Federal Register / Vol. 63, No. 82 /Wednesday, April 29, 1998 / Notices 23633

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N–0048]

RIN 0910–AA59

Dietary Supplements; Comments on

Report of the Commission on Dietary

Supplement Labels

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing its

views on recommendations and

guidance of the Commission on Dietary

Supplement Labels, as presented in the

Commission’s Final Report. The

document also responds to

recommendations and guidance

directed to FDA. Elsewhere in this issue

of the Federal Register, FDA is issuing

a proposed rule that responds to

guidance in the Commission Report

concerning statements about the effect

of dietary supplements on the structure

or function of the body.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Ilisa

B.G. Bernstein, Office of Policy (HF–23),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–3380, IBernste@oc.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

Section 12 of the Dietary Supplement

Health and Education Act of 1994 (the

DSHEA) (Pub. L. 103–417) established

an independent agency within the

Executive Branch known as the

Commission on Dietary Supplement

Labels (the Commission). The

Commission was charged with

conducting a study on, and providing

recommendations for regulating label

claims and statements for dietary

supplements, including the use of

literature in connection with the sale of

dietary supplements and procedures for

evaluating such claims.

The Commission was appointed in

October 1995 and convened its first

meeting in February 1996. Interested

persons presented oral and written

testimony at several Commission

meetings. A draft report of the

Commission was released for public

comment on June 24, 1997. On

November 24, 1997, the final report of

the Commission (Commission Report)

was released.

Under section 12(d)(3) of the DSHEA,

within 90 days of issuance of the

Commission’s final report, the Secretary

of Health and Human Services is

required to publish in the Federal

Register

a notice of any recommendation of [the]

Commission for changes in regulations of the

Secretary for the regulation of dietary

supplements and shall include in such notice

a notice of proposed rulemaking on such

changes together with an opportunity to

present views on such changes. Such

rulemaking shall be completed not later than

2 years after the date of issuance of such

report.

The Commission divided its

conclusions into three categories:

Findings, guidance, and

recommendations. The Commission

Report did not contain any

recommendations for changes to FDA’s

‘‘regulations * * * for the regulation of

dietary supplements.’’ The Commission

made only two recommendations

directed to FDA. These

recommendations pertain to botanicals

and are discussed in section VIII of this

document. Neither of the two

recommendations suggests changes in

regulations governing dietary

supplements. Therefore, there are no

recommendations subject to the

deadlines imposed under section 12 of

the DSHEA. In this document the

agency is announcing its views on the

Commission’s recommendation and

guidance, as well as a description of the

actions the agency intends to take

because of these recommendations and

guidance. In addition, based on

guidance set forth in the Commission

Report, the agency is issuing a proposed

rule elsewhere in this issue of the

Federal Register concerning statements

about the effects of dietary supplements

on the structure or function of the body.

This document addresses only

guidance and recommendations made in

the Commission Report that are

addressed to FDA or relevant to its

responsibilities.

II. Safety of Dietary Supplements

The Commission Report states that

existing postmarket surveillance

systems for dietary supplements could

be improved. The Commission Report

notes that there is no mandatory

requirement for industry, consumers, or

health care professionals to report

adverse events resulting from

consumption of foods and dietary

supplements, and specifically states that

the Commission is not recommending

such a requirement. However, the

Commission Report does urge FDA,

industry, the scientific community, and

consumer groups to work together

voluntarily to improve passive

postmarketing surveillance systems.

The agency agrees that greater

cooperation among FDA, industry, and

other interested parties to enhance the

effectiveness of current surveillance

systems would improve the ability of

these systems to identify potential safety

problems and thereby improve their

public health utility. FDA currently

collects reports of adverse events

associated with the use of dietary

supplements through its MedWatch

system, which accepts voluntary reports

of adverse events from health

professionals and consumers for serious

adverse events related to FDA-regulated

products. FDA also receives reports of

adverse events associated with the use

of dietary supplements through the

Center for Food Safety and Applied

Nutrition (CFSAN) Adverse Event

Monitoring System. All reports FDA

receives concerning adverse events

associated with dietary supplements are

entered into CFSAN’s Special

Nutritionals Adverse Event Monitoring

System database for evaluation and

monitoring.

The agency intends to respond to the

Commission Report’s guidance by

initiating a process to further

cooperation among interested parties.

The agency has asked the FDA Foods

Advisory Committee (composed of

outside experts who advise the agency

on food issues) to consider the issue of

postmarket surveillance and

particularly, how best to collect and

share surveillance information. The

Foods Advisory Committee (FAC)

considered these issues at its February

1998 meeting and referred them to a

FAC internal working group to develop

recommendations for consideration by

the full FAC.

The Commission Report strongly

suggests that dietary supplement

manufacturers include appropriate

warning statements in product

information where necessary. Although

no corresponding guidance or

recommendation to the agency was

made, the agency intends to work with

the FDA Foods Advisory Committee and

industry in developing guidance on the

use of warning statements on dietary

supplement labeling.

Also related to safety of dietary

supplements, the Commission Report

urges FDA to use its authority under the

DSHEA to take swift enforcement action

to address potential safety issues. The

agency takes seriously its mission to

promote and protect the public health.

When the agency becomes aware of the

presence of harmful dietary

supplements in the marketplace, it is
23634 Federal Register / Vol. 63, No. 82 /Wednesday, April 29, 1998 / Notices

1The Commission Report refers to statements

under section 403(r)(6) of the act as ‘‘statements of

nutritional support.’’ As noted in the 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.

committed to taking timely action,

within the legal limits of its authority,

to remove unsafe products from the

market or to take other steps to protect

consumers from adverse health effects

that may result from the use of unsafe

dietary supplements.

III. Nutritional Labeling and Education

Act (NLEA) Claims in Dietary

Supplement Labeling (Health Claims)

A health claim is ‘‘any claim made on

the label or in labeling of a food,

including a dietary supplement, that

expressly or by implication * * *

characterizes the relationship of any

substance to a disease or health-related

condition’’ (21 CFR 101.14(a)(1)

(§ 101.14(a)(1)). The Federal Food, Drug,

and Cosmetic Act (the act) provides that

FDA may authorize a health claim for a

conventional food only if the agency

determines,

based on the totality of 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.

21 U.S.C. 343(r)(3)(B)(i)).

Any person may petition FDA to

authorize a particular health claim by

regulation; however, the health claim

may not be made until authorized by

regulation. Current regulations at 21

CFR 101.14 and 101.70 set forth general

requirements for health claims on the

labels or in the labeling of conventional

foods and dietary supplements. These

regulations apply the same standard

(i.e., ‘‘significant scientific agreement’’)

and set forth the same process (i.e.,

petition process) for health claims for

dietary supplements as for health claims

for conventional foods.

The Commission Report states that

the significant scientific agreement

standard is appropriate and serves the

public interest. The Commission Report

also states that the scientific standard

and approval process for health claims

for dietary supplements should be the

same as for conventional foods, which

is an endorsement of FDA’s current

regulations for health claims on dietary

supplements. The Commission Report

does not recommend any changes in

FDA’s health claim regulations for

dietary supplements.

The Commission Report does suggest,

however, that ‘‘FDA should ensure that

broad input is obtained to ascertain the

degree of scientific agreement that exists

for a particular health claim.’’ FDA

agrees. The agency has considered and

will continue to consider the opinions

of scientific experts outside the agency

in its deliberations on whether there is

significant scientific agreement

supporting the validity of a particular

disease-substance relationship. For

example, FDA considered and relied on

data and opinions from several other

governmental agencies and professional

organizations in deciding to authorize a

health claim for folate and neural tube

defects. See 58 FR 53254 at 53262–63.

The agency is open to input from

interested parties as to how to improve

its process for considering proposed

health claims.

On November 21, 1997, 3 days before

the Commission Report was issued, the

President signed into law the ‘‘Food and

Drug Administration Modernization Act

of 1997’’ (FDAMA) (Pub. L. 105–115).

FDAMA, among other things, amended

the health claims provisions of the act

in several respects. The Commission

Report does not discuss the provisions

of the FDAMA as enacted, although it

mentions the predecessor House and

Senate bills. The effect of the FDAMA

on health claim requirements for dietary

supplements is beyond the scope of this

document. FDA will address such issues

during the rulemaking process to

implement the FDAMA.

IV. Scope of Structure/Function

Statements for Dietary Supplements

The DSHEA added section 403(r)(6)

(21 U.S.C. 343(r)(6)) to the act. If certain

conditions are met, section 403(r)(6) of

the act permits several categories of

statements to be made for dietary

supplements, including statements that

‘‘describe[] the role of a nutrient or

dietary ingredient intended to affect the

structure or function in humans [or]

characterize[] the documented

mechanism by which a nutrient or

dietary ingredient acts to maintain

structure or function,’’ also known as

‘‘structure/function’’ claims. The

Commission Report contains general

guidance for what would constitute an

acceptable structure/function claim.

Elsewhere in this issue of the Federal

Register the agency is proposing

regulations, consistent with the

Commission’s guidance, that describe

the types of statements that can be made

by a manufacturer of a dietary

supplement concerning the effect of the

dietary supplement on the structure or

function of the body in accordance with

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

V. Notification Letters for Statements of

Nutritional Support (Statements made

under section 403(r)(6) of the act)1

The act, as amended by the DSHEA,

requires the manufacturer of a dietary

supplement bearing a statement made

under section 403(r)(6) of the act to

notify the Secretary no later than 30

days after the first marketing of the

dietary supplement with the statement.

In the Federal Register of September 27,

1996 (61 FR 50771), the agency

proposed procedures for such

notifications. A final rule was issued

September 23, 1997 (62 FR 49883). The

regulations set forth the requirements

for when and where such a notification

is to be made and what information the

notification must contain (see 21 CFR

101.93(a)).

The Commission Report suggests that

manufacturers include certain

information in the notification letter,

including some information not

required by FDA’s regulations.

Specifically, the Commission Report

suggests that the notification letter

include the following: A statement of

the purpose of the notification letter,

including the exact wording of the

statement that is the subject of the

notification; the name, address, and

telephone number of the manufacturer

or distributor; the trade name of the

product, the common or usual name of

the product, and a description of the

product; a copy of the product label or

label mock-up, if labels have not yet

been printed; the identity of individual

ingredients or combinations of

ingredients for which the statement is

being made, including, for botanicals,

the common or usual name, the Latin

binomial and its scientific authority,

and the part(s) of the plant(s) used; and

a statement of intended use, including

the recommended dosage and

appropriate contraindications or

warnings. The Commission Report also

suggests that, either in the notification

letter or in a separate public notice, the

manufacturer affirm that it has

substantiation that the statement made

under 403(6)(r) is truthful, not

misleading, and scientifically valid and

that the product does not present a

significant or unreasonable risk of

illness or injury under the conditions of

use recommended or suggested in the
Federal Register / Vol. 63, No. 82 /Wednesday, April 29, 1998 / Notices 23635

labeling. The Commission Report notes

that these are suggestions and expresses

the view that the rulemaking process

need not be reopened at this time. The

agency agrees with the guidance in the

Commission Report. The agency also

agrees that the rulemaking need not be

reopened at this time, but will

reconsider the need to do so in the

future if experience warrants.

The Commission Report also suggests

that the notification letters continue to

be made available to the public. The

agency will continue making these

notification letters publicly available by

placing them in Docket No. 97S–0162 at

FDA’s Docket Management Branch

(address above). In addition, the agency

will consider other mechanisms to make

these submissions available.

VI. Substantiation Files for Statements

of Nutritional Support (Statements

made under section 403(r)(6) of the act)

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

the manufacturer of a dietary

supplement making a statement of

nutritional support to have

substantiation that such statement is

truthful and not misleading. Section

403(r)(6) of the act, however, does not

specify what constitutes adequate

substantiation. The Commission Report

includes guidance on what quantity and

quality of evidence should be used to

substantiate claims made under section

403(r)(6) of the act. The Commission

Report also includes guidance on the

content of substantiation files for

statements made under section 403(r)(6)

of the act, including the notification

letter, identification of the product’s

ingredients, evidence to substantiate the

statements, evidence to substantiate

safety, assurances that good

manufacturing practices were followed,

and the qualifications of the person(s)

who reviewed the data on safety and

efficacy. The agency agrees with the

guidance.

VII. Publications Exempt From

Classification as Labeling When Used

in Connection With Sales

The DSHEA added section 403B of

the act (21 U.S.C. 343–2). This provision

exempts certain publications used in

connection with the sale of dietary

supplements from the definition of

‘‘labeling’’ in section 201(m) of the act

(21 U.S.C. 321(m)). Under section 403B

of the act, a ‘‘publication’’ will be

exempt when it:

(1) is not false or misleading; (2) does not

promote a particular manufacturer or brand

of a dietary supplement; (3) is displayed or

presented, or is displayed or presented with

other such items on the same subject matter,

so as to present a balanced view of the

available scientific information on a dietary

supplement; (4) if displayed in an

establishment, is physically separate from the

dietary supplements; and (5) does not have

appended to it any information by sticker or

any other method.

21 U.S.C. 343–2.

The Commission Report supports the

requirement that information about the

uses of dietary supplements be balanced

and truthful and advises the dietary

supplement industry to strictly observe

the five requirements necessary to

qualify for the exemption from the

labeling definition for publications used

in connection with the sale of dietary

supplements. The Commission Report

states that:

[b]ecause more experience with the

implementation of this provision may

provide additional information about the use

of publications in connection with a sale, the

Commission suggests that proactive

monitoring of practice in this area be

undertaken by FDA as resources permit and

that regulatory guidance be developed if

necessary.

The agency agrees with the suggestion

that it should proactively monitor the

use of publications in connection with

the sale of dietary supplements and

provide guidance, as necessary, to the

industry. The agency intends to monitor

the use of publications under section

403B of the act. Consistent with FDA’s

practice with claims made under section

403(r)(6) of the act, the agency intends

to continue assisting industry in

complying with the requirements of this

section. If experience demonstrates a

need for regulatory guidance, the agency

will develop such guidance in the

future.

VIII. Botanical Products

As previously noted, the DSHEA’s

charge to the Commission encompassed

the regulation of label claims. The

Commission intrepreted this charge to

include the marketing of botanical

products as over-the-counter (OTC)

drugs when a preventive or therapeutic

claim is made.

The Commission Report recommends

that botanical products should continue

to be available to consumers as dietary

supplements when properly labeled as

such in compliance with the

requirements of the DSHEA. The

Commission did not recommend any

changes to FDA’s regulation of botanical

products that are marketed as dietary

supplements.

The Commission Report, however,

did note that there may be instances in

which consumers would be better

served by having certain botanical

products marketed as OTC drug

products, so that statements regarding

the prevention or treatment of disease

may accompany the product. As the

Commission Report also notes, some

botanical ingredients are recognized for

specific preventive and therapeutic

uses, and botanical pharmacopeias have

been established in a number of

developed countries. Yet, as the

Commission observed, in the United

States, many botanicals are being

labeled with statements of nutritional

support that suggest only indirectly the

type of therapeutic use that is

traditionally associated with the

product.

To address this concern, the

Commission Report advises that a study

is needed ‘‘regarding the establishment

of some alternative system for regulating

botanical products that are used for

purposes other than to supplement the

diet but that cannot meet OTC drug

requirements.’’ In addition, the

Commission Report states that a

comprehensive evaluation is needed of

the regulatory systems that other

countries have adopted to regulate

botanicals with preventive or

therapeutic uses. While the U.S. drug

regulatory system ‘‘as it currently

exists’’ may allow some botanical

remedies to be marketed OTC, the

Commission Report suggests that

existing FDA requirements might

preclude others from entering the OTC

drug market.

Finally, the Commission Report

recommends ‘‘that FDA promptly

establish a review panel for OTC claims

for botanical products that are proposed

by manufacturers for drug uses,’’ and

suggests that FDA ‘‘give special

attention to the feasibility of approving

botanical remedies for OTC uses in

which sufficient evidence is available.’’

For several years, FDA has been

engaged in discussions with experts

within the Government, academia, and

industry, regarding the regulatory status

of botanical products. FDA has actively

participated in symposia and workshops

sponsored by the National Institutes of

Health (NIH) and the Drug Information

Association (DIA), which focused on

topics such as identification and

characterization of botanical products,

the safety and efficacy evaluation of

botanical products, the various

regulatory pathways to market that a

botanical product could take, and the

necessary information that would be

required for a particular regulatory

route.

Since 1994, FDA has reviewed the

relevant laws and regulations, policies

and, in some cases, draft policies, from

regulatory and advisory authorities

around the world. Although the agency

agrees that a much more comprehensive

evaluation would be helpful, the project
23636 Federal Register / Vol. 63, No. 82 /Wednesday, April 29, 1998 / Notices

as outlined by the Commission would

be costly and resource-intensive.

Unfortunately, because resources have

not been allocated for such a

comprehensive study, FDA is unable to

act on its own to implement the

Commission’s suggestion at this time.

Agency personnel, however, are

available to work with persons

interested in conducting such a study

on study design features to provide

other technical assistance.

With respect to the Commission

Report’s points regarding evaluating

botanicals under FDA’s OTC drug

review, under FDA’s existing statutory

framework, a drug product may avoid

‘‘new drug’’ premarket approval

requirements and may be eligible for

marketing under an OTC drug

monograph if (1) the product is

generally recognized as safe and

effective under the conditions for use

for which it is labeled; and (2) if the

product has been used to a material

extent and for a material time under

those conditions. See section 201(p) of

the act. (21 U.S.C. 321(p)). FDA

recognizes, however, the need to clarify

the criteria for eligibility under the OTC

drug review for certain additional OTC

drug active ingredients, indications,

dosage forms, dosage strengths, routes of

administration, and combinations. The

agency has interpreted section 201(p)(2)

of the act to mean use in the United

States (see 61 FR 51625, 51626 (October

3, 1996)).

In the Federal Register of October

1996, FDA issued an advance notice of

proposed rulemaking (ANPRM) seeking

comment on eligibility requirements

and, among other matters, whether OTC

marketing experience abroad could be

used to establish ‘‘material time’’ and

‘‘material extent’’ requirements (61 FR

51625, October 3, 1996). For many

botanical products, the history of use is

based on marketing experience outside

the United States.

Based on the comments received in

response to the October 1996 ANPRM,

the agency expects to issue a proposed

rule setting forth criteria for eligibility

in the OTC drug monograph system,

including definitions of the terms

‘‘material extent’’ and ‘‘material time.’’

Unless and until regulations are in place

that would allow FDA to accept foreign

marketing experience, it may be difficult

for many botanical products to qualify

for inclusion in the existing OTC

monograph system. Consequently,

establishing an OTC advisory panel to

evaluate therapeutic and preventive

drug claims for botanical products, as

the Commission recommends, would be

premature at this time. The agency,

however, intends to work expeditiously

on rulemaking for this issue.

In the interim, if there were a

situation in which the scientific

evidence and marketing experience

submitted to the agency are sufficient to

allow a botanical ingredient to be

considered under the existing

framework, then the agency would work

expeditiously to assess whether the

submitted data and experience supports

marketing under an OTC drug

monograph.

In addition, recognizing the need for

guidance for manufacturers seeking to

develop botanicals as either OTC or

prescription drug products, and

recognizing the unique nature of

botanical products, the agency currently

is developing a draft guidance for

industry that discusses the kinds of data

necessary to satisfy drug regulatory

requirements based on existing statutes

and regulations. The draft guidance will

be made available for public comment

before a final guidance is issued.

IX. Information for Consumers and

Health Professionals

As required by the DSHEA, the

Commission considered how best to

ensure that consumers receive

information that is truthful,

scientifically valid, and not misleading

so that they may make informed and

appropriate health choices. The

Commission Report calls for consumer

research to determine whether

consumers want and can use the

information provided to them under the

DSHEA, existing FDA regulations, and

the recommendations of the

Commission. Because advice from

health professionals can be critical in

helping consumers to make appropriate

decisions about dietary supplement use,

the Commission Report also states that

health care and nutrition professionals

should become more knowledgeable

about these products. Additionally, the

Commission Report urges manufacturers

to develop balanced and nonmisleading

summaries of the evidence

substantiating any statements made

under section 403(r)(6) of the act and of

the evidence substantiating product

safety for the intended use at the

recommended dosage. The Commission

Report further suggests that

manufacturers make these summaries

publicly available.

FDA agrees that a better

understanding of consumer information

needs is desirable. The agency has asked

the FDA Foods Advisory Committee

(FAC) to consider how best to gather

data on how consumers use information

on dietary supplement labels to make

decisions on whether a dietary

supplement is appropriate for them.

FDA has also asked the FAC to consider

the development of guidelines or

criteria that could be used by the dietary

supplement industry and others to

conduct consumer research studies or to

evaluate the results of consumer

research studies. FAC considered these

issues at its February 1998 meeting and

referred them to a FAC internal working

group to develop recommendations for

consideration by the full FAC.

X. Research

The Commission Report addresses

various issues related to research about

dietary supplements. The Commission

Report states that the public interest

would be served by more research to

assess the relationships between dietary

supplements and the maintenance of

health and/or prevention of disease.

Additionally, the Commission Report

states that incentive mechanisms should

be developed to encourage the dietary

supplement industry to invest in

research on these products. To that end,

the Commission Report suggests that

FDA consider a ‘‘mechanism for review

of research conducted to validate a

statement of nutritional support so that

the label disclaimer mandated by

DSHEA could be modified or removed.’’

The Commission Report notes that

consideration is needed of ways to

provide FDA with sufficient resources

to make it possible for the agency to take

on such an additional responsibility.

FDA agrees that additional research

should be undertaken in the public and

private sector to assess the relationships

between dietary supplements and the

maintenance of health and/or

prevention of disease. The agency has

provided, and will continue to provide,

assistance and guidance to industry and

other Federal agencies in designing

studies for these types of assessments.

Additionally, the agency has worked

closely, and will continue to work, with

NIH’s Office of Dietary Supplements.

With regard to the Commission Report

suggestion that FDA consider reviewing

research to validate structure/function

claims and other statements made under

section 403(r)(6) of the act so that the

currently required disclaimer could be

removed, the agency notes that current

law prevents it from adopting this

suggestion. Because the disclaimer

requirement is statutory, FDA cannot

permit the disclaimer to be removed

unless Congress amends section

403(r)(6)(C) of the act accordingly.
Federal Register / Vol. 63, No. 82 /Wednesday, April 29, 1998 / Notices 23637

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. 98–11293 Filed 4–24–98; 4:27 pm]

BILLING CODE 4160–01–F