Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body

SUMMARY: The Food and Drug Administration (FDA) is proposing

regulations defining the types of statements that can be made

concerning the effect of a dietary supplement on the structure or

function of the body. The proposed regulations also establish criteria

for determining when a statement about a dietary supplement is a claim

to diagnose, cure, mitigate, treat, or prevent disease. This action is

intended to provide direction to the dietary supplement industry and to

respond to guidance on this issue provided by the Commission on Dietary

Supplement Labels (the Commission).

DATES: Written comments and recommendations by August 27, 1998.

ADDRESSES: Submit written comments and recommendations to the Dockets

Management Branch (HFA-305), Food and Drug Administration, 12420

Parklawn Dr., rm. 1-23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Jeanne Latham, Center for Food Safety

and Applied Nutrition (HFS-456), Food and Drug Administration, 200 C

St. SW., Washington, DC 20204, 202-205-4697.

SUPPLEMENTARY INFORMATION:

I. Introduction

The Dietary Supplement Health and Education Act of 1994 (the DSHEA)

authorizes manufacturers of dietary supplements to make certain types

of statements about the uses of their products. Among the types of

permitted statements are certain claims that, prior to enactment of the

DSHEA, could have rendered the product a ``drug'' under the Federal

Food, Drug, and Cosmetic Act (the act). Specifically, section 403(r)(6)

of the act (21 U.S.C. 341(r)(6)), added by the DSHEA, allows dietary

supplement labeling to bear a statement that ``describes the role of a

nutrient or dietary ingredient intended to affect the structure or

function in humans'' or that ``characterizes the documented mechanism

by which a nutrient or dietary ingredient acts to maintain such

structure or function.'' These types of claims are generally referred

to as ``structure/function claims.''

Certain other types of statements about dietary supplements

continue, under the DSHEA, to cause the product to be regulated as a

drug. Statements permitted under section 403(r)(6) of the act ``may not

claim to diagnose, mitigate, treat, cure, or prevent a specific disease

or class of diseases,'' except that such statements may claim a benefit

related to a classical nutrient deficiency disease, provided that they

also disclose the prevalence of the disease in the United States. Such

statements are generally referred to as ``disease claims.'' FDA notes

that certain statements that pertain to a disease or health-related

condition are permitted on food products, including dietary

supplements. These statements are known as health claims (see section

403(r)(1)(B) of the act) and describe the relationship between a

nutrient and a disease or health-related condition. Unlike structure/

function claims, health claims must be authorized by FDA before they

may be used on the label or in the labeling of a food or dietary

supplement (see section 403(r)(3) and (r)(4) and 21 CFR 101.14 and

101.70). Thus, certain claims about disease may be made for foods and

dietary supplements without causing these products to be regulated as

drugs, provided the claim has been authorized for use by FDA in

accordance with the applicable regulations. FDA also notes that a

dietary supplement for which only structure/function claims are made in

the label or labeling in accord with section 403(r) of the act may

nevertheless be subject to regulation as a drug if the agency has other

evidence (see 21 CFR 201.128) that the intended use of the product is

for the diagnosis, cure, mitigation, treatment, or prevention of

disease.

A dietary supplement manufacturer who wishes to make a permitted

structure/function statement under section 403(r)(6) of the act must

have substantiation that the statement is truthful and not misleading,

and must include in the statement the following disclaimer: ``This

statement has not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure, or prevent any

disease.'' The DSHEA requires the manufacturer of a dietary supplement

bearing a statement under section 403(r)(6) of the act to notify FDA,

no later than 30 days after the first marketing of the dietary

supplement with the statement, that such a statement is being made for

the product. Regulations implementing these requirements were published

in the Federal Register of September 23, 1997, and are codified at

Sec. 101.93 (21 CFR 101.93) (62 FR 49859 at 49883, September 23, 1997,

OMB Control Number 0910-0351).

Diseases, by definition, adversely affect some structure or

function of the body, and it is possible to describe most products

intended to treat or prevent disease in terms of their effects on the

structure or function of the body. The DSHEA, thus, does not authorize

the use of all claims that describe the effect of a dietary supplement

on the structure or function of the body. Instead, section 403(r)(6) of

the act authorizes only those structure/function claims that describe

an effect of a product on the structure or function of the body but

that are not also disease claims. Because the distinction between

allowable structure/function claims and disease claims is not always

obvious, the dietary supplement industry has requested clarification

from FDA on structure/function claims that can be made for dietary

supplements under section 403(r)(6) of the act. To develop clarifying

criteria for such claims, FDA has reviewed the notification letters

that have been submitted to FDA under section 403(r)(6) of the act. In

addition, FDA has reviewed the report of the Commission, which was

established by the DSHEA to provide guidance and recommendations for

the regulation of label claims and statements for dietary supplements.

The Commission issued a draft report (the draft report) on June 24,

1997, among other things, the report included the Commission's views on

``what constitutes an acceptable statement * * * of the structure/

function type'' (the draft report, p. 36). The Commission received

public comment on the draft report and issued a final report (the

report) on November 24, 1997. Guidance in the report ``represents

advice to specific agencies, groups, or individuals. Guidance should be

considered by the identified recipients as they develop or implement

activities related to the availability of dietary supplements in the

marketplace'' (the report, p. vi).

The Commission's final report contains the following guidance (the

guidance) on the scope of permissible structure/function claims:

GUIDANCE

While the Commission recognizes that the context of a

claim has to be considered on a case-by-case basis, the Commission

proposes the following general guidelines:

[[Page 23625]]

1. Statements of nutritional support should provide useful

information to consumers about the intended use of a product.

2. Statements of nutritional support should be supported by

scientifically valid evidence substantiating that the statements are

truthful and not misleading.

3. Statements indicating the role of a nutrient or dietary

ingredient in affecting the structure or function of humans may be

made when the statements do not suggest disease prevention or

treatment.

4. Statements that mention a body system, organ, or function

affected by the supplement using terms such as ``stimulate,''

``maintain,'' ``support,'' ``regulate,'' or ``promote'' can be

appropriate when the statements do not suggest disease prevention or

treatment or use for a serious health condition that is beyond the

ability of the consumer to evaluate.

5. Statements should not be made that products ``restore''

normal or ``correct'' abnormal function when the abnormality implies

the presence of disease. An example might be a claim to ``restore''

normal blood pressure when the abnormality implies hypertension.

6. Health claims are specifically defined under NLEA as

statements that characterize the relationship between a nutrient or

a food component and a specific disease or health-related condition.

Statements of nutritional support should be distinct from NLEA

health claims in that they do not state or imply a link between a

supplement and prevention of a specific disease or health-related

condition.

7. Statements of nutritional support are not to be drug claims.

They should not refer to specific diseases, disorders, or classes of

diseases and should not use drug-related terms such as ``diagnose,''

``treat,'' ``prevent,'' ``cure,'' or ``mitigate.''

(The report, pp. 38-39).

The guidance thus focuses on the distinction between allowable

structure/function claims and claims that a product can diagnose,

treat, prevent, cure, or mitigate disease (disease claims), and makes

clear that structure/function claims made for dietary supplements

should not imply treatment or prevention of disease. The guidance also

provides examples of types of structure/function claims that do and do

not imply disease claims. In its findings, the Commission expressed the

view that ``guidance by FDA to manufacturers making statements [under

section 403(r)(6) of the act]\1\ is appropriate and helpful in

clarifying the appropriate scope of these statements'' (the report, p.

38).

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\1\ The report refers to statements under section 403(r)(6) of

the act as ``statements of nutritional support.'' As noted in a

September 23, 1997 final rule regarding labeling claims for dietary

supplements, FDA no longer uses the term ``statements of nutritional

support'' because many of the substances that can be the subject of

this type of claim have no nutritional value. Thus, the term

``statement of nutritional support'' is not accurate in all

instances (62 FR 49859 at 49863).

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FDA agrees with the Commission that an acceptable structure/

function claim must not imply prevention or treatment of disease. FDA

believes that the Commission's guidelines provide a useful framework

for clarifying the sometimes difficult distinction between structure/

function claims and disease claims. Based upon the Commission's advice

and the agency's experience in reviewing notification letters submitted

under section 403(r)(6) of the act, FDA has developed proposed

regulations to define the types of claims that are ``disease claims''

and thus not acceptable as structure/function claims.

II. Provisions of the Proposed Rule and Guidance

As described in section I of this document, the manufacturer of a

dietary supplement may make a truthful, nonmisleading labeling

statement claiming that the product affects the structure or function

of the body, unless the statement expressly or implicitly claims an

effect on a disease or class of diseases (other than a classical

nutrient deficiency disease). Therefore, to determine the scope of

structure/function claims that may be made for a dietary supplement, it

is necessary to define the types of claims about the effects of a

product that are prohibited disease claims. The proposed rule is

designed to provide criteria for determining when a statement about a

product constitutes a disease claim.

The agency used several methods and sources to develop the proposed

criteria for discerning which categories of labeling statements

constitute express or implied claims that a product can diagnose, cure,

mitigate, treat or prevent disease. To establish what types of claims

the agency had already determined to be disease claims, FDA reviewed

the letters it has sent in response to notifications from dietary

supplement manufacturers, listing specific claims the agency regards as

disease claims, as well as other regulatory actions taken in response

to dietary supplement claims. FDA also reviewed the Commission Report's

guidance on distinguishing structure/function claims and disease

claims. In addition, the agency developed a definition of ``disease.''

As described below, the agency relied upon standard medical and legal

definitions of disease as a basis for a proposed regulatory definition.

The agency then used the proposed definition of disease to generate

workable criteria, by applying the proposed definition to a wide

variety of statements currently made by dietary supplement

manufacturers to determine whether the statements claimed an effect on

``disease,'' as tentatively defined. Based upon the information derived

from these reviews, the agency developed the general criteria below.

The proposed rule applies only to structure/function claims and

disease claims within the meaning of section 403(r)(6) of the act.

DSHEA generally, and section 403(r)(6) of the act specifically, apply

only to dietary supplements for human consumption, and were enacted to

provide a unique regulatory regime for these products. Thus, the

proposed rule is not intended to apply to products other than dietary

supplements for human consumption nor to interpret other provisions of

the act.

A. Permitted Structure/Function Claims

Under proposed Sec. 101.93(f), dietary supplement labels and

labeling may bear structure/function statements that are not disease

claims within the meaning of proposed Sec. 101.93(g) and that otherwise

comply with the notification and disclaimer provisions of Sec. 101.93

(a) through (e), including the requirement that any structure/function

statement be substantiated.

B. Definition of Disease

To assist in describing what constitutes a disease claim, the

proposed rule contains a definition of ``disease.'' The proposed

definition is based on standard medical and legal definitions of the

term (Refs. 1, 2, 3 and 4). Under proposed Sec. 101.93(g)(1), a

``disease'' is any deviation from, impairment of, or interruption of

the normal structure or function of any part, organ, or system (or

combination thereof) of the body that is manifested by a characteristic

set of one or more signs or symptoms. For purposes of this definition,

``signs or symptoms'' include laboratory or clinical measurements that

are characteristic of a disease, such as elevated cholesterol fraction,

uric acid, blood sugar, and glycosylated hemoglobin, and characteristic

signs of disease, such as elevated blood pressure or intraocular

pressure.

To eliminate any inconsistency between this definition of

``disease'' and the definition of ``disease or health-related

condition'' found in Sec. 101.14(a)(6) and used for purposes of the

agency's regulation of health claims, the proposal would also amend

Sec. 101.14(a)(6). That section defines ``disease or health-related

condition'' as ``damage to an organ, part, structure, or system of the

body such that it does not function properly (e.g., cardiovascular

disease), or a state of health leading to such dysfunctioning (e.g.

hypertension);

[[Page 23626]]

except that diseases resulting from essential nutrient deficiencies

(e.g., scurvy, pellagra) are not included in this definition * * *''

Under the proposed amendment to 101.14(a)(6), ``disease or health-

related condition'' would be defined, in relevant part, as:

``any deviation from, impairment of, or interruption of the

normal structure or function of any part, organ, or system (or

combination thereof) of the body that is manifested by a

characteristic set of one or more signs or symptoms (including

laboratory or clinical measurements that are characteristic of a

disease), or a state of health leading to such deviation,

impairment, or interruption; except that diseases resulting from

essential nutrient deficiencies (e.g., scurvy, pellagra) are not

included within this definition * * *.

FDA believes that the proposed amendment of Sec. 101.14(a)(6) is

appropriate because experience since the issuance of the health claims

regulations has shown that the current definition is too narrow in some

respects. The term ``damage'' can be interpreted as limiting the

definition to serious or long-term diseases, and as excluding certain

conditions that are medically understood to be diseases, such as

headaches. The proposed amendment, which covers both ``damage'' to an

organ, part, structure, or system leading to dysfunction, and other

deviations from, impairments of, or interruptions of the normal

functioning of an organ, part, or system, more accurately covers the

range of conditions that are medically understood to be diseases. FDA

notes that the definition in Sec. 101.14(a)(6) is intended to cover

both diseases and ``health-related conditions.'' As amended, the

proposed definition in Sec. 101.14(a)(6) would remain broader than the

proposed definition of ``disease'' in proposed Sec. 101.93(g)(1)

because proposed Sec. 101.14(a)(6) includes the phrase ``or a state of

health leading to such deviation, impairment, or interruption.''

C. Criteria for Identifying Disease Claims

Based upon the definition of disease in proposed Sec. 101.93(g)(1),

Sec. 101.93(g)(2) of the proposed rule lists criteria for determining

whether a statement about a product is a disease claim. To illustrate

these criteria, FDA has provided examples of statements that would be

considered disease claims under the proposed rule. FDA has also

provided examples of statements that would not, by themselves, be

considered disease claims. FDA emphasizes that in determining whether a

statement about a product constituted a disease claim under these

criteria, FDA would also consider the context in which the statement

appeared. A statement that by itself would be considered an acceptable

structure/function claim could become a disease claim if, in context,

an effect on disease were expressed or implied. FDA seeks comment on

the examples and the provisions of the proposed rule. To assist the

industry, and especially small businesses, if the agency issues a final

rule, it will issue an accompanying guidance providing examples of

claims that would and would not be considered disease claims under the

final rule.

1. Under proposed Sec. 101.93(g)(2)(i), a statement would be

considered a disease claim if it explicitly or implicitly claimed an

effect on a specific disease or class of diseases. Examples of such

disease claims include: ``protective against the development of

cancer,'' ``reduces the pain and stiffness associated with arthritis,''

``decreases the effects of alcohol intoxication,'' or ``alleviates

constipation.'' Claims that do not refer explicitly or implicitly to an

effect on a specific disease state would not be disease claims under

this criterion. Examples include: ``helps promote urinary tract

health,'' ``helps maintain cardiovascular function and a healthy

circulatory system,'' ``helps maintain intestinal flora,'' and

``promotes relaxation.'' FDA has tentatively concluded that these

examples do not contain express or implied references to specific

diseases. Instead, they refer broadly to body systems or functions

without sufficient reference to specific abnormalities or symptoms to

be understood as references to particular diseases.

2. Proposed Sec. 101.93(g)(1) defines disease as any one of several

types of abnormalities that are ``manifested by a characteristic set of

one or more signs or symptoms.'' FDA believes that reference to a

characteristic set of signs or symptoms, even in the absence of the

name of the disease, can be understood as a reference to the disease

itself. Under proposed Sec. 101.93(g)(2)(ii), a statement would be

considered a disease claim if it explicitly or implicitly claimed an

effect (using scientific or lay terminology) on one or more signs or

symptoms that are recognizable to health care professionals or

consumers as being characteristic of a specific disease or of a number

of diseases. Examples of such disease claims include: ``improves urine

flow in men over 50 years old'' (characteristic symptoms of, e.g.,

benign prostatic hypertrophy); ``lowers cholesterol'' (characteristic

sign of, e.g., hypercholesterolemia); ``reduces joint pain''

(characteristic symptom of, e.g., arthritis); and ``relieves headache''

(characteristic symptom of, e.g., migraine or tension headache). In

each of these cases, the symptoms described are sufficient to

characterize one or more specific diseases. To determine whether a

reference to a set of signs and symptoms constituted a disease claim,

FDA would interpret the reference in context. Claims of an effect on

symptoms that are not recognizable as characteristic of a specific

disease or diseases would not constitute disease claims. Examples

include: ``reduces stress and frustration,'' ``inhibits platelet

aggregation,'' and ``improves absentmindedness.'' In these examples,

the signs or symptoms noted may be broadly associated with a number of

diseases, but are not, by themselves, sufficient to characterize a

specific disease or diseases. If the context did not suggest treatment

or prevention of a disease, a claim that a substance helps maintain

normal function would not ordinarily be a disease claim. Examples

include: ``helps maintain a healthy cholesterol level,'' or ``helps

maintain regularity.''

FDA requests comment on the distinction between maintaining normal

function, which is potentially the basis for an allowable structure/

function claim, and preventing or treating abnormal function, which is

potentially a disease claim. This can be a difficult distinction

conceptually, especially if the only reason for maintaining normal

function is to prevent a specific disease or diseases associated with

abnormal function. According to the report, ``Commission members who

were troubled about the wording of structure/function statements

suggested that the most problematic wording is seen in statements

ostensibly relating to `normal healthy function' that actually imply

the need to remedy an underlying abnormal or unhealthy state * * *''

(the report, pp. 36-37).

The Commission concluded that ``statements that mention a body

system, organ, or function affected by the supplement using terms such

as ``stimulate,'' ``maintain,'' ``support,'' ``regulate,'' or

``promote'' can be appropriate when the statements do not suggest

disease prevention or treatment or use for a serious health condition

that is beyond the ability of the consumer to evaluate`` (the report,

p. 38). This is consistent with the criterion proposed by FDA. As the

report illustrates, however, there can be disagreement about the

circumstances in which a reference to maintaining normal function

implies disease treatment or prevention. Therefore, FDA welcomes

[[Page 23627]]

comment on the basis for the distinction between maintaining normal

function and preventing or treating abnormal function and on factors

that help distinguish between claims relating to normal, healthy

function that do not imply disease treatment or prevention and those

that do. Because of the Commission's concerns that claims relating to

maintaining healthy cholesterol levels raise particularly difficult

issues (the report, p. 37), FDA seeks comment on these claims.

3. Certain natural states, such as pregnancy, aging, or the

menstrual cycle, that are themselves not ``diseases,'' are sometimes

associated with abnormalities that are characterized by a specific set

of signs or symptoms, and thus meet the proposed definition of disease.

Under proposed Sec. 101.93(g)(2)(iii), a statement would be considered

a disease claim if it explicitly or implicitly claimed an effect on a

consequence of a natural state that presents a characteristic set of

signs or symptoms recognizable to health care professionals or

consumers as constituting an abnormality of the body, such as toxemia

of pregnancy, premenstrual syndrome, or abnormalities associated with

aging such as presbyopia, decreased sexual function, Alzheimer's

disease, or hot flashes. Claims that did not refer to a recognizable

abnormality resulting from a natural state or to its signs or symptoms

(e.g., ``for men over 50 years old,'' and ``to meet nutritional needs

during pregnancy'') would not be disease claims under this criterion.

These examples do not include references to specific abnormalities or

symptoms. FDA thus believes that they would not be understood as

references to particular diseases.

4. Various aspects of a product's labeling may be used to express

or imply that the product will diagnose, cure, mitigate, treat, or

prevent disease. Under proposed Sec. 101.93(g)(2)(iv), a statement

would be considered a disease claim if it explicitly or implicitly

claimed an effect on disease through one or more of the following

factors:

(a) The name of the product (e.g., ``Carpaltum'' (carpal tunnel

syndrome), ``Raynaudin'' (Raynaud's phenomenon), ``Hepatacure'' (liver

problems)). Names that did not imply an effect on a disease, such as

``Cardiohealth'' and ``Heart Tabs,'' would not constitute disease

claims;

(b) Statements about the formulation of the product, including a

claim that the product contained an ingredient that has been regulated

primarily by FDA as a drug and is well known to consumers for its use

in preventing or treating a disease (e.g., aspirin, digoxin, or

laetrile). FDA notes that this proposed rule is not intended to

interpret section 201(ff)(3)(A) of the act (21 U.S.C. 321(ff)(3)(A)),

and that a product may be included in or excluded from the definition

of ``dietary supplement'' under that provision regardless of whether

the statement made for the product under section 403(r)(6) of the act

meets the criteria specified here;

(c) Citation of a title of a publication or other reference, if the

title refers to a disease use. For example, labeling for a vitamin E

product that included a citation to an article entitled ``Serial

Coronary Angiographic Evidence That Antioxidant Vitamin Intake Reduces

Progression of Coronary Artery Atherosclerosis,'' would create a

disease claim under this criterion;

(d) Use of the term ``disease'' or ``diseased;'' or

(e) Otherwise suggesting an effect on disease by use of pictures,

vignettes, symbols, or other means (e.g., electrocardiogram tracings,

pictures of organs that suggest prevention or treatment of a disease

state, the prescription symbol (Rx), or any reference to prescription

use). A picture of a body would not constitute a disease claim under

this criterion.

5. Certain product class names are so strongly associated with

diagnosis, cure, mitigation, treatment or prevention of a disease or

diseases, that a claim that a product belonged to such a class would be

understood as a disease claim. Under proposed Sec. 101.93(g)(2)(v), a

statement would be considered a disease claim if it claimed that the

product belonged in a class of products recognizable to health care

professionals or consumers as intended for use to diagnose, mitigate,

treat, cure, or prevent a disease (e.g., claims that the product was an

``antibiotic,'' a ``laxative,'' an ``analgesic,'' an ``antiviral,'' a

``diuretic,'' an ``antimicrobial,'' an ``antiseptic,'' an

``antidepressant,'' or a ``vaccine''). The foregoing examples do not

constitute an exclusive list of product class names that convey disease

claims. Claiming that a product was in a class that is not recognizable

to health care professionals or consumers as intended for use to

diagnose, mitigate, treat, cure or prevent disease (e.g., an

``energizer,'' a ``rejuvenative,'' a ``revitalizer,'' or an

``adaptogen'') would not constitute a disease claim under this

criterion.

6. A statement may imply that a dietary supplement has an effect on

disease by claiming that the effect of the dietary supplement is the

same as that of a recognized drug or disease therapy. A statement may

also imply an effect on disease by suggesting that the dietary

supplement should be used as an adjunct to a recognized drug or disease

therapy in the treatment of a disease. In both cases, the statement

implies that the dietary supplement is intended for the same purpose as

the drug or disease therapy, i.e., for the diagnosis, cure, mitigation,

treatment, or prevention of disease. Under proposed

Sec. 101.93(g)(2)(vi) and (g)(2)(vii), a statement would be considered

a disease claim if it explicitly or implicitly claimed that the product

was a substitute for another product that is a therapy for a disease

(e.g., ``Herbal Prozac'') or that it augmented a particular therapy or

drug action (e.g., ``use as part of your diet when taking insulin to

help maintain a healthy blood sugar level''). A claim that did not

identify a specific drug, drug action, or therapy (e.g., ``use as a

part of your weight loss plan'') would not constitute a disease claim

under this criterion.

7. A statement may contain an express or implied disease claim if

it suggests that the product cures, mitigates, treats or prevents a

disease or diseases by augmenting the body's own disease-fighting

capabilities. Under proposed Sec. 101.93(g)(2)(viii), a statement would

be considered a disease claim if it explicitly or implicitly claimed a

role in the body's response to a disease or to a vector of disease. A

vector of disease is an organism or object that is able to transport or

transmit to humans an agent, such as a virus or bacterium, that is

capable of causing disease in man. A claim that a product ``supports

the body's antiviral capabilities'' or ``supports the body's ability to

resist infection'' would constitute a disease claim under this

criterion. Infections are well-known disease states that result from

the action of pathogenic (disease-causing) microorganisms, such as

bacteria and viruses, and are deviations from and impairments of the

normal structure and/or function of the body with characteristic signs

and symptoms. Claims that a product is intended to affect the body's

ability to kill or neutralize pathogenic microorganisms, or to mitigate

the consequences of the action of pathogenic microorganisms on the body

(i.e., the signs and symptoms of infection) are disease claims because

they are claims exclusively associated with the body's ability to

prevent or respond to infectious diseases. A more general reference to

an effect on a body system that has several functions, only one of

which is resistance to disease, would not constitute a disease claim

under this criterion (e.g., ``supports the immune system'').

[[Page 23628]]

8. Many adverse reactions to drugs or medical procedures meet the

proposed definition of disease because they are abnormalities of

structure or function manifested by a characteristic set of signs or

symptoms. In addition, the clinical management of adverse events that

are consequences of medical intervention is an integral part of the

overall medical management of the underlying disease state for which

the therapeutic intervention is intended. Therefore, claims that a

product is intended to counter adverse events resulting from medical

intervention are claims that the product is intended as a part of the

treatment program and, as such, are claims that the product is to

mitigate, treat, or cure the disease state. Under proposed

Sec. 101.93(g)(2)(ix), a statement would be considered a disease claim

if it explicitly or implicitly claimed to treat, prevent, or mitigate

adverse events associated with a medical therapy or procedure and

manifested by a characteristic set of signs or symptoms (e.g.,

``reduces nausea associated with chemotherapy,'' ``helps avoid diarrhea

associated with antibiotic use,'' and ``to aid patients with reduced or

compromised immune function, such as patients undergoing

chemotherapy''). A claim that did not mention a therapy for disease

(e.g., ``helps maintain healthy intestinal flora'') would not

constitute a disease claim under this criterion.

9. Under proposed Sec. 101.93(g)(2)(x), a statement would be

considered a disease claim if it otherwise suggested an effect on a

disease or class of diseases.

III. Legal Authority

This proposed rule is authorized under sections 201, 403(r), and

701(a) of the act (21 U.S.C. 321, 343(r), and 371(a)).

IV. Effective Date and Implementation Plan

The agency proposes that any final rule based on this proposal will

become effective 30 days after the date of publication of the final

rule in the Federal Register. However, for a product marketed by a

small business (as defined below) that was on the market as of the date

of publication of the final rule, the agency is proposing to allow an

additional 17 months within which claims made about such product as of

the date of publication of the final rule must be brought into

compliance with the final rule, provided that the small business has

notified FDA of the claim as required by section 403(r)(6) of the act

and Sec. 101.93(a) and that FDA has not objected to the claim. A

``small business'' for purposes of this proposal is a business with

total annual revenues of less than $20 million. For all other products

that were on the market as of the date of publication of the final

rule, the agency is proposing to allow an additional 11 months within

which claims made about such products as of the date of publication of

the final rule must be brought into compliance, again provided that the

firm has notified FDA of the claim as required by section 403(r)(6) of

the act and Sec. 101.93(a) and that FDA has not objected to the claim.

Any product that is marketed for the first time after publication of

the final rule, and any new claims made for an existing product for the

first time after publication of the final rule, will be expected to be

in compliance beginning 30 days after publication of the final rule.

During the pendency of this rulemaking, manufacturers will continue

to be under an obligation to comply with section 403(r)(6) and other

applicable provisions of the act and applicable regulations. FDA will

continue to respond to notifications submitted under section 403(r)(6)

of the act, and the agency will continue to enforce that provision and

all other applicable legal requirements.

V. Environmental Impact

The agency has determined under 21 CFR 25.30(h), (k) and 25.34(f)

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 economic implications of this proposed rule

as required by Executive Order 12866. Executive Order 12866 directs

agencies to assess all costs and benefits of available regulatory

alternatives and, when regulation is necessary, to select the

regulatory approach which maximizes net benefits (including potential

economic, environmental, public health and safety effects; distributive

impacts; and equity). According to Executive Order 12866, a rule is

significant if it meets any one of a number of specified conditions,

including having an annual effect on the economy of $100 million or

adversely affecting in a material way a sector of the economy,

competition, or jobs, or if it raises novel legal or policy issues.

Because it raises novel policy issues, FDA finds that this proposed

rule is a significant regulatory action as defined by Executive Order

12866.

In addition, FDA has determined that this rule does not constitute

a significant rule under the Unfunded Mandates Reform Act of 1995

requiring cost-benefit and other analyses. A significant rule is

defined in Section 1531(a) as ``a Federal mandate that may result in

the expenditure by State, local, and tribal governments in the

aggregate, or by the private sector, of $100,000,000 (adjusted annually

for inflation) in any 1 year * * *''.

Finally, in accordance with the Small Business Regulatory

Enforcement Fairness Act, the administrator of the Office of

Information and Regulatory Affairs of the Office of Management and

Budget has determined that this proposed rule is not a major rule for

the purpose of Congressional review.

There are several different types of products that may be

considered to be dietary supplements. These products include but are

not limited to vitamin and mineral supplements, herbal products, and

products that contain other similar nutritional substances. Estimates

of the number of dietary supplements are approximate because no one

source collects information on all types of dietary supplements. In

fact, until the DSHEA, there was no agreed upon definition of a dietary

supplement. Some sources include only dietary supplements of vitamins

and minerals, others include herbals or botanicals, and still others

include other types of products that may or may not be dietary

supplements, such as sports nutrition products and ``functional

foods,'' a term for which there is no regulatory definition. FDA's

preliminary estimate of the number of such products is approximately

29,000. FDA's estimate of the number of stockkeeping units (skus), a

more accurate count of the number of labels, is approximately 75,000.

In its analysis of the rule establishing nutrition labeling

requirements for dietary supplements (62 FR 49826 at 49843), FDA

provided an estimate of the number of dietary supplement firms.

According to Dun's Market Identifiers (Ref. 5), there are approximately

250 manufacturers of vitamin and mineral products. According to

Nutrition Business Journal (Ref. 6), the dietary supplement industry

includes 850 supplement manufacturing companies. The Journal reports

1995 industry revenues at $4.5 billion. The Journal's estimate of 850

firms is an overestimate of the dietary supplement industry as defined

by FDA because it includes homeopathic products, which are drugs by

statutory definition, and ``functional

[[Page 23629]]

foods'' and sports nutrition products, which may be either conventional

foods or dietary supplements depending on how they are marketed and

used. Although the Journal does not break down the number of firms by

the type of dietary supplement produced, it does specify that 250 firms

produce herbal or botanical products.

For purposes of determining the costs of regulation, FDA has used

850 as an upper bound estimate of the number of firms. As a lower bound

estimate, FDA has used 500 (250 vitamin/mineral firms plus 250 herbal/

botanical firms). Since publication of the nutrition labeling final

rule in September 1997 (62 FR 49826), FDA has not been challenged on

these estimates. Therefore, the same range of estimates is used in this

analysis.

In this proposed rule, FDA is clarifying the distinction between

disease claims and structure/function claims in dietary supplement

labeling. If the proposed rule becomes final, any firm currently making

a claim that was not previously classified as a disease claim but is

classified as a disease claim by the rule will be required to change

the claim to an acceptable structure/function claim, remove the claim

from labeling, petition and be granted permission to carry a health

claim, or bear the consequences of being classified as an unapproved

drug. FDA has received approximately 2,300 notifications of structure/

function claims and has sent objection letters for approximately 150 of

the notifications. FDA believes that those firms have made the

necessary changes to make their claims come into compliance. FDA has

estimated the number of additional notifications to which it would have

objected under the criteria in this proposed rule. Using conservative,

worst-case estimates, FDA estimated that it would have objected to

approximately 60 additional notifications. The firms making these 60

products will have to change their claims if the proposal becomes

final; these firms would bear the costs of this proposed rule.

FDA is aware that, despite the notification requirements in section

403(r)(6) of the act and Sec. 101.93(a), some firms that have not sent

notifications are in fact marketing products whose labeling contains

structure-function claims. If the labels contain claims that are

unacceptable under the criteria FDA is proposing to adopt, and if the

firms change those labels in response to this proposed rule, then the

costs of those labeling changes can be attributed to the rule.

1. Costs

Only those firms who must change their labeling will bear the

costs of this rule. Categories of costs for relabeling include

administrative, analytical, printing, and inventory disposal. FDA will

first estimate compliance costs for the 60 products for which the

agency has received notifications of claims that would be classified as

disease claims under the criteria in the proposed rule. These costs

will be the lower-bound costs of the proposed rule. FDA will then

estimate the compliance costs for the products for which FDA has not

received notification, but whose labeling contains claims that would be

classified as disease claims under the criteria in the proposed rule.

The sum of the compliance costs for the two categories of products will

be the upper-bound costs of the proposed rule.

a. Lower-bound Estimate

The administrative costs associated with a labeling regulation

result from the incremental administrative labor expended in order to

comply with a regulation. FDA estimates administrative costs at

approximately $425 per firm for a 1-year compliance period and

approximately $320 for an 18-month compliance period. Longer compliance

periods decrease administrative effort because firm executives often

delegate downward decisions that are less immediate. FDA will assume

that the number of firms affected by the proposed rule is proportional

to the number of labels affected. FDA therefore estimates the number of

firms affected by multiplying the upper-bound estimate of total firms

in the industry by the fraction of the labels in violation, or 850 x

(60/2,300) = 22. Total administrative costs are estimated to be $7,040

(22 x $320) with an 18-month compliance period and $9,350 (22 x $425)

with a 1-year compliance period.

Based on an average of the estimates provided in comments to

earlier rules, FDA estimates that the average redesign cost for a 1-

year compliance period is $1,700 per dietary supplement label. Redesign

costs associated with an 18 - month compliance period are typically 3/4

of those for a 1 year compliance period, or $1,300 per dietary

supplement label. Therefore, FDA estimates total redesign costs to be

$102,000 (60 x $1,700) for a 12-month compliance period and $78,000 (60

x $1,300) for an 18-month compliance period.

FDA received information from an earlier rule affecting the entire

dietary supplement industry indicating that inventory disposal costs

would be $8 million for an 18-month compliance period and $15 million

for a 12-month compliance period. FDA has some experience suggesting

that some firms will experience minimal inventory disposal costs due to

the rapid frequency with which they change labels or move product.

Because FDA is assuming that 0.08 percent (60/75,000) of the industry

will incur costs as a result of this rule, total inventory disposal

costs are estimated to be $6,400 (0.0008 x $8 million) for an 18-month

compliance period and $12,000 (0.0008 x $15 million) for a 12-month

compliance period.

FDA has estimated the impact of the proposed regulation and has

determined that, for a 1-year compliance period, lower-bound total

costs would be approximately $123,400. Alternatively, if FDA were to

provide 18 months for compliance, lower-bound total costs would be

approximately $91,400. The components of lower-bound total costs are

shown in the following table.

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

Cost Category 12-month compliance 18-month compliance

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

Administrative $9,400 $7,000

Redesign $102,000 $78,000

Inventory $12,000 $6,400

Total $123,400 $91,400

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

b. Upper-bound Estimate

Some manufacturers of dietary supplements may not have notified FDA

that their product labels contain structure-function claims. Because

these manufacturers have not complied with the existing legal

requirement to notify FDA of the claims they are making for their

products, FDA believes that it is unlikely that they would change their

labels to comply with new regulations defining acceptable structure/

function claims. However, to ensure that all possible costs are

considered in this impact analysis, the agency is including costs that

might be incurred by such manufacturers as an upper bound on its

estimate of the costs of this proposed rule. Based on visual

observation of dietary supplements sold in retail establishments

(grocery, drug, and health food stores), FDA estimates that up to 30

percent of all labels contain structure-function claims. FDA therefore

estimates that up to 22,500 (0.3 x 75,000) dietary supplement labels

may contain structure-function claims. Although it is uncertain how

many of these labels contain claims that would be disease claims under

the proposed rule, if the proportion of all labels containing such

claims is the same as the proportion of notifications containing such

claims, then there may

[[Page 23630]]

be up to 585 [(60/2,300) x 22,500] labels that would need to be changed

if the proposed rule becomes final. Subtracting the 60 unacceptable

labels for which FDA has received notifications leaves about 525

additional labels that may be affected by the rule.

Based on its model of food labeling compliance costs, FDA assumes

that compliance costs per label double with each halving of the

compliance period (Ref. RTI Final Report, ``Compliance Costs of Food

Labeling Regulations''). The cost per label for a 12-month compliance

period is approximately $2,000 ($123,400/60). The compliance period for

claims for which no notification has been received is 30 days. Based on

the model, FDA expects that compliance costs will double as the

compliance period falls from 12 to 6 months, and double again as the

compliance period falls to 3 months. Although the model does not

predict compliance costs for periods shorter than 3 months, FDA assumes

that as the compliance period falls from 3 months to 30 days,

compliance costs are likely to double again. Estimated costs per label

should therefore be approximately 8 times (2 x 2 x 2) higher for a

compliance period of 30 days than for a compliance period of 12 months.

FDA therefore estimates compliance costs per label for current

structure-function claims for which no notification has been received

to be $16,000 (8 x $2,000). The total costs for 525 label changes would

be $8.4 million (525 x $16,000). Although FDA believes that it is very

unlikely that all of these label changes would be made, the upper-bound

total cost of this proposed rule is the sum of the costs for the 60

unacceptable claims for which notifications have been received and the

costs of the additional unacceptable claims. The total cost will thus

range between approximately $0.1 million and $8.5 million.

2. Benefits

Most of the benefits from this rule will come from the reduced

uncertainty associated with structure/function claims in dietary

supplement labeling. Some manufacturers of dietary supplements, as

shown by the submission of a significant number of notifications for

purported structure/function statements that are clearly disease

claims, are uncertain about what constitutes an acceptable structure/

function claim. This proposed rule establishes clarifying criteria that

will reduce and perhaps eliminate this uncertainty.

FDA cannot quantify the benefits from this proposed rule. Because

of the uncertainty about what constitutes an acceptable structure/

function claim, some manufacturers of dietary supplements may have

hesitated to attempt to make structure/function claims. These

clarifying criteria will enable those firms to go forward with those

claims. To the extent that the lack of these claims has caused

consumers to seek out the information from other sources, this rule

will benefit consumers by reducing the cost of searching for

information and ensuring that the information provided to consumers is

appropriate.

Manufacturers who were considering making claims that would be

considered unacceptable will be provided with clear criteria showing

that the claims are unacceptable. As evidenced by notifications of

structure/function claims already received by FDA, several firms have

had to bear the cost of redesigning labeling to incorporate the changes

recommended by the agency. By providing criteria to firms before they

submit notifications to FDA, this rule will reduce costs to firms by

reducing the probability of having to redo labels. Government costs

will also be lessened by reducing the number of letters informing firms

of inappropriate label statements.

3. Regulatory Alternatives

FDA considered, but did not adopt, other regulatory options. First,

the agency considered treating a statement about a dietary supplement

as a disease claim only if the statement included an express reference

to a specific disease. This option would have resulted in a

significantly larger number of permitted claims for dietary

supplements, and reduced costs for dietary supplement manufacturers.

FDA did not adopt this option for several reasons. First, it would be

inconsistent with FDA's longstanding policy of considering both express

and implied claims when determining whether a product falls within

various definitions under the act. Second, it would be inconsistent

with the interpretation of ``disease claims'' that FDA has used in

administering section 403(r)(6) of the act prior to issuing this

proposed rule. Finally, because many implied claims, e.g., claims that

list the symptoms of a disease without naming the disease, are well-

understood by consumers as disease treatment or prevention claims, this

option would be inconsistent with the intent of section 403(r)(6).

Second, FDA considered treating any mention of an abnormality of

the structure or function of the body as a disease claim, even if the

abnormality was not characterized by a set of signs or symptoms

recognized as a disease. This option would have resulted in a

significantly smaller number of permitted claims for dietary

supplements, and greater costs for dietary supplement manufacturers.

FDA did not adopt this option because section 403(r)(6) of the act

prohibits only claims of an effect on a disease. Because not all

abnormalities are recognized by health professionals or consumers as

diseases, this option would have been overbroad, and would have

prevented manufacturers from making claims permitted by the statute.

Finally, FDA considered taking no new regulatory action. This

option would have resulted in no immediate change in the number of

permitted claims, and no costs for dietary supplement manufacturers.

FDA rejected this option because there is substantial confusion among

dietary supplement manufacturers and consumers about what types of

claims are permitted for dietary supplements, and the agency has been

called upon to provide clarification of permitted and prohibited

claims. In the absence of direction from the agency, an increasing

number of products in the marketplace carry express and implied disease

claims, misleading consumers and creating unfairness to those

manufacturers who have attempted to comply with advice from FDA.

B. Small Entity Analysis

According to the Regulatory Flexibility Act, the definition of a

small entity is a business independently owned and operated and not

dominant in its field. The Small Business Administration (SBA) has set

size standards for most business categories through use of four-digit

Standard Industrial Classification (SIC) codes. Dietary supplements of

vitamins and minerals are included in the industry group Pharmaceutical

Preparations (SIC 2834); a business in that classification is

considered small if it has fewer than 750 employees. According to Dun's

Market Identifiers, there are approximately 250 producers of vitamin

and mineral supplements, of which 200 have fewer than 750 employees.

The remaining dietary supplement products--mainly herbs, other

botanicals, and amino acids--do not fit in any classification, but come

closest to the industry groups Food Preparations Not Elsewhere

Classified (SIC 2099) and Medicinal Chemicals and Botanical Products

(SIC 2833). The SBA size standards are 500 or fewer employees for food

preparations and 750 or fewer employees for medicinal and botanical

products.

According to Nutrition Business Journal (Ref. 6), 11 of the 850

dietary supplement manufacturing firms have

[[Page 23631]]

total revenues over $100 million, accounting for 53 percent of total

sales; 30 firms have sales revenues between $20 and $100 million,

accounting for 28 percent of industry sales; and 809 firms have sales

under $20 million, accounting for 19 percent of industry sales. The 809

firms in the under $20 million category have an average sales revenue

of $800,000 and will be considered small by FDA.

No employment data are available for some of these firms. Many of

the firms are in the SIC codes 2833 and 2834, however. According to

Dun's Market Identifiers, no firms for which both employment and sales

data are available in SIC code 2833 have less than $20 million in

annual sales and more than 500 employees. Indeed, 96% of the firms in

that sales category have fewer than 100 employees. By contrast, over

90% of the firms in SIC codes 2833 and 2834 (vitamin and minerals sub-

category) with annual sales greater than $100 million have more than

750 employees. If the relationship between sales and employment for SIC

codes 2833 and 2834 holds for other sectors of the dietary supplement

industry, then the proportion of firms with sales under $20 million

should be approximately the same as the proportion of firms with fewer

than 500 employees, an employment category that is classified as small

for any SIC code involving the manufacture of foods, chemicals and

kindred or allied products. FDA concludes therefore that as many as 809

firms in the dietary supplement industry, or 95 percent of firms, could

be considered small (sales under $20 million). As stated previously in

this analysis, 809 small firms may be an overestimate because it counts

firms that produce homeopathic products, which are drugs, and sports

nutrition products and ``functional foods,'' which may be either foods

or dietary supplements. If there are as few as 500 dietary supplement

firms, there may be 475 small dietary supplement firms.

Because virtually all firms affected by this rule will be

classified as small under SBA standards, FDA assumes that small

entities will bear 100 percent of the costs. Because per firm labeling

costs are probably burdensome for small firms and because the costs of

this rule are borne entirely by small firms, FDA tentatively concludes

that this rule will result in a significant economic impact on a

substantial number of small entities. In section VI. A. of this

document, entitled Benefit--Cost Analysis, FDA estimated that, as a

lower-bound, 22 firms would be affected by this proposed rule and that

the lower-bound costs with a compliance period of 12 months would be

approximately $123,400, or about $5,600 per small firm. FDA estimated

upper-bound costs, $8.5 million, by adding the costs of changing 525

additional labels (with a 30-day compliance period) to the lower-bound

costs. If the number of additional firms affected is proportional to

the number of additional labels changed, the upper-bound number of

firms affected by this proposed rule is 215, for an upper-bound average

cost of about $40,000 per small firm.

The Regulatory Flexibility Act requires agencies to examine

regulatory alternatives that would minimize the impact on small

entities. FDA considered exempting small entities from this rule, which

would eliminate the costs borne by small entities. FDA rejected this

option for several reasons. First, the agency has no authority to

exempt small entities from their statutory obligations, and this

proposed rule merely clarifies a statutory requirement. Second, as

described above, virtually all manufacturers covered by this proposal

are small entities. Exempting small entities would thus eliminate the

benefits of the proposed rule. Finally, some of the benefits of the

rule, such as reducing the uncertainty associated with structure/

function claims and reducing the probability of having to re-do labels,

will accrue to small entities.

FDA has examined the impact of different compliance periods and

has determined that extending the compliance period from 12 to 18

months for firms that have notified the agency of a claim and have not

received an objection reduces the burden on small entities in this

category. Extending the compliance period from 12 to 18 months reduces

lower-bound estimated costs borne by small firms by $32,000, and

average costs per firm would fall from $5,600 to about $4,200.

Extending the compliance period beyond 18 months could provide

additional relief to these small entities. Based on FDA's experience

with the dietary supplement industry, however, the agency believes that

labels are changed more often than every 18 months; therefore, FDA

believes that this additional relief would be small. FDA has

tentatively concluded that the compliance period for those firms whose

products contain structure/function claims but who have not complied

with the legal requirement to notify FDA of those claims should not be

extended.

VII. Paperwork Reduction Act of 1995

FDA tentatively concludes that this proposed rule contains no

collections of information. Therefore, clearance by the Office of

Management and Budget under the Paperwork Reduction Act of 1995 is not

required.

VIII. Comment Request

Interested persons may, on or before August 27, 1998, submit to the

Dockets Management Branch (address above) written comments regarding

this proposal. 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 Dockets Management

Branch between 9 a.m. and 4 p.m., Monday through Friday.

IX. 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. Dorland's Illustrated Medical Dictionary, 28th Edition, W.B.

Saunders Co., Philadelphia, p. 478, 1994.

2. Stedman's Medical Dictionary, 26th Edition, Williams &

Wilkins, Baltimore, p. 492, 1995.

3. The Encyclopedia Americana, International Edition, Grolier

Inc., Danbury, p. 168, 1985.

4. Black's Law Dictionary, 6th Edition, West Publishing Co., St.

Paul, p. 467, 1990.

5. Dun's Market Identifiers, Knight-Ridder Information, Inc.,

Mountain View, CA, 1998.

6. Nutrition Business Journal, 1(1):15, 16, 1996.

List of Subjects in 21 CFR Part 101

Food labeling, Nutrition, Reporting and recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs, it is

proposed that 21 CFR part 101 be amended as follows:

PART 101--FOOD LABELING

1. The authority citation for 21 CFR part 101 continues to read as

follows:

Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,

343, 348, 371.

2. Section 101.14, as currently in effect, is amended by revising

paragraph (a)(6) to read as follows:

Sec. 101.14 Health claims: general requirements.

(a) * * *

(6) Disease or health-related condition means any deviation from,

impairment

[[Page 23632]]

of, or interruption of the normal structure or function of any part,

organ, or system (or combination thereof) of the body that is

manifested by a characteristic set of one or more signs or symptoms

(including laboratory or clinical measurements that are characteristic

of a disease), or a state of health leading to such deviation,

impairment, or interruption; except that diseases resulting from

essential nutrient deficiencies (e.g., scurvy, pellagra) are not

included in this definition (claims pertaining to such diseases are

thereby not subject to this section or Sec. 101.70).

* * * * *

3. Section 101.93, as currently in effect, is amended by revising

the section heading and by adding paragraphs (f) and (g) to read as

follows:

Sec. 101.93 Certain types of statements for dietary supplements.

* * * * *

(f) Permitted structure/function statements. (1) Dietary supplement

labels or labeling may, subject to the requirements of this section,

bear statements that describe the role of a nutrient or dietary

ingredient intended to affect the structure or function in humans or

that characterize the documented mechanism by which a nutrient or

dietary ingredient acts to maintain such structure or function, but may

not bear statements that are disease claims under paragraph (g) of this

section.

(g) Disease claims. (1) Definition of disease. For purposes of 21

U.S.C. 343(r)(6), a ``disease'' is any deviation from, impairment of,

or interruption of the normal structure or function of any part, organ,

or system (or combination thereof) of the body that is manifested by a

characteristic set of one or more signs or symptoms, including

laboratory or clinical measurements that are characteristic of a

disease.

(2) Disease claims. FDA will find that a statement about a product

claims to diagnose, mitigate, treat, cure, or prevent disease (other

than a classical nutrient deficiency disease) under section 403(r)(6)

of the act if it meets one or more of the criteria listed in this

paragraph (g)(2). In determining whether a statement is a disease claim

under these criteria, FDA will consider the context in which the claim

is presented. A statement claims to diagnose, mitigate, treat, cure, or

prevent disease if it claims, explicitly or implicitly, that the

product:

(i) Has an effect on a specific disease or class of diseases;

(ii) Has an effect, using scientific or lay terminology, on one or

more signs or symptoms that are recognizable to health care

professionals or consumers as being characteristic of a specific

disease or of a number of different specific diseases;

(iii) Has an effect on a consequence of a natural state that

presents a characteristic set of signs or symptoms recognizable to

health care professionals or consumers as constituting an abnormality

of the body;

(iv) Has an effect on disease through one or more of the following

factors:

(A) The name of the product;

(B) A statement about the formulation of the product, including a

claim that the product contains an ingredient that has been regulated

by FDA as a drug and is well known to consumers for its use in

preventing or treating a disease;

(C) Citation of the title of a publication or reference, if the

title refers to a disease use;

(D) Use of the term ``disease'' or ``diseased''; or

(E) Use of pictures, vignettes, symbols, or other means;

(v) Belongs to a class of products that is intended to diagnose,

mitigate, treat, cure, or prevent a disease;

(vi) Is a substitute for a product that is a therapy for a disease;

(vii) Augments a particular therapy or drug action;

(viii) Has a role in the body's response to a disease or to a

vector of disease;

(ix) Treats, prevents, or mitigates adverse events associated with

a therapy for a disease and manifested by a characteristic set of signs

or symptoms; or

(x) Otherwise suggests an effect on a disease or diseases.

Dated: April 22, 1998.

Michael A. Friedman,

Lead Deputy Commissioner for the Food and Drug Administration.

Donna E. Shalala,

Secretary of Health and Human Services.

[FR Doc. 98-11294 Filed 4-24-98; 4:27 pm]

BILLING CODE 4160-01-F