[Federal Register Volume 62, Number 184 (Tuesday, September 23, 1997)]
[Rules and Regulations]
[Pages 49886-49892]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 97-24737]


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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.

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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:
    [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 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 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).


[[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