[Federal Register: June 25, 2007 (Volume 72, Number 121)]
[Rules and Regulations]
[Page 34959-34969]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25jn07-22]
[[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%
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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, http://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