49886 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

notify FDA that they are marketing a

dietary supplement product that bears

on its label or in its labeling a statement

provided for in section 403(r)(6) of the

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

that the agency be notified, with a

submission about such statements, no

later than 30 days after the first

marketing of the dietary supplement.

Information that is required in the

submission includes: (1) The name and

address of the manufacturer, packer, or

distributor of the dietary supplement

product; (2) the text of the statement

that is being made; (3) the name of the

dietary ingredient or supplement that is

the subject of the statement; (4) the

name of the dietary supplement

(including the brand name); and (5) a

signature of a responsible individual

who can certify the accuracy of the

information presented.

In § 101.93, the agency is establishing

procedures for submitting required

information. Section § 101.93 provides

details of the procedures associated

with the submission and identifies the

information that must be included in

the submission in order to meet the

requirements of section 403 of the act.

Description of Respondents:

Businesses or other for-profit

organizations.

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN

21 CFR Section No. of

Respondents

Annual Frequency

per Response

Total Annual ResponsesHours per

Response Total Hours

101.93 420 1 420 0.5–1 210–420

(Through inadvertent error, the agency

misreported the number of respondents

and the annual frequency per response

and omitted the total annual response in

the proposal. Hours per response and

total hours were reported correctly. In

this final rule, FDA is correcting the

inadvertent errors that it made in the

proposal).

Individuals and organizations may

submit comments on these burden

estimates or on any other aspect of these

information collection provisions,

including suggestions for reducing the

burden, and should direct them to the

Office of Special Nutritionals (HFS–

450), Center for Food Safety and

Applied Nutrition, Food and Drug

Administration, 200 C St. SW.,

Washington, DC 20204.

The information collection provisions

in this final rule have been approved

under OMB control number 0910–0331.

This approval expires on October 31,

1999. An agency may not conduct or

sponsor, and a person is not required, to

respond to a collection of information

unless it displays a currently valid OMB

control number.

List of Subjects in 21 CFR Part 101

Food labeling, Nutrition, Reporting

and recordkeeping requirements.

PART 101—FOOD LABELING

1. The authority citation for 21 CFR

part 101 continues to read as follows:

Authority: Secs. 4, 5, 6 of the Fair

Packaging and Labeling Act (15 U.S.C. 1453,

1454, 1455); secs. 201, 301, 402, 403, 409,

701 of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 321, 331, 342, 343, 348, 371).

2. Section 101.93 is added to subpart

F to read as follows:

§ 101.93 Notification procedures for

certain types of statements on dietary

supplements.

(a)(1) No later than 30 days after the

first marketing of a dietary supplement

that bears one of the statements listed in

section 403(r)(6) or the Federal Food,

Drug, and Cosmetic Act, the

manufacturer, packer, or distributor of

the dietary supplement shall notify the

Office of Special Nutritionals (HFS–

450), Center for Food Safety and

Applied Nutrition, Food and Drug

Administration, 200 C St. SW.,

Washington, DC 20204, that it has

included such a statement on the label

or in the labeling of its product. An

original and two copies of this

notification shall be submitted.

(2) The notification shall include the

following:

(i) The name and address of the

manufacturer, packer, or distributor of

the dietary supplement that bears the

statement;

(ii) The text of the statement that is

being made;

(iii) The name of the dietary

ingredient or supplement that is the

subject of the statement, if not provided

in the text of the statement; and

(iv) The name of the dietary

supplement (including brand name), if

not provided in response to paragraph

(a)(2)(iii) on whose label, or in whose

labeling, the statement appears.

(3) The notice shall be signed by a

responsible individual or the person

who can certify the accuracy of the

information presented and contained in

the notice. The individual shall certify

that the information contained in the

notice is complete and accurate, and

that the notifying firm has

substantiation that the statement is

truthful and not misleading.

(b) through (e) [Reserved]

Dated: August 20, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–24738 Filed 9–22–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 190

[Docket No. 96N–0232]

Premarket Notification for a New

Dietary Ingredient

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is establishing the

procedure by which a manufacturer or

distributor of dietary supplements or of

a new dietary ingredient is to submit

under the Federal Food, Drug, and

Cosmetic Act (the act) the information

on which it has concluded that a dietary

supplement containing a new dietary

ingredient will reasonably be expected

to be safe. FDA is issuing this regulation

to enable industry to comply with the

requirements of the Dietary Supplement

Health and Education Act of 1994 (the

DSHEA).

EFFECTIVE DATE: October 23, 1997.

FOR FURTHER INFORMATION CONTACT:

Carolyn W. Miles, Center for Food

Safety and Applied Nutrition (HFS–

456), Food and Drug Administration,

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

202–401–9858.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of September

27, 1996 (61 FR 50774), FDA published
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49887

a proposed rule, entitled ‘‘Premarket

Notification for a New Dietary

Ingredient’’ (hereinafter referred to as

‘‘the September 1996 proposal’’). FDA

issued this proposal in response to

section 8 of the DSHEA (Pub. L. 103–

417). This section of the DSHEA

amended the act by adding, among other

provisions, section 201(ff) (21 U.S.C.

321(ff)), which defines a dietary

supplement, and by adding section

413(a) (21 U.S.C. 350b(a)), which

provides, among other things, for the

notification of the Secretary of Health

and Human Services (the Secretary)

(and by delegation FDA) at least 75 days

before the introduction or delivery for

introduction into interstate commerce of

a dietary supplement that contains a

new dietary ingredient. Section 413(a)

of the act states that a dietary

supplement that contains a new dietary

ingredient shall be deemed adulterated

unless it meets one of two requirements.

One requirement is that ‘‘the dietary

supplement contains only dietary

ingredients which have been present in

the food supply as an article used for

food in a form in which the food has not

been chemically altered.’’ The

alternative requirement is that:

[T]here is a history of use or other evidence

of safety establishing that the dietary

ingredient when used under the conditions

recommended or suggested in the labeling of

the dietary supplement will reasonably be

expected to be safe and, at least 75 days

before being introduced or delivered for

introduction into interstate commerce, the

manufacturer or distributor of the dietary

ingredient or dietary supplement provides

the Secretary with information, including

any citation to published articles, which is

the basis on which the manufacturer or

distributor has concluded that a dietary

supplement containing such dietary

ingredient will reasonably be expected to be

safe.

FDA published the September 1996

proposal to establish a procedure that

would enable industry to comply with

this notification requirement in an

efficient manner. Adoption of this

procedure will help to facilitate

compliance with the notification

required by section 413(a)(2) of the act.

Interested persons were given until

December 26, 1996, to comment on the

proposal.

FDA received four letters each

containing one or more comments from

consumer groups, a trade association,

and industry in response to the

proposal. All of the comments generally

supported the proposal. Several

comments suggested modifications or

revisions of various aspects of the

proposal. A summary of the comments

and the agency’s responses follows.

II. New Dietary Ingredients Subject to

Notification Requirements

1. Several comments expressed

concern that proposed § 190(a),

published in the September 1996

proposal, implied that any ‘‘new dietary

ingredient’’ is subject to the notification

requirements. The comments argued

that the statutory requirement for

notification under section 413(a)(2) of

the act does not apply to those new

dietary ingredients that have been

present in the food supply as an article

used for food in a form in which the

food has not been chemically altered, as

described in section 413(a)(1) of the act.

FDA agrees with the comments that

the notification requirements of this

regulation apply only to new dietary

ingredients described in section

413(a)(2) of the act. Section 413(a)(1) of

the act applies to dietary supplements

that contain only dietary ingredients

that have been present in the food

supply as an article used for food in a

form in which the food has not been

chemically altered, and the statute does

not require that FDA be notified before

these products are marketed. To make

clear which new dietary ingredients are

subject to the notification requirement

in section 413(a)(2) of the act, FDA is

modifying proposed § 190.6(a) by

incorporating the phrase ‘‘that has not

been present in the food supply as an

article used for food in a form in which

the food has not been chemically

altered’’ to define which new dietary

ingredients are subject to the

notification requirement.

III. The Notification

2. One comment opposed the

requirement in proposed § 190.6(b)(3)(i)

that the notification include the level of

the new dietary ingredient in the dietary

supplement. The comment claimed that

notices may be submitted by vendors

who will not know the level of the new

ingredient in the supplement and

argued that these vendors should not be

barred from the sale of these

ingredients.

FDA does not agree that it would be

appropriate to remove the requirement

that the notification include the level of

the new dietary ingredient in the dietary

supplement. First, § 190.6(b)(3)(i)

responds to section 413(a)(2) of the act

that states that the manufacturer or the

distributor is to provide the information

on a dietary supplement that contains a

new dietary ingredient. Both of these

parties would have access to

information on the level of the new

dietary ingredient. If a vendor wants to

stand in the position of a manufacturer

or distributor, it needs to be able to

provide the information that they can

provide.

Second, section 413(a) of the act also

states that a dietary supplement that

contains a new dietary ingredient is

adulterated unless there is a history of

use or other evidence of safety

establishing that the dietary ingredient,

when used under the conditions

recommended or suggested in the

labeling of the dietary supplement, will

reasonably be expected to be safe, and

that the notification must include the

information on which the manufacturer

or distributor has determined that the

dietary supplement containing the

dietary ingredient will meet this

standard. It is not possible to have a

reasonable expectation of safety without

knowledge of the level of the new

dietary ingredient in the supplement.

The dietary ingredient may be safe

under certain conditions of use, but it

may be unsafe under other conditions of

use. For example, the essential trace

mineral selenium is safe when

consumed in amounts necessary to meet

a person’s nutrient requirements, but it

is toxic when consumed at high levels.

Some dietary ingredients contain

constituents that have potent

pharmacologic actions that could cause

the dietary ingredient to present a

significant or unreasonable risk of injury

or illness under the labeled conditions

of use. The bark of Pausinystalia

yohimbe (K. Schumann) (commonly

called yohimbe) contains the

indolalkylamine alkaloid yohimbine,

which is a potent alpha-2-adrenergic

antagonist that may be toxic when

ingested in high doses.

Thus, if the notification does not

contain the level of the dietary

ingredient in the product, the

notification would not contain a piece

of information that is necessary if the

manufacturer or distributor is to

conclude that the dietary supplement

will reasonably be expected to be safe

under the conditions of use

recommended or suggested in its

labeling. Without this information, the

dietary supplement would be

adulterated under section 402(f)(1)(B) of

the act (21 U.S.C. 342(f)(1)(B)).

Therefore, FDA is not persuaded to

remove or revise proposed

§ 190.6(b)(3)(i). This provision is

necessary to ensure that a manufacturer

has considered information that directly

bears on the safety of the new dietary

ingredient of interest.

3. One comment stated that FDA’s

proposed rule on the notification for a

new dietary ingredient is a procedural

regulation when what is needed is a

substantive regulation that provides

adequate guidance to the manufacturer
49888 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

as to the quality and quantity of the

information necessary to meet the

requirements of section 413(a)(2) of the

act. The comment disagreed with FDA’s

assertion that the manufacturer is only

required to provide the basis on which

it has concluded that the dietary

supplement will reasonably to expected

to be safe and that the manufacturer or

distributor is not required to do a

complete search of all available sources

of information on the new dietary

ingredient. The comment maintained

that under the proposed regulation,

manufacturers could knowingly market

products with documented deleterious

effects as long as they provide FDA with

articles citing only a product’s benefits.

The comment requested that FDA

examine how the DSHEA amended

section 402 of the act as well as section

413 of the act. Section 402(f)(1)(B) of the

act states that a ‘‘food shall be deemed

to be adulterated if it is a dietary

supplement or contains a dietary

ingredient that is a new dietary

ingredient for which there is inadequate

information to provide reasonable

assurance that such ingredient does not

present a significant or unreasonable

risk of illness or injury.’’ The comment

argued that without a minimal safety

data requirement, FDA risks that its

interpretation of the DSHEA could

cause a manufacturer to challenge the

validity of the DSHEA on the grounds

that the statute is void for vagueness

because it does not provide fair warning

to the manufacturer of what is expected.

The comment requested that FDA issue

regulations that elaborate on omissions

in the statute by Congress.

The comment further suggested that

FDA should require that a new dietary

ingredient, when used under the

conditions recommended or suggested

in the labeling of the dietary

supplement, be generally recognized as

safe (GRAS); that is, that FDA apply to

a new dietary ingredient the standard

that there is general recognition that a

dietary supplement containing the new

dietary ingredient ‘‘will reasonably be

expected to be safe.’’ The comment

further suggested that FDA should

provide industry with examples of

publications that are acceptable as

evidence of safety and a list of sources

to search for evidence of adverse effects

associated with a new dietary

ingredient. Further, the comment

maintained that manufacturers should

be required to provide FDA with a

summary of studies and scientific data,

including known adverse effects. The

comment stated that, in the absence of

an appropriate scientific standard of

evidence, manufacturers would be free

to submit articles from questionable

publications or unpublished materials

to establish the safety of the new dietary

ingredient. The comment argued that

reliance on a GRAS standard would not

be contrary to the statute or to

congressional intent because it would

still permit the marketing of dietary

supplements without prior approval.

FDA disagrees with the comment that

a substantive, rather than a procedural,

regulation is necessary to respond to

section 413(a)(2) of the act. The

comment appears to be opposed to

proposed § 190.6(b)(4), which sets out

the substantive information that the

notification must include. Significantly,

§ 190.6(b)(4) simply tracks the language

of section 413(a)(2) of the act. It is

appropriate that the regulation do so

because, contrary to what the comment

asserts, the manufacturer or distributor

is not required to do a complete

literature search. It is required only to

provide ‘‘the basis on which [it] has

concluded that a dietary supplement

containing such dietary ingredient will

reasonably be expected to be safe’’

(section 413(a)(2) of the act). That is all

that the regulation requires.

FDA agrees with the comment that

sections 402(f)(1)(B) and 413 of the act

are related in that they both relate to

new dietary ingredients. FDA also

acknowledges that Congress has

provided in section 413(a) of the act that

a failure to provide the information

under section 413(a) of the act would

render the dietary supplement

adulterated under section 402(f) of the

act. The agency, however, in deciding

what information needs to be provided,

is bound by the standard in the act. It

is not free to rewrite the law, as the

comment appears to suggest.

The fact that Congress did not create

a minimal safety data requirement in

section 413(a)(2) of the act does not

render the DSHEA void for vagueness.

The manufacturer’s or distributor’s

obligation under section 413(a)(2) of the

act is clear. It must make a showing as

to why it considers that consumption of

a new dietary ingredient will be safe.

FDA also does not agree that the

GRAS concept has relevance here. The

concept of GRAS was adopted by

Congress in 1958, as a limitation on the

scope of the ‘‘food additive’’ definition

(section 201(s) of the act). Congress

excluded from the definition of ‘‘food

additive’’ substances that are generally

recognized, among experts qualified by

scientific training and experience to

evaluate their safety, as having been

adequately shown through scientific

procedures (or, in the case of a

substance used in food prior to January

1, 1958, through experience based on

common use in food) to be safe under

the conditions of their intended use.

However, dietary ingredients, which are

used in dietary supplements, are not

food additives. Congress excluded them

from the definition of a ‘‘food additive’’

in the DSHEA (section 201(s)(6) of the

act, which was added by section 3(b) of

the DSHEA). Thus, the concept of GRAS

is not relevant to how dietary

ingredients are regulated.

Furthermore, there is a fundamental

difference between who is to make at

least the initial judgment as to the safety

of an ingredient under section 413(a)(2)

of the act and whose judgment is

relevant to a determination that an

ingredient is GRAS. Whether an

ingredient is GRAS is based on the

judgment of ‘‘experts qualified by

scientific training and experience to

evaluate’’ the ingredient’s safety. In

contrast, the requirement in section

413(a)(2) of the act that a notification be

made for a new dietary ingredient

provides that the manufacturer or

distributor is to determine whether a

dietary supplement containing such

dietary ingredient will reasonably be

expected to be safe. While this

determination is subject to review by

FDA, section 413(a) of the act does not

specify that the manufacturer or

distributor must rely on any specified

third party in making its judgment. For

these reasons, FDA is not requiring in

§ 190.6(b)(4) that the notification for a

new dietary ingredient include

information establishing that the new

dietary ingredient is GRAS or the

subject of any other type of general

recognition.

Furthermore, FDA is not persuaded

that it is necessary for the agency to

provide examples of scientific

publications that are adequate to

provide the information that can be the

basis on which the manufacturer or

distributor has concluded that a dietary

supplement containing the new dietary

ingredient will reasonably be expected

to be safe. The agency also is not

persuaded that the act requires that a

manufacturer or distributor provide to

FDA information on all known adverse

effects attributable to the new dietary

ingredient that is the subject of the

submission. Section 413(a)(2) of the act

requires only that the notification

provide information ‘‘which is the basis

on which the manufacturer or

distributor has concluded that a dietary

supplement containing such dietary

ingredient will reasonably be expected

to be safe when used under the

conditions recommended or suggested

in the labeling.’’ Thus, the statute does

not specify or limit what evidence a

manufacturer or distributor may rely on

in determining whether the use of the
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49889

ingredient will reasonably be expected

to be safe. Nonetheless, FDA expects

that, in making a determination that a

new dietary ingredient is reasonably

expected to be safe and does not present

a significant or unreasonable risk of

illness or injury, a manufacturer or

distributor will consider the evidence of

safety that is available in the scientific

literature and from examination of

reports of adverse effects associated

with the use of a new dietary ingredient.

FDA does not find that the statute

requires that the agency determine the

relative merit of different types of

evidence of safety, and therefore, the

agency is not modifying § 190.6 to

specify specific safety requirements for

new dietary ingredients or to establish

standards that the evidence of safety

must meet.

4. One comment opposed the

proposed requirement in § 190.6(b)(4)

that the premarket notification for a

‘‘new dietary ingredient’’ contain

reprints or photostatic copies,

including, if necessary, English

translations of all references to

published information offered in

support of the notification. The

comment stated that with FDA’s

diminished resources the handling,

cataloging, and storage of such copies

could place a substantial burden on the

agency and that this requirement for

submission of copies of cited articles

would be expensive and cumbersome

for the manufacturer. The comment

suggested that the requirement for

submission of copies of references

should not become a part of the final

rule on new dietary ingredient

notifications because of the availability

of scientific data through electronic data

bases.

FDA is not persuaded to delete

proposed § 190.6(b)(4). FDA finds that it

would take significantly more agency

resources to find and obtain copies of

references than would be expended to

managing them as a part of each

notification. Furthermore, FDA has

found in reviewing the notifications that

have been received since the passage of

the DSHEA that many of the references

cited in the notifications are not readily

available in the United States or are not

easily obtained electronically. In some

cases, English translations are not

available unless provided by the party

making the notification. On the other

hand, the manufacturer or distributor,

who has reviewed the published

information in concluding that there is

a reasonable expectation of safety, will

have ready access to the articles and

thus would be in a position to supply

them to FDA.

Thus, FDA is not persuaded that the

requirement that the new ingredient

notification include copies of all

references used to support the

notification will impose an excessive or

unnecessary burden on FDA or on

manufacturers or distributors who make

a notification. Consequently, it is not

revising § 190.6(b)(4).

5. Several comments opposed the

proposed § 190.6(b)(5) requirement that

the premarket notification of the

marketing of a new dietary ingredient

include the signature of an authorized

official of the manufacturer or

distributor of the dietary supplement

that contains the new dietary ingredient.

One comment asked that the

regulation be changed to require the

signature of the person who is directly

responsible for assimilating and

submitting the premarket notification.

The comment stated that in its

company, an ‘‘authorized official’’

usually means an officer of the

company, but that the assimilation and

submission of documents such as

premarket notifications to FDA is the

responsibility of someone who is not an

officer of the company.

Another comment stated that it had

no objection to the requirement in

proposed § 190.6(b)(5) that the

notification be signed by an authorized

official of the manufacturer or

distributor. The comment did state,

however, that such a signature does not

constitute a certification of the accuracy

or completeness of the data set out in

the notification. The comment argued

that section 8 of the DSHEA is entirely

silent with respect to the signature or

certification of notices, and that the

agency’s proposal creates an

administrative amendment to DSHEA

and is, therefore, inappropriate.

In the preamble to the September

1996 proposal, FDA stated that it was

‘‘including this provision to ensure that

the individual that is responsible for the

accuracy, completeness, and

understandability of the notification is

identified’’ (61 FR 50774 at 50775).

Section 8 of the DSHEA does not

designate a specific employee or

representative of a manufacturer or

distributor who is to submit the notice

on behalf of a manufacturer or

distributor. FDA did not intend by its

use of the word ‘‘authorized’’ to

designate a particular person that the

firm must assign the responsibility of

preparing the notification required

under section 413(a)(2) of the act.

Instead, the agency only intended that

§ 190.6(b)(5) provide that the person

who signs the notification be familiar

with the information contained in it and

be available to answer questions or

provide additional information to FDA

if questions about a notification arise.

Therefore, FDA is modifying

§ 190.6(b)(5) by replacing the term

‘‘authorized official’’ with the word

‘‘person.’’ This change will make clear

that a manufacturer or distributor may

assign responsibility for the notification

to a person without concern about that

person’s official capacity within the

management structure of the firm.

The September 1996 proposal did not

represent that the signature of the

individual that is responsible for the

accuracy, completeness, and

understandability of the notification

constitutes a ‘‘certification.’’ However,

the person signing the notice, and the

company on whose behalf he or she

signs it, should recognize that there are

significant consequences to their action,

including potential liability under 18

U.S.C. 1001. The intent of section

413(a)(2) of the act is for the firm to

provide to FDA the information that is

the basis on which the manufacturer or

distributor has concluded that a dietary

supplement containing such dietary

ingredient will reasonably be expected

to be safe. A firm must have such

information, or the dietary supplement

may well be adulterated under section

402(f)(1)(B) of the act. The notification

is intended to be the mechanism by

which that information is made

available to FDA, so that the agency is

aware of the basis that a manufacturer

or distributor has for concluding that

there is reasonable assurance that a new

dietary ingredient is safe. Consequently,

the information in the notification must

be a fair and accurate representation of

the information that a firm used in

developing its conclusion that a new

dietary ingredient is safe. A notification

that intentionally omitted information

that would indicate that a new dietary

ingredient presents a significant or

unreasonable risk of illness or injury or

that contained false or misleading

information would be a knowing and

willful submission of false information

to the Federal Government and could

subject the parties involved to criminal

sanctions under 18 U.S.C. 1001.

However, the person who signs the

notification need not certify the

information in the notification. The

signature is intended to identify the

person to whom FDA may address

questions to concerning the notification.

However, such persons should be

cognizant of their responsibility in

providing this notification and of the

consequences of submitting of false or

misleading information to the Federal

Government.
49890 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

IV. Administrative Procedures

6. One comment requested that

proposed § 190.6(c) be revised to state

that FDA will send an acknowledgment

of the receipt of the premarket

notification of the marketing of a new

dietary ingredient noting the filing date,

so that manufacturers will know when

the 75-day notice period expires.

FDA is persuaded to make this

revision. However, the agency cautions

that the acknowledgment of the receipt

of the premarket notification of the

marketing of a new dietary ingredient

does not constitute a finding by FDA

that the new dietary ingredient, or the

dietary supplement that contains the

new dietary ingredient, is safe, or that

it is not adulterated under section 402

of the act. Therefore, FDA has required

§ 190.6(c) by adding the sentence: ‘‘FDA

will acknowledge the receipt of the

notification made pursuant to section

412(a) of the act and will notify the

submitter of the date of receipt of such

a notification.’’

7. One comment asked that proposed

§ 190.6(c) be revised by removing the

last sentence which states: ‘‘For 75 days

after the filing date, the manufacturer or

distributor of a dietary supplement that

contains a new dietary ingredient shall

not introduce or deliver for

introduction, into interstate commerce

the dietary supplement that contains the

new dietary ingredient.’’ The comment

stated that this language is not found in

the act, and that the language is

unnecessarily restrictive. The comment

argued that if the agency completes its

review and decides there is no concern,

the manufacturer should not be

prohibited from marketing the dietary

supplement when such a determination

by FDA is made prior to the 75th day

after the notification was filed.

FDA does not agree that this sentence

should be removed from the regulation.

While the comment is correct that the

language in the regulation is not stated

in the law, section 413(a)(2) of the act

states, as stated in the previous

paragraph, that at least 75 days before

introducing or delivering for

introduction, a new dietary ingredient

into interstate commerce, the

manufacturer or distributor is to provide

information that the dietary ingredient

will reasonably be expected to be safe.

The comment is based on a

misunderstanding of the notification

process. Because there is no

requirement that the notification

provide a comprehensive safety review

of the new dietary ingredient, it is not

likely to provide the agency with a basis

to find that there is no concern. Rather,

the process is more likely to identify

those new dietary ingredients that do

present a concern. Thus, it is the people

who have provided a notice that raises

concerns, rather than one that does not,

who are likely to hear from the agency.

Given this fact, and to ensure that the

system runs smoothly, FDA is codifying

its expectation based on the act that

manufacturers and distributors that

submit a notification to FDA will not

market their product for 75 days from

the date of submission of the notice.

Consequently, FDA has not modified

proposed § 190.6(c) as requested by this

comment.

8. One comment asked that proposed

§ 190.6(d) be changed to state that:

* * * if additional information is provided

in support of the new ingredient notification,

the agency will determine whether the

additional information is a substantive

amendment to the submission. If the agency

determines that the new submission is a

substantive amendment, FDA will assign a

new filing date. FDA will acknowledge

receipt of the additional information and,

when applicable, notify the manufacturer of

the new filing date, which is the date of

receipt by FDA of the information that

constitutes the substantive amendment.

The comment argued that proposed

§ 190.6(d) would require that any

additional information, regardless of

how significant (for example, a single

response to an inquiry from the agency

about a submission), would reset the 75-

day period. Furthermore, the comment

stated that its suggested language would

provide flexibility for submitting

additional information without

unnecessarily prolonging the 75-day

period.

FDA agrees with the substance of this

comment that the agency should be

flexible in its handling of the

submission of additional materials.

Therefore, FDA has revised § 190.6(d) to

reflect that if it receives additional

information, the agency will review all

submissions pertaining to the

notification in question, including

responses made to inquires from the

agency, to determine whether they are

significant and whether they require

that the 75-day period be reset.

V. Environmental Impact

The agency had determined under 21

CFR 25.24(a)(8) 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 Impacts

A. Benefit-Cost Analysis

FDA has examined the economic

implications of this final 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

regulatory approaches that maximize

net benefits (including potential

economic, environmental, public health,

safety, distributive, and equity effects).

Executive Order 12866 classifies a rule

as significant if it meets any one of a

number of specified conditions,

including: Having an annual effect on

the economy of $100 million, adversely

affecting some sector of the economy in

a material way, adversely affecting jobs

or competition, or raising novel legal or

policy issues.

In the economic analysis of the

proposed rule, FDA estimated the

number of new ingredients to be 0 to 12

per year and the cost per notification to

be $410, for an annual cost range of $0

to $4,920 per year. In the most recent

year, the industry introduced six new

ingredients for an estimated cost of

$2,460. FDA received no comments on

these estimates and consequently

concludes that the actual costs of this

rule will not be significant.

FDA finds that this final rule does not

constitute a significant rule as defined

by Executive Order 12866. Furthermore,

it has been determined that this rule is

not a major rule for the purpose of

Congressional Review (Public Law 104–

121).

B. Small Business Analysis

FDA has examined the economic

implications of this final rule as

required by the Regulatory Flexibility

Act (5 U.S.C. 601–612). If a rule has a

significant economic impact on a

substantial number of small entities, the

Regulatory Flexibility Act requires

agencies to analyze regulatory options

that would lessen the economic effect of

the rule on small entities.

FDA received no comments on the

regulatory flexibility analysis of the

proposed rule. As the agency stated in

the analysis of the proposed rule, the

dietary supplement industry does not

have its own standard industrial

classification code. The industry’s

products come closest to the industry

groups Food Preparations (not

elsewhere classified) (Standard

Industrial Classification code 2099) and

Medicinal Chemicals and Botanical

Products (Standard Industrial

Classification code 2833). The Small

Business Administrations’ (SBA) size

standards for ‘‘small’’ are 500 or fewer

employees for food preparations and

750 or fewer employees for medicinal

and botanical products. The use of this

size standard will cause the majority of
Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations 49891

firms in the dietary supplement

industry to be classified as small

businesses.

Without further information on the

identity of the businesses introducing

new ingredients, FDA concludes that

the total number of businesses affected

by the proposed rule will be no more

than the number of new ingredients

(estimated to be 0 to 12 per year). Before

the event, FDA cannot determine the

sizes of firms that introduce new dietary

ingredients. Small businesses could

introduce all new ingredients or none.

The annual number of small businesses

potentially affected by the proposed rule

will therefore be the same as the annual

number of new ingredients, 0 to 12.

Whether the cost of notification,

approximately $410 per submission,

will be a substantial burden depends

partly on the revenues of the smallest

businesses in the dietary supplement

industry. For the smallest businesses in

the industry, the cost of notification

considered alone could be a significant

burden. This cost, however, cannot be

considered in isolation from the total

cost of introducing a new dietary

ingredient. A dietary supplement firm

introducing a new ingredient must first

determine that the ingredient can

reasonably be expected to be safe.

Technical, legal, and marketing costs of

introducing a new dietary ingredient

and ensuring its safety will be much

larger than the cost of providing the

information required under this rule.

The costs of notification are therefore

not likely to be a substantial part of the

total cost of introducing a new dietary

ingredient. Small businesses capable of

bearing the cost of introducing new

ingredients, then, would be highly

unlikely to find the additional cost

imposed by the 75-day premarket

notification procedure to be an

economically significant burden.

FDA finds that this final rule will not

have a significant economic impact on

a substantial number of small entities.

Accordingly, under the Regulatory

Flexibility Act (5 U.S.C. 605(b)), the

Secretary certifies that this final rule

will not have a significant impact on a

substantial number of small entities.

VII. Paperwork Reduction Act of 1995

This final rule contains information

collection requirements that are subject

to review by the Office of Management

and Budget (OMB) under the Paperwork

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

3520). The following title, description,

and respondent description of the

information collection provisions are

shown with an estimate of the annual

reporting and recordkeeping burden.

Included in the estimate is the time for

reviewing instructions, searching

existing data sources, gathering and

maintaining the data needed, and

completing and reviewing each

collection of information.

Title: Dietary supplements; dietary

ingredients; premarket notification.

Description: FDA is requiring, by

regulation, the submission to the agency

of information that is the basis on which

a manufacturer or distributor of a new

dietary ingredient or a dietary

supplement containing a new dietary

ingredient has concluded that the

dietary supplement containing such

dietary ingredient will reasonably be

expected to be safe. This information

must be submitted to the agency at least

75 days prior to the first commercial

distribution of a dietary supplement

containing a new dietary ingredient.

FDA will review the submitted

information to determine whether the

submission meets the requirements of

section 413 of the act. The agency is

establishing § 190.6 as the procedural

regulation for this program. This

regulation provides details of the

administrative procedures associated

with the submission and identifies the

information that must be included in

the submission in order to meet the

requirements of section 413 of the act

and to show the basis on which a

manufacturer or distributor of a new

dietary ingredient or a dietary

supplement containing a new dietary

ingredient has concluded that the

dietary supplement containing such

dietary ingredient will reasonably be

expected to be safe.

Description of Respondents:

Businesses or other for-profit

organizations.

ESTIMATED ANNUAL REPORTING BURDEN

21 CFR Section No. of

Respondents

Annual

Frequency per

Response

Total Annual

Responses

Hours per

Response Total Hours

190.6 6 1 6 20 120

Total 120

There are no capital or operating and maintenance costs associated with this collection of information.

Individuals and organizations may

submit comments on these burden

estimates or on any other aspect of these

information collection provisions,

including suggestions for reducing the

burden, and should direct them to the

Office of Special Nutritionals (HFS–

450), Center for Food Safety and

Applied Nutrition, Food and Drug

Administration, 200 C St. SW.,

Washington, DC 20204.

The information collection provisions

in this final rule have been approved

under OMB control number 0910–0330.

This approval expires October 31, 1999.

An agency may not conduct or sponsor,

and a person is not required to respond

to a collection of information unless it

displays a currently valid OMB control

number.

List of Subjects in 21 CFR Part 190

Food ingredients, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, title 21 CFR chapter

I is amended by adding new part 190 to

read as follows:

PART 190—DIETARY SUPPLEMENTS

Subpart A—[Reserved]

Subpart B—New Dietary Ingredient

Notification

Sec.

190.6 Requirement for premarket

notification.

Authority: Secs. 201(ff), 301, 402, 413, 701

of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 321(ff), 331, 342, 350b, 371).
49892 Federal Register / Vol. 62, No. 184 / Tuesday, September 23, 1997 / Rules and Regulations

Subpart A—[Reserved]

Subpart B—New Dietary Ingredient

Notification

§ 190.6 Requirement for premarket

notification.

(a) At least 75 days before introducing

or delivering for introduction into

interstate commerce a dietary

supplement that contains a new dietary

ingredient that has not been present in

the food supply as an article used for

food in a form in which the food has not

been chemically altered, the

manufacturer or distributor of that

supplement, or of the new dietary

ingredient, shall submit to the Office of

Special Nutritionals (HFS–450), Center

for Food Safety and Applied Nutrition,

Food and Drug Administration, 200 C

St. SW., Washington, DC 20204,

information including any citation to

published articles that is the basis on

which the manufacturer or distributor

has concluded that a dietary

supplement containing such dietary

ingredient will reasonably be expected

to be safe. An original and two copies

of this notification shall be submitted.

(b) The notification required by

paragraph (a) of this section shall

include:

(1) The name and complete address of

the manufacturer or distributor of the

dietary supplement that contains a new

dietary ingredient, or of the new dietary

ingredient;

(2) The name of the new dietary

ingredient that is the subject of the

premarket notification, including the

Latin binomial name (including the

author) of any herb or other botanical;

(3) A description of the dietary

supplement or dietary supplements that

contain the new dietary ingredient

including:

(i) The level of the new dietary

ingredient in the dietary supplement;

and

(ii) The conditions of use

recommended or suggested in the

labeling of the dietary supplement, or if

no conditions of use are recommended

or suggested in the labeling of the

dietary supplement, the ordinary

conditions of use of the supplement;

(4) The history of use or other

evidence of safety establishing that the

dietary ingredient, when used under the

conditions recommended or suggested

in the labeling of the dietary

supplement, will reasonably be

expected to be safe, including any

citation to published articles or other

evidence that is the basis on which the

distributor or manufacturer of the

dietary supplement that contains the

new dietary ingredient has concluded

that the new dietary supplement will

reasonably be expected to be safe. Any

reference to published information

offered in support of the notification

shall be accompanied by reprints or

photostatic copies of such references. If

any part of the material submitted is in

a foreign language, it shall be

accompanied by an accurate and

complete English translation; and

(5) The signature of the person

designated by the manufacturer or

distributor of the dietary supplement

that contains a new dietary ingredient.

(c) FDA will acknowledge its receipt

of a notification made under section 413

of the Federal Food, Drug, and Cosmetic

Act (the act) and will notify the

submitter of the date of receipt of such

a notification. The date that the agency

receives the notification submitted

under paragraph (a) of this section is the

filing date for the notification. For 75

days after the filing date, the

manufacturer or distributor of a dietary

supplement that contains a new dietary

ingredient shall not introduce, or

deliver for introduction, into interstate

commerce the dietary supplement that

contains the new dietary ingredient.

(d) If the manufacturer or distributor

of a dietary supplement that contains a

new dietary ingredient, or of the new

dietary ingredient, provides additional

information in support of the new

dietary ingredient notification, the

agency will review all submissions

pertaining to that notification, including

responses made to inquiries from the

agency, to determine whether they are

substantive and whether they require

that the 75-day period be reset. If the

agency determines that the new

submission is a substantive amendment,

FDA will assign a new filing date. FDA

will acknowledge receipt of the

additional information and, when

applicable, notify the manufacturer of

the new filing date, which is the date of

receipt by FDA of the information that

constitutes the substantive amendment.

(e) FDA will not disclose the

existence of, or the information

contained in, the new dietary ingredient

notification for 90 days after the filing

date of the notification. After the 90th

day, all information in the notification

will be placed on public display, except

for any information that is trade secret

or otherwise confidential commercial

information.

(f) Failure of the agency to respond to

a notification does not constitute a

finding by the agency that the new

dietary ingredient or the dietary

supplement that contains the new

dietary ingredient is safe or is not

adulterated under section 402 of the act.

Dated: August 22, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–24737 Filed 9–22–97; 8:45 am]

BILLING CODE 4160–01–F