and provided on the Internet

(‘‘http://www.nalusda.gov/ttic/tektran/

data/000007/41/0000074185.html’’

accessed on 12/3/97) (ARS Report

Number 74185). It describes the nature

and outcome of one study, which is

attributed to ten researchers, the first

author being Beverly Clevidence.

FDA finds that the statement is not

‘‘about the relationship between a

nutrient and a disease or health-related

condition’’ because no disease is

identified in the statement. Therefore,

FDA has concluded that the statement

does not address a disease or healthrelated condition and therefore is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act.

K. Statement 11

Statement 11 reads: ‘‘A wealth of

epidemiological evidence has linked a

high intake of green leafy and deep

yellow vegetables—both rich in betacarotene—with lower rates of many

types of cancer * * *. Men over 65 who

took a 50-milligram beta-carotene

supplement every other day during the

12-year study had natural killer cells

that were more active than their

counterparts who got a placebo. Natural

killer cells—or NK cells—are the

immune system’s sentinels, ever on

watch for viruses and cancer cells.’’ The

notification identified statement 11 as

an ‘‘authoritative statement’’ for

purposes of making the claim that is the

subject of this rulemaking. The

statement is found in Human Nutrition

(quarterly reports of selected research

projects, 4th quarter 1996) (see

discussion of statement 3 in section III.C

of this document), which is issued by

the USDA’s ARS and provided on the

Internet (‘‘http://www.ars.usda.gov/is/

qtr/q496/hn496.htm’’ accessed on 12/3/

97) in a description of research entitled:

‘‘Older people who get plenty of beta

carotene may have a better chance of

preventing virus infections or a

cancerous growth.’’ The paragraph

describes the nature and outcome of a

study and is attributed to Simin Nikbin

Meydani of the USDA Human Nutrition

Research Center on Aging at Tufts,

Boston, MA.

The agency asked USDA whether the

statement is an ‘‘authoritative

statement’’ under FDAMA. USDA

responded to FDA that the statement is

not an authoritative statement of USDA

because it was not based upon a

deliberative review of the scientific

evidence regarding a relationship

between the nutrient and the disease in

question (Ref. 3). Therefore, FDA has

concluded that the statement is not an

‘‘authoritative statement’’ under section

403(r)(C)(3) of the act because it is not

based on a deliberative review of the

scientific evidence.

In summary, FDA has concluded that

the notification does not include any

authoritative statements published by a

scientific body as required by section

403(r)(3)(C) of the act. Accordingly, the

subject claim relating to the relationship

between antioxidant vitamin A and

beta-carotene and the risk in adults of

atherosclerosis, coronary heart disease,

and certain cancers is not authorized

under section 403(r)(3)(C) of the act and

is, therefore, prohibited. The agency

notes that, at any future time, a

notification may be submitted to the

agency that bases such a claim or claims

on a statement that meets the

requirements of section 403(r)(3)(C) of

the act. If there is no authoritative

statement that may serve as a basis for

such claims, an interested person may

petition the agency under section

403(r)(4) and 21 CFR 10.70 to authorize

the health claim or claims by regulation

under section 403(r)(3)(B).

IV. Issuance of an Interim Final Rule,

Immediate Effective Date, and

Opportunity for Public Comment

For the reasons described in this

section of this document, FDA is issuing

this rule as an interim final rule,

effective immediately, with an

opportunity for public comment. New

section 403(r)(7)(B) of the act, added by

section 301 of FDAMA, provides that

FDA ‘‘may make proposed regulations

issued under [section 403(r)] effective

upon publication pending consideration

of public comment and publication of a

final regulation’’ if the agency

‘‘determines that such action is

necessary * * * to enable [FDA] to act

promptly to ban or modify a claim’’

under section 403(r) of the act. For

purposes of judicial review, ‘‘[s]uch

proposed regulations shall be deemed

final agency action.’’ The legislative

history indicates that the agency should

issue rules under this authority as

interim final rules (H. Conf. Rept. No.

105–399, at 98 (1997)).

As described previously in section III

of this document, FDA has determined

that the statements submitted in support

of the prospective health claim do not

meet the requirements for authoritative

statements in section 403(r)(3)(C) of the

act. FDA has determined that it is

necessary to act promptly to prohibit the

claim’s use under section 403(r)(3)(C) of

the act, and, accordingly, is issuing this

interim final rule to ban its use under

section 403(r)(3)(C).

FDA invites public comment on this

interim final rule. The agency will

consider modifications to this interim

final rule based on comments made

during the comment period. Interested

persons may, on or before September 8,

1998, submit to the Dockets

Management Branch (address above)

written comments regarding this interim
Federal Register / Vol. 63, No. 119 / Monday, June 22, 1998 /Rules and Regulations 34097

final rule. Comments must be received

by that date. Two copies of any

comments are to be submitted, except

that individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

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

Monday through Friday.

V. Environmental Impact

The agency has determined under 21

CFR 25.30(k) 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.

VI. Analysis of Economic Impacts

A. Benefit-Cost Analysis

FDA has examined the impacts of this

interim final rule under Executive Order

12866. Executive Order 12866 directs

Federal agencies to assess the 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). According to

Executive Order 12866, a regulatory

action is ‘‘significant’’ if it meets any

one of a number of specified conditions,

including having an annual effect on the

economy of $100 million; adversely

affecting in a material way a sector of

the economy, competition, or jobs; or if

it raises novel legal or policy issues.

FDA finds that this interim final rule is

not a significant regulatory action as

defined by Executive Order 12866. In

addition, it has been determined that

this interim final rule is not a major rule

for the purpose of congressional review.

If in the future FDA authorizes health

claims relating to the relationship

between antioxidant vitamin A and

beta-carotene and the risk in adults of

atherosclerosis, coronary heart disease,

and certain cancers after finding that

there is significant scientific agreement

about these relationships, the cost to

consumers of prohibiting this claim at

this time would be the cost of having

kept, in the interim, information from

appearing in food labeling that would

ultimately be shown to be scientifically

valid, truthful, and not misleading. At

this time, the benefit to consumers of

prohibiting this claim is that a claim

that has not been shown to be

scientifically valid will not appear in

food labeling. Accordingly, consumers

will be able generally to have

confidence when they read food

labeling that any diet/disease

relationship information in that labeling

has been shown to be scientifically

valid.

A health claim relating to the

relationship between antioxidant

vitamin A and beta-carotene and the

risk in adults of atherosclerosis,

coronary heart disease, and certain

cancers has not been authorized under

existing regulations. The prohibition of

this claim in this interim final rule

results in no regulatory changes for

firms, and therefore no costs to firms are

attributable to this interim final rule.

B. Small Entity Analysis

FDA has examined the impacts of this

interim final rule under the Regulatory

Flexibility Act. The Regulatory

Flexibility Act (5 U.S.C. 601–612)

requires Federal agencies to consider

alternatives that would minimize the

economic impact of their regulations on

small businesses and other small

entities. In compliance with the

Regulatory Flexibility Act, FDA finds

that this interim final rule will not have

a significant impact on a substantial

number of small entities.

A health claim related to the

relationship between antioxidant

vitamin A and beta-carotene and the

risk in adults of atherosclerosis,

coronary heart disease, and certain

cancers has not been authorized under

existing regulations. The prohibition of

this claim in this interim final rule

results in no regulatory changes for

firms, and therefore this interim final

rule will not result in a significant

increase in costs to any small entity.

Therefore, this interim final rule will

not have a significant economic impact

on a substantial number of small

entities. Accordingly, under the

Regulatory Flexibility Act (5 U.S.C.

601–612), the agency certifies that this

interim final rule will not have a

significant economic impact on a

substantial number of small entities.

C. Unfunded Mandates Reform Act of

1995

FDA has examined the impacts of this

interim final rule under the Unfunded

Mandates Reform Act of 1995 (UMRA)

(Pub. L. 104–4). This interim final rule

does not trigger the requirement for a

written statement under section 202(a)

of UMRA because it does not impose a

mandate that results in an expenditure

of $100 million or more by State, local,

and tribal governments in the aggregate,

or by the private sector, in any 1 year.

VII. The Paperwork Reduction Act of

1995

This interim final rule contains no

collections of information. Therefore,

clearance by the Office of Management

and Budget under the Paperwork

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

3520) is not required.

VIII. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

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

through Friday.

1. Notification to Donna E. Shalala, DHHS,

from Jonathan W. Emord et al., Emord &

Associates, P. C., Counsel for Weider

Nutrition International, Inc., February 23,

1998.

2. LSRO, FASEB, ‘‘Nutrition Monitoring in

the United States—An Update Report on

Nutrition Monitoring,’’ prepared for USDA

and DHHS, DHHS Pub. No. (PHS) 89–1255,

PHS, DHHS, U.S. Government Printing

Office, Washington, DC, inside front cover

and pp. iii to vii, September, 1989.

3. Letter to Christine Lewis, CFSAN, FDA,

from Eileen Kennedy, USDA, May 7, 1998.

4. Letter to Christine Lewis, CFSAN, FDA,

from William R. Harlan, NIH, April 30, 1998.

Dated: June 16, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–16455 Filed 6–19–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 98N–0427]

Food Labeling: Health Claims; BComplex Vitamins, Lowered

Homocysteine Levels, and the Risk in

Adults of Cardiovascular Disease

AGENCY: Food and Drug Administration,

HHS.

ACTION: Interim final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing an

interim final rule to prohibit the use on

foods of a claim relating to the

relationship between B-complex

vitamins (folic acid, vitamin B6, vitamin

B12), lowering elevated serum

homocysteine levels, and the risk in

adults of cardiovascular disease. This

interim final rule is in response to a

notification of a health claim submitted

under section 303 of the FDA

Modernization Act of 1997 (FDAMA).

FDA has reviewed statements that the