[Federal Register Volume 72, Number 121 (Monday, June 25, 2007)]
[Rules and Regulations]
[Pages 34959-34969]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 07-3038]



[[Page 34959]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 111

[Docket No. 2007N-0186]
RIN 0910-AB88


Petition to Request an Exemption From 100 Percent Identity 
Testing of Dietary Ingredients: Current Good Manufacturing Practice in 
Manufacturing, Packaging, Labeling, or Holding Operations for Dietary 
Supplements

AGENCY: Food and Drug Administration, HHS.

ACTION: Interim final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing an interim 
final rule (IFR) that sets forth a procedure for requesting an 
exemption from the requirement in the final rule ``Current Good 
Manufacturing Practice in Manufacturing, Packaging, Labeling, or 
Holding Operations for Dietary Supplements,'' published elsewhere in 
this issue of the Federal Register, that the manufacturer conduct at 
least one appropriate test or examination to verify the identity of any 
component that is a dietary ingredient. This IFR allows for submission 
to, and review by, FDA of an alternative to the required 100 percent 
identity testing of components that are dietary ingredients, provided 
certain conditions are met and establishes a requirement for retention 
of records relating to the FDA's response to an exemption request.

DATES: This rule is effective August 24, 2007.
    Compliance Dates: The compliance date is June 25, 2008; except that 
for businesses employing fewer than 500, but 20 or more full-time 
equivalent employees, the compliance date is June 25, 2009; and except 
that for businesses that employ fewer than 20 full-time equivalent 
employees, the compliance date is June 25, 2010.
    Submit written or electronic comments by September 24, 2007.
    Submit comments regarding information collection by July 25, 2007, 
to OMB (see ADDRESSES).

ADDRESSES: You may submit comments, identified by Docket No. 2007N-
0186, and/or RIN number 0910-AB88, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following ways:
    <bullet> Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
    <bullet> Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.

Written Submissions

    Submit written submissions in the following ways:
    <bullet> FAX: 301-827-6870.
    <bullet> Mail/Hand delivery/Courier (for paper, disk, or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and docket number and Regulatory Information Number (RIN) for this 
rulemaking. All comments received may be posted without change to 
http://www.fda.gov/ohrms/dockets/default.htm, including any personal 
information provided. For additional information on submitting 
comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION 
section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.
    Information Collection Provisions: Submit written comments on the 
information collection provisions to the Office of Information and 
Regulatory Affairs, Office of Management and Budget (OMB). To ensure 
that comments on the information collection are received, OMB 
recommends that written comments be faxed to the Office of Information 
and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Vasilios Frankos, Center for Food 
Safety and Applied Nutrition (HFS-810), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1696.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is issuing a final rule establishing current good manufacturing 
practice requirements (CGMPs) for dietary supplements elsewhere in this 
issue of the Federal Register (hereinafter referred to as the CGMP 
final rule). The CGMP final rule establishes the minimum CGMPs 
necessary for activities related to manufacturing, packaging, labeling, 
or holding dietary supplements to ensure the quality of the dietary 
supplement. Dietary ingredients are the central defining ingredients of 
a dietary supplement. Because of the critical importance of ensuring 
the proper identity of dietary ingredients, we are requiring in the 
CGMP final rule that each manufacturer perform its own testing or 
examination (identity testing) to verify the identity of each dietary 
ingredient prior to use in the manufacturing process. This identity 
testing requirement applies to a manufacturer who purchases a dietary 
ingredient from a dietary ingredient supplier or who manufactures its 
own dietary ingredient for use in the manufacture of its dietary 
supplement. This requirement for 100 percent identity testing of 
dietary ingredients is found at Subpart E--Requirement to Establish a 
Production and Process Control System, Sec.  111.75 ``What must you do 
to determine whether specifications are met?'' in the CGMP final rule. 
Section 111.75(a)(1) (21 CFR 111.75(a)(1)) of the CGMP final rule 
requires (a) Before you use a component, you must: (1) Conduct at least 
one appropriate test or examination to verify the identity of any 
component that is a dietary ingredient * * * *.
    This provision is discussed at length in section X of the CGMP 
final rule, published elsewhere in this issue of the Federal Register, 
particularly in the discussions relating to comments submitted in 
response to the 2003 CGMP proposed rule (68 FR 12157, March 13, 2003) 
(see the responses to Comments 145 and 174).
    Section 111.75(a)(1) of the CGMP final rule reflects our 
determination that manufacturers that test or examine 100 percent of 
the incoming dietary ingredients for identity can be assured of the 
identity of the ingredient. However, we recognize that it may be 
possible for a manufacturer to demonstrate, through various methods and 
processes in use over time for its particular operation, that a system 
of less than 100 percent identity testing would result in no material 
diminution

[[Page 34960]]

of assurance of the identity of the dietary ingredient as compared to 
the assurance provided by 100 percent identity testing. To provide an 
opportunity for a manufacturer to make such a showing and reduce the 
frequency of identity testing of components that are dietary 
ingredients from 100 percent to some lower frequency, we decided to add 
to Sec.  111.75(a)(1), an exemption from the requirement of 100 percent 
identity testing when a manufacturer petitions the agency for such an 
exemption to 100 percent identity testing under Sec.  10.30 and the 
agency grants such exemption. Such a procedure would be consistent with 
our stated goal, as described in the CGMP final rule, of providing 
flexibility in the CGMP requirements.
    We also include a requirement to ensure that the manufacturer keeps 
the FDA's response to a petition submitted under Sec.  111.75(a)(1)(ii) 
as a record under Sec.  111.95 (21 CFR 111.95).
    We did not include this exemption procedure in the CGMP final rule 
because we wanted to provide an opportunity for interested persons to 
comment on whether this exemption procedure should be modified, and if 
so, whether there is any additional information that may be helpful to 
articulate with respect to what a petition needs to show that may 
inform future guidance. We believe, based on comments to the proposed 
rule, that some manufacturers may have already developed internal 
processes or methods, that involve less than 100 percent identity 
testing, to ensure the identity of dietary ingredients. For example, 
some comments recommended that the frequency of testing requirements, 
in general, be established using a statistically valid method and that 
the extent of testing be reduced taking into account the history of the 
supplier. Other comments mentioned the use of vendor audits. Therefore, 
we did consider the possibility of alternatives to the requirement of 
100 percent identity testing of dietary ingredients in the CGMP final 
rule. We chose to issue this IFR to provide an opportunity to obtain 
additional comment on an exemption process (see the Comments section of 
this document). We also determined that the manufacturer's opportunity 
to collect data to establish such an assurance should not be delayed 
until a decision on whether the exemption procedure set forth in this 
IFR should be modified.
    Our legal authority for the provision in Sec.  111.75(a)(1)(i) and 
(a)(1)(ii), and the provision in Sec.  111.95(b)(6), set forth in the 
following paragraph, is the same as that used in the CGMP final rule. 
Therefore, we incorporate by reference the discussion of our legal 
authority for the CGMP final rule (section V of the CGMP final rule) in 
this IFR.

II. Discussion and Description of Amendments to Sec.  Sec.  111.75 and 
111.95

    In this IFR we are announcing amendments to the CGMP final rule, 
published elsewhere in this Federal Register. We redesignate Sec.  
111.75(a)(1) as Sec.  111.75(a)(1)(i) and set forth a procedure for 
submission of a petition to FDA in a new Sec.  111.75(a)(1)(ii), under 
which manufacturers may request an exemption from the requirements set 
forth in Sec.  111.75(a)(1)(i) when the dietary ingredient is obtained 
from one or more suppliers identified in the petition. The codified 
provision set forth in this IFR clarifies that FDA is willing to 
consider, on a case-by-case basis, a manufacturer's conclusion, 
supported by appropriate data and information in the petition 
submission, that it has developed a system that it would implement as a 
sound, consistent means of establishing, with no material diminution of 
assurance compared to the assurance provided by 100 percent identity 
testing, the identity of the dietary ingredient before use. For 
example, the level of continued testing at a rate less than 100 percent 
should provide the statistical confidence that the probability of 
receiving a dietary ingredient that does not meet the established 
specifications for identity is less than a small chosen percentage at a 
statistical confidence level, e.g., 95 percent. The petition must set 
forth proposed alternative testing for identity while an exemption is 
in effect. If FDA grants the petition, the manufacturer must conduct 
the tests and examinations for the dietary ingredient, otherwise 
required under Sec.  111.75(a)(1)(i), under the terms specified by FDA 
when the petition is granted.
    If this IFR is not modified, we would consider a manufacturer's 
request for an exemption from the testing required by Sec.  
111.75(a)(1) of the CGMP final rule once the compliance date for that 
manufacturer (based on the varying compliance dates based on size of 
the firm, as in the CGMP final rule) passes (see the DATES section of 
this document). In the interim, a manufacturer who may want to request 
such an exemption, could gather the data and information it needs to 
support a petition for exemption under Sec.  111.75(a)(1)(ii).
    The petition would need to set forth the scientific rationale, and 
must be accompanied by the supporting data and information, for the 
proposed alternative testing that will demonstrate that there is no 
material diminution of assurance, compared to the assurance provided by 
100 percent identity testing, of the identity of the dietary ingredient 
before use in manufacturing a dietary supplement product when the 
dietary ingredient is obtained from one or more suppliers identified in 
the petition. We would consider such a petition under Sec.  10.30 (21 
CFR 10.30), the citizen petition process. Generally, Sec.  10.30 
requires your petition to include:
    <bullet> The action requested (i.e., a request for an exemption 
from the requirements of Sec.  111.75(a)(1)(i));
    <bullet> A statement of grounds;
    <bullet> A section on environmental impact, including either a 
claim for categorical exclusion under Sec.  25.30 (21 CFR 25.30) or 21 
CFR 25.32 or an environmental assessment under 21 CFR 25.40;
    <bullet> A statement certifying that, to the best of your knowledge 
and belief, your petition includes all information and views on which 
the petition relies, and that it includes representative data and 
information known to you which are unfavorable to the petition.
    You should identify any information in the petition that you 
consider to be confidential commercial or trade secret information and 
you should segregate such information from other information in your 
petition. Information in a petition for exemption under Sec.  
111.75(a)(1)(ii) that is confidential or trade secret information is 
not available for public disclosure (21 CFR 20.61). However, that would 
not preclude the agency from considering such information, such as that 
about a particular supplier's reliability, when it considers whether to 
grant or deny other petitions for exemption from 100 percent identity 
testing from other manufacturers. For example, other manufacturers may 
use the same supplier as a source of the same dietary ingredient.
    If the petition is granted, Sec.  111.75(a)(1)(i) would require the 
manufacturer to implement the system identified in the petition, which 
would include the scientific method developed by the manufacturer that 
would provide data demonstrating that less than 100 percent identity 
testing did not materially diminish assurance that the dietary 
ingredient is the correct dietary ingredient. If the petition is 
granted by FDA, the exemption from the requirement of 100 percent 
identity testing in Sec.  111.75(a)(1) would apply to the specific 
dietary ingredient, and any of its attributes (see discussion in 
section X.G.2 of the CGMP final rule), and the specific dietary 
ingredient

[[Page 34961]]

supplier or suppliers as provided in the petition.\1\ The manufacturer 
would be responsible for documenting the tests and examinations for the 
dietary ingredient under the terms specified by FDA when the petition 
is granted, and must make and keep such records under Sec.  111.325 (21 
CFR 111.325).
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    \1\ The identity of the dietary ingredient may include more than 
one attribute (see discussion in section X.G.2 of the CGMP final 
rule). For example, identity may include physical characteristics 
(such as crystal or powder), state of hydration, or part of the 
plant (roots or leaves). The term ``identity'' would include the 
manufacturer's specification(s) that would identify the attributes a 
supplier must meet.
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    When we review a manufacturer's petition requesting an exemption 
from the requirement of 100 percent identity testing, we will consider 
taking into account other data and information that we may have--for 
example, from other manufacturers who use the same supplier--in order 
to reduce the 100 percent identity testing requirements applicable to 
the particular dietary ingredient from the particular supplier. 
Relevant information from other sources may assist in the determination 
made on the manufacturer's request for exemption. FDA may request 
additional data and information from the manufacturer to assist in the 
review of the petition.
    At this juncture, dietary supplement manufacturers are best 
positioned to develop a system to ensure dietary ingredient identity, 
according to their particular specifications, that they can use to 
determine what reduced frequency of testing can be appropriately 
substituted for 100 percent identity testing. The manufacturer may 
decide that such a system could include gathering evidence of 
consistency of analytical results of the dietary ingredient within an 
acceptable range over a period of time through a history of 100 percent 
identity testing by the manufacturer, along with evidence that the 
period of time accurately reflects the range of variability of each 
specific incoming ingredient (e.g., it would capture variability caused 
by diverse factors and also would accurately reflect the prevalence of 
``errors,'' i.e., incorrect ingredients, in the incoming ingredient 
shipment lots). All sources of variability and ``error'' in incoming 
product should be identified and documented. It is important to the 
public health to ensure that the dietary ingredient, intended to be the 
dietary ingredient in the finished dietary supplement, is in fact the 
dietary ingredient used in the manufacture of the dietary supplement.
    FDA will issue guidance on the information and type of data it 
recommends be included in the citizen petition. We will issue guidance 
on what such a petition should contain and how it would be processed. 
The guidance will include our recommendations about the type of 
information that a manufacturer could obtain about each supplier that 
it intends to use for the ingredient and its specifications that would 
assist us in evaluating the petition.
    The approval of an exemption petition will be only for the dietary 
ingredient(s) and supplier(s) stated in the petition and/or FDA's 
approval, under the circumstances outlined in the petition. 
Manufacturers may use one petition to request an exemption from 100 
percent identity testing for one or more dietary ingredients and one or 
more suppliers; however, the petition needs to provide data and 
information that are specific to each dietary ingredient and each 
supplier. If the manufacturer changes dietary ingredient(s) or 
supplier(s), or any other combination thereof, FDA's approval would not 
apply to the particular changed dietary ingredient (including the 
supplier of that ingredient). FDA's approval also would not apply to 
any dietary ingredient(s) for which the supplier(s) has been changed. 
In these circumstances, the manufacturer would have to resume 100 
percent identity testing of the dietary ingredient so affected. 
However, the manufacturer would not have to necessarily resume 100 
percent identity testing for other dietary ingredients, approved in the 
same petition, that are not changed, and for which suppliers are not 
changed. Further, if at any time the verification testing conducted by 
the manufacturer, under the terms of the approved petition, results in 
the identification of an ingredient that is not the correct dietary 
ingredient, the FDA approval for that dietary ingredient and supplier 
would no longer be in effect and the manufacturer would have to return 
to 100 percent identity testing until such time as it could re-petition 
of a new exemption. If the manufacturer holding an approved petition 
becomes aware of information suggesting a change in the nature or 
quality of the supplier(s) (e.g., change in ownership or management) or 
of the dietary ingredient(s) (e.g., change in the source of the dietary 
ingredient) that may affect the identity of the dietary ingredient, the 
manufacturer should consult with FDA as to whether the approved 
petition remains in effect or whether the manufacturer should resume 
100 percent identity testing.
    In addition, we are adding a new paragraph (b)(6) to Sec.  111.95. 
The agency's response to a petition would be a record of the 
manufacturer's Production and Process Control System that the 
manufacturer must retain under Sec.  111.95. Current Sec.  111.95 Under 
this subpart, what records must you make and keep? requires that you 
must make and keep records required under this subpart in accordance 
with subpart P. The new paragraph (b)(6) added by this IFR requires 
that a manufacturer keep FDA's response to a petition submitted under 
Sec.  111.75(a)(1)(ii) as a record.

III. Final Regulatory Flexibility Analysis

A. Final Regulatory Impact Analysis

    FDA has examined the economic impacts of the IFR under 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 
and safety, and other advantages; distributive impacts; and equity). 
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 in a material way, adversely affecting 
competition, or adversely affecting jobs. A regulation is also 
considered a significant regulatory action if it raises novel legal or 
policy issues. FDA has determined that this IFR is not an economically 
significant regulatory action as defined by Executive Order 12866.
1. Need for Regulation
    Elsewhere in this issue of the Federal Register, FDA published a 
final rule, ``Current Good Manufacturing Practice in Manufacturing, 
Packaging, Labeling, or Holding Operations for Dietary Supplements'' 
(the CGMP final rule). The CGMP final rule sets forth the manufacturing 
practices necessary to ensure that dietary supplements are 
manufactured, packaged, labeled, or held in a manner that will ensure 
the quality of the dietary supplements during manufacturing, packaging, 
labeling, or holding operations.
    Under Sec.  111.75(a)(1), the CGMP final rule requires the 
manufacturer of a dietary supplement to conduct at least one 
appropriate test or examination on every incoming lot to verify the 
identity of any component that is a dietary ingredient before it is 
used in the manufacture of a dietary supplement.

[[Page 34962]]

This IFR modifies Sec.  111.75(a)(1) and renumbers it as Sec.  
111.75(a)(1)(i) and adds Sec.  111.75(a)(1)(ii). Section 
111.75(a)(1)(i) requires what is in Sec.  111.75(a)(1) of the CGMP 
final rule, but adds the following exception, ``unless you petition the 
agency under paragraph (a)(1)(ii) of this section and the agency 
exempts you from such testing.'' We will use the term ``testing'' in 
this analysis to refer to either testing or examination of incoming 
ingredients, whichever is appropriate.
    Section 111.75(a)(1)(ii) sets forth criteria for what must be 
included in a petition for an exemption from the need for 100 percent 
identity testing of dietary ingredients. Specifically, the petition 
must set forth the scientific rationale, and must be accompanied by 
scientific data and information, for the proposed alternative testing 
that will demonstrate that there is no material diminution of 
assurance, compared to the assurance provided by 100 percent identity 
testing, of the identity of the dietary ingredient before use when the 
dietary ingredient is obtained from one or more suppliers identified in 
the petition.\2\
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    \2\ The identity of the dietary ingredient may include more than 
one attribute (see discussion in section X.G.2 of the CGMP final 
rule). For example, identity may include physical characteristics 
(such as crystal or powder), state of hydration, or part of the 
plant (roots or leaves). The term ``identity'' would include the 
manufacturer's specification(s) that would identify the attributes a 
supplier must meet.
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    If the petition is granted, then the manufacturer of the dietary 
supplement would not have to complete 100 percent identity testing on 
that particular dietary ingredient when it is received from the 
supplier specified in the petition.\3\ Instead, the manufacturer would 
have to conduct the tests and examinations for the dietary ingredient 
under the terms specified by FDA when the petition is granted. Such 
alternative testing would be based on a scientific method (as explained 
in the manufacturer's petition to FDA) to establish that there is no 
material diminution of assurance of the identity of the ingredients, 
compared to the assurance provided by 100 percent identity testing. For 
example, the level of continued testing at a rate less than 100 percent 
should provide the statistical confidence that the probability of 
receiving a dietary ingredient that does not meet the established 
specifications for identity is less than a small chosen percentage at a 
statistical confidence level, e.g., 95 percent.
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    \3\ Multiple dietary ingredients and suppliers can be discussed 
in the petition as long as testing on each ingredient and 
information about each supplier is fully documented.
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    The exemption from 100 percent identity testing of dietary 
ingredients gives dietary supplement manufacturers, who choose to 
request an alternative testing regime and obtain permission from FDA 
for an exemption, potential relief from the burden of having to test 
the identity of every lot of dietary ingredients, while not reducing 
the quality of such ingredients used in the manufacture of finished 
products.
2. IFR Coverage
    Number of establishments affected
    In the regulatory impact analysis of the CGMP final rule, published 
elsewhere in this issue of the Federal Register, FDA identifies 1,460 
establishments that manufacture, pack, hold, label, or otherwise 
process dietary supplements. The CGMP final rule requires 100 percent 
identity testing of all dietary ingredients used in the manufacture of 
dietary supplements. Firms who take advantage of the exemption petition 
process in this IFR would not have to complete 100 percent identity 
testing after a sufficient period of time\4\ in which 100 percent 
identity testing has been done by the firm and data has been collected 
to support its alternative testing regime.
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    \4\ What a ``sufficient period of time'' is would likely vary, 
depending, for example, on the supplier, the identity 
specifications, controls that are in place to ensure that a 
consistent product is produced, and the risk of false identity of 
the dietary ingredient. Therefore, the provision does not specify 
how long testing would need to be done before a petition would be 
appropriate. For purposes of this analysis, we assume that the 
timeframe would be 1 year.
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    We do not know how many firms will take advantage of the option to 
petition FDA. For purposes of this analysis we present two petition 
application rate scenarios in our following estimates; a slower rate 
and a faster rate of application. The slower rate assumes that 10 
percent of firms will petition FDA in the first year and an additional 
20 percent of firms will petition FDA in years 2 through 4. A steady 
state is assumed for year 5 and beyond where 30 percent of firms will 
still be conducting 100 percent identity testing, 60 percent of firms 
will be conducting verification testing only and 10 percent of firms 
will be petitioning FDA. The faster petition submission rate scenario 
assumes 50 percent of firms will petition FDA in the first year, 20 
percent of firms will petition in year 2, and 10 percent of firms will 
petition in each of years 3 and 4. The steady state rate for year 5 and 
beyond assumes that 10 percent of firms will still be conducting 100 
percent identity testing, 80 percent of firms will be conducting 
verification testing only, and 10 percent of firms will be petitioning 
FDA.
3. Costs and Benefits of Exemption Provision
    The baseline for this analysis is the costs and benefits of the 
CGMP final rule, published elsewhere in this issue of the Federal 
Register. We will discuss the changes from the baseline (the changes in 
costs and benefits from the final rule), as the result of the petition 
process and possible outcomes, in this IFR analysis.
    In order to achieve a level of assurance for incoming ingredients 
that will demonstrate that there is no material diminution of 
assurance, compared to the assurance provided by 100 percent identity 
testing, firms would have to use models that incorporate representative 
sampling, to ensure that the incoming materials they receive are what 
they are intended to be. We will assume that firms may, through a 
combination of supplier risk evaluations and 100 percent sampling 
followed by verification testing, achieve a level of assurance that 
continued 100 percent testing would generate. The level of continued 
testing at a rate less than 100 percent should provide the statistical 
confidence that the probability of receiving a dietary ingredient that 
does not meet the established specifications for identity is less than 
a small chosen percentage at a statistical confidence level, e.g., 95 
percent. Although FDA is not prescribing exactly what each manufacturer 
would do to establish this assurance, we will present a likely 
mechanism as a means of estimating the cost savings (from 100 percent 
testing) of this approach.
    In any given year, a firm may be in one of three states with 
respect to incoming ingredients:
    <bullet> State 1 consists of 100 percent testing of all incoming 
ingredients (default-baseline).
    <bullet> State 2 consists of:
    1. 100 percent sampling over a period of time (such as a year) with 
no tests indicating that the ingredient purporting to be the dietary 
ingredient was not the dietary ingredient;
    2. Completed risk evaluations of the ingredient supplier (performed 
by the manufacturer or third party auditors) finding a low risk of 
shipping the wrong ingredient (as well as assuring that the supplier 
firm had a comprehensive quality control system described later in this 
analysis); and,
    3. A scientific showing that the information from the two prior 
results

[[Page 34963]]

would allow a reduced rate of testing that would result in no material 
diminution of assurance in the identity of the dietary ingredient as 
compared to continued 100 percent testing. This data will be contained 
in a petition to the agency as support for the recommended 
representative testing scheme.
    If FDA grants the petition, firms will be required to do 
verification testing, instead of ongoing 100 percent identity testing, 
and to keep records of such testing.\5\ State 2 is presumed to exist 
any time there is a new supplier, new ingredients, new 
specification(s), or a new dietary supplement manufacturer who receives 
incoming dietary ingredients.
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    \5\ The records of the verification testing would be subsumed 
under subpart J, Sec.  111.325 of the CGMP final rule published 
elsewhere in this issue of the Federal Register.
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    <bullet> State 3 consists of verification testing only.
    Assumptions and costs associated with this IFR
    We assume that some manufacturers will complete the 100 percent 
identity testing of dietary ingredients and supplier risk evaluations 
to provide data to support a petition request to the agency. The cost 
savings associated with the petition exemption process would come from 
those manufacturers who complete 100 percent identity testing of 
dietary ingredients for a period of time, obtain data that can be used 
as part of a qualitative evaluation of risk associated with a 
particular dietary ingredient/supplier combination, develop a 
verification testing process, and then petition the agency for the 
identity testing exemption. For purposes of this analysis, we expect 
the petition to include information about the supplier(s), the dietary 
ingredient(s) and its identity specification(s), information about the 
manufacturer and its testing, and the test results from the supplier 
and manufacturer for the dietary ingredient(s). We expect that the 
manufacturer will provide data to support a system to assure no 
material diminution of assurance as 100 percent identity testing, e.g., 
the level of continued testing at a rate less than 100 percent should 
provide the statistical confidence that the probability of receiving a 
dietary ingredient that does not meet the established specifications 
for identity is less than a small chosen percentage at a statistical 
confidence level.
    We also assume that firm size, resources available, and number of 
incoming ingredient lots received annually will likely play a large 
role in which firms apply for an exemption from 100 percent testing. 
Firms that do not receive many ingredient lots annually will probably 
not find it cost effective to apply for an exemption because the costs 
of developing a verification testing method and conducting third party 
audits would reduce or eliminate any cost savings from reduced identity 
testing.
    For those firms that do see an incentive to petition for an 
exemption, we assume that some proportion of them will be able to 
develop the information described previously in bullets 1 and 2 under 
State 2. We also assume that, for some firms, this information provides 
adequate support to allow them to implement a verification testing 
scheme with a the level of continued testing at a rate less than 100 
percent that should provide the statistical confidence that the 
probability of receiving a dietary ingredient that does not meet the 
established specifications for identity is less than a small chosen 
percentage at a statistical confidence level, e.g., 95 percent. Table 1 
of this document shows a verification testing scheme for identity 
verification testing that is equal to the square root (SQRT) of (n) 
+1.\6\ We request comment on the use of this sampling plan for this 
purpose. Under this verification testing scheme, the cost savings of 
applying for an exemption increases as the number of lots increase 
above 100 lots per year. Thus, applying for an exemption is more cost 
effective for firms that receive 100 lots or greater for a particular 
ingredient per year.
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    \6\ While statistical sampling plans are numerous, we chose the 
SQRT of (n) +1 from a normal distribution for ease of use. The above 
sampling chart (of SQRT of (n) + 1 values) assumes normal Gaussian 
distribution of error and loses accuracy in the lower ends of the 
distribution. This method of sampling was not specifically designed 
for confirming identity. FDA's Office of Regulatory Affairs, 
Investigations Operation Manual (IOM) uses the SQRT of (n) + 1 rule 
for compliance sampling, including chemical contamination, filth, 
pesticides, mold, bacteria, and identity.

                                           Table 1.--Testing Rates at
                                                  SQRT (n) + 1
                                             Number of Lots per Year
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Total                          10            50           100            1,000            5,000           10,000
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Sampled                         4             8            11               32               72              101
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Percent sampled               40%           16%           10%             3.0%             1.4%             1.0%
----------------------------------------------------------------------------------------------------------------

    If, for example, the petitioner chooses to follow FDA Office of 
Regulatory Affairs' inspection guidelines that direct the conduct of 
field investigational activities, including those related to the 
assessment of violations under the adulteration provisions of the 
act,\7\ the petitioner would propose setting an upper and lower limit 
for verification testing of incoming ingredient lots. For example, 
plausible limits would be a minimum of 11 lots for manufacturers with 
incoming lots of 100 or less per ingredient (about 10 percent of lots), 
all lots if the total was less than 10 annually (these manufacturers 
would not apply for an exemption as they would still be testing 100 
percent with or without the exemption) and a maximum of 32 lots for all 
manufacturers that have 1,000 or more incoming lots per ingredient 
tested annually. We use these verification testing limits when we 
estimate the cost savings that follow.
---------------------------------------------------------------------------

    \7\ See FDA Investigations Operations Manual 2006, sec 4.3.7.2 
on Random Sampling.
---------------------------------------------------------------------------

    Costs to firms who petition for exemption

    As stated previously, firms that intend to petition for an 
exemption from 100 percent identity testing will incur costs which, at 
a minimum will include: Employing a statistical expert to develop a 
verification testing plan that can prove the firm can adhere to the 
standard of ``no material diminution of assurance''; performing in-
house, or contracting out for, a risk evaluation for each ingredient 
and supplier; and, providing the results of some period of 100 percent 
testing (which we assume

[[Page 34964]]

for purposes of this analysis to be 1 year).
    In addition, as part of the supplier risk evaluation, we assume 
suppliers would demonstrate to manufacturers that they have a quality 
management system (QMS) in place and that it has been independently 
audited (certified) by a third party. We assume this QMS would, at a 
minimum, contain the following procedures:
    1. Monitoring of manufacturing processes to ensure they are 
producing quality product;
    2. Keeping proper records;
    3. Checking outgoing product for defects, with appropriate 
corrective action where necessary; and,
    4. Regularly reviewing individual processes and the quality system 
itself for effectiveness.
    100 percent identity testing
    The costs for 100 percent identity testing are calculated using the 
Identity Testing Model from the CGMP final rule published elsewhere in 
this issue of the Federal Register. The costs of 100 percent identity 
testing are costs of the final rule, not this IFR.
    Statistical sampling plan for verification testing
    Developing a statistical sampling plan that will assure a firm of 
adhering to the standard of ``no material diminution of assurance'' may 
vary with firm size, supplier or manufacturer characteristics, nature 
of the dietary ingredient, or type of dietary supplement manufactured. 
Thus, firms wishing to get an exemption from 100 percent identity 
testing may hire a statistician to develop a verification testing plan 
that will be acceptable to FDA. Using a statistician's mean hourly wage 
of $31.79, (Ref. 1), plus 50 percent for overhead, we estimate it will 
take a statistician 20 hours to develop an appropriate plan. The total 
cost for a statistician would be $954 ($47.69 per hour X 20 hours). We 
request comment on this estimate.
    Supplier risk evaluations (Third party audits)
    We assume that qualitative supplier risk evaluations would be 
developed and then administered to a firm's suppliers. We expect 
manufacturing firms would hire a risk analyst to develop an appropriate 
supplier risk evaluation, administer it to the suppliers in question, 
and then analyze the results. We estimate that it will take a risk 
analyst 40 hours to conduct the work necessary to have complete 
evaluations of ingredient suppliers' risk.\8\ We use the hourly mean 
wage of a risk management analyst ($27.90) (Ref. 1), plus 50 percent 
for overhead to calculate the cost of completing the supplier risk 
evaluations. The total cost for supplier risk evaluations is $1,674 
($41.85 per hour x 40 hours). We request comment on this estimate.
---------------------------------------------------------------------------

    \8\ This is an average cost. The time needed and therefore the 
cost of evaluations may be more or less depending on the number of 
suppliers and ingredients that are being evaluated.
---------------------------------------------------------------------------

    As stated previously, since FDA is not prescribing a specific 
scientific method for how dietary supplement manufacturers can assure 
the identity of a dietary ingredient when less than 100 percent 
identity testing is performed, there may be many ways that dietary 
supplement manufacturers may conduct risk evaluations or develop a 
verification testing plan as part of the petition process.
    One possible scenario is that market forces could cause a new 
industry to evolve whereby a third party or an intermediary conduct 
identity tests on dietary ingredients and/or perform supplier risk 
evaluations and sell the results. Certain suppliers of dietary 
ingredients may find it to their competitive advantage to hire an 
independent third party to conduct such testing. These intermediaries 
might obtain samples from a variety of suppliers over the course of a 
year, test those samples for identity using certain specifications, and 
then sell the results of the year's testing to dietary supplement 
manufacturers--e.g., small businesses who cannot test on their own and 
would have to contract out the testing. Another possibility is that 
manufacturers sell the results of testing and risk evaluation to other 
manufacturers or the original supplier. The supplier may use such 
information in marketing as an incentive for manufacturers to buy that 
supplier's product.
    Petition process
    The petitions, which we assume would include the results of 1 
year's testing (for purposes of this analysis), the recommended 
verification testing plan, and the supplier risk evaluation, will sort 
those manufacturers who have reliable suppliers from those that do not. 
The petition is assumed to take 8 hours per plant for assembly of the 
information.\9\ The wage for a first-line production supervisor 
($23.66) (Ref. 1), plus 50 percent for overhead, is used to estimate 
the costs of petition assembly. The total cost of assembling a single 
petition, for single or multiple ingredients and suppliers, is 
estimated to be about $284 (8 hours x $35.49 per hour).
---------------------------------------------------------------------------

    \9\ In the analysis of the final rule we determined that vitamin 
and mineral products contain about 13 listed dietary ingredients per 
product and other dietary supplements, mainly herbals, contain about 
4 listed dietary ingredients per product.
---------------------------------------------------------------------------

    Costs of quality management systems and certification
    For those suppliers who do not have QMS, the costs of putting them 
into place are likely to run into tens of thousands of dollars. A 
supplier would only install this type of system if they wish to sell, 
or continue selling, to manufacturers who are likely to petition the 
agency for an exemption from 100 percent testing. As presently 
constructed, it is likely that only larger firms who are more able to 
bear the fixed costs of the rule (supplier risk evaluations, 
certification costs, and costs of preparing petitions) are likely to 
petition the agency for an exemption. Further, we assume that virtually 
all suppliers to these large manufacturers already have some sort of a 
QMS in place, particularly those that are domestic. However, it is 
unclear how many foreign suppliers have these systems. FDA has no data 
on the number of supplier firms who might have such systems and is 
unable to estimate the likely cost additions of either putting these 
systems in or the cost of certifying these systems. Therefore, all cost 
estimates contained in this analysis should be viewed as lower bounds.
    Total costs to firms
    Table 2 shows the total costs per firm to submit a petition for an 
exemption from 100 percent identity testing of dietary ingredients used 
in the manufacture of dietary supplements.

 Table 2.--Total Costs per Firm to Submit a Petition for Exemption from
                      100 Percent Identity Testing
------------------------------------------------------------------------
                          Activity                               Cost
------------------------------------------------------------------------
Verification Testing Plan                                           $954
------------------------------------------------------------------------
Risk Evaluation                                                   $1,674
------------------------------------------------------------------------
Petition Assembly                                                   $284
------------------------------------------------------------------------
Total Cost Per Firm                                               $2,912
------------------------------------------------------------------------

    Petition review
    It will take FDA approximately 40 hours to review a petition. The 
cost of each petition review would be $1,826 (40 hours x $45.65 per 
hour).\10\
---------------------------------------------------------------------------

    \10\ Pay for an employee earning a GS-13, step 7 adjusted to 
include locality pay for Washington, DC and the surrounding area.
---------------------------------------------------------------------------

    Amendments and updates to petitions
    In cases where a petition has been granted and the manufacturer has 
changed ingredients, specifications, or suppliers or any combination 
thereof,

[[Page 34965]]

we assume that the original petition would no longer be applicable and 
a new petition would need to be submitted. We do not attempt to 
calculate the costs of amendments and updates to petitions here. 
However, we note that manufacturers are likely to take the likelihood 
of these changes into account before beginning the process of gathering 
information to submit a petition. The sooner the likelihood of a 
change, the less likely a manufacturer will petition for an exemption.
    If at any time verification testing conducted by the manufacturer 
produces an ingredient that is not the correct ingredient, the approved 
petition would no longer be considered in effect, and the manufacturer 
would need to return to 100 percent identity testing and re-petition 
for another exemption.
    Petition approval uncertainty
    We assume that not all firms that petition FDA will be approved for 
an exemption from 100 percent identity testing (for example, some 
petitions may contain insufficient data or an unacceptable verification 
testing plan). Another reason for the uncertainty in application and 
acceptance rates is the degree of uncertainty manufacturers face about 
acceptance of their plan. However, at some point, FDA may have 
sufficient data to provide more information about classes of dietary 
ingredients and supplier conditions so as to be able to provide 
manufacturers with more standardized information that will help them 
choose a plan. Some degree of uncertainty also exists for small firms 
as, given the verification testing plan outlined previously, firms 
receiving fewer than 10 incoming lots of a specific ingredient annually 
will not benefit from a petition exemption (all lots would still have 
to be tested).
    We cannot know what percentage of firms will apply for exemption or 
what percentage of firms will be successful in their petition 
submission. Table 3 diagrams how firms may respond to the option of 
petitioning FDA for exemption based on firm size.

         Table 3.--Likelihood of Petition Attempts by Firm Size
------------------------------------------------------------------------
                                               Likelihood of Petition
                                                     Submission
                 Firm Size                 -----------------------------
                                             Do not             Petition
                                            Petition  Petition   Success
------------------------------------------------------------------------
Very Small (< 20 employees)                     Most       Few         ?
------------------------------------------------------------------------
Small (20 to 499 employees)                     Some      Some         ?
------------------------------------------------------------------------
Large (500 or more employees)                    Few      Most         ?
------------------------------------------------------------------------

    Estimated cost savings from petition exemptions
    The cost savings associated with the testing exemption provided for 
in this IFR are highly dependent on:
    <bullet> The number of tests required for verification that is 
allowed in the place of on-going 100 percent identity testing,
    <bullet> How many firms apply for exemption,
    <bullet> How many ingredients firms apply for exemption from 
testing for, and,
    <bullet> The likelihood that FDA will approve the exemption.
    Nevertheless, we assume that it is likely that firms will assume 
their petition exemption will be successful if they provide the 
required documentation and assert that they will follow a verification 
sampling plan based on the bounded square root of (n)+1 methodology 
outlined previously.
    Expected cost savings from petition exemptions: $7.3 to $37.3 
million per year
    Years 1 through 5 cost estimates for 100 percent testing and for 
verification testing are shown in table 4 of this document. The cost 
savings associated with this IFR are calculated by subtracting the cost 
estimates for year 5, respectively, from the estimated cost for 100 
percent testing. Steady state costs are calculated, where the fixed 
costs of the risk evaluation and petition process are amortized over a 
10-year period.\11\
---------------------------------------------------------------------------

    \11\ Amortization rate over 10 years for fixed costs is 7 
percent. The estimates do not change when the amortization rate is 3 
percent.
---------------------------------------------------------------------------

    Table 4 presents the cost savings as they would be realized under 
two petition application rate scenarios; a slower rate and a faster 
rate of application. The slower rate assumes that about 10 percent of 
firms will petition FDA in the first year and an additional 20 percent 
of firms will petition FDA in years 2 through 4. A steady state is 
assumed for year 5 and beyond where 30 percent of firms will still be 
conducting 100 percent identity testing, 60 percent of firms will be 
conducting verification testing only and 10 percent of firms will be 
petitioning FDA. The faster petition submission rate scenario assumes 
about 50 percent of firms will petition FDA in the first year, 20 
percent of firms will petition in year 2, and 10 percent of firms will 
petition in each of years 3 and 4. The steady state rate for year 5 and 
beyond assumes that 10 percent of firms will still be conducting 100 
percent identity testing, 80 percent of firms will be conducting 
verification testing only, and 10 percent of firms will be petitioning 
FDA. Given the uncertainty of petition success, we expect the lower 
petition exemption submission rate by industry is more likely, and if 
so, would mean a lower cost savings for this IFR.
    We also base the cost savings in table 4 on the probability that 
verification testing plans for very small and small firms will require 
10 percent testing and that verification testing plans for large firms 
will require 3 percent testing. We base this on the assumption that 
very small and small firms would receive 100 lots or less annually of a 
particular dietary ingredient and, following the verification testing 
plan outlined previously, would be required to test at most 10 lots or 
10 percent of all lots; large firms are assumed to receive 1,000 or 
more lots annually of a specific ingredient and would be required to 
test 30 lots at most or no more than 3 percent of all lots.
    We cannot know if dietary supplement manufacturers will petition 
for exemptions for all dietary ingredients used in their products. In 
the analysis of the CGMP final rule we determined that vitamin and 
mineral products contain about 13 listed dietary ingredients per 
product and other dietary supplements, mainly herbals, contain about 4 
listed dietary ingredients per product. We do not specify in our cost 
savings how many ingredients and suppliers are included in a 
manufacturer's petition. The cost estimate for risk evaluations 
calculated previously and used in table 4 is meant

[[Page 34966]]

to take into consideration multiple ingredients and suppliers might be 
included in a single petition.
    Several cost savings scenarios are shown in table 4 to represent 
uncertainty about who will petition for an exemption.

   Table 4.--Costs of Identity Testing for 100% Testing and for Verification Sampling (in Millions of Dollars)
                                     Cost Estimate of 100% Identity Testing
----------------------------------------------------------------------------------------------------------------
                                                                                                  Steady State
                         Year 1         Year 2         Year 3         Year 4         Year 5      After Year 5 (r
                                                                                                      = 7%)
----------------------------------------------------------------------------------------------------------------
Total Costs for              $45.9          $45.9          $45.9          $45.9          $45.9             $45.9
 100% Identity
 Testing
----------------------------------------------------------------------------------------------------------------
Slower adoption of exemption
----------------------------------------------------------------------------------------------------------------
  Total Costs for            $42.4          $34.8          $26.5          $18.2          $17.5             $16.9
   Verification
   Testing
----------------------------------------------------------------------------------------------------------------
  Cost Savings                $3.5          $11.1          $19.4          $27.7          $28.4             $29.0
----------------------------------------------------------------------------------------------------------------
Faster adoption of exemption
----------------------------------------------------------------------------------------------------------------
  Total Costs for            $28.6          $18.2          $13.3          $13.3           $9.2              $8.6
   Verification
   Testing
----------------------------------------------------------------------------------------------------------------
  Cost Savings               $17.3          $27.7          $32.6          $32.6          $36.7             $37.3
----------------------------------------------------------------------------------------------------------------

    Table 5 takes the estimates from table 4 and adjusts them to 
represent different rates of petition success.

   Table 5. Cost Savings when Petition Success Rate is not 100% Based on Steady State After Year 5 (r=7%) from
                                        Table 3 (in Millions of Dollars)
----------------------------------------------------------------------------------------------------------------
                                        100% Exemption     75% Exemption      50% Exemption      25% Exemption
                                         Success Rate       Success Rate       Success Rate       Success Rate
----------------------------------------------------------------------------------------------------------------
Cost Savings slower adoption rate                 $29.0              $21.8              $14.5               $7.3
----------------------------------------------------------------------------------------------------------------
Cost Savings faster adoption rate                 $37.3              $28.0              $18.7               $9.3
----------------------------------------------------------------------------------------------------------------

    Benefits
    The IFR provisions will cause no net change in the benefits from 
the final rule with the exception of any potential benefits from 
suppliers putting QMS in place. The provisions of the IFR still lead to 
the following benefits:
    <bullet> Reduced health costs associated with a reduced number of 
acute illnesses;
    <bullet> Fewer product recalls; and
    <bullet> Reduced health costs associated with a reduced number of 
chronic illnesses and conditions.
    The opportunity the IFR provides for reduced identity testing of 
dietary ingredients should not change these benefits.
    If, in fact, any suppliers install QMSs as a result of this rule, 
the benefits would be that raw materials would be less likely to be 
contaminated or adulterated. So if the raw material is less likely to 
be contaminated or adulterated, then dietary supplements that are made 
with that raw material are also less likely to be contaminated and 
adulterated.

B. Final Regulatory Flexibility Analysis

    FDA has examined the economic implications of this IFR 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 has concluded that this IFR will not have a significant 
economic impact on a substantial number of small entities.
    FDA determined in the CGMP final rule that there are 774 very small 
establishments (less than 20 employees) and 526 small establishments 
(20 to 499 employees) that will be affected by the requirements of the 
CGMP final rule. These establishments may or may not take advantage of 
the petition exemption process provided for in this IFR.
    The likelihood of very small and small firms taking advantage of 
the exemption depends largely on the annual minimum number of lots of 
dietary ingredients for which they will have to test for identity and 
the size of the fixed costs associated with the supplier risk 
evaluation and petition costs. FDA has not specified how many lots are 
an acceptable minimum. If a plausible limit is a minimum of 10 lots for 
manufacturers with incoming lots of 100 or less per ingredient (about 
10 percent of lots) and all lots total less than 10 annually, then 
there will be some small and very small manufacturers who will not 
apply for an exemption because they would still have to test 100 
percent of incoming lots for identity whether they applied for an 
exemption or not.

[[Page 34967]]

C. Unfunded Mandates

    Title II of the Unfunded Mandates Reform Act of 1995 (Public Law 
104-4) requires cost-benefit and other analyses before any rulemaking 
if the rule would include a ``Federal mandate that may result in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any one year.'' The current threshold after 
adjustment for inflation is $118 million, using the most current (2004) 
Implicit Price Deflator for the Gross Domestic Product. FDA has 
determined that this IFR does not constitute a significant rule under 
the Unfunded Mandates Reform Act.

IV. Paperwork Reduction Act of 1995

    This IFR contains information collection requirements that are 
subject to review by the Office of Management and Budget (OMB) under 
the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-3520). 
The title, description, and respondent description of these provisions 
are shown in the following paragraphs with an estimate of the annual 
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.
    FDA invites comments on: (1) Whether the interim final collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
interim final collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Current Good Manufacturing Practice in Manufacturing, 
Packaging, Labeling, or Holding Operations for Dietary Supplements
    Description: Section 402(g) of the Federal Food, Drug, and Cosmetic 
Act (the act) (21 U.S.C. 342(g)) gives us explicit authority to issue a 
rule establishing CGMP requirements for dietary supplements. Section 
402(g)(1) of the act states that a dietary supplement is adulterated if 
``it has been prepared, packed, or held under conditions that do not 
meet current good manufacturing practice regulations.'' Section 
402(g)(2) of the act authorizes us to, by regulation, ``prescribe good 
manufacturing practices for dietary supplements.'' Under section 701(a) 
of the act (21 U.S.C. 371), FDA may issue regulations necessary for the 
efficient enforcement of the act. Other relevant legal authority is 
discussed in section V of the CGMP final rule. In the PRA analysis of 
the CGMP final rule (section XXVIII), we discuss why records are an 
indispensable component of CGMP (and incorporate that discussion by 
reference in this IFR).
    Under Sec.  111.75(a)(1), the CGMP final rule requires the 
manufacturer of a dietary supplement to conduct at least one 
appropriate test or examination on every incoming lot to verify the 
identity of any component that is a dietary ingredient before it is 
used in the manufacture of a dietary supplement. This IFR modifies 
Sec.  111.75(a)(1) and renumbers it as Sec.  111.75(a)(1)(i) and adds 
Sec.  111.75(a)(1)(ii). Section 111.75(a)(1)(i) requires what is in 
Sec.  111.75(a)(1) of the CGMP final rule, but adds the following 
exception, ``unless you petition the agency under subparagraph (1)(ii) 
of this paragraph and the agency exempts you from such testing.'' 
Section 111.75(a)(1)(ii) sets forth criteria for what must be included 
in a petition for an exemption from the need for 100 percent identity 
testing of dietary ingredients. Specifically, the petition must set 
forth the scientific rationale, and must be accompanied by scientific 
data and information, for proposed alternative testing that will 
demonstrate that there is no material diminution of assurance, compared 
to the assurance provided by 100 percent identity testing, of the 
identity of the dietary ingredient before use when the dietary 
ingredient is obtained from one or more suppliers identified in the 
petition.
    Description of Respondents: Manufacturers, dietary supplement 
manufacturers, packagers and re-packagers, labelers and re-labelers, 
holders, distributors, warehousers, exporters, importers, large 
businesses, and small businesses.
    FDA estimates the burden for this information collection as 
follows:

                             Table 6.--Estimated One-Time Burden to Petition FDA\1\
----------------------------------------------------------------------------------------------------------------
                       Number of        Frequency per
  21 CFR Section     Recordkeepers      Recordkeeping      Total  Records   Hours  per Record     Total Hours
----------------------------------------------------------------------------------------------------------------
111.75 (a)1(b)                 1,460                  1              1,460                8               11,680
----------------------------------------------------------------------------------------------------------------
111.95                         1,460                  1               1460                0.1                146
----------------------------------------------------------------------------------------------------------------
Total One time burden                                                                                     11,826
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating costs associated with the collection of information under this IFR.

One-time Burden
    In the regulatory impact analysis of the CGMP final rule, published 
elsewhere in this issue of the Federal Register, FDA identifies 1,460 
establishments that manufacture, pack, hold, label, or otherwise 
process dietary supplements. We assume that at least some manufacturers 
would like to take advantage of the opportunity to petition FDA to 
eliminate the need to do 100 percent identity testing for the dietary 
ingredients they use in the manufacture of their products. Therefore, 
for this PRA analysis, we will make an assumption that every 
establishment will submit a petition to FDA for review and approval 
requesting an exemption from 100 percent identity testing for at least 
one dietary ingredient from at least one supplier. We ask for comment 
about whether manufacturers would be interested in seeking an exemption 
for 100 percent identity testing, and if so, for how many ingredients 
and from how many suppliers.
    As stated in the previous analysis, the petitions, which we assume 
would include the results of 1 year's testing, verification testing 
plan, and the supplier risk evaluation, will take 8 hours per plant for 
assembly of the information. Assuming that all establishments submit a 
petition for exemption for at least one dietary ingredient/supplier 
combination, the hour burden estimate for this activity is

[[Page 34968]]

11,680 hours (1,460 establishments x 8 hours per establishment).
Recordkeeping Burden
    We assume that the only recurring burden would be only for 
maintenance of records. The records of the verification testing would 
be subsumed under Sec.  111.325 of the final rule published elsewhere 
in this issue of the Federal Register. FDA's response to the petition 
submitted under Sec.  111.75(a)(1)(ii) would be a new record associated 
with this IFR under Sec.  111.95. This would be, at a minimum, a one-
time burden for each establishment that petitioned the agency for an 
exemption. Again, assuming that each firm petitions the agency, the 
burden would be 146 hours (0.1 hours x 1460 firms).
    The information collection provisions of this IFR have been 
submitted to OMB for review. Interested persons are requested to fax 
comments regarding the information collection by (see DATES), to the 
Office of Information and Regulatory Affairs, OMB (see ADDRESSES).
    Prior to the effective date of this IFR, FDA will publish a notice 
in the Federal Register announcing OMB's decision to approve, modify, 
or disapprove the information collection provisions in this final rule. 
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.

V. Comments

    FDA is issuing this rule as an IFR, with an opportunity for public 
comment. Although the agency is seeking comment on this IFR, it is 
effective August 24, 2007.
    Compliance Dates: The compliance date is June 25, 2008; except that 
for businesses employing fewer than 500, but 20 or more full-time 
equivalent employees, the compliance date is June 25, 2009; and except 
that for businesses that employ fewer than 20 full-time equivalent 
employees, the compliance date is June 25, 2010. This means that the 
rule's requirements will be in effect and have the force and effect of 
law from those dates until any subsequent modification by the issuance 
of a final rule.
    FDA will consider all comments submitted. FDA is dedicated to 
updating the Regulatory Impact Analysis with the best available 
information in order to inform decisionmakers who may be considering 
regulatory alternatives in developing a final rule. Interested persons 
may submit to the Division of Dockets Management (see ADDRESSES) 
written or electronic comments regarding this IFR. Two copies of any 
comments are to be submitted, except that individuals may submit one 
copy. Submit one electronic copy. Comments are to be identified with 
the docket number found in brackets in the heading of this document. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday. We will address 
comments received and confirm or modify the IFR in a final rule. We 
will not consider any comments previously considered during the 
rulemaking for the CGMP final rule, published elsewhere in this Federal 
Register.

VI. Analysis of Environmental Impact

    The agency has carefully considered the potential environmental 
effects of this action. We have concluded under Sec.  25.30(h) 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.

VII. Federalism

    FDA has analyzed this IFR in accordance with the principles set 
forth in Executive Order 13132. Section 4(a) of the Executive Order 
requires agencies to ``construe * * * a Federal statute to preempt 
State law only where the statute contains an express preemption 
provision or there is some other clear evidence that the Congress 
intended preemption of State law, or where the exercise of State 
authority conflicts with the exercise of Federal authority under the 
Federal statute.'' FDA has determined that the IFR does not contain 
policies that have substantial direct effects on the States, on the 
relationship between the National Government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government. Accordingly, we conclude that the IFR does not contain 
policies that have federalism implications as defined in the Executive 
order and, consequently, a federalism summary impact statement is not 
required.

VIII. References

    The following references have been placed on display in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. ISO 9001-2005, Quality Management Systems--Fundamentals and 
Vocabulary.
    E1. Occupational Employment and Wages, May 2005, Bureau of Labor 
Statistics, www.bls.gov, accessed March 20, 2006.

List of Subjects

21 CFR Part 111

    Dietary foods, Drugs, Foods, Packaging and containers.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
111 is amended as follows:

PART 111--CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, 
PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS

0
1. The authority citation for 21 CFR part 111 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 342, 343, 371, 374, 381, 393; 42 
U.S.C. 264.

0
2. Section 111.75 is amended by revising paragraph (a)(1) to read as 
follows:


Sec.  111.75  What must you do to determine whether specifications are 
met?

    (a) * * *
    (1)(i) Conduct at least one appropriate test or examination to 
verify the identity of any component that is a dietary ingredient, 
unless you petition the agency under paragraph (a)(1)(ii) of this 
section and the agency exempts you from such testing;
    (ii) You may submit a petition, under 21 CFR 10.30, to request an 
exemption from the testing requirements in paragraph (a)(1)(i) of this 
section. The petition must set forth the scientific rationale, and must 
be accompanied by the supporting data and information, for proposed 
alternative testing that will demonstrate that there is no material 
diminution of assurance, compared to the assurance provided by 100 
percent identity testing, of the identity of the dietary ingredient 
before use when the dietary ingredient is obtained from one or more 
suppliers identified in the petition. If FDA grants the petition, you 
must conduct the tests and examinations for the dietary ingredient, 
otherwise required under Sec.  111.75(a)(1)(i), under the terms 
specified by FDA when the petition is granted; and
* * * * *

0
3. Section 111.95 is amended by adding new paragraph (b)(6) to read as 
follows:


Sec.  111.95  Under this subpart E, what records must you make and 
keep?

* * * * *

[[Page 34969]]

    (b) * * *
    (6) Documentation of FDA's response to a petition submitted under 
Sec.  111.75(a)(1)(ii) providing for an exemption from the provisions 
of Sec.  111.75(a)(1)(i).

    Dated: May 8, 2007.
Andrew C. von Eschenbach,
Commissioner of Food and Drugs.

    Dated: May 8, 2007.
Michael O. Leavitt,
Secretary of Health and Human Services.
[FR Doc. 07-3038 Filed 6-22-07; 8:45 am]
BILLING CODE 4160-01-S