Federal Register / Vol. 72, No. 121 / Monday, June 25, 2007 / Rules and Regulations 34959 

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. 

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: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• 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: 

• FAX: 301–827–6870. 

• 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 email. 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, § 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 


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34960 Federal Register / Vol. 72, No. 121 / Monday, June 25, 2007 / Rules and Regulations 

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 

§ 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 § 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 § 111.75(a)(1)(ii) as a record 

under § 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 § 111.75(a)(1)(i) and (a)(1)(ii), and the 

provision in § 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 § § 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 § 111.75(a)(1) 

as § 111.75(a)(1)(i) and set forth a 

procedure for submission of a petition 

to FDA in a new § 111.75(a)(1)(ii), under 

which manufacturers may request an 

exemption from the requirements set 

forth in § 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 

§ 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 

§ 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 

§ 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 § 10.30 (21 CFR 10.30), 

the citizen petition process. Generally, 

§ 10.30 requires your petition to 

include: 

• The action requested (i.e., a request 

for an exemption from the requirements 

of § 111.75(a)(1)(i)); 

• A statement of grounds; 

• A section on environmental impact, 

including either a claim for categorical 

exclusion under § 25.30 (21 CFR 25.30) 

or 21 CFR 25.32 or an environmental 

assessment under 21 CFR 25.40; 

• 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 § 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, 

§ 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 § 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 


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1The 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. 

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 

§ 111.325 (21 CFR 111.325). 

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 § 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 

§ 111.95. Current § 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 § 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 § 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. 


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2The 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. 

3Multiple 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. 

4What 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. 

This IFR modifies § 111.75(a)(1) and 

renumbers it as § 111.75(a)(1)(i) and 

adds § 111.75(a)(1)(ii). Section 

111.75(a)(1)(i) requires what is in 

§ 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

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. 

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 time4 in which 100 percent identity 

testing has been done by the firm and 

data has been collected to support its 

alternative testing regime. 

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: 

• State 1 consists of 100 percent 

testing of all incoming ingredients 

(default-baseline). 

• 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 


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5The records of the verification testing would be 

subsumed under subpart J, § 111.325 of the CGMP 

final rule published elsewhere in this issue of the 

Federal Register. 

6While 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. 

7See FDA Investigations Operations Manual 

2006, sec 4.3.7.2 on Random Sampling. 

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. 

• 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. 

TABLE 1.—TESTING RATES AT

SQRT (n) + 1 

Number of Lots per Year 

Total 10 50 100 1,000 5,000 10,000 

Sampled 4 8 11 32 72 101 

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. 

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 


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8This 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. 

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. 

10Pay for an employee earning a GS-13, step 7 

adjusted to include locality pay for Washington, DC 

and the surrounding area. 

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. 

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). 

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

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, 


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11Amortization rate over 10 years for fixed costs 

is 7 percent. The estimates do not change when the 

amortization rate is 3 percent. 

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

Firm Size 

Likelihood of Petition Submission 

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: 

• The number of tests required for 

verification that is allowed in the place 

of on-going 100 percent identity testing, 

• How many firms apply for 

exemption, 

• How many ingredients firms apply 

for exemption from testing for, and, 

• 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

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 


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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 

Year 1 Year 2 Year 3 Year 4 Year 5 

Steady State 

After Year 5 (r = 

7%) 

Total Costs for 100% Identity Testing $45 .9 $45 .9 $45 .9 $45 .9 $45 .9 $45 .9 

Slower adoption of exemption 

Total Costs for Verification Testing $42 .4 $34 .8 $26 .5 $18 .2 $17 .5 $16 .9 

Cost Savings $3 .5 $11 .1 $19 .4 $27 .7 $28 .4 $29 .0 

Faster adoption of exemption 

Total Costs for Verification Testing $28 .6 $18 .2 $13 .3 $13 .3 $9 .2 $8 .6 

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 

Success Rate 

75% Exemption 

Success Rate 

50% Exemption 

Success Rate 

25% Exemption 

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: 

• Reduced health costs associated 

with a reduced number of acute 

illnesses; 

• Fewer product recalls; and 

• 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. 


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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 § 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 § 111.75(a)(1) and 

renumbers it as § 111.75(a)(1)(i) and 

adds § 111.75(a)(1)(ii). Section 

111.75(a)(1)(i) requires what is in 

§ 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 repackagers, 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 FDA1

21 CFR Section Number of 

Recordkeepers 

Frequency per 

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 

1There 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 


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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 § 111.325 of the final rule 

published elsewhere in this issue of the 

Federal Register. FDA’s response to the 

petition submitted under 

§ 111.75(a)(1)(ii) would be a new record 

associated with this IFR under § 111.95. 

This would be, at a minimum, a onetime 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 

§ 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. 

■ 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 

■ 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. 

■ 2. Section 111.75 is amended by 

revising paragraph (a)(1) to read as 

follows: 

§ 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 

§ 111.75(a)(1)(i), under the terms 

specified by FDA when the petition is 

granted; and 

* * * * * 

■ 3. Section 111.95 is amended by 

adding new paragraph (b)(6) to read as 

follows: 

§ 111.95 Under this subpart E, what 

records must you make and keep? 

* * * * * 


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Federal Register / Vol. 72, No. 121 / Monday, June 25, 2007 / Rules and Regulations 34969 

(b) * * * 

(6) Documentation of FDA’s response 

to a petition submitted under 

§ 111.75(a)(1)(ii) providing for an 

exemption from the provisions of 

§ 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 


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