Law Library


Federal Register: September 23, 1997 (Volume 62, Number 184)

Rules and Regulations

Page 49886-49892


 

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

 

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

 

Page 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:

    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, 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 Sec. 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 Sec. 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

Sec. 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, Sec. 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 Sec. 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

 

Page 49888

 

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

Sec. 190.6(b)(4), which sets out the substantive information that the

notification must include. Significantly, Sec. 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 Sec. 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

 

Page 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 Sec. 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 Sec. 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 Sec. 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 Sec. 190.6(b)(4).

    5. Several comments opposed the proposed Sec. 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 Sec. 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

Sec. 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

Sec. 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.

 

Page 49890

 

IV. Administrative Procedures

 

    6. One comment requested that proposed Sec. 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 Sec. 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 Sec. 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 Sec. 190.6(c) as requested

by this comment.

    8. One comment asked that proposed Sec. 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 Sec. 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 Sec. 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

 

Page 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

Sec. 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

 

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

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

      Annual

 

         21 CFR Section               No. of       Frequency per   Total Annual

     Hours per      Total Hours

    Respondents      Response        Responses

     Response

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

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

190.6   6               1               6

       20             120

Total

      120

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

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

There are no capital or operating and maintenance costs associated with this col

lection 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).

 

 

Page 49892

 

 

 

Subpart A--Reserved

 

Subpart B--New Dietary Ingredient Notification

 

 

Sec. 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