[Federal Register Volume 63, Number 119 (Monday, June 22, 1998)]
[Rules and Regulations]
[Pages 34092-34097]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-16455]



[[Page 34092]]

-----------------------------------------------------------------------

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 Beta-
Carotene 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 beta-carotene 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,''

[[Page 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:<a href="http://www.usda.gov/fcs/
library/0102-1.txt">www.usda.gov/fcs/
library/0102-1.txt</a>'' 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

[[Page 34094]]

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 (``<a href="http://www.ars.usda.gov/is/qtr/q496/
hn496.htm">http://www.ars.usda.gov/is/qtr/q496/
hn496.htm</a>'' 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 Oxidant-induced Damage,'' and provided 
on the Internet (``<a href="http://www.nalusda.gov/ttic/tektran/data/000006/92/
0000069264.html">http://www.nalusda.gov/ttic/tektran/data/000006/92/
0000069264.html</a>'' 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

[[Page 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'' (``<a href="http://www.barc.usda.gov/
bhnrc/success.htm">http://www.barc.usda.gov/
bhnrc/success.htm</a>'' 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 (``<a href="http://
www.ars.usda.gov/is/qtr/q496/hn496.htm">http://
www.ars.usda.gov/is/qtr/q496/hn496.htm</a>'' 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) (``<a href="http://cancernet.nci.nih.gov/clinpdq/
screening/Prevention__of__cervical__">http://cancernet.nci.nih.gov/clinpdq/
screening/Prevention__of__cervical__</a> cancer__Physician.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 nutrient-disease 
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

[[Page 34096]]

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 (``<a href="http://
www.ars.usda.gov/is/qtr/q395/hn395.htm">http://
www.ars.usda.gov/is/qtr/q395/hn395.htm</a>'' 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 Carotenoid-Rich Vegetables Increases T-Lymphocyte 
Proliferation and Plasma Levels of Carotenoid Oxidation Products'' and 
provided on the Internet (``<a href="http://www.nalusda.gov/ttic/tektran/data/
000007/41/0000074185.html">http://www.nalusda.gov/ttic/tektran/data/
000007/41/0000074185.html</a>'' 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 health-related 
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 beta- carotene--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

[[Page 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