[Federal Register: December 21, 2007 (Volume 72, Number 245)]
[Notices]               
[Page 72738-72740]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr21de07-94]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0464]

 
Health Claims and Qualified Health Claims; Dietary Lipids and 
Cancer, Soy Protein and Coronary Heart Disease, Antioxidant Vitamins 
and Certain Cancers, and Selenium and Certain Cancers; Reevaluation; 
Opportunity for Public Comment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on its intent to reevaluate the 
scientific evidence for two previously authorized health claims 
(dietary lipids (fat) and cancer; soy protein and risk of coronary 
heart disease) and two qualified health claims that were the subject of 
letters of enforcement discretion (antioxidant vitamins and risk of 
certain cancers; selenium and certain cancers). The agency is 
undertaking a reevaluation of the scientific basis for these authorized 
health claims and qualified health claims because of new scientific 
evidence that has emerged for these substance-disease relationships. 
The new scientific evidence may have the effect of weakening the 
substance-disease relationship for these authorized health claims and 
either strengthening or weakening the scientific support for the 
substance-disease relationship for these qualified health claims.

DATES: Submit written or electronic comments by February 19, 2008.

ADDRESSES: You may submit comments, identified by Docket No. 2007N-
0464, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. 

Follow the instructions for submitting comments.
     Agency Web site: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier (for paper, disk, or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described previously, in 
the ADDRESSES portion of this document under Electronic Submissions.
    Instructions: All submissions received must include the agency name 
and docket number for this notice. All comments received may be posted 
without change to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, 

including any personal information provided. For additional information 
on submitting comments, see the ``How to Submit Comments'' heading of 
the SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm 

and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Claudine Kavanaugh, Center for Food 
Safety and Applied Nutrition (HFS-830), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 301-436-1450, 
FAX: 301-436-2636.

SUPPLEMENTARY INFORMATION:

I. Background

    The Nutrition Labeling and Education Act of 1990 (NLEA) (Public Law 
101-553) was designed to give consumers more scientifically valid 
information about foods they eat. Among other provisions, the NLEA 
directed FDA to issue regulations providing for the use of statements 
that describe the relationship between a substance and a disease 
(health claims) in the labeling of foods, including dietary 
supplements, after such statements have been reviewed and authorized by 
FDA.\1\ For these health claims, that is, statements about substance-
disease relationships, FDA has defined the term ``substance'' by 
regulation as a specific food or food component (Sec.  101.14(a)(2) (21 
CFR 101.14(a)(2))). An authorized health claim may be used on both 
conventional foods and dietary supplements, provided that the substance 
in the product and the product itself meet the appropriate standards in 
the authorizing regulation. Health claims are directed to the general 
population or designated subgroups (e.g., the elderly) and are intended 
to assist the consumer in maintaining healthful dietary practices.
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    \1\In 1997, Congress enacted the Food and Drug Administration 
Modernization Act, which established an alternative authorization 
procedure for health claims based on authoritative statements of 
certain federal scientific bodies or the National Academy of 
Sciences. This notice does not address that alternative procedure.
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    Under section 403(r)(4)(A)(i) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 343(r)(4)(A)(i)), any person may 
petition FDA to issue a health claim regulation. In evaluating the 
petition, FDA considers whether there is ``significant scientific 
agreement'' (SSA) based on the totality of publicly available 
scientific evidence concerning the relationship that is the

[[Page 72739]]

subject of the claim. This standard derives from section 
403(r)(3)(B)(i) of the act (21 U.S.C. 343(r)(3)(B)(i)), which provides 
that FDA shall authorize a health claim to be used on conventional 
foods if the agency ``determines based on the totality of the publicly 
available scientific evidence (including evidence from well-designed 
studies conducted in a manner which is consistent with generally 
recognized scientific procedures and principles), that there is 
significant scientific agreement, among experts qualified by scientific 
training and experience to evaluate such claims, that the claim is 
supported by such evidence.'' This scientific standard was prescribed 
by statute for conventional food health claims; by regulation, FDA 
adopted the same standard for dietary supplements health claims (see 
Sec.  101.14(c)).
    In evaluating a petition for an authorized health claim, if FDA 
concludes that the evidence supporting the relationship that is the 
subject of the claim does not meet the SSA standard, the agency 
considers whether there is credible evidence to support a qualified 
health claim. FDA may issue a letter of enforcement discretion for a 
qualified health claim where the totality of scientific evidence 
supporting the relationship that is the subject of the claim is 
credible but does not meet the SSA standard. Qualified health claims 
contain qualifying language about the level of scientific evidence to 
ensure consumers receive accurate information about the claim.
    The genesis of qualified health claims was the court of appeals 
decision in Pearson v. Shalala (Pearson). In that case, the plaintiffs 
challenged FDA's decision not to authorize health claims for four 
specific substance-disease relationships in the labeling of dietary 
supplements. Although the district court ruled for FDA (14 F. Supp. 2d 
10 (D.D.C. 1998)), the U.S. Court of Appeals for the D.C. Circuit 
reversed the lower court's decision (164 F.3d 650 (D.C. Cir.1999)). The 
appeals court held that the First Amendment does not permit FDA to 
reject health claims that the agency determines to be potentially 
misleading unless the agency also reasonably determines that a 
disclaimer would not eliminate the potential deception.
    In the Federal Register of October 26, 1999 (64 FR 57700), the 
agency authorized a health claim for soy protein and risk of coronary 
heart disease (21 CFR 101.82). Since authorizing this health claim, 
numerous studies have evaluated the relationship between soy protein 
and coronary heart disease, and the findings of these studies are 
inconsistent. The Agency for Healthcare Research and Quality (AHRQ) 
released a report in July 2005 outlining the effects of soy products on 
health outcomes including cardiovascular disease and concluded that soy 
products appear to exert a small benefit on low-density lipoprotein 
(LDL)-cholesterol (Ref. 1). However, it is not clear whether soy 
protein (versus other types of soy products) was responsible for such a 
benefit. The AHRQ report included studies that evaluated substances in 
addition to soy protein (e.g., isoflavones). In addition, the AHRQ 
report used markers of cardiac function (e.g., triglycerides, 
endothelial function, oxidized LDL) that are not validated surrogate 
endpoints recognized by the agency for heart disease risk. The agency 
intends to evaluate the scientific evidence on soy protein and the risk 
of coronary heart disease to determine if the totality of the 
scientific evidence continues to meet the significant scientific 
agreement standard.
    In the Federal Register of January 6, 1993 (58 FR 2787), FDA 
authorized a health claim on dietary lipids (fat) and cancer (21 CFR 
101.73). In the years since authorizing this health claim, numerous 
studies have been published evaluating this substance-disease 
relationship. The Institute of Medicine (IOM) of the National Academy 
of Sciences, an authoritative body, published a report that reviewed 
the evidence on dietary lipid consumption and cancer risk (Ref. 2). The 
IOM reported in its review of the literature that the association 
between diets high in fat and increased cancer risk has been weakened 
by recent epidemiological studies. The IOM report set an acceptable 
macronutrient distribution range (AMDR) for total fat, however, it was 
not set based on cancer as a disease outcome because of insufficient 
scientific evidence linking consumption of fat with cancer risk. One 
factor in determining the AMDR is the long-term intake level of a 
nutrient that can minimize the potential for chronic disease. The 
agency intends to reevaluate the scientific evidence on dietary lipids 
and cancer risk and determine if the totality of the evidence continues 
to meet the significant scientific agreement standard.
    Section 10.25(b) (21 CFR 10.25(b)) states that the Commissioner of 
Food and Drugs may initiate a proceeding to issue, amend, or revoke a 
regulation or take or refrain from taking any other form of 
administrative action. FDA intends to evaluate whether the currently 
available scientific evidence concerning the substance-disease 
relationship for the authorized health claims, dietary lipids and 
cancer and soy protein and coronary heart disease, continues to support 
its previous decisions on these authorized health claims. If the agency 
decides to take action to amend or revoke one or both of these health 
claims, after completing its review of the current scientific evidence, 
the agency will publish its findings and solicit comments on them 
before the agency takes any action with respect to revising the 
particular health claim. Interested persons may submit scientific 
information about these two specific health claims in response to this 
notice.
    In 2003, FDA issued two letters on the use of the agency's 
enforcement discretion for qualified health claims on antioxidant 
vitamins (vitamins E and C) and risk of certain cancers (Ref. 3) and 
selenium and certain cancers and anticarcinogenic effects in the body 
(Ref. 4). In May 2006, AHRQ issued a report evaluating the use of 
multivitamin/mineral supplements and the risk of chronic disease (Ref. 
5). The report did not identify any studies on the efficacy of vitamin 
C supplements and cancer risk. In addition, the report concluded that 
the overall strength of the evidence for vitamin E and selenium 
supplements on cancer risk is very low (vitamin E) and low (selenium). 
The agency intends to reevaluate the scientific evidence on these two 
qualified health claims and determine if the scientific evidence 
continues to support the qualified health claim, and if so, whether the 
qualified health claim language should be modified to reflect a 
stronger or weaker relationship.
    If the agency decides a change may be needed with respect to one or 
both of these claims, the agency intends to publish its findings and 
solicit comments on them. Interested persons may submit scientific 
information about these two specific qualified health claims in 
response to this notice.

Reevaluating Cancer Health Claims by Cancer Site

    In the final rule authorizing a health claim for dietary fat and 
cancer, FDA considered whether such a claim should specifically address 
the types of cancer affected by a diet that is low in total fat, or 
whether the claim should not be site-specific (58 FR 2787 at 2788 
through 2789). FDA ultimately decided that the identification of 
specific sites of affected cancers would not be appropriate due, in 
part, to weaker data on the relationship between dietary fat and breast 
cancer and the possibility of a wider variety of affected sites for the 
dietary fat and cancer relationship.

[[Page 72740]]

Therefore, FDA required that the terms ``some types of cancer'' or 
``some cancers'' be used in specifying the disease for this health 
claim relationship (id.). The antioxidant and cancer and selenium and 
cancer qualified health claims also contain similar language, i.e., 
``certain forms of cancer,'' to be used in specifying the disease. 
However, in other qualified health claims for a substance and cancer 
relationship (Refs. 6, 7, and 8), the agency considered separate 
qualified health claims for each type of cancer.
    Cancer is a constellation of more than 100 different diseases, each 
characterized by the uncontrolled growth and spread of abnormal cells 
(Ref. 9). Cancer is categorized into different types of diseases based 
on the organ and tissue sites (Ref. 10). Cancers at different organ 
sites have different risk factors, treatment modalities, and mortality 
risk (Ref. 9). Both genetic and environmental (including diet) risk 
factors may affect the risk of different types of cancers. Risk factors 
may include a family history of a specific type of cancer, cigarette 
smoking, alcohol consumption, overweight and obesity, exposure to 
ultraviolet or ionizing radiation, exposure to cancer-causing 
chemicals, and dietary factors. The etiology, risk factors, diagnosis, 
and treatment for each type of cancer are unique (Refs. 11 and 12). 
Because each form of cancer is a unique disease based on organ site, 
risk factors, treatment options, and mortality risk, FDA's current 
approach is to evaluate each form of cancer individually in a health 
claim or qualified health claim petition to determine whether the 
scientific evidence supports the potential substance-disease 
relationship for any type of cancer, each of which constitutes a 
disease under Sec.  101.14(a)(5).
    The agency intends to consider, as part of its reevaluation of the 
scientific evidence for dietary fat, antioxidant, and selenium and 
their association with a reduced risk of cancer, claim language to 
reflect specific types of cancer rather than ``certain forms of 
cancer'' (or similar language).

II. How to Submit Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individual may submit one paper 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 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
    Please note that in January 2008, the FDA Web site is expected to 
transition to the Federal Dockets Management System (FDMS). FDMS is a 
Government-wide, electronic docket management system. After the 
transition date, electronic submissions will be accepted by FDA through 
the FDMS only. When the exact date of the transition to FDMS is known, 
FDA will publish a Federal Register notice announcing that date.

III. References

    The following references have been placed on display in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday. 
(FDA has verified the Web site addresses, but we are not responsible 
for subsequent changes to the Web sites after this document publishes 
in the Federal Register.)
    1. Balk E, Chung M, Chew P, Ip S, Raman G, Kupelnick B, Tatsioni 
A, Sun Y, Wolk B, DeVine D, Lau J. Effects of Soy on Health 
Outcomes. Summary, Evidence Report/Technology Assessment No. 126. 
(Prepared by the Tufts-New England Medical Center Evidence-based 
Practice Center under Contract No. 290-02-0022.) AHRQ Publication 
No. 05-E024-1. Rockville, MD: Agency for Healthcare Research and 
Quality. July 2005.
    2. Institute of Medicine, National Academy of Sciences. Dietary 
Referece Intakes for energy, carbohydrate, fiber, fat, fatty acids, 
cholesterol, protein and amino acids, Chapter 11 page 808. National 
Academy Press. Washington, D.C. 2005.
    3. Antioxidant vitamins and risk of certain cancers, April 1, 
2003, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~dms/ds-ltr34.html.

    4. Selenium and certain cancers, February 21, 2003, Docket No. 
2002P-0457 (formerly Docket No. 02P-0457), http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~dms/ds-ltr35.html
.

    5. Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer 
C, Wilson RF, Cheng TY, Prokopowicz G, Barnes II GJ, Vassy J, Bass 
EB. Multivitamin/Mineral Supplements and Prevention of Chronic 
Disease. Evidence Report/Technology Assessment No. 139. (Prepared by 
The Johns Hopkins University Evidence-based Practice Center under 
Contract No. 290-02-0018). AHRQ Publication No. 06-E012. Rockville, 
MD: Agency for Healthcare Research and Quality. May 2006.
    6. Tomatoes and prostate, ovarian, gastric and pancreatic 
cancers, November 8, 2005, Docket No. 2004Q-0201, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~dms/qhclyco.html
.

    7. Green tea and prostate and breast cancer risk, June 30, 2005, 
Docket No. 2004Q-0083, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~dms/qhc-gtea.html.

    8. Calcium and colon/rectal, breast and prostate cancers and 
recurrent polyps, October 12, 2005, Docket No. 2004Q-0097, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cfsan.fda.gov/~dms/qhcca2.html
.

    9. American Cancer Society, Cancer Facts and Figures, 2004.
    10. National Cancer Institute, Dictionary of Cancer Terms, 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=45333.

    11. Hord NG, Fenton JI. Context is everything: mining the normal 
and preneoplastic microenvironment for insights into the diet and 
cancer risk conundrum. Molecular Nutrition and Food Research, 2007, 
51:100-106.
    12. Milner JA. Diet and Cancer: Facts and Controversies. 
Nutrition and Cancer, 2006, 56:216-224.

    Dated: December 6, 2007.
Barbara Schneeman,
Director, Office of Nutritional Products, Labeling, and Dietary 
Supplements, Center for Food Safety and Applied Nutrition.
[FR Doc. E7-24813 Filed 12-20-07; 8:45 am]

BILLING CODE 4160-01-S